Acute Poisonings

Emergency Care of Acute Poisonings


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Most cases of acute poisoning are self-inflicted but not all. Poisoning can be caused by pharmaceuticals or illegal drugs but also by gases, chemicals, mushrooms and many other types of biological toxins. A primary assessment should try to determine whether the poisoning is intentional or inadvertent and if it is self-inflicted or caused by another, this should be documented and recorded and it also affects the diagnosis classification. Here are general guidelines for care of acute poisoning, but treatment may vary and each case must be assessed based on the severity of poisoning and patient condition.

Patients with acute poisoning must be treated with careful monitoring, which is of great importance for a good prognosis. In most cases, the main treatment is symptomatic. Most importantly, adequate monitoring of breathing, circulation and alertness is required. Emergency care includes securing of vital functions by establishing and securing free airway and optimization of breathing and circulation.

At the same time, careful care is given on the identification of intake of poison, alcohol, pharmaceutical or illegal drugs. Which medicines have been taken and when did this happen? Adequate antidote treatment is given in specific severe cases.

The most important issue in most cases of poisoning is to:

  • Carefully monitor alertness and breathing
  • Assist breathing and circulation when needed
  • Treat acute confusion and mental anxiety calmly and safely
  • Identify the toxic agent
  • Perform active elimination when indicated, for example by gastric emptying and gastric lavage
  • Give activated charcoal or dialysis treatment when indicated
  • Antidote treatment when a clear indication is present and the benefit contemplates the risks
  • Refer the patient into a department with the correct level of care and avoid low levels of care when consciousness is reduced or breathing is impaired
  • Arrange a follow-up service through psychiatry and social services

Establish Free Airway

  • Recovery position
  • Nasal tube, oropharyngeal airway device or, in exceptional cases, laryngeal mask
  • Endotracheal intubation if necessary, in case of emergency laryngeal mask
  • Assisted ventilation if required
  • Oxygen is given liberally
  • Pulse oxymetry
  • Prevent aspiration, emptying the stomach by a nasogastric tube

Establish Venous Access 

  • Peripheral venous catheter (PVC), with unconsciousness, preferably two
  • Arterial line if unconsciousness, metabolic acidosis or circulatory impairment
  • CVC, unconsciousness or circulatory failure 

Gastric Emptying – see also below during treatment

  • Manually, only on toddlers at the initial stage
  • Emetic syrup is no longer recommended in the treatment
  • Gastric lavage through a coarse tube by the mouth

Activated Charcoal see also below during treatment

  • Manually in mug or pediatric closed cup
  • Dissolved in water and disposed (instilled) into the stomach via a nasogastric tube

Laboratory Tests

  • Blood and urine samples according to local routines for cases of acute intoxication (ethanol, methanol, paracetamol, etc.)
  • Biological alcohol markers in suspicion of alcohol abuse (PEth, CDT)
  • Drug screening of urine samples (in patients with urinary catheter)
  • Targeted toxicological samples (urine, serum, possibly hair or nails)
  • Serial electrolyte status checks (routine status, Na, K, Mg, Ca)
  • Arterial blood gases with acid base status (including lactate and CO-Hb)
  • SvO2 and lactate in case of suspicion of cyanide poisoning or severe heart failure
  • B-glucose
  • Myoglobin in serum (rhabdomyolysis)
  • Heart failure enzyme markers (TNT, Pro-BNP) in carbon monoxide poisoning or ECG changes or cardiac ischemic indicators plus CO-Hb
  • Save and freeze blood serum from time of admittance of supplementary diagnostics in unclear or very serious cases

Differential Diagnosis

Any patient under the age of 50 with unclear unconsciousness should be regarded as poisoning or intoxication until the opposite is proven!  The diagnosis intoxication or poisoning should always be considered in case of unclear unconsciousness, and rarely is the correct diagnosis when stroke has been the preliminary diagnosis! Conversely, the diagnosis of intoxication has been erroneously set when the correct diagnosis has been, for example, hypoglycemic coma! Drug test strips may quickly give an indication if poisoning is present.

Always consider a differential diagnosis in case of unclear unconsciousness! Consider alcohol and drugs when patients are messy and worried. Smell the breath! Among patients with unclear unconsciousness below 40 years of age, more than 80 percent have been reported to be poisoned or intoxicated, whereas more than 90 percent of patients over 60 years of age are caused by other causes than acute poisoning. In case of unclear unconsciousness, a CT brain scan should be performed on relatively wide indications. Trauma and poisoning are common parallel diagnoses.

MONITORING

Circulatory and respiratory monitoring

  • ECG with arrhythmia monitoring, continuous and stored in the patient’s electronic records at the time of admittance. Determine cardiac rhythm, QT-time and QRS-time.
  • Invasive monitoring, continuous arterial pressure and central venous pressure (CVP) in severe cases.
  • Ultrasound of the heart (UCG) in cardiac failure or pronounced hypotension.
  • Pulse oximetry and respiratory rate.
  • Spirometry on ventilator-treated patients as well as after exposure to irritant gas
  • Urinary catheter with urinary output and body core temperature measurement.

Prolonged QT time is relatively common in drug poisoning. In repeated episodes of ventricular tachycardia or ventricular fibrillation, consider drug-induced prolonged QT time.

Alertness

Continuous grading of the patient’s alertness and consciousness must be performed and recorded. Consciousness grading should be done continuously (1-2 times/hour) and several different scales are available for this purpose. A common scale in the Nordic region is the so-called RLS scale (Reaction Level Scale, 0-8 p) , but internationally, Glascow Coma Scale (GCS) is more commonly used. What scale you use is less important. The important thing is that the level of consciousness is graded and recorded regularly. Neurological deficit symptoms must be reported and investigated promptly.

A grading instrument that can be used clinically to assess the severity of poisoning is the Poisoning Severity Score (PSS). A negative change in the patient’s degree of consciousness must be observed and adequate countermeasures taken. Serious poisoning symptoms such as respiratory distress or cardiac arrhythmias often occur suddenly after a decrease in vigilance.

An anxious patient may have a clinical picture compatible with a so-called “toxicodrome”. Various “toxicodromes” (clinical syndromes due to poisoning) have been described in connection with poisons, namely

  • Anticholinergic syndrome
  • Serotonergic syndrome
  • Malignant neuroleptic syndrome
  • Agitated delirium

Patients with a toxicodromes have a characteristic clinical picture and may require specific treatment. Common to these syndromes is that they are often associated with hyperthermia and anxiety that can be life threatening. Basic treatment for these syndromes therefore becomes sedation and cooling. Most important is to detect hyperthermia and control the temperature in the care of an anxious or drug-affected patient. Note that patients taking amphetamine usually have hyperthermia but may also come across with hypothermia.

Blood Sampling

Quantitative concentration determination should be followed when poisoning with any of the following substances:

  • Paracetamol (4, 8, 12 and 24 hours after ingestion)
  • Carbamazepine
  • Salicylic acid
  • Digoxin
  • Ethanol
  • Ethylene glycol
  • Iron
  • Isopropyl alcohol
  • Lithium
  • Methanol
  • Theophylline

Measure serum concentrations of relevant drugs 1-4 times on the first day. The following day or when concentrations have fallen below toxic values, controls can be taken once a day. Note that when a given elimination treatment such as hemodialysis is interrupted, the serum concentrations may rise (rebound), for example, by lithium poisoning. In refined diagnostics, both arterial and venous samples can be taken to provide information about continued uptake of drug from the intestine or redistribution in the different compartments of the body. In most cases, it is sufficient to follow venous blood concentrations. Note that alcohol can be measured in both blood, exhaled air and urine.

Drug Screening

Drug screening is taken on the patient’s urine to detect psychoactive substances, which can often explain unconsciousness in acute poisoning cases. This applies in particular to the occurrence of psychomotoric anxiety and psychotic symptoms or seizures. Drug screening test strips usually measure the presence of cocaine, cannabis, morphine, amphetamine and benzodiazepines. New drug test strips can measure more substances, usually between 8 and 14 different drugs. This screening should be performed liberally in the case of unclear unconsciousness in younger patients with known addiction.

A screening test usually provides responses within 5-10 minutes, facilitating the emergency diagnosis of a poisoned patient. Also send urine samples to laboratory chemistry for analysis with GC-MS (gas chromatography mass spectrometry) for verification or suspicion of GHB poisoning. Note that GHB and LSD are usually not available on regular drug screening test strips. Newer test strips can provide answers to as many as 14 different substances. Selected strips are now also available for “Spice” (synthetic cannabinoids), buprenorphine, methadone, ecstasy and GHB.

Indications for Admittance to an Intensive Care Unit (ICU)

  • Life-threatening poisoning
  • Ingestion of very toxic substances
  • Large quantities of drugs or other poisons have been taken
  • Significant respiratory irritation when exposed to irritant gas
  • Significant alertness reduction
  • RLS 3 or higher
  • GCS lower than 10
  • Significantly worried or confused patient
  • Sudden consciousness reduction
  • Inability to keep the airway free in the supine position
  • Cardiac arrhythmias
  • Hypoxia with SaO2 <90% on air breathing or SaO2 < 95% with oxygen
  • Respiratory rate less than 10 or greater than 30 breaths per minute
  • Pulse below 40 or above 130 beats per minute
  • Systolic blood pressure below 90 mm Hg despite fluid administration
  • Myoclonic seizures
  • Metabolic acidosis or marked lactatemia (> 5 mmol/L)
  • Hypothermia or hyperthermia
  • Pronounced electrolyte disturbances
  • Other significant worrying states!

TREATMENT

The treatment of acute poisoning is essentially symptomatic and antidotes are available only in a limited number of cases. Conscioussness, breathing and hemodynamics can change suddenly during the first six hours. Seizures, psychomotor dysfunction, unconscioussness, nausea and vomiting are common. Insufficient breathing is supported as needed by endotracheal intubation and respiratory treatment in an intensive care unit. Uncomplicated poisoning cases often require no more than four hours of close monitoring; in complicated cases, longer time is required as the condition varies. 

Activated Charcoal

Activated charcoal is valuable if administered early in treatment, preferably within one hour after ingestion of toxic agents. Activated charcoal administration should be the standard treatment of acute drug poisoning. Charcoal is of limited value if it is given late in treatment, more than six hours after the poisoning offer. The usual dose is 50 g of activated charcoal for adults and 1 g/kg for children up to 12 years of age. Charcoal adsorbs most drugs; but not iron, lithium, ethanol, methanol or cyanide. Activated charcoal can be given later than one hour in life-threatening poisoning and should supplement gastric lavage when carried out. See special guidelines for gastric lavage and activated charcoal.

Gastric Lavage

Gastric lavage is of limited value and should only be performed if the patient arrives early in hospital after the poisoning, usually within one hour after ingestion (e.g. less than 25 % of all cases). In case of very serious poisoning (life-threatening poisoning), after intake of very large doses or in anticholinergic drugs, gastric lavage may be advantageous and performed at a later stage or repeatedly, in each case up to 24 hours after ingestion.

See special guidelines for gastric lavage. Examples of particularly toxic agents are chloroquine, potassium and various heavy metals.

Sodium bicarbonate is an important part of the treatment of many toxins, especially in pronounced metabolic acidosis as in poisoning with methanol, ethylene glycol and other toxic alcohols. Sodium bicarbonate is also an important part of overdose of tricyclic antidepressant drugs and some other cardiovascular preparations. Alkalinization means that a smaller proportion of overdose drug is free in the bloodstream, with a small amount being able to pass to the cells of the myocardium. The toxicity decreases by tricyclic antidepressants when treated with sodium bicarbonate. In case of serious poisoning give an initial dose of about 200 ml sodium bicarbonate (120 mmol). Then titrate after blood gas analysis. Strive for a pH above 7.45 and a positive Base Excess.

Sleeping or Comatose Patient

If the patient is sleeping deeply and cannot be awakened, he or she should be monitored in an intensive care unit with intubation preparedness.

If vital parameters are stable and the patient breathes calmly and regularly it is usually enough with careful supervision and the patient is allowed to sleep until he or she wakes up. Comatose patients are placed stable on the side and turned every other hour. Any other reason for deep unconsciousness than poisoning should of course be ruled out. Check electrolytes, intoxication blood samples and an arterial blood gas as well as the blood alcohol level (BAL). Perform a CT scan with x-ray of the brain (and sometimes stomach as well) in unclear cases of unconsciousness or in the presence of focal neurological symptoms.

In drug poisoning, the patient usually sleeps for 3-12 hours. Longer unconsciousness than 12 hours often depends on other causes, but may be compatible with certain poisons, such as antidepressant drugs, barbiturates or long-life depot preparations (Voxra®, Propavan®, Lithium®). The awakening is usually calm and if the patient appears to be extremely worried during awakening, the patient should be sedated to provide further sleep and a quieter awakening, for example, with midazolam (Dormicum®) 1-2 mg iv.

Serious incidents with poisoned patients usually occur within six hours of arrival in hospitals such as seizures, blood pressure fall or cardiac arrhythmias.

Confused or Agitated Patient

If the patient is agitated and mentally unstable, you can give sedative drugs, for example benzodiazepines. Although sedative neuroleptics have been used they should possibly be avoided in poisoning with other neuroleptics or at unstable blood pressure; Clomethiazole (Heminevrin®) should be avoided completely.

The following medications may conveniently be used for sedation:

  • Midazolam (Dormicum®) 1-5 mg i.v., i.m. or in continuous infusion 1-5 mg/h (1 mg/ml). Can also be given orally (10-15 mg).
  • Diazepam (Stesolid®) 2.5-5 mg i.v.
  • Propofol 20-40 mg i.v. or in continuous infusion, 20 mg/ml with 3-10 ml/h.
  • Olanzapine (Zyprexa®) 5-20 mg i.m. x 2.
  • Droperidol (Dridol®) 5-10 mg i.m. (SIC)

Note that the vigilance fluctuates and that the patient can quickly become unconscious with insufficient breathing after administration of sedative drugs.

If the patient is heavily agitated and/or violent, it may be necessary to completely sedate or anesthetize the patient, secure the airway by intubation and connect him or her to a ventilator. This may only be done when it benefits the patient. One can then use midazolam (Dormicum®) 5 mg i.v. plus propofol (Propofol) 50-200 mg i.v. until the patient is sleeping lightly. Patients usually require continuous infusion of propofol for 3 to 8 hours. Infusion rate is controlled by the degree of alertness, approximately 200-400 mg of propofol is given per hour (5-10-20 ml/hour).

The patient should be monitored in an intensive care unit and the respiratory tract must be secured by endotracheal intubation and respiratory treatment. After that, you can usually wean off sedation and the patient usually wakes up calmly and peacefully.

Sedation of the patient with propofol intravenously should only be done by an anesthesiologist when the situation is unsustainable with immediate danger to the patient’s life. This usually requires intubation and respiratory treatment for at least 4-6 hours.

Agitated patients should not be discharged from emergency care when they are still drug-affected, worried with lack of self-control. They can still be violent against themselves, relatives and staff. Patients with anxiety and agitation and a so-called “Anticholinergic Syndrome” may be significantly improved by administration of physostigmine intravenously, for example after poisoning with antidepressants, phenothiazines or neuroleptics. However, there is a risk that the seizure threshold will be lowered; Physostigmine has been described to induce seizures and bradycardia why one should be careful in the initial phase of a poisoning.

In case of severe poisoning, such as methanol poisoning or severe hepatic failure due to paracetamol poisoning, you should refer the patient to a regional hospital.

Antidote Treatment

Antidotes are given when the patient’s condition so requires and there is an opportunity to significantly improve outcome. Some common and important antidotes are:

  • N-Acetylcysteine ​​when poisoning with paracetamol or fly fungus. Note that overdose with paracetamol in modified release form (MR) 665 mg requires a particular acetylcysteine ​​schedule with prolonged phase II dosage.
  • 4-methylpyrazole (Fomepizol®) in poisoning with methanol or ethylene glycol
  • Hydroxocobolamine (Cyanokit®) when poisoned with cyanide (hydrogen cyanide by inhalation) or other cyanide compounds
  • Beclometasone (Becotide®) in the case of poisoning with irritant gases (corticosteroids by inhalation)
  • Desferoxamine (Desferal®) in poisoning with iron
  • Digoxin antibodies (DigiFab TM®) in poisoning with digoxin
  • Flumazenil (Lanexat®) when poisoned with benzodiazepines
  • Naloxone (Naloxon®, Nexodal®) in case of poisoning with opioids
  • Obidoxime (Toxogonin) in nerve gas poisoning (unregistered)
  • Immune serum (Vipera TAB®) in European viper bites, other exotic snakes require specific serum according to species.

Treatment with Vasoactive Drugs

In case of difficulty in maintaining blood pressure after delivery of crystalloid and colloid fluid, vasoactive drugs can be used to raise blood pressure and cardiac output and increase oxygen delivery to vital organs and peripheral tissues. Essentially, you use the same drugs as in pronounced cardiac failure of other origin. The most commonly used drugs are dopamine, dobutamine, norepinephrine and adrenaline in continuous infusion. In addition, isoprenaline is used for severe heart failure with bradycardia, for example after poisoning with calcium channel inhibitors, beta blockers or tricyclic antidepressants. Even inotropic drugs that act as cardiac enhancers independent of beta-receptors in the heart can be used, such as glucagon. Glucagon may be tested by poisoning with beta blockers or calcium channel inhibitors. Also high-dose glucose-insulin can be tested. In case of pronounced bradycardia and heart failure, treatment with transvenous pacemaker may also be positive. Calcium administration may improve blood pressure and circulation but often only temporarily.

Intravenous Lipid Emulsion Therapy (ILE)

Intravenous Lipid Emulsion therapy (ILE) treatment may be lifesaving in cardiovascular collapse following overdose with local anesthetics, especially bupivacaine (Marcain®) and several other drugs. In case of overdose of other fat-soluble drugs, eg verapamil (Isoptin®), intravenous lipid emulsion (Intralipid®) treatment has been effective in several cases. One theory is that intravenous lipid therapy creates a depot in the bloodstream that extracts toxic agents from the cardiac cells so that cardiac toxicity is reduced (“sink theory by redistribution”).

Initially, 100-200 ml of Intralipid® is administered intravenously at the same time as cardiopulmonary resuscitation is initiated (CPR). See treatment of overdose with local anesthetic agents. The treatment is still controversial and is only recommended as a last resort for cardiovascular collapse after ingestion of fat-soluble drugs.

Treatment with ExtraCorporeal Circulation Support (ECCS, ECMO, Aortic Balloon Pump)

In cardiovascular collapse due to poisoning, mechanical circulation support can be lifesaving. In case of poisoning, pronounced heart failure is usually transient, for a few hours or up to 2-3 days. Initially, a mechanical cardiac compression device can be lifesaving, like a Lucas® pump. Thereafter, the patient can be transported to a thoracic surgery or intensive care department where you can insert an aortic balloon pump or other mechanical circulation support (ECMO/ECCS). If this procedure can be initiated quickly without injuring the brain, life will usually be saved. ECMO may be required for 2-3 days after which the cardiac function usually is restored. The method is invasive and resourceful but very effective. Consideration should be given to this treatment in the presence of heavily widespread QRS complexes (> 160 msec) and pronounced hypotension, severe bradycardia or very low SvO2 (< 45 %). Examples of drug overdoses where ECMO may be relevant is poisoning with:

  • Tricyclic antidepressant drugs (TCA)
  • Antipsychotic drugs
  • Antiepileptic drugs
  • Chloroquine
  • Beta-blocking drugs
  • Rhythm-regulating cardiac medications (flecainide)
  • Calcium-channel inhibitors (calcium antagonists)

Several of these drugs are described as membrane-stabilizing drugs with negative inotropic effects due to blockade of fast sodium ion channels. In the case of overdose, a gradual broadening of the QRS complex on ECG is usually seen while decreasing blood pressure and bradycardia transfers into circulatory shock.

FOLLOW-UP

Psychiatric and social follow-up of the patient is important as the poisoning occurs in connection with suicide attempts or when the patient has an active substance abuse with pharmaceutical drugs, alcohol or illicit drugs. Referral to psychiatric treatment, dependence care or social services is desirable. In case of life-threatening addiction (GHB, opioids, amphetamine), social services should always be contacted, by writing a referral or orally.

Abuse of central stimulants (amphetamines, cocaine, ecstasy, party drugs) and cannabis is common among younger patients with drug poisoning as well as general social problems in these cases. Cases with adolescents under the age of 18 must be reported to social authorities and adolescent psychiatric consultants (child and adolescent psychiatric clinic). Even school healthcare may need to be connected.

In case of repeated acute overdose, notification to the social service should be made and care under the Youth Care Act (<20 years) or Law on Care of Abusers should be considered. The application for social services may be oral or written.

Long-term Side Effects

A drug overdose usually does not cause long lasting side effects unless severe complications occur such as apnea, aspiration pneumonia, acute liver failure, acute renal failure or pronounced general hypoxia. The risk of developing withdrawal after abuse of alcohol, or drugs must always be taken into account at discharge. A transient sleep disorder with severe sleep difficulties for 3-4 weeks is not uncommon. Other side effects described are abdominal pain, difficulty concentrating, numbness, anxiety and impotence. Many patients experience low quality of life for a long time after being treated for acute poisoning. The risk of a new lethal poisoning within a week after the current care is though very low.

 ICD-10 Codes

  • Poisoning of drugs, drugs and biological substances T36-T50
  • Toxic effect of substances with substantially non-medical use T51-T65
  • Toxic effect of alcohol T51
  • Toxic effect of other and unspecified substances T65
  • Poisoning accidents and exposure to harmful substances by accident X40-X49
  • Intentional self-destructive action through poisoning X60-X69
  • Abuse by poisoning X85-X90
  • Poisoning with obscure intention Y10-Y19
  • Mental disorders and behavioral disorders caused by sedatives and hypnotics, acute infections F13.0

References

  1. Jones AL, Volans G. Management of self poisoning. BMJ 1999;319:1414–1417.
  2. Bateman DN, Bain M, Gorman D, Murphy D. Changes in paracetamol, antidepressants and opioid poisoning in Scotland during the 1990s. QJM 2003; 96:125–132.
  3. Burillo-Putze G, Munne P, Duenas A, Pinillos MA, Naveiro JM, Cobo J, Alonso J. National multicentre study of acute intoxication in emergency departments of Spain. Eur J Emerg Med 2003; 10:101–104.
  4. Hovda KE, Bjornaas MA, Skog K, Opdahl A, Drottning P, Ekeberg O, Jacobsen D. Acute poisonings treated in hospital in Oslo: A one-year prospective study (I): Pattern of poisoning. Clin Toxicol 2007.
  5. Dargan PI, Jones AL. Management of paracetamol poisoning. Trends Pharmacol Sci 2003; 24:154–157.
  6. Newton RW. Physostigmine salicylate in the treatment of tricyclic antidepressant overdosage. JAMA 1975; 231:941–943.
  7. Vale JA. Position statement: Gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35:711–719.
  8. Nice A, Leikin JB, Maturen A, Madsen-Konczyk LJ, Zell M, Hryhorczuk DO. Toxidrome recognition to improve efficiency of emergency urine drug screens. Ann Emerg Med 1988; 17:676–680.
  9. Merigian KS, Woodward M, Hedges JR, et al. Prospective evaluation of gastric emptying in the self-poisoned patient. Am J Emerg Med 1990;8:479483.
  10. Neuvonen PJ, Olkkola KT. Oral activated charcoal in the treatment of intoxication. Role of single and repeated doses. Med Toxicol 1988;3:3358.

Published with permission from Internetmedicin AB


Gastric Emptying and Activated Charcoal


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Gastric emptying and gastric lavage have long been standard procedures in the treatment of acute poisoning patients who have toxic substances left in the gastrointestinal tract. Today, there are significantly fewer poisoned patients undergoing gastric emptying compared with 10-20 years ago. This since several studies has shown doubts about the usefulness of the procedure. However, it is still a method that can be lifesaving in some cases and how to do this practically in a safe and easy way should be known to everyone serving a medical emergency department.

Gastric emptying has been previously done by gastric lavage with water via a tube or by vomiting (manually or by emetic medication). There is no longer considered to be scientific support for gastric emptying using emetic drugs. Manual vomiting provocation is only performed on toddlers immediately after ingestion of toxic agents, e.g. at home or in preschool. Adult gastric emptying can be performed at the correct indication by using a orogastric tube performing gastric lavage with normal tap water.

The benefit of gastric lavage is evidence-based in scientific animal experiments and experimental human studies. However, in controlled randomized clinical trials, the benefit of gastric lavage has been demonstrated only when performed very early in the poisoning course, usually within one hour after ingestion of toxic substances. The same applies to the supply of medical charcoal (activated charcoal). Gastric emptying later than one hour after ingestion of toxic drugs has not been shown to improve the clinical course in controlled randomized scientific studies.

However, in clinical studies it is difficult to select those patients who may benefit from the procedure. Experience has shown that some patients may still benefit from gastric lavage even in late stages of severe poisoning (> 1 hour) or in the case of poisoning with slow release preparations (depot preparations). Each case of poisoning must therefore be evaluated and tested individually with regard to what has been ingested, what amount and the condition in which the patient is.

The following advice should act as General Guidelines

The guidelines concern both gastric emptying and gastric lavage. The supply of activated charcoal to reduce the adsorption of toxic substances is a routine procedure following gastric emptying. Charcoal can also be supplied without gastric lavage through a nasogastric tube or by mouth (oral suspension – suspension of charcoal). The supply of medical charcoal is considered the first-hand measure in the treatment of acute poisoning and should be far more common than gastric lavage. All patients entering the hospital with serious poisoning should be evaluated for gastric emptying and treatment with medical charcoal.

Guidelines for Gastric Emptying in Acute Poisonings 

Gastric Lavage

Gastric emptying in adults should be performed by means of gastric lavage through a coarse tube (28-32 Ch) ​​in the stomach by the mouth. The procedure is subject to gastric emptying plus a gastric lavage, usually with tap water.

After performing gastric lavage, in most cases activated charcoal should be supplied to the patient through the same tube, usually 50 g of charcoal, in some cases more. Gastric emptying should be carried out within a reasonable time (<1 h) if very serious poisoning is estimated based on data on the toxicity, intake and timing of ingestion. Gastric emptying should be conducted liberally in complex and severe cases.

Complicated and serious poisoning cases often occur after overdose with any of the following drugs:

  • Beta blockers
  • Calcium channel inhibitors
  • Digoxin
  • Tricyclic antidepressant drugs
  • Antiepileptic drugs
  • Barbiturates
  • Chloroquine
  • Oral antidiabetics
  • Potassium tablets
  • Slow release-formulations

Gastric Emptying should be Performed in Case of Acute Poisoning

 

  • Within 1 hour after overdose of tablets or liquid preparations (drug mixes, suspensions).

Gastric lavage can be considered:

  • Within 12 hours after overdose of tablets in a very large amount, or after ingestion of strong toxic agents or slow release preparations. For example, paracetamol in modified release form 665 mg or antidepressive agents in depot form.
  • Within 24 hours if toxic plants or mushrooms have been taken (amatoxin-containing fungi).

 

If the medicines taken are not highly toxic and more than one hour elapsed after ingestion, most of the cases can be prevented from gastric lavage. In many of these cases one can just supply medical charcoal or refrain from the whole procedure. However, gastric lavage can be performed later than one hour after ingestion of hard-smelting material such as sponges and parts of plants, antidepressant drugs (TCA) or in the formation of conglomerate in the intestine (iron, lead, potassium) or otherwise impaired intestinal peristalsis. Deeply unconscious patients usually have no or severely impaired intestinal peristalsis. The presence of conglomerate can and should be detected by X-rays (abdominal overview by x-ray or CT scan). Note that paracetamol in the preparation 665 mg contains a double layer drug with sustained release, therefore gastric lavage and activated charcoal may be considered even later than 1 hour. There is a risk that this preparation may form conglomerate in the intestine. If the circulation and respiration is stable, the patient’s alertness is adequate (the patient is responding to verbal information) and the ingested drug is unknown as well as the time of intake, one can usually refrain from gastric emptying.

Note that patients after ingestion of some highly toxic drugs may be relatively unaffected initially. This includes intake of, for example, chloroquine (Chloroquine Phosphate Recip®), paracetamol (Alvedon®, Reliv®, Panodil®, etc.), venlafaxine (Efexor Depot®) or digoxin (Digoxin®). Therefore, careful documentation of intake preparation, intake amount, timing of intake, and observation of alertness, respiration and circulation is necessary. Note if paracetamol taken is in immediate release or modified release form.

The patient’s clinical picture must be weighed in each case so that the benefit of the gastric lavage is set against the risk of the procedure. The amount of drug or toxin eliminated by gastric lavage must have a beneficial effect on the clinical course for the patient to be given the procedure. This aspect is, of course, difficult to evaluate in advance and some overwork becomes necessary.

Gastric lavage should not be performed if there is suspicion of corrosive acids, alkali, lye, petroleum products such as ignition and lamp oil, or alcohol intake. In exceptional cases, it may be warranted to perform gastric lavage even after ingestion of alcohols in cases where the patient has taken very large amounts recently (for example at the hospital!). However, in most cases it is meaningless in poisoning with ethanol, methanol, ethylene glycol, isopropyl alcohol or GHB. The measure only means an extra risk moment for the patient. In case of ingestion of isopropyl alcohol (2-propanol, hand disinfectant, lavage fluid) it may be warranted with gastric lavage for up to one hour after ingestion. 

Gastric Lavage – Procedure

A routinely performed gastric lavage in habit is a relatively simple and safe procedure. In case of insufficient or insufficient airway, the patient should be intubated before gastric lavage. The assessment of the airway is free and the in vivo reflexes are clinical and may be difficult. If you are very doubtful, the patient should be intubated first to ensure the airway and to avoid complications. Anesthetist should then assist during the procedure.

  • In gastric lavage use a coarse tube (28-32 Ch) ​​which allows aspiration of tablets from the stomach.
  • The patient is stably left in the left side position during the procedure and the tube is put into the stomach through the mouth. One can sometimes be helped by a tongue pad to insert the tube through the mouth. The tube should be gelled. The tube is inserted when the patient swallows. The position of the tube may need to be changed a few times in the stomach during the procedure. A normal distance down to the stomach is 35-50 cm. If the tube has not been inserted properly in the stomach, there is an increased risk of respiratory distress (beyond cardia). There is also a risk of leakage of gastric contents beside the tube.
  • Oxygen is supplied to the patient via catheter or nasal cannula throughout the procedure (2-4 L/min O2).
  • When the orogastric tube is placed in the stomach, empty the stomach by aspiration (gastric aspiration) before lavage with water or saline through the tube. Simply use tap water to lavage the stomach. You should use no more than 200 ml at a time to not flush the contents of the stomach into the intestine. You lavage and aspirate the instilled water. You lavage with tap water until you get a clear exchange, but the procedure should not take more than 10 minutes.
  • One can use a closed coil system (similar to urinary bladder system) with two bags and coarse hose clips to the hoses that allow for flushing and flushing without air mixing. You must then check that there is no net fluid left in the patient.
  • One should assume that a certain part (about 25%) of the contents of the stomach is flushed into the small intestine during the procedure. There is some risk that the conglomerate of tablets will be dissolved. An increased risk of toxic reactions may therefore occur 20-30 minutes after the lavage has ended. During this period, the patient should not be in transit between departments or at an X-ray department!
  • After gastric lavage, administration (instill) 50 g of medical charcoal is dissolved in a suspension through the oral tube.
  • When you then pull out the tube it is advisable to turn it off proximally with a pinch (clamping the tube). The tube is closed so that the tip of the tube does not drain into the pharynx at the level of the laryngeal introitus and into the trachea.
  • It’s not uncommon for the patient to choke just the moment you retract the orogastric tube out of the mouth, you have to be prepared with a suction catheter. Soak cleanly in the pharynx.
  • Careful observation of the patient is necessary immediately after gastric lavage.
  • Intubated patients should not be extubated directly after completion of gastric lavage without being monitored in the respirator for at least four hours following the procedure.

Bowel Irrigation, “Whole Bowel Irrigation”

Bowel irrigation may be indicated in heavy metal poisoning, e.g. poisoning with lead or arsenic, but has also been used in potassium poisoning. One method of accelerating the elimination of toxic agents from the gastrointestinal tract is to try to flush tablets through the intestine with as fast intestinal passage as possible, thus a type of bowel lavage. This method is used more in some countries than others and is common in, for example, Canada and Australia. Liquids are given by drink or tube with laxative effect, such as Laxabon®. A regular dose is 4 liters in adults and 25 ml/kg in children. 1-1.25 liter is initially transmitted via tube. The first bowel emptying occurs approximately one hour after the intake of Laxabon has begun, so the method is considered to be somewhat slow. The active ingredient is mainly macrogol but note that Laxabon also contains potassium, why this preparation should be avoided in potassium poisoning! An alternative to Laxabon is to lavage with a polyethylene glycol solution.

Activated Charcoal

All patients who enter the hospital as an incidence case of acute poisoning should be valued if they are to receive medical charcoal (activated charcoal). The benefit of activated charcoal is greatest within the first hour after ingestion of toxic agent. The effect then decreases rapidly over time.

Activated charcoal should be given routinely in the case of overdose of a toxin that is adsorbed to charcoal when a toxic reaction can be avoided within the hour. Almost all drugs bind to activated charcoal except iron and lithium, but potassium is also poorly adsorbed to charcoal. Neither ethanol, methanol nor cyanides bind to activated charcoal. Activated charcoal slurried in water can also be given prehospital if the patient is cooperative. However, it should not be given if there is a significant risk of vomiting and pulmonary aspiration of charcoal.

Supply of medical charcoal without gastric lavage can be applied when poisoning is judged to be mild to moderate (unaffected vital parameters) or when the patient arrives relatively late after the poisoning, for example later than one hour after drug intake or in case of mushroom poisoning, even late.

In such cases, activated charcoal can be given to the patient as a suspension via a beverage cup where the patient drinks himself or via a gastric tube. In these cases, a thinner tube (18 Ch) than the one used for gastric lavage can be used as then inserted through the nose. Provision of activated charcoal through a tube passed through the nose is suggested with the patient half-seated in the back condition. The nasal opening, like the nasogastric tube, is properly gelled and the procedure is usually done quickly and painlessly when performed by skilled staff.

The amount of medical charcoal supplied to the patient should exceed the intake of poisoning amount ten times by weight. Routinely, a single dose of 50 g of charcoal in suspension is added. Thus, if the intake of toxin exceeds 5000 mg, more than 50 grams of charcoal must be added.

Children up to one year of age are given 1 g/kg body weight. Children between 1 and 12 years of age are given 25-50 grams. Adolescents and adults are given 25-100 grams of charcoal in a single dose.

In case of serious poisoning, the supply of activated charcoal should be repeated four to six times the first day. This procedure is simply referred to as “repeated activated charcoal”. In this procedure, gastric lavage has also been performed. A gastric tube can be left in the stomach after it is rinsed with saline and fixed with tape. Adults are given 25 g of medical charcoal via the tube every four hours the first day (25 g x 6), children are given 5-10 g of charcoal every four hours (5-10 g x 6).

Repeated Activated Charcoal should be given in case of serious poisoning with:

  • Barbiturates (Fenemal®)
  • Phenytoin (Epanutin®, Fenantoin®, Lehydan®)
  • Carbamazepine (Hermolepsin®, Tegretol®, Trimonil retard®)
  • Kinin (Kinin Recip®)
  • Chloroquin (Chloroquine Phosphate Recip®)
  • Salicylates (Albyl minor®, Aspirin®, Alka-Seltzer®, Asasantin Retard®, Bamyl®, Magnecyl®, Treo®, Trombyl®)
  • Theophylline (Theo-Dur®)
  • Poisonous mushroom (white and lame fly fungus)

 

Diagnostic Code according to ICD-10

  • V9227 Insertion of gastric tube
  • V9229 Gastric lavage

References

1. National Institute for Public Health and Environment. The Dutch Public Health Status and Forecast Report 2006.

2. Jones A. L., Volans G. Clinical review; Recent advances Management of self poisoning. National Poisons Information Service (London), Medical Toxicology Unit, Guy’s and St. Thomas’s NHS Trust, London SE BMJ 1999; 319: 1414-1417.

3. American Academy of Clinical Toxicology and European Association of Poisons Centers and Clinical Toxicologists. Position paper: Single dose of activated charcoal. Clinical Toxicology 2005: 43; 61-87.

4. Jurgens G., Graudal N.A. Position paper: The effect of single dose activated charcoal on drug absorption during the first 6 hours after drug ingestion- A metanalysis. Clin Toxicol 2005: 43: 61-87.

5. Alaspaa A.O., Kuisma M.J., Hoppu K. Out-of-hospital administration or activated charcoal by emergency medical services. Annals of Emergency Medicine 2005: 45; 2.

6. Person M. Use of activated charcoal in the pre-hospital situation. Journal of Toxicology 2004: 42; 4; 395-564.

7. Lamminpaa A., Vilska J., Hoppu K. Medical Charcoal for a child’s poisoning at home: Availability and success of administration in Finland. Human and Experimental Toxicology 1993: 12 29-32.

8. Vale JA: Position statement: gastric lavage. American Academy of Clinical Toxicology; European Association of Poison Centers and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35: 711-719

9. Position paper: gastric lavage. American Academy of Clinical Toxicology; European Association of Poison Centers and Clinical Toxicologists. J Toxicol Clin Toxicol 2004; 42,933-943.

10. Arnold FJ, Hodges JB, Barta RA. Evaluation of the efficacy of lavage and induced emesis in treatment of salicylate poisoning. Pediatrics 1959 23: 286-301.

11. Corby DG, Lisciandro RC, Lehman RH, Decker WJ. De efficiëntie van de methoden die gebruikt worden om te evacueren de stomach na acute ingesties. Pediatrics 1967; 40: 871-874.

12. Abdallah AH, Tye A. A comparison of the efficacy of emetic drugs and stomach lavage. Am J’s Child 1967; 113: 571-575.

13. Auerbach PS, Osterloh J, Braun O, et al. Efficacy of gastric emptying: gastric lavage versus emesis induced with ipecac. Ann Emerg With 1986; 15: 692-698.

14. Tandberg D, Diven BG, McLeod JW. Ipecacinduced emesis versus gastric lavage : a controlled study in normal adults. Am J Emerg With 1986; 4: 205-209.

15. Young WF, Bivins HG. Evaluation of gastric emptying using radionuclides: gastric lavage versus ipecac-induced emesis. Ann Emerg With 1993; 22: 1423-1427.

16. Tenenbein M, Cohen S, Sitar DS. Efficacy of ipecac-induced emesis, orogastric lavage , and activated charcoal for acute drug overdose. Ann Emerg With 1987; 16: 838-841.

17. Danel V, Henry JA, Glucksman E. Activated charcoal, emesis, and gastric lavage in aspirin overdose. BMJ 1988;296:1507.

18. Lapatto-Reiniluoto O, Kivisto KT, Neuvonen PJ. Gastric decontamination performed 5 min. after the ingestion of temazepam, verapamil and moclobemide: charcoal is superior to lavage. Br J Clin Pharmacol 2000; 49:274–278.

19. Lapatto-Reiniluoto O, Kivisto KT, Neuvonen PJ. Efficacy of activated charcoal versus gastric lavage half an hour after ingestion of moclobemide, temazepam, and verapamil. Eur J Clin Pharmacol 2000;56:285–288.

20. Lapatto-Reiniluoto O, Kivisto KT, Neuvonen PJ. Effect of activated charcoal alone or given after gastric lavage in reducing the absorption of diazepam, ibuprofen and citalopram. Br J Clin Pharmacol 1999;48:148–153.

21. Grierson R, Green R, Sitar DS, Tennenbein M. Gastric lavage for liquid poisons. Ann Emerg Med 2000;35:435–439.

22. Position paper update: Gastric lavage for gastrointestinal decontamination. Benson B E et al. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Clinical Toxicology 2013;51,140–146.

23. Position paper: Whole Bowel Irrigation. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 2004;42,843–854.

24. Position paper update: ipecac syrup for gastrointestinal decontamination. Höjer J et al. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Clinical Toxicology 2013;51,134–139.

Author

Kai Knudsen

Dep of Anesthesia and Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden.

Published with permission from Internetmedicin AB


Alcohol Intoxication


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Acute alcohol intoxication is the most common of all intoxications in many countries and occurs in thousands every month. Common alcohol abuse gradually changes into alcohol intoxication without any specific boundary. About 5% of all adult men and 2% of all women in Sweden have alcohol dependence. Approximately 300,000 people in Sweden are expected to have risky alcohol consumption, but in some estimates, a significantly higher number is indicated.

About 20% of the population has more or less temporary alcohol problems. These figures are estimated and therefore relatively uncertain, as large variations occur in different estimates and scientific studies from, inter alia, the Federal Association for Alcohol and Drug Information (CAN), which publishes annual reports. Total alcohol consumption in Sweden has decreased slightly in recent years from a peak 2004 when the average consumption was 10.5 liters of pure alcohol per person per year and 9 liters of pure alcohol per person and 2016. Alcohol consumption is distributed in 42% of wine, 37% of beer, 21% spirits, 5% almonds and 1% cider.

Risky alcohol consumption refers to an intake of alcohol which eventually causes medical and social complications. Risky alcohol consumption usually refers to intake of more than 14 standard glasses of alcohol per week for men and 9 standard glasses per week for women. This corresponds to men 56 cl liquor or 2.2 bottles of wine and for women 36 cl liquor or 1.4 bottles of wine per week. A standard glass (or standard unit) corresponds to 12 g of alcohol or a jar of medium strong beer of 50 cl, a bottle of strong beer of 33 cl, 12 cl of table wine or 4 cl of alcohol.

Binge Drinking

Binge drinking usually means that men drink 5 standard glasses and women 4 standard glasses or more at one and the same time. A bottle of wine is counted as 6 standard units.

Mild and moderate alcohol intoxication is usually not subject to hospital care. Most patients who come to hospital with alcohol intoxication also have physical injuries they need medical treatment for, for example, scrubbing, stabbing, contusions, fractures or cuts. Other serious incidents such as drowning, drug intoxication, smoke inhalation injury, abuse or hypothermia are common in acute alcohol intoxication. Hypothermia with intake of drugs mixed with alcohol can lead to prolonged uptake of the drugs, which causes a drunk person to become increasingly drug-poisoned when he or she is warmed up. Vomiting and diarrhea are common in alcohol intoxication, sometimes with pulmonary aspiration. Fluid balancing and electrolyte disturbances are common in prolonged drinking. Hypokalemia, hyponatremia and hypomagnesaemia are relatively common in alcohol abuse. In acute care, these electrolyte disturbances should be checked.

Pure alcohol intoxication can cause hospitalization if it is pronounced, is part of a mixed drug or affects young, retarded, sick or particularly sensitive individuals. Expression of alcohol intoxication usually occurs with an alcohol content of blood alcohol level (BAL) > 2.0 per mille but with large individual differences depending on the degree of tolerance. Usually you can stand up stable up to about 2 per mille. The most common cause of death due to alcohol intoxication is respiratory depression with hypoxia, pulmonary aspiration of gastric contents. Hypothermia is also common in fatal alcohol intoxication.

Approximately 150-200 people die every year due to acute alcohol intoxication in Sweden, of which only 2-3 are under 30 years of age. Approximately 2000 people die annually due to adverse effects. The dose of alcohol can be about 30-40 cl pure alcohol (100%), which corresponds to 1-1.5 full bottles of alcohol (75 cl, 40%) or 3.3-4,4 bottles of wine or 11-14 cans of strong beer intake for a short period of time. At very high levels alcohol (> 3 per mille) in the blood, it is usually spirits that is consumed. Wine and beer usually take longer to drink, so the maximum concentration is rarely as high as after drinking spirits.

Moderate alcohol consumption has been described in several studies with positive health effects. These positions are controversial and may be regarded as scientifically unsafe. Observational studies are limited by methodological problems, mainly confusion factors and error classification. It is always difficult to prove causality as opposed to cohabitation among groups with low alcohol consumption and stable social conditions.

Amount of alcohol in regular drinks

DrinkVolume (cl)Concentration (%)Amount of alcohol (g)
Beer 3.5%503.512
Beer 5.0%50520
Wine751265
Spirit204070
Spirit7540240

Translation of amount of alcohol in beer, cider, wine to corresponding amount spirit

SortAlkohol Conc (%)Volume (cl)Corresponding
amount of
40% spirit (cl)
Light Beer2.25331.9
Intermediate Beer3.5504.4
Strong Beer5.6507
Wine127522.5
Strong Wine187533.8
Strong Wine227541.5

Technical alcohol solutions

Various chemical alcohol solutions are used as fuel, detergents and solvents in technical spirits. Common solutions with technical spirits are T-Red, T-Blue, T-Yellow, K-Spirits and M-Spirits. Intoxication with these agents is not uncommon.

Alcohol content in technical spirits varies between 70 and 95%. Technical spirits generally contain denaturing additives that will make the solution undrinkable, but some people, usually battered alcoholics or experimental young people, still drink denatured spirits.

In addition to ethanol, technical spirits contain methyl ethyl ketone, acetone, ethyl acetate, propanol, paraffin and, in some cases, Bitrex. Denatured spirits are also found in many hand cleaning products, disinfectants, after shaving solution, perfumes and in some drug solutions. In Sweden, methanol is not used as denaturant, but it occurs in some other countries.

Pharmacokinetics of Alcohol

Consumed alcoholic beverages are quickly absorbed into the bloodstream from the mucous membrane of the duodenum and small intestine but not as much in the stomach. Alcohol has no protein binding but is distributed into the body’s different tissues. Apparent volume of alcohol distribution (Vd) is 0.7 L/kg. The effect in the brain (“target site”) occurs within a few minutes after ingestion (about 60-90 sec), which is familiar to most normal consumers. Alcohol levels in blood may increase for about one hour after ingestion.

A normal adult who drinks 3-4 cans of strong beer or 4-6 glasses of wine (12 cl, 12%) achieves an approximately BAL at 1 g/L blood concentration equivalent to 1 per mille. An adult woman achieves the same BAL after ingestion of about 3 cans of strong beer or 3-5 glasses of wine (12 cl).

1 per mille corresponds to 27 mmol/L ethanol in blood. Conversion factor from mmol to per mille: mmol/L x 0.0376.

Achieved per mille content varies with body size, how fast you drink alcohol while taking food.

Ninety percent of alcohol is broken down by oxidation if the majority occurs in the liver. Ethanol degrades at relatively constant velocity in the human body using the enzyme alcohol dehydrogenase. Ethanol is converted into acetaldehyde which is then rapidly decomposed into acetic acid and then into carbon dioxide and water. The degradation of acetaldehyde is already started in the stomach but occurs mainly in the liver. Acetaldehyde (etanal) is an intermediate in the decomposition of alcohol. There is some evidence that acetaldehyde causes some of the classic symptoms of hangover, such as nausea, dizziness, headache, nausea and tiredness. Acetaldehyde, in turn, is broken down to acetic acid by the enzyme acetaldehyde dehydrogenase in the peripheral cell respiration. The acetic acid is then broken down to carbon dioxide and water in several steps.

The enzyme alcohol dehydrogenase, which breaks down alcohol, is already saturated at a BAL above 0.1, above this limit, the degradation is constant with an elimination according to the 0:th order pharmacokinetics. About 90% of alcohol is eliminated by hepatic decomposition and 10% eliminated via exhalation, sweating and urine. The distribution between blood and exhalation air is approximately 2100: 1. Normal degradation of alcohol is about 0.1 g/kg body weight per hour, i.e. 5-10 g alcohol per hour for most people. This corresponds to 2-3 cl of spirits, 6-12 cl of wine or 12-25 cl of beer per hour, i.e. about 1 “unit of alcoholic drink” per hour. In an adult, it is estimated that the amount of per mille usually decreases by about 0.15 per hour. The alcohol in a light beer is degraded in about 15-30 minutes while a strong beer usually takes 60-90 minutes. Relatively large individual variations occur.

Normal Degradation of Alcoholic Beverages

Beverage and AmountDegradation Time (approximately)
Bottle of light beer, 33 cl (2.2%)1 hour
Can of intermediate beer, 50 cl (2.8%)1,5 - 2 hours
Bottle of intermediate beer, 33 cl (3,5 %)1,5 - 2 hours
Can of intermediate beer, 50 cl (3,5 %)2 - 2,5 hours
Bottle of strong beer, 33 cl (5.0%)2 - 2,5 hours
Glass of wine, 15 cl (12%)2 - 2,5 hours
Glass of wine, 12 cl (13 %)2 - 2,5 hours
Bottle of wine,, 75 cl (13 %)11 - 12 hours
Spirit, 4 cl (40 %)2 - 2,5 hours
Half bottle of spirits, 35 cl (40 %)16 - 17 hours

Tolerance

The tolerance for alcohol is heavily varied depending on age and experience. The more often you get intoxicated, the higher the degree of tolerance will develop over time. Most people without alcohol problems have difficulty drinking to levels above 2 per mille of ethanol in the blood.

Life-threatening intoxication is usually found at an alcohol content of 4.5 per mille in women and over 5 per mille in men but even lower concentrations can be life-threatening and have resulted in death. It is difficult to get into these levels by simply drinking beer or wine, usually consuming spirits in large quantities. It is not entirely unusual for alcoholics who are taken care of in hospital for acute alcohol intake have a per mille content of 5, sometimes up to 7-8 per mille, in some cases even higher. Serious alcohol intoxication among adolescents already occurs at a level of more than 2.5 per mille. Serious alcohol intoxication is usually associated with memory loss, hangover and anxiety symptoms in the aftermath.

Symptoms of Intoxication

Degree of alcohol poisoningBlood Alcohol Level (g/L)Symptoms
Mild alcohol poisoning0,5-1,0 per milleVerbosity, intoxication, euphoria, slowered speech, slowered reaction time
Moderate alcohol poisoning1,0-2,0 per milleCoordination difficulties, severe intoxication, alcohol drowsiness, nausea, mood swings, aggressiveness, balance difficulties, hanging eyelids, moist glance, slurred speech
Pronounced alcohol poisoning2,0-4,0 per milleNausea, vomiting, very severe intoxication, abdominal pain, diarrhea, difficulty walking, unstable temperament, violent or messy behavior, detoriation of consciousness, somnolence, cohesion in speech and thought
Life-threatening alcohol poisoningMore than 4-5 per milleComa, seizures, deep sleep with snoring, slow breathing, circulatory instability, respiratory depression, hypoxia (blue-scintillating skin, cyanotic lips/face), hypercapnea (reddish/bluish face color), hypothermia

Light (social) intoxication is considered to be present at an alcohol content of 0.5-1 per mille (see table above). At levels in the blood of 1-1.5 per cent, most adults feel as moderately drunk (some units of strong beer or a bottle of wine) and over 1.5 per mille most people feels heavily drunk (one to two bottles of wine). Young girls in lower teens may feel drunk only with one single strong beer and show clear symptoms of intoxication after two strong units of beer.

Mixed intoxication

Concomitant intake of drugs, such as sleepers or analgesics (opioids) potentiates the toxic effect of alcohol. Particularly risky is the use of opioids, benzodiazepines, neuroleptics, barbiturates or some antidepressants while taking alcohol. Over 2 per mille alcohol in combination with flunitrazepam, opioids or other respiratory deprivatory drugs are considered to be life threatening. Moderate alcohol intoxication can turn into life-threatening intoxication in combination with moderate or high levels of sleepers or analgesics. The combination of alcohol and energy drinks makes you get excited and many do not know the drunkenness as clearly why you drink more and achieve a higher degree of intoxication, not seldom associated with memory loss.

Technical alcohol

The symptoms of intoxication with denatured spirits are similar to those with “common” ethanolic beverages; different degrees of intoxication, loss of consciousness, impaired balance, hyperventilation, nausea and vomiting. Often a characteristic acetone-like odour occurs from the exhaled air. The risk of metabolic acidosis, nausea and vomiting is high.

Clinical and Laboratory Investigation

  • S-ethanol
  • S-methanol
  • S-acetone
  • Pulse and blood pressure
  • Oxygen saturation with pulse oximetry (SaO2)
  • Drug screening for illegal drugs (drug test strips)
  • Arterial acid base status (blood gas measurement)
  • Measure the anion gap
  • Infection Parameters (CRP, SR, Pro-Calcitonin)
  • Hb, glucose, Na, K, Mg
  • Ev alcohol markers such as B-PEth (phosphatidyl ethanol), S-CDT (low-fat transferrin)
  • Ev U-Ethylglucuronide (EtG), U-Etylsulfate (EtS) (demonstrates alcohol consumption last 3 days)
  • Liver enzyme parameters
  • ECG
  • Body Temperature
  • Check neurologic status, palpate the skull, exclude trauma. CT brain on unconsciousness and on suspicion of trauma to exclude epi- or subdural hematoma, as well as other intracranial haemorrhage or stroke
  • In case of suspicion of respiratory distress, X-ray of the lungs
  • In case of intoxication with illegal liquor or home burn products, control of methanol and ethylene glycol levels
  • In serum as well as anion gap and osmolal gap.

Electrolyte disturbances

Observe the risk of electrolyte disturbances. It is common with hyponatraemia, hypokalaemia and hypomagnesaemia in alcohol intoxication and alcohol abuse.

  • Pronounced hyponatraemia causes a risk of brain edema and consciousness reduction. Acute hyponatraemia usually results in a significant reduction in alertness. Pronounced hyponatraemia (<120 mmol/L) with low degree of consciousness indicates chronic hyponatraemia. Chronic hyponatraemia must be corrected slowly over several days. All too fast correction of hyponatraemia can lead to membrane damage in brain cells (myelin lesions), so called “pontin myelysis”, with severe neurological damage as a consequence. Hyponatremia is most commonly seen in beer alcoholists, but increased risk is also present when co-administered with SSRIs (antidepressant drugs).
  • Hypocalcaemia causes fatigue and risk of cardiac arrhythmias.
  • Hypomagnesaemia increases the risk of cardiac arrhythmias (common, especially atrial fibrillation) and seizures.

Other deviations in routine samples 

Note the occurrence of anemia and hypoglycaemia.

Biological alcohol markers

  • U-Etylglucuronide (EtG) and U-Etylsulfate (EtS) indicate alcohol consumption for the last 3 days.
  • CDT (months) (low-fat transferrin) rises after a couple of weeks of high alcohol consumption and can show chronic high alcohol consumption. CDT has high specificity for determining high consumption of alcohol.
  • B-PEth (phosphatidyl ethanol) is a collective name for a group of phospholipids formed from phosphatidylcholine in the presence of alcohol. PEth reflects the last few weeks of alcohol consumption.
  • S-GT (gamma-glutamyltransferase) is a membrane protein that is predominantly in the liver and is increased in chronic alcohol consumption. Some drugs may induce increased GT levels in plasma. The GT can also be elevated in diabetes, brain tumors, obesity and biliary disease. A good control of high alcohol consumption can consist of EtG, CDT and PEth. One can say that EtG reflects high alcohol consumption in recent days, PEth in recent weeks and CDT in recent months.

It is likely that one week of high consumption of alcohol is required for PEth to rise, but a high value clearly speaks for high alcohol consumption, because the value has high specificity.

VITAMIN DEFICIENCY

In particular, note the risk of acute vitamin B deficiency. K and B vitamins often need to be substituted with intramuscular injections for three days. 

Substitute B vitamins and K vitamins in alcoholics as needed:

  • Neurobion (B-vitamine complex) 3 ml x 1 i.m. in 3 days
  • Phytomenadion (Konakion) 1 ml x 1 i.v. (10 mg/ml)

Withdrawal

Observe the risk of severe withdrawal symptoms during the recovery with risk of delirium and general myoclonal seizures.

Acidosis

Metabolic acidosis is common in the case of intoxication with both ordinary alcoholic beverages and technical spirits. If pH measured in the arterial blood gas is below 7.1, intoxication is considered to be life threatening. Base excess less than -10 mmol/L indicates a different cause than ingestion of common ethyl alcohol.

TREATMENT

All patients, including those who are alcoholic, have the right to good general care and to be treated with respect. Stay calm and safe in contact with the patient. General supervision to prevent traumatic injury and moody behavior is the primary. The treatment of acute alcohol intoxication is essentially symptomatic and no antidote is present. Determine the appropriate level of care, but keep in mind that waking and breathing can change suddenly. In case of uncomplicated alcohol intoxication, food canister, liquid, sleep under supervision and antacids may be sufficient. Avoid high-rise bed or bunk to reduce the risk of fall injuries. Resting on the mattress on the floor can be an option. For example, in the case of anxiety and restlessness, give diazepam (Stesolid) 2.5-5 mg intravenously with caution or orally.

In case of more severe intoxication or when complicating factors exist, the situation is different:

  • Monitor alertness and breathing carefully.
  • Give oxygen liberally
  • Suck cleanly in the mouth and throat when there is an increased incidence of mucus or any gastric contents
  • Support breathing and circulation if necessary (ensure free airway, treat hypoxia)
  • Fluid and possibly inotropic drugs at circulation failure. See below for details.
  • In the presence of paradoxical breathing patterns, improve airway conditions (orolaryngeal airway device) and usually intubation are needed.
  • Check body temperature. In hypothermia, heating.
  • Treat acute confusion and motor anxiety.
  • Fluid, per os or intravenously. Poisoned patients usually need rehydration with intravenous fluid. Give isotonic solutions or buffered glucose solutions. If necessary, adjust any electrolyte disturbances.
  • In case of suspicion of respiratory distress, X-ray of the lungs and antibiotics against respiratory infection (cefotaxim (Zinacef) 1.5 g x 3 i.v.). With pulmonary aspiration: intubation, ventilation and respiratory treatment with PEEP. Bronchoscopy.
  • Possible prophylaxis against delirium and general seizures (ex carbamazepine (Hermolepsin, Tegretol) 200 mg 1 × 3 p.o. or levetiracetam). Exclude status epilepticus.
  • Gastric lavage and activated charcoal are only administered when the intoxication is mixed with drugs when the patient is received within 1 hour after ingestion.

Free airway

The respiratory tract may be more or less blocked in alcohol intoxication. Free airway creation has the highest priority. Suck cleanly in the mouth and throat when there is an increased incidence of mucus. Nose tube or oropharyngeal airway device is the first aid. Note that the nasal tube may cause severe nasal bleeding and that the risk of nasal bleeding is increased during alcohol intoxication (due to the vasodilatory effect of alcohol). Therefore, use plenty of gel when introducing into the nose. The position of the patient under vigilance should be in a lateral position, the tongue drawn through a solid jaw lift. Patients who fail to keep the airway in the supine position or not wakeful should be monitored in the intensive care department. Endotracheal intubation is made if necessary in case of insufficient airway, hypoxia or carbon dioxide retention (hypercapnia).

Breathing

Avoid hypoxia and hypercapnia, liberate treatment with oxygen. If breathing is insufficient, endotracheal intubation and respiratory treatment on a ventilator in the intensive care unit must be considered. Clean the airways from mucus.

Circulation

Treat blood pressure drops with intravenous fluid and, if necessary, sympathomimetic drugs (inotropic drugs), e.g. ephedrine, phenylephrine, dopamine or norepinephrine. 

Confusion and Aggressiveness

Stubborn and aggressive patients may need to be tranquilized with drugs to prevent the patient from injuring himself or others. Such sedation is difficult and difficult to handle properly. The treatment itself involves risks in the form of a drop in blood pressure or sudden onset of somnolence with difficulty in maintaining free airway and respiratory depression. Therefore, sedative drugs must be used with caution and under supervision. The treatment requires the ability to take over the patient’s respiration with controlled ventilation and respiratory treatment. Suitable agents for sedation are haloperidol (Haldol) 1-5 mg iv, droperidol (Dridol), midazolam (Dormicum) 1-5 mg iv or propofol (Propofol) 20-100 mg iv. Propofol should only be used by an experienced anesthetist who can handle respiratory problems, as there is a significant risk of hypotension and apnea. Haloperidol (Haldol) should not be used in patients with convulsions or previously known convulsions.

Hangover

The hangover is characterized by nausea, dizziness, fatigue, feeling uneasiness, anxiety and headache. The hangover occurs when the blood alcohol level is close to zero. The hangover is primarily explained by the amount of alcohol consumed, but also at the rate of drinking and on the type of alcoholic beverages consumed. Colored beverages such as whiskey are considered to give more hangovers compared to unleavened spirits. Red wine often gives more hangover than white wine. When taking alcohol at the same time, the risk of hangover and headache increases. Alcoholic beverages should therefore not be used as thirst extinguishers. The hangover is explained, among other things, by acetaldehyde but not entirely. New theories suggest an inflammatory component as a cause of the hangover. The susceptibility to hangover is individual but affects most people who have reached an alcohol level of over 1.5 per mille. About 25% of the population gets little or no hangover. The symptoms are also due to relative dehydration and the intake of so called congeners. Congeners are by-products formed in the fermentation of alcohol and consist of furfural, tannins and fusel oil. Whether drinking water after alcohol can prevent hangover is scientifically unclear, although many people have good personal experience of it. The main cause of the nausea experienced and the general discomfort is due to acetaldehyde that is formed during the breakdown of alcohol. The treatment of the hangover is symptomatic of primarily rehydration, rest, sleep, simple analgesics and antacids.

FOLLOW-UP

In case of pronounced alcohol abuse, the patient is monitored through psychiatry, dependence medicine and social services. Possible mental cohabitation (comorbidity) is investigated and treated accordingly.

Diagnostic codes according to ICD-10

  • F10 Mental disorders and behavioral disorders caused by alcohol
  • T51.0 Ethanol
  • Y91.0 Alcoholic toxicity
  • Y91.1 Moderate alcohol toxicity
  • Y91.2 Difficult alcohol intoxication
  • Y91.3 Very severe alcohol toxicity  

References

  1. Alcohol tests in hospitals not quite easy to use for legal use. Conversion of ethanol to plasma or serum to blood level. Jones AW, Medical Journal No. 6 2008 Volume 105 Link to the article
  2. Norwegian Public Health Institute, Statistics Sweden (2011). National Public Health Review – Health on equal terms. More about the survey
  3. Andersson P, Moller L & Galea G (2012). Alcohol in the European Union: Consumption, harm and policy approaches. WHO Regional Office for Europe. Link
  4. Anderson P & Baumberg B (2006). Alcohol in Europe – A public health perspective. A report for the European Commission. London: Institute of Alcohol Studies. Link
  5. CAN (2012). Drug development in Sweden 2011. Report no. 130. Stockholm: Central Association for Alcohol and Drug Information. Link to the report
  6. Hibell B and others (2012). The ESPAD report 2011. Alcohol and Other Drug Use Among Students in 36 European Countries. Stockholm: Swedish Council for Information on Alcohol and Other Drugs (CAN), the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), and the Pompidou Group at the Council of Europe. Link
  7. Ramstedt M, Lindell A & Raninen J (2013a). Talk about alcohol – a statistical annual report from the Monitor project. SoRAD. University of Stockholm.
  8. Kühlhorn E, Ramstedt M, Hibell B, Larsson S & Zetterberg H (1999). Alcohol consumption in Sweden in the 1990s. Stockholm: Ministry of Social Affairs.
  9. Stockwell T, Zhao J, Panwar S, et al. Do “moderate” drinkers have reduced mortality risk? A systematic review and meta-analysis of alcohol consumption and all-cause mortality. J Stud Alcohol Drugs. 2016; 77 (2): 185-198. Link to the article

Published with permission from Internetmedicin AB


Bensodiazepines – Intoxication and Abuse


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Benzodiazepines are a group of anxiolytics that began to be used in Sweden and other countries in the 1960s as sedatives and hypnotics. Benzodiazepines are internationally accepted standard remedies for treatment of anxiety disorders and temporary sleep disorders. They have also to varying degrees been used in the treatment of milder forms of anxiety and restlessness. Women are more commonly prescribed benzodiazepines, which may be related to that anxiety disorders are more common in women than in men. The use of benzodiazepines is also related to age. People over the age of 65 accounts for more than half of the consumption.

Benzodiazepines are commonly associated with drug-induced overdose and acute toxicity, often associated with alcohol. Diazepam is converted in the body into various active metabolites, mainly nordiazepam and temazepam, but also oxazepam which is excreted in the urine. Maximal blood concentrations of diazepam occur after 30-90 minutes with a half-life that can vary between 20-40 hours for diazepam and 50-99 hours for nordiazepam (long half-life!).

All benzodiazepines have a certain risk of addiction development. Dependence means when an individual persists in use of the drug despite problems related to use of the substance. Compulsive and repetitive use may result in tolerance to the effect of the drug and withdrawal symptoms when use is reduced or stopped. In Sweden it is estimated that 65,000 people have a drug addiction and that 315,000 have a risk use. Being addicted means feeling in need of the drug, difficulty in controlling the use, difficulty in discontinuing the drug, and developing withdrawal without it. The different preparations do not have the same risk of addiction but have a substantially similar pharmacological profile with comparable risks in overdose and abuse. Diazepam is classified as a drug according to LVFS 2011: 10, list IV.

The benzodiazepines with the greatest risk of addiction are those who have rapid onset and high potency. These are flunitrazepam, alprazolam, oxazepam and lorazepam. The greatest risk of addiction appears today with alprazolam (Xanor®, Alprazolam®, Xanor Depot®). Regular intake of some of these benzodiazepines implies a risk of tolerance increase and the occurrence of withdrawal symptoms in discontinuation trials.

Flunitrazepam (Flunitrazepam Mylan® 0.5 mg/1 mg) is primarily a sedative hypnotic, but due to a significant abuse risk, it is also illegal in Sweden. Previously, flunitrazepam was present in several preparations such as Rohypnol®, Flupam® and Fluscand®, all of which are now unregistered preparations.

Benzodiazepines are predominantly prescribed as sleep inducer for elderly patients, but they are also used as premedication for surgical operations. In premedication, benzodiazepines have had a minor role in recent years and have been replaced by other pharmacological preparations, e.g. clonidine.

As a sleeping tablet, flunitrazepam has been extensively replaced by the so-called Z-formulations zopiklon (Imovane®), zolpidem (Stilnoct®) and zaleplon (Sonata®). Zopiklon is recommended as a first aid in treating sleep disorders. As an additive, flunitrazepam has to a certain extent been replaced by these agents, as well as diazepam (Stesolid®), oxazepam (Sobril®), lorazepam (Temesta®) and alprazolam (Xanor®).

Bensodiazepines and similar drugs

BensodiazepineBrand nameFormula
DiazepamStesolid, Diazepam, (Valium Apozepam - unreg)Tablet, rectal solution
KlonazepamIktorivil, RivotrilTablet, injektionslösning, oral solution
LorazepamTemesta, LorazepamTablet
MidazolamDormicum, Midazolam, BuccolamInjection solution, blend
NitrazepamNitrazepam, Mogadon, ApodormTablet
FlunitrazepamFlunitrazepam, (Fluscand, Rohypnol - unreg)Tablet
OxazepamSobril, OxascandTablet
AlprazolamXanor, Xanor depot, Alprazolam, XanacTablet, Tablet extended release
TriazolamHalcionTablet
ZolpidemStilnoct, Zolpidem, EdluarTablet
ZopiklonImovane, Zopiklon, Zopiclon, ZopicloneTablet
ZaleplonSonata (unreg. 2015)Tablet

Approximate equipotent doses and clearance times of different benzodiazepines

BensodiazepineEquivalent dose (mg)Terminal half-life (h)
Alprazolam0.56-12
Klordiazepoxid255-30
Klonazepam0.518-50
Diazepam1020-100
Flunitrazepam118-26
Flurazepam15-3040-250
Loprazolam16-12
Lorazepam110-20
Lormetazepam110-12
Nitrazepam1015-38
Oxazepam204-15
Temazepam208-22
Zolpidem202-3
Zopiklon155-6
Zaleplon202

Addiction

Benzodiazepines can be used as intoxicants since they have a relaxing and euphoric effect with some risk of abuse, often in combination with alcohol. The relaxing and restraining effect is enhanced by alcohol. Often, development goes from regular use via overuse to risk use and abuse. This development is seen as in chronic pain conditions and in long-term anxiety and nervous disorders.

In case of drug abuse, the recommended daily dose is usually exceeded by more than twice (from one to two tablets to four five tablets or more per day). Misuse of benzodiazepines occurs as a mere drug addiction or as a substance abuse with alcohol, analgesics or other illicit drugs. One can see a sliding transition from normal consumption, to risk use and abuse. Flunitrazepam, alprazolam (Xanor®) and oxazepam (Sobril®) are those with the greatest potential for addiction development, but there is a risk of dependence in all benzodiazepines without exception. At the same time, there are many patients who work well with unchanged dosage without tolerance development or dose increase, especially older ones.

Alprazolam (Xanor®) has a significant risk of addiction and abuse. The effect of higher doses than 1 mg of alprazolam or more than 10 mg of diazepam usually causes, but not always, drowsiness and sleepiness that passes into sleep, deeper sleep or coma. A person who has taken such a dose may be drunk and have symptoms such as widened pupils, flushing, pride, slow reflexes, relaxed muscles, numbness, drowsiness, sleepiness, and finally coma.

In some individuals, a paradoxical effect may occur with increased intake, with “increased vigilance” (“excitation state of mind”) in combination with an inhibition effect. The risk of an excitation state increases with the concurrent intake of amphetamine or other central stimulants. It is not uncommon with psychomotor disorders, such as difficulty in being still, hyperactivity, as well as increased aggressiveness and increased impulsivity. This paradoxical effect has occurred in connection with surgical premedication, both among children and adults. The effect on children is sometimes described as the child “climbs on the walls”.

The excitatory stage involves a change of vigilance that can pass into sleep or coma. However, people with regular abuse may maintain the “increased alertness” and avoid sleep by choosing the right dose range or by combining benzodiazepines with central stimulants such as amphetamine, methamphetamine, cocaine, synthetic cannabinoids or ecstasy. This is seen primarily among people with a substance abuse and an increased tolerance for the drug. The excitation stage can be transformed into acute confusion with agitation, rarely with aggressiveness, numbness and hallucinations. Several illegal benzodiazepine preparations are present in European countries or purchased online. These include adinazolam, bromazepam, flubromazepam, diclazepam, flubromazolam, flunitrazolam, N-desmethylflunitrazepam, norfludiazepam, phenazepam, clonazolam, cloniprazepam, zapizolam, meclonazolam, pyrazolam and etizolam.

Withdrawal

In the case of developed dependence on benzodiazepines, withdrawal symptoms occur during abrupt drug withdrawal. Symptoms such as feeling complacent, increased nervousness, unspecified discomfort, intrusive anxiety and nervousness. Seizures may develop. Somatic symptoms such as palpitations, tremors, stomach pain, cold sweating and abstinence seizures are also present. In case of prolonged abuse, a slow and gradual drug discontinuation usually requires, for example, tablet diazepam (Stesolid®), which may take several months and up to one year. The withdrawal symptoms start to occur a few days after the end of the drug. Not so often, such a discontinuation begins far above recommended daily doses. Initial doses may be as high as 60-100 mg diazepam per day, which is then given in a decreasing dose. Alternative medicines in the treatment of withdrawal symptoms have not yet shown better results than treatment with benzodiazepines in declining doses. Among the drugs tested are beta blockers and buspirone (Buspiron®). 

Special risks of Substance Abuse 

There are particular risks of abuse where benzodiazepines and analgesics (opioids) are combined. The enhancement of depressant effects on the brain’s respiratory and circulatory centers can lead to overdoses and death, especially in combination with opioids or alcohol. When the use of different drugs is discontinued at the same time, different withdrawal symptoms occur. Benzodiazepines enhance the anti-inflammatory effect of analgesics. Benzodiazepines reinforce the rush of other drugs such as cannabis, amphetamines and opiates.

Cross Tolerance

When tolerance of a drug within a specific group of drugs occurs, tolerance also increases for other preparations within the same category. For example, anesthesia personnel who is to be anesthetizing a patient prior to an operation finds that the patient does not fall asleep on a normal dose of anesthetic drugs. It is usually because the patient is a major consumer of a similar preparation. 

Cross Sensitization

Certain drug effects are instead reinforced for prolonged use, such as the “drug affection”, but also the psychosuppressive effects. Sensitization to a drug can lead to cross-sensitization to another drug. In practice, it means that the person dependent on a drug becomes more dependent on another.

OVERDOSE 

Toxicity

Twentyfive to fifty (25-50) mg alprazolam in combination with alcohol at a blood level of 2 per mille has given lethal toxicity. 0.3 mg/kg to 8-year-old gave moderate – severe intoxication. 10 mg to 13 years gave moderate toxicity. 15 mg (and alcohol) in adults gave severe toxicity, while 20-40 mg to adults only caused moderate inhibition.

Symptoms of Acute Overdose

  • Somnolence, drowsiness
  • Dizziness
  • Hypotension
  • Bradycardia
  • Hypothermia
  • Apnea episodes
  • Mydriasis, large pupils (even small miotic pupils occur especially in unconsciousness)
  • Ataxia
  • Dysartria, slow slurred speech
  • Nausea
  • Muscle weakness
  • Respiratory depression
  • Anxiety
  • Excitation
  • Tachycardia
  • Hallucinations
  • Coma

 

Treatment of Acute Overdose

  • General supervision to prevent injuries and disability
  • Establish free airway. The patient should be placed in advanced side position. The so-called “orofacial airway device” or equivalent can be used.
  • Oxygen liberally
  • If a significant amount of drug has been taken, gastric lavage should be performed within 1 hour after ingestion
  • Active charcoal is given only within 1 hour after ingestion
  • Monitoring of respiration, circulation and alertness
  • Intravenous fluid supply of isotonic crystalloid solutions, e.g., Ringer Acetate
  • Intubation and controlled ventilation at deep unconsciousness or respiratory depression
  • Antidote treatment with flumazenil (Lanexat®), as appropriate

 

Specific antidote flumazenil (Lanexate® 0.1 mg/ml, 5 ml in an ampoule = 0.5 mg) can be given slowly intravenously to wake a comatose or semicomatous patient at doses of 0.3-0.5 mg.The dose should be repeated after one minute in case of no effect. Usually 2 to 3 doses are sufficient. The maximum dose for adults is 2 – 5 mg flumazenil. Note the number of ampoules. New injection is sometimes necessary after 1 – 4 hours. In some cases, flumazenil may be administered in continuous infusion. Flumazenil can be combined with naloxone in case of unclear unconsciousness in suspicion of drug-induced unconsciousness. Flumazenil (Lanexat®) is unsuitable for co-administration with drugs that can induce general seizures, such as antidepressant drugs, as the antidote lowers the seizure threshold.

In case of doubt, the patient may instead be monitored for respiratory and respiratory tract care in an intensive care unit. Treatment should be guided by what is best for the patient and not after the ICU availability situation. Gastric lavage should be performed only if a large amount of benzodiazepines have been taken or if the drug has been taken in combination with other dangerous preparations up to one hour after ingestion. If there is doubt as to whether the patient can protect his respiratory tract, experienced anesthetist should participate in the procedure.

Patients who are deeply unconscious or who have insufficient breathing should be intubated and monitored in an intensive care unit. Patients usually wake up after overdosage of benzodiazepines after 4-12 hours depending on intake and type of preparation. Note that several benzodiazepines have active metabolites with a long half-life, which means that even longer-term unconsciousness more than 12 hours occurs.

The half-life is further prolonged in case of reduced hepatic function. With guaranteed vital features where breathing and airway is ensured, the prognosis is usually very good with only symptomatic treatment.

FOLLOW-UP

It is important to control the patient during the emergency phase at the correct level of care so that vital functions can be ensured in a medical emergency department or an intensive care unit.

In the aftermath, the drug abuse must be treated; assessment of psychiatrists and referral to dependence clinic and contact with social services are some measures that are almost always needed. Discontinued withdrawal treatment should be planned as expected with severe withdrawal.

The application for social services must always be performed in life-threatening addiction, in the treatment of children under the age of 18 or when adults have children at risk of neglect.

Psychosocial support efforts are necessary to give parallel to drug treatment of existing withdrawal symptoms. It is important to get a picture of the patient’s personality, emotional state and cognitive ability to give the patient the correct treatment. The investigation needs to assess whether psychotic symptoms, increased suicidality or addiction are present. Provided depression and psychotic symptoms, the risk is great for suicide.

Outpatient treatment is individualized and based on frequent contacts with psychiatrists or psychologists who have experience of drug dependence, as well as regular urine tests with benzodiazepine, THC (tetrahydrocannabinol) and other drugs. Initially after a period of abuse, it is common with a disturbance of attention and poor motivation for drug-freeness.

Social aspects must also be evaluated in the patient’s treatment and the curator (social services) is connected. In addition, it should be understood that the risk factors and the safety factors (relatives) the patient has in his/her immediate environment in order to be able to provide the correct support measures. An important issue to investigate is the type of living the patient has. A personal interaction between dependent clinics and social services is often necessary in these cases. A referral to a psychologist or curator with special skills regarding dependence diseases and the use of benzodiazepines is essential for the continued care of the patient. In the treatment of schoolchildren, school health care should also be announced. An assessment of the patient’s addiction development and suicidality should be done with established psychological instruments such as ASI interview, AUDIT and measuring instruments to assess suicide risk.

Diagnostic code according to ICD-10

  • T42.4 Benzodiazepines
  • X60-X69 Intentional self-destructive action through poisoning
  • Y10-Y19 Poison with obscure intention
  • F13.0 Mental disorders and behavioral disorders caused by sedatives and hypnosis, acute intoxication

Call as required your local Poisons Information Center.

References

  1. Rohypnol – not just a sleep piller. A mapping of drug abuse. Gunnar Hermansson. Polish Academy of Law 1998.
  2. Abuse liability of flunitrazepam among methadone-maintained patients. Magi Farré et al. Psychopharmacology 1998: 140: 486-495
  3. Benzodiazepines – side effects, abuse risk and alternatives. Lance P. Longo et al. American Family Physician April 1, 2000, Vol 61, No. 7, 2121-2128
  4. Abuse of Flunitrazepam (Rohypnol) and other benzodiazepines in Austin and South Texas. Sarah R. Calhoun et al. Journal of Psychoactive Drugs. Vol. 28 (2), April-June 1996.
  5. Benzodiazepines and other psychotropic drugs abused by patients in a Methadone maintenance program: familiarity and preference. Christian Barnas et al. Journal of Clinical Psychopharmacology Vol. 12 No. 6 1992.
  6. Dépendence aux psychotropes et traitements de substitution: tendances récentes. X. Thirion et al. Therapy 1999; 54: 243-249.
  7. Consommation abusive de flunitrazepam par les toxicomanes aux opiacés. J. Salvaggio et al. Ann. With. Internal 151, Suppl. A, pp. A6-A9, 2000 France
  8. The role of benzodiazepines in elderly suicides. Anders Carlsten et al. Scand J Public Health 2003; 31: 224-228.
  9. Sudden Death and Benzodiazepines. The American Journal of Forensic Medicine and Pathology 17 (4): 336-342, 1996. O. H. Drummer and David L. Ranson
  10. Flunitrazepam: an evaluation of use, abuse and toxicity. Henrik Druid et al. Forensic Science International 3123 (2001) 1-6
  11. Club Drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate. Kelly M.Smith et al. Am J Health-Syst Pharm vol 59 jun 1, 2002.
  12. Adverse effects of prolonged benzodiazepine use. Heather Ashton. Adverse Drug Reaction Bulletin june 1986 no 118 440-443
  13. Comment: use and abuse of flunitrazepam. Marta Mas et al. The Annals of Pharmacotherapy 1998 September, vol 32, 980-981
  14. Flunitrazepam consumption among heroin addicts admitted for in-patient detoxification. Luis San et al. Drug and Alcohol Dependence, 32 (1993) 281-286.
  15. Benzodiazepine misuse in poly-drug users L. Ferreira et al.
  16. Date rape among adolescents andyoung adults. V.I. Rickert and C.M. Wiemann. J Pediatr Adolesc Gynecol 1998:11:167-175
  17. Flunitrazepam (Rohypnol) abuse in combination with alcohol causes premditated grievous violence in male juvenile offenders. Anna M Dåderman and Lars Lidberg. J Am Acad Psychiatry Law vol 27, no 1, 1999.
  18. Flunitrazepam abuse and personality characteristics in male forensic psychiatric patients. Anna M. Dåderman and Gunnar Edman. Psychiatry Research 103 (2001) 27-42
  19. Violent behaviour, impulsive decision-making, and anterograde amnesia while intoxicated with flunitrazepam and alcohol or other drugs: a case study in forensic psychiatric patients. Anna M. Dåderman et al. The Journal of the American Academy of Psychiatry and the Law 30:238-51, 2002

 

Author

Kai Knudsen

Dep of Anesthesia and Intensive Care,

Sahlgrenska University Hospital, Gothenburg

Published with permission from Internetmedicin AB


Phenothiazines

By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2019-02-18


Phenothiazines are a group of older neuroleptics with antipsychotic properties that can cause serious poisoning. This group includes drugs such as levomepromazine (Nozinan), flufenazine (Siqualone), perfenazine (Trilafone) and procloperazine (Stemetil). Previously, medicines such as Hibernal, Mallorol and Esucos also belonged to this group, but these are now deregistered. Phenothiazines are closely related to tricyclic antidepressants and, in case of overdose, may cause life-threatening conditions with coma and severe cardiac arrhythmias.

Phenotiazine  derivatives are a type of neuroleptic agent used for systemic use with sedative, anticholinergic and antihistaminergic properties. Phenotiazine  derivatives are commonly found in drug poisoning, often in combination with other drugs used for anxiety and anxiety. Prescription of prometazine (Lergigan) has increased sharply in Sweden in recent years as well as the number of poisoning cases, although this is an older drug. In 2017, more than 600 poisoning cases occurred. Most poisoning cases have mild or moderate symptoms but deaths occur. Toxnet (Toxicology Data Network) states that there are cases of respiratory depression, sleep apnea and sudden infant deaths reported in a number of infants or toddlers. It is further stated that sudden and unexpected deaths have occurred in patients receiving phenotiazine s, especially during prolonged administration.

Phenotiazine  derivatives are thus derivatives of phenotiazine s where some preparations lack actual antipsychotic effects such as Theralen, Lergigan and Propavan, while other preparations have distinct antipsychotic effects (those with piperazine ring). Phenotiazine  derivatives are often used for anxiety, anxiety, and insomnia, but also for seasickness, nausea and allergic reactions. Chemically, they can be divided into aliphatic side chain substances such as chlorpromazine (Hibernal), levomepromazine (Nozinan), promazine, acepromazine, triflupromazine or those with piperazine ring such as flufenazine (Siqualone) or perfenazine (Trilafone). Phenotiazine  derivatives generally produce less severe poisoning compared to phenotiazine s but have become more numerous. Tioxants are other related preparations that provide similar symptomatology in poisoning, e.g. chlorprotixen (Truxal), zuclopentixol (Cisordinol), and flupentixol (Fluanxol).

The drugs are present as tablets, oral drops and oral solution. Previously, prometazine was also used for injection but it is deregistered. Abroad, fentiazine derivatives are found in several other drugs in various dosage forms that sometimes appear in Sweden in connection with poisoning incidents.

The most common phenotiazine  derivatives are:

  • Alimemazine (Theralen (tablets, drops), Alimemazine (capsules, drops)
  • Prometazine (Lergigan (tablets, oral solution), Prometazine (tablets))
  • Prometazine in combination preparations like: Lergigan Comp (tablets)
  • Propiomazin (Propavan)

Phenothiazines may cause prolonged QT time and severe cardiac arrhythmias after overdose. Heart palpitations, tachycardia and irregular heartbeat occur but are not very common. However, one should be aware that prolonged QT time occurs and that malignant arrhythmias may occur as ventricular tachycardia and Torsade de Pointes arrhythmia. In many cases, the QT extension is very limited and lacks clinical relevance. The absolute risk of suffering may be seen as very small, but it is difficult to assess the risk in an individual patient. Other risk factors must be considered, such as cardiovascular disease, high or low age, and heredity for myocardial infarction / stroke.

In combination preparations, besides prometazine, caffeine and ephedrine are also included which can produce a different form of poisoning. The main effects seen with overdose and poisoning with phenotiazine  derivatives are fatigue, somnolence and, increasingly, wakefulness and coma. The sedative effect is potentiated by other sedatives, hypnotics or alcohol. Propiomazin (Propavan) is a centrally acting phenotiazine  derivative where the poisoning image is mainly characterized by decreased alertness or coma with respiratory failure in pronounced cases.

Diagnosis of poisoning of phenotiazine  derivatives is based on the history and eventuality. findings of tablet cases, packages or medicines. Usually no drug determination is made in blood or urine. Diagnosis and treatment of anticholinergic syndrome is based on the clinical picture. The treatment is mainly symptomatic. Antidote treatment with physostigmine may be effective in some cases with mainly central nervous symptoms. Phenotiazine  derivatives may cause prolonged QT time, therefore ECG must always be taken with QT time determination.

Toxicity

The toxicity of phenotiazine  derivatives varies with the ingested dose, the patient’s age and condition, and the concomitant intake of other substances. Most incidents only give moderate symptoms. Taking 20-100 mg may cause toxicity in children under one year of age. Intake of 100-1000 mg can result in moderate intoxication to children between one and ten years of age. Ingestion of 1-2.5 g in the adult usually gives moderate intoxication if simultaneous intake of other substances has not occurred. Intake over 2.5 g should be considered severe but the symptomatology may vary widely.

Common symptoms of poisoning

  • Lowered degree of consciousness
  • Confusion
  • Hallucinations
  • Impaired vision
  • Light sensitivity
  • Restlessness
  • Motor worry, “craziness”, twitching
  • Aggressiveness

Common clinical findings

  • Hyperthermia
  • Extended QT time
  • Dry mucous membranes
  • Dry warm skin
  • Large, often bright pupils
  • Sinus tachycardia
  • Reduced bowel sounds
  • Urinary retention
  • Normally – increased blood pressure
  • Contractions in the stretch muscles
  • Opistotonus, positive Babinski

Anticholinergic Syndrome

Phenothiazine derivatives have potent anticholinergic properties that can give the patient characteristic symptoms of overdose. Symptoms that characterize the image can be anxiety, confusion, large pupils, tachycardia, dry mouth, hallucinations and sometimes a full-scale delirium. Cramps are more unusual but spastic muscle contractions occur. Usually the patient appears to be “witty” with involuntary muscle twitching. In some cases, opistotonus as well as strange twitching in bonfires and larger muscle groups are also seen, the symptom picture can be difficult to interpret. The English memory frame for the anticholinergic syndrome describes the symptoms well:

“Blind as a bat, mad as a hatter, save as a bite, hot as hades (or hot as a hare), dry as a bone, the bowel and bladder lose their tone , and the heart runs alone. ”

The anticholinergic syndrome can be treated with physostigmine intravenously for the central nervous effects manifested as a delirium. When treated with physostigmine, a troubled and confused patient may suddenly wake up, become mentally clear and oriented, which seems like an awakening that dramatically improves the clinical picture and soothes everyone present.

Treatment

The most important in most cases of fentiazine derivative poisoning is that:

  • Identify toxic agents
  • Carefully monitor alertness and breathing
  • Support breathing and circulation as needed
  • Perform active elimination when indicated, eg, by gastric emptying, and administration (instillation) of medical charcoal
  • Treat acute confusion and motor anxiety in a calm and safe manner
  • Antidote treatment with physostigmine when there is a clear indication and benefit outweighs the risks of anticholinergic syndrome
  • Treatment of heart failure and hypotension with conventional inotropic drugs such as noradrenaline or adrenaline
  • Treatment with intravenous fat emulsion (ILE) can be tested as the last resort in cardiovascular collapse.
  • Adding the patient to a department with the right level of care and avoiding too low a level of care when consciousness is lowered or breathing is impaired
  • Organize a follow-up through psychiatry and social services

Ventricular rinsing and installation of activated carbon is indicated if a large dose has been taken and the patient arrives within one to two hours after ingestion. Usually 50 g of coal suspended in water per os is given via a coarse probe.

If the patient is circulatory and respiratory stable but worried and delirious, one can try physostigmine intravenously, usually with good effect. Contraindications are mixed intoxication with other cardio-depressant drugs such as tricyclic antidepressants or drugs that cause reduced seizure threshold. Physostigmine should also not be given if the patient has wide-spread QRS complexes, bradycardia (pulse <50 beats / min) or other cardiac arrhythmias. If anticholinergic syndrome is suspected, physostigmine should be tested prior to benzodiazepines. Benzodiazepines have only moderate effects in anticholinergic syndrome. However, the physostigmine reduces the seizure threshold, so there is a risk of seizures if drugs that can provoke seizures such as TCA are ingested.

Dosage of physostigmine

1-2 mg is given slowly in adults to adults and 0.02-0.04 mg / kg in v to children. In pronounced cases, an infusion can also be tested at a dose of 1-3 mg / h. Effect can be expected within minutes, and the duration is about 90 minutes. The dose may sometimes have to be repeated at an hourly interval if pronounced symptoms reappear, but the clinical experience is that one need seldom need to give an additional dose later than 8 hours after the first. At the physostigmine injection, the patient should be connected to the cardioscope, and atropine should be available.

Follow-up

Psychiatric and social follow-up of the patient is important when intoxication occurs in connection with suicide attempts or when the patient has an active abuse with drugs, alcohol or drugs. Return visits to psychiatry, dependency care or to social services is desirable, referral should be written. In case of a life-threatening addiction (alcohol, opioids or illegal drugs), the social services must always be contacted, in writing or orally.

Cases of adolescents under the age of 18 must be reported to social authorities and BUP (child and adolescent psychiatric clinic). School health care may also need to be connected.

In case of repeated acute overdoses, notification to the social services should be made and care taken under the LVU (the Act on the Care of Young People <20 years) or LVM (the Act on the Care of Addicts) should be considered. Registration for the social services can be oral or written.

Lasting side effects

A drug overdose with phenotiazine  derivatives generally gives no lasting but, unless serious complications occur, such as apnea, aspiration pneumonia, severe arrhythmias, acute liver failure, acute renal failure or pronounced general hypoxia. The risk of developing withdrawal after abuse of alcohol, drugs or medication must always be taken into consideration in a discharge. A transient sleep disorder with severe sleep problems for 3-4 weeks is not uncommon. Other side effects described are stomach pain, concentration difficulties, depression, anxiety, and impotence. Many patients experience low quality of life for a long time after having been treated for acute poisoning. There is always the risk of a new poisoning or overdose in the next year.

References

  • Raises J, Tellerup M. Renaissance for Lergigan with a sharp increase in intoxication cases. Läkartidningen. 2018; 115: E9EZ.
  • Owczuk R, Twardowski P, Dylczyk-Sommer A, Wujtewicz MA, Sawicka W, Drogoszewska B, Wujtewicz M. Influence of promethazine on cardiac repolarisation: a double blind, midazolam controlled study. Anesthesia. 2009 Jun; 64 (6): 609-14.
  • Nachimuthu S, Assar MD, Schussler JM. Drug-induced QT interval prolongation: mechanisms and clinical management. Ther Adv Drug Saf. 2012 Oct; 3 (5): 241-53. doi: 10.1177 / 2042098612454283. Review.
  • from Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol. 2010 Jul; 70 (1): 16-23.
  • Phenergan Product Summary FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/07935s030lbl.pdf
  • Conventional N, Hiasa Y, Kishi K, Fujinaga H, Ohishi Y, Ohtani R, Wada T, Aihara T [A case of life-threatening ventricular arrhythmias probably due to psychotropic drugs]. Kokyu To Junkan. 1993 Nov; 41 (11): 1117-20.

Tricyclic Antidepressant Agents


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Tricyclic antidepressant drugs (TCAs) constitute second-generation antidepressants that became common in the treatment of depression in most countries in the 1970s. These drugs are predominantly prescribed against endogenous mental depression but also against several other conditions such as severe pain states, OCD, panic syndrome, PTSD, narcolepsy and nocturia. Several nearby pharmacological variants occur as bicyclic and tetracyclic antidepressant drugs.

Poisoning with tricyclic antidepressant drugs (TCAs) is still common and deaths occur regularly, although serious poisoning was significantly more common in the 1980s and 90s than today. Antidepressants are common in self-inflicted deliberate poisoning and have significant morbidity and mortality. Poisoning with TCA has higher mortality compared with other antidepressant drugs. The suicide risk of depressed patients remains during treatment until remission has occurred and may even increase initially, as in some cases the inhibition may decrease before mood is improved. Amitriptyline is one of the most common drugs in fatal suicide poisoning worldwide. TCA poisoning is usually diagnosed according to ICD with the code T43.0. In 2014, 47 deaths of these poisons were caused in Sweden, 24 women and 23 men (about 250 deaths per year in England).

Drug poisoning with TCA usually requires intensive care. In total, approximately 12 million daily doses (DDD) of TCA are sold per year in Sweden, compared to the SSRIs sold in approximately 170 million DDD. A number of tricyclic antidepressants have been deregistered in Sweden in recent years, due to the fact that they have been replaced by more modern drugs with fewer side effects. Classical TCAs have relatively strong side effects that may be felt in early treatment such as orthostatism with dizziness and feeling unwell, as well as palpitations, dry mouth and constipation.

Acute poisoning with TCA may give rise to an anticholinergic syndrome with large pupils, palpitation, big pupils, excitement and mental confusion. The anticholinergic syndrome should be distinguished from the serotonergic syndrome that may occur after overdose with SSRIs. Serious poisoning is characterized by coma, seizures and cardiac arrhythmias. In ECG, widened QRS complexes and irregular rhythm are commonly seen. Really wide-necked QRS complexes indicate serious poisoning, the wider the more dangerous. QRS width over 140 msec indicates serious poisoning, and over 160 msec very serious poisoning.

Toxicity

The toxic effect of overdose is mainly due to:

  • An inhibition of noradrenaline uptake presynaptically in nerve terminals
  • A direct alpha receptor blockade
  • A membrane stabilizing effect in myocardium (quinidine-like)
  • An anticholinergic effect

Highest toxicity has amitriptyline and dosulepin.

Degree of poisoning

Intake of less than 10 mg/kg gives easier poisoning. Intake of 15-20 mg/kg is likely to cause serious poisoning. Ingestion of 1 to 2 g usually causes moderate poisoning; over 2.5 g causes serious poisoning. Intake over 5 g produces very serious poisoning.

Common cyclic antidepressants 

  • Amitriptylin
  • Clomipramine
  • Nortriptyline
  • Maprotilin
  • Mianserin

Other antidepressant drugs

These have previously been prescribed in Sweden but have been deregistered in recent years of which some may be available in other countries:

  • Desipramine
  • Imipramine
  • Lofepramin
  • Protriptylin
  • Trimipramine
  • Opipramol
  • Trimipramine
  • Dothiepin
  • Dibenzepin
  • Protriptyline
  • Doxepin
  • Iprindole
  • Melitracen
  • Butriptyline
  • Dosulepin
  • Amoxapine
  • Dimetakrin

Symptoms of acute poisoning

  • Somnolence and coma

Reduced alertness to unconsciousness, ranging from little influence to deep unconsciousness for several days. The length of the comatous period depends on the preparation taken, the amount taken and the plasma half-life. In case of serious poisoning, it is common for at least one day of unconsciousness.

  • Confusion

Confusion and agitation are common

  • Large pupils

Depend on an anticholinergic effect.

  • Hypotension

Blood pressure may initially be increased but is more often slightly lowered with a systolic blood pressure around 80-90 mm Hg. Blood pressure may become even lower in case of severe poisoning.

  • Cardiac arrhythmias

Tachycardia is common, as is ventricular arrhythmias. In severe cases, multiple VES with complete irregularity and “Torsade de Pointes” arrhythmias. Arrhythmias often coincide with heart failure.

  • Respiratory depression

Slow, regular but insufficient breathing with risk of hypoventilation and carbon dioxide retention (hypercapnia).

  • Seizures

Increased “excitement”, with tingling in the extremities is common as well as convulsive seizures.

Anticholinergic Syndrome

  • Big pupils
  • Dry hot skin
  • Tachycardia
  • Confusion
  • Hallucinations

The English Anti-Cholinergic Syndrome Memory Frame is nice to keep in mind

  • Mad as a hatter
  • Dry as a bone
  • Red as a beet
  • Blind as a bat
  • Hot as a desert

Serious poisoning (intake over 2500 mg) 

  • Severe hypotension
  • ECG changes
  • Broadened QRS complex, AV block, extended QT time, ST-T changes.
  • Heart failure

Cardiogenic shock is associated with bradycardia and pronounced broadening of QRS on ECG and ventricular arrhythmias. In the end, bradycardia and asystoli and a sinusoidal curve on ECG develops. At a QRS over 100 ms, the risk of seizures increases. At a QRS over 160 ms, the risk of ventricular arrhythmias increases significantly.

EMERGENCY CARE

Medical history

  • What preparation? Amount? Time of intake? Mixed poisoning with other substances? Signs of deliberate suicide action?

Investigations

  • Clinical diagnostics
  • Intox samples, including blood alcohol level (BAL)
  • ECG
  • Pulse oximetry
  • Blood pressure
  • Check blood samples including myoglobin for signs of prolonged unconsciousness
  • Drug screening

The treatment is predominantly symtomatic and one should avoid hypotension, hypoxia and metabolic acidosis. Most TCAs have high fat solubility and a large volume of distribution, which means that elimination methods like hemodialysis become ineffective in treatment. Tricyclic antidepressants have anticholinergic effects that are dose dependent and decrease during treatment. Antidotal treatment with physostigmine may be considered after the initial phase when circulation and respiration is stable.

Preparedness must be prepared for the treatment of respiratory depression, convulsions, cardiac arrhythmias and blood pressure drop, which means that the patient should always be treated within the ICU (> 2.5 g) in severe cases. In case of pronounced hypotension, isotonic fluids is given crystalloid fluid, hypertonic salt (RescueFlow) and sodium bicarbonate.

It should also be avoided to provide membrane-stabilizing drugs such as quinidine, beta blockers, calcium antagonists and flecainide (Tambocor). Amiodarone (Cordarone) should probably be avoided in the treatment of arrhythmias as it may prolong QT interval, and cause hypotension, bradycardia and possibly arrhythmias.

Treatment

  • Gastric lavage

Within an hour of intake – until clear exchange. Upon later arrival, gastric lavage may be considered for life-threatening poisoning up to 24 hours after the incidence.

  • Medical charcoal

The dose should be at least 50 g. Give at least 10 times the dose taken of TCA.

  • Alkalinization

Sodium bicarbonate is given on wide indications – correct acidosis until Base Excess (BE) becomes positive in the blood gas analysis. The pH should be above 7.45. Alkalinization can reverse parts of the conduction barrier in the heart and improve depolarization. Even hypotension can be improved. Sodium bicarbonate reduces the free fraction of the drug in the bloodstream, which allows smaller amounts of TCA to bind into the heart, plasma protein binding increases. You can often start immediately with two bottles of 100 ml Sodium Bicarbonate (60 mmol/unit).

  • Hypertonic saline

For wide-spread QRS complexes on ECG (> 160 ms). Immediately give 200 mmol sodium intravenously.

  • Oxygen

Intubation and controlled ventilation in respiratory insufficiency

  • Adequate fluid supply, sodium chloride and optionally. dextran (macrodex)
  • Physostigmine

In the case of anticholinergic symptoms, symptoms of confusion, psychomotor disturbance and agitation physostigmine can be given intravenously, but not if circulatory instability or bradycardia occurs. There is a small risk that physostigmine induces convulsions.

  • Inotropic treatment with vasopressor substances

Noradrenaline or adrenaline may be given continuously. Dopamine sometimes has insufficient effect. Adrenaline has given rise to less arrhythmias than noradrenaline in experimental studies and may be preferred. In case of pronounced bradycardia, isoprenaline may be given.

  • Arrhythmia therapy

Magnesium sulphate (20-40 mmol intravenously) may be given, in ventricular tachyarrhythmias, or in rare cases lidocaine. In the treatment of arrhythmias, polypharmacy should be avoided.

  • Diazepam  In case of seizures or anxiety, 5 mg iv.
  • In case of circulatory collapse, extracorporeal support such as arteriovenous ECMO may be life-saving.
  • ILE (Intravenous Lipid Emulsion Therapy)

ILE can be considered during circulatory collapse. ILE has been shown to be efficient primarily with overdose with local anesthetic agents, mainly bupivacaine. In case of overdose with TCA, a large number of positive case reports are published. However, a thorough review of the topic published in 2016 has left a major question mark for the effectiveness of this treatment in TCA poisoning. In controlled animal studies, a small entrapment has been demonstrated by amitriptyline, but no beneficial hemodynamic effect or improved survival. The evidence for this treatment is therefore considered to be only low when poisoned with TCA. In some animal studies, even increased mortality has been detected with ILE and theoretically there is a risk of ARDS and pancreatitis as a result of treatment.

ICD-10

  • Tricyclic and tetracyclic antidepressant drugs T43.0
  • Observation of suspected toxic effect of intake substance Z03.6

References

  1. Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: a review. Emerg Med J 2001;18:236–41. Länk
  2. Hawton K, Bergen H, Simkin S, Cooper J, Waters K, Gunnell D et al. Toxicity of antidepressants: rates of suicide relative to prescribing and non-fatal overdose. Br J Psychiatry 2010;196:354–8. Länk
  3. Body R, Bartram T, Azam F, Mackway-Jones K. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose. Emerg Med J 2011;28:347–68. Länk
  4. Levine M, Hoffman RS, Lavergne V, Stork CM, Graudins A, Chuang R, et al. Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity. Clin Toxicol (Phila) 2016;epubl ahead of print. Länk
  5. Engels PT, Davidow JS. Intravenous fat emulsion to reverse haemodynamic instability from intentional amitriptyline overdose. Resuscitation 2010;81:1037–9. Länk
  6. Harvey MG, Cave G. Case report: successful lipid resuscitation in multi-drug overdose with predominant tricyclic antidepressant toxidrome. Int J Emerg Med 2012;5:8. Länk
  7. Kiberd MB, Minor SF. Lipid therapy for the treatment of a refractory amitriptyline overdose. CJEM 2012;14:193–7. Länk
  8. Litonius ES, Niiya T, Neuvonen PJ, Rosenberg PH. No antidotal effect of intravenous lipid emulsion in experimental amitriptyline intoxication despite significant entrapment of amitriptyline. Basic Clin Pharmacol Toxicol 2012;110:378–83. Länk
  9. Heinonen JA, Litonius E, Backman JT, Neuvonen PJ, Rosenberg PH. Intravenous lipid emulsion entraps amitriptyline into plasma and can lower its brain concentration – an experimental intoxication study in pigs. Basic Clin Pharmacol Toxicol 2013;113:193-200. Länk
  10. Forsberg M, Forsberg S, Höjer J. Inget stöd för att lipidterapi är en effektiv antidot vid akut förgiftning. Lakartidningen 2015;112:1723-6. Länk
  11. Knudsen K, Abrahamsson J. Effects of magnesium sulfate and lidocaine in the treatment of ventricular arrhythmias in experimental amitriptyline poisoning in the rat. Crit Care Med 1994;22:494–8. Länk
  12. Knudsen K, Abrahamsson J. Magnesium sulphate in the treatment of ventricular fibrillation in amitriptyline. Eur Heart J;18:881–2. Länk
  13. Knudsen K, Heath A. Effects of self poisoning with maprotiline. BMJ 1984;288:601–3. Länk
  14. Knudsen K, Abrahamsson J. Effects of epinephrine and norepinephrine on haemodynamic parameters and arrhythmias during a continuous infusion of amitriptyline in rats. Clin Toxicol 1993;31:461–71. Länk
  15. Knudsen K, Abrahamsson J. Epinephrine and sodium bicarbonate independently and additively increase survival in experimental amitriptyline poisoning. Crit Care Med 1997;25:669–74. Länk

Author Kai Knudsen

Anesthesia department, Sahlgrenska University Hospital, Gothenburg

Published with permission from Internetmedicin AB


SSRI, SNRI and NaSSA


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


The prescription of other antidepressants than classical tricyclic antidepressive agents (TCA) has increased significantly over the past 20 years in Sweden. By 2015, it is estimated that approximately 600,000 patients were treated with antidepressants. The drugs can be divided into three groups; SSRIs – Selective Serotonin Reuptake Inhibitors, SNRI preparations – Selective Norepinephrine Reuptake Inhibitors and NaSSA Preparations – Noradrenergic and Specific Serotonergic Antidepressants. Generally, the SSRIs have taken over most of the antidepressant drug market. SSRIs were sold in 2015 at 82 doses per 1000 inhabitants per day (DDD). SSRIs accounted for 413,000 of a population of 600,000 patients (68%) treated with antidepressant drugs.

Clinical cases of poisoning of SSRIs or other antidepressants have therefore become common in the emergency department. SSRIs have significantly lower acute toxicity compared to classical TCAs, while SNRIs have an intermediate status for toxicity. About 7% of all poisonings with these agents are reported as serious cases. Cardiac toxicity is lower for SSRIs but pronounced heart failure may occur after intake of high doses, usually more than 5 g. General seizures occur relatively often and may be difficult to treat. In addition, SSRI preparations may cause a so-called “Serotonin syndrome”. This syndrome may occur after taking several drugs that inhibit reuptake of serotonin in the CNS – such as an SSRI preparation and an analgesic (tramadol, fentanyl) – or various illicit drugs such as amphetamine and ecstasy which give an increased risk of seizures. Some special SSRIs require special attention in case of acute poisoning and are described below. In 2013, 49 people died in Sweden as a result of poisoning with classical antidepressants, while 69 people died of other and unspecified antidepressants (Death Register Data – Code T43.2).

Some common Antidepressive Agents

SSRI

SNRI

NaSSA 

Venlafaxine (Efexor®) is an antidepressant drug that acts by inhibiting the reuptake of both noradrenaline and serotonin in the brain and is classified as so-called SNRI. Even dopamine uptake is inhibited to some extent. Efexor is sold as tablets in the strength of 37.5 and 75 mg, respectively, and in the depot form at the strength of 75 or 150 mg. The high strength of the tablets causes the risk of excessive overdose to be high. This medicine deserves some extra attention in case of acute overdose. Intake of up to 1 g venlafaxine in adults is a mild poisoning and intake of 1-1.5 g is moderate poisoning.

Intake of 1.5-2.5 g is considered to be serious poisoning and over 2.5 g as very serious poisoning. Note that patients taking Efexor Depot® may deteriorate up to 24 hours after ingestion. A mild symptomatology upon arrival at a hospital does not therefore rule out a stormy poisoning process. There are several poisoning cases reported in Sweden in recent years with fatal outcome. In one case, the intake amount was approximately 4.8 g Efexor Depot and in another case 7.5 g Efexor and an unknown amount of oxazepam (Sobril®) for suicide intention.

Similar preparations

There are several antidepressants such as mianserin (Mianserin®), mirtazapine (Remeron®, Mirtazapin®), bupropion (Zyban®), reboxetine (Edronax®), atomoxetine (Strattera®) and duloxetine (Cymbalta®, Yentreve®) that not classified under tricyclic preparations or as SSRIs, but as SNRIs or NaSSAs. Edronax® and Strattera® are selective noradrenaline reuptake inhibitors. Strattera is a relatively new preparation used for concentration difficulties in the indication of ADHD in children and adults. Bupropion (Zyban®, Voxra®, Bupropion®) has a special indication of smoking cessation. Bupropion has been present as an addictive substance and may in this context have some central stimulant effect. In the case of overdose, bupropion has two long-term metabolites (> 30 h) that allow patients to be comatose for a very long time, in some cases for several days.

Clinically these drugs have similar effects to overdose of the SSRIs, but the pharmacological effect varies. In particular, note the risk of prolonged QT-time and the risk of seizures in acute poisoning. Myoclonus or convulsions may start without other warning signs, for example, following venlafaxine intake (Efexor®) or bupropion (Zyban®, Voxra®). In case of moderate or severe poisoning, extra attention should be paid to the occurrence of muscle spasms or general seizures. These may appear suddenly in a condition with only mild symptomatology. The seizures may be prolonged and persistent and recur after the addition of diazepam (Stesolid®). ST-T changes in ECG and prolonged QT time have also been observed in younger heart-healthy patients. Unexpected ECG changes do not exclude serious poisoning as opposed to poisoning with classical antidepressants. Patients with moderate or high intake of these drugs and initially mild symptomatology should therefore be monitored in an intensive care unit with careful monitoring for at least 12 hours in severe poisoning and for at least 24 hours in severe poisoning with depot preparations (Efexor depot®). Pay attention to QT time on ECG as prolonged QT time increases the risk of severe cardiac arrhythmias. Check with prolonged QT time especially when venlafaxine poisoning (Efexor®), citalopram (Cipramil®) and mirtazapine (Remeron®) are poisoned.

In the case of unconsciousness in the elderly, the clinical picture may be relatively unspecific and other clinical signs are missing. Diagnosis can easily be missed; a careful history is extremely important as well as checking empty cartons. Sampling of urine can be performed in unclear cases.

Symptoms and Clinical Picture

CNS symptoms in Overdose

  • Excitation with anxiety, agitation, confusion, dizziness, hallucinations
  • Tremor, chills
  • Ocular oscillations
  • Dizziness
  • CNS depression with coma or decreased consciousness.
  • Seizures may occur suddenly, even in relatively unaffected patients
  • Extrapyramidal side effects; rigidity, rupture, tremor, acatasia (inability to remain still)
  • Easily resolved late reflexes, clonus
  • Hyperthermia

Circulatory symptoms

  • Blood pressure drops, but blood pressure may also be elevated (autonomic instability)
  • Tachycardia or bradycardia. AV blocks, prolonged QT time, ST-T changes, broad-range QRS complexes
  • Ventricular arrhythmias and extrasystoles
  • Circulatory collapse and ventricular fibrillation in pronounced cases. Ventricular fibrillation can occur suddenly without significant previous ECG changes. Ventricular fibrillation is often preceded by convulsions.

Other symptoms

  • Rigidity, tremor, hyperthermia, rhabdomyolysis, serotonin syndrome
  • Respiratory failure
  • Myoclonus (muscle twitching)
  • Mydriasis
  • Sweating
  • Gastrointestinal symptoms; diarrhea, nausea and vomiting
  • Liver and kidney injury in rare cases
  • Electrolyte disorders – hyponatraemia, hypokalaemia, hypomagnesaemia

Serotonin Syndrome

Overdose with SSRIs, SNRIs and atypical antidepressants may all cause a serotonergic syndrome. The syndrome may occur after acute overdose but also after ingestion of therapeutic doses. Serotonin syndrome refers to a major overactivity in the serotonergic neurotransmission of the CNS and the symptomatology that this causes. Symptomatology is dominated by CNS symptoms with acathasia, tremor, sweating, anxiety, agitation, confusion, diarrhea, hyperreflexia, clonus, tachycardia, rigidity and hyperthermia. It is a serious condition that in the worst case leads to death. The risk is especially great if an antidepressant drug is combined with other agents that also release serotonin. Examples of other agents are different analgesics and central stimulant drugs such as amphetamine, cocaine and ecstasy. Also, sumatriptan (Imigran®), valproate (Absenor®, Ergenyl®, Orfiril®), levodopa (Madopark®, Sinemet®), bromocriptine (Pravidel®), lamotrigine (Lamictal®), lithium (Lithionit®) and certain health food preparations may induce a serotonin syndrome. Among the analgesics are tramadol (Dolatramyl®, Gemadol®, Nobligan®, Tiparol®, Tradolan®, Tramadol®), petidin (Petidin®) and fentanyl (Leptanal®, Fentanyl®). Symptoms may be rapid ingestion of fever, muscle rigidity and excitation as a rule.

Usually, the syndrome is relatively modest and transient. In severe cases rhabdomyolysis, general seizures, renal failure, respiratory insufficiency, liver failure and multiple organ failure occur. The most important thing in the treatment of the syndrome is sedation and suffocation. If necessary, specific drugs may be given with some “antidote effect” such as cyproheptadin (Periactin® license preparation) and haloperidol (Haldol®). Beta-blockers (metoprolol, atenolol), bromocriptine (Pravidel®) or dantrol (Dantrium® license preparation) have no place in the treatment.

In the case of serotonin syndrome, treatment with any of the following medicines may be considered:

Treatment and Medical Care

The treatment of acute poisoning with SSRIs and SNRIs is essentially symptomatic and similar to the treatment of poisoning with classical antidepressants. Awareness, breathing and hemodynamics can suddenly deteriorate without warning. Seizures, psychomotor disorders, nausea and vomiting are common. Insufficient breathing is supported as needed by endotracheal intubation and respiratory treatment in an intensive care unit. If vital parameters are stable and the patient breathes calmly and regularly it is usually enough for supervision and the patient is allowed to sleep until he or she wakes up. Comatose patients are placed stable in side mode and turn every other hour. Another reason for deep unconsciousness than poisoning should of course be ruled out.

Check electrolytes, toxicology samples and an arterial blood gas as well as the blood alcohol level. Perform a CT scan with x-ray in unclear cases of unconsciousness or in the presence of focal neurological symptoms. 

Activated charcoal is valuable if administered early in treatment, especially within one hour after ingestion of toxic agents. Medical charcoal administration should be standard treatment in case of serious poisoning. Coal is of limited value if it is given later than one hour after the poisoning ingestion. Early-administered charcoal is very effective and adsorbs most antidepressants. Medical charcoal can also be given later than one hour in life-threatening poisoning and should supplement gastric lavage when carried out. See special guidelines for gastric lavage and medical charcoal.

Gastric lavage is of value but should only be performed if the patient arrives early in hospital after the poisoning occurs, preferably within one hour. In case of very serious poisoning (life-threatening poisoning), after intake of very large doses or after ingestion of depot preparations, gastric lavage may need to be performed at a later stage. See special guidelines for gastric lavage.

See Overview Gastric Lavage

  • Gastric lavage if warranted.
  • Activated charcoal (Carbomix, Charcoal suspension 150 mg/ml) 50 g orally, or more if poisoned with more than 5 g of any drug. Insert a nasogastric tube if repeated activated carbon is to be given.
  • Appropriate fluid substitution with crystalloid infusion solutions; for example 2000-3000 ml Ringer’s Acetate, or dextran (Macrodex®) 500 ml.
  • Monitoring of circulation, respiration and diuresis. Follow lactate.
  • Diazepam 5-10 mg i.v. in case of anxiety, hyperthermia, rigidity or seizures. Treatment with diazepam has resulted in prolonged unconsciousness.
  • Sodium Bicarbonate in acidosis, arrhythmias or broad-scale QRS complexes. Initially give 100-300 ml of sodium bicarbonate i v.
  • Be liberal with intubation and controlled ventilation.
  • Inotropic treatment, dopamine, norepinephrine or adrenaline in refractory hypotension.
  • In case of pronounced circulatory failure consider treatment with extracorporeal circulation (ECMO system).
  • In case of circulatory arrest, cardiopulmonary resuscitation should be performed immediately and intravenous lipid therapy (ILE) may be tested.
    • The bolus of a 20% lipid emulsion (Intralipid®) 1.5 ml/kg i.v. or 100 ml quickly intravenously.
    • Start an infusion with a lipid emulsion of 0.25 ml/kg/min for 10 minutes, while cardiovascular resuscitation is performed, give 100 ml intravenously – which can be repeated.
    • Bolus doses can be repeated every 5 minutes, two or three times if necessary, 1 ml/kg Intralipid. More than 8 ml/kg lipid emulsion should not be given.
  • Hypertonic saline (Rescue-flow®) can be tested in broad-scale QRS complexes (200 mmol over 20 minutes).
  • Possible arrhythmia treatment with magnesium sulphate. Twenty (20) mmol of magnesium in 100 ml of sodium chloride is administered intravenously for 20 minutes.
  • In Serotonin syndrome: sedation and cooling. Muscle relaxation.
  • Specific treatment for serotonin syndrome may be given with: Cyproheptadin (Periactin®) 8 mg x 3 orally  – license preparation.
  • Other symptomatic treatment, such as treating acidosis, hypovolemia, hypotension, arrhythmias and electrolyte disturbances.
  • In hyperthermia:
    • Undress the patient.
    • Cool the patient with cold bags in the axils, groins and over the forehead.
    • Give 1000 ml cold sodium chloride intravenously into the peripheral catheter over 30 minutes. NOTE! Never give cold solutions in a central venous catheter!
    • In pronounced conditions with hyperthermia: sedation, respiratory care and muscle relaxation.
  • Register in the medical journal time for tablet intake, type of drug, amount (total in mg), possibly empty drug packages and from whom the data comes.
  • Control of any signs of external trauma, needle marks etc.
  • Call as required your local Poisons Information Center

Follow-up

Psychiatric and social follow-up of the patient is important as the toxicity occurs in connection with suicide attempts or when the patient has an active substance abuse with drugs, alcohol or drugs. A visit to psychiatry or social services is desirable. Referral should always be written. Evaluate the patient’s degree of depression and the presence of psychotic symptoms. In case of increased suicidality with an active death wish, treatment under restricted conditions (LPT) must be considered.

Persistent symptoms

A drug overdose usually does not last but unless serious complications are given as apnea, aspiration pneumonia, acute liver failure, acute renal failure or pronounced general hypoxia. The risk of developing withdrawal after abuse of alcohol, pharmaceutical drugs or illicit drugs must always be taken into account. Transient sleep disturbance with severe sleep difficulties for 3-4 weeks is not uncommon as well as fatigue and muscle aches. Other side effects described are stomach pain, difficulty concentrating, numbness, anxiety and impotence.

ICD-10

T43 Poisoning with psychotropic drugs not classified elsewhere

T43.2 Other and non-specified antidepressant drugs

X60-X69 Intentional self-destructive action through poisoning

Z03.6 Observation of suspected toxic effect of intake substance

REFERENCES

  1. Howell C, Wilson AD, Waring WS. Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235 consecutive cases. Br J Clin Pharmacol. 2007;64(2):192-7.
  2. Kelly CA, Dhaun N, Laing WJ, Strachan FE, Good AM, Bateman DN. Comparative toxicity of citalopram and the newer antidepressants after overdose. J Toxicol Clin Toxicol. 2004;42(1):67-71.
  3. Colbridge MG, Volans GN. Venlafaxine in overdose – experience of the National Poisons Information Service (London centre) [abstract]. J Toxicol Clin Toxicol. 1999;37:383.
  4. Blythe D, Hackett LP. Cardiovascular and neurological toxicity of venlafaxine. Hum Exp Toxicol. 1999;18(5):309-13.
  5. Cumpston S, Chao M, Pallasch E. Massive venlafaxine overdose resulting in arrythmogenic death [abstract]. J Toxicol Clin Toxicol. 2003;41:659.
  6. Mazur JE, Doty J, Krygiel A. Fatality related to a 30-g venlafaxine overdose. Pharmacotherapy. 2003;23(12):1668-72.
  7. Pascale P, Oddo M, Pacher P, Augsburger NM, Liaudet L. Severe rabdomyolysis following venlafaxine overdose. Ther Drug Monit. 2005;27(5):562-4.
  8. Daniels RJ. Serotonin syndrome due to venlafaxine overdose. J Accid Emerg Med. 1998; 15:333-4.
  9. Whyte I, Dawson A, Buckley N. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM. 2003;96:369-74.
  10. Hernández JL, Ramos F, Infante J, Rebello M, Gonzales-Macias J. Severe serotonin syndrome induced by mirtazapine monotherapy. Ann Pharmacother. 2002;36:641-3.
  11. Personne M, Sjöberg G. Toxicitet vid överdosering av nya antidepressiva. Läkartidningen 2008; 105 (3):125-7.
  12. Hanekamp, et al. Serotonin syndrome and rabdomyolysis in venlafaxine poisoning. The Netherlands Journal of Medicine. 2005;63(8):316-318
  13. Danescu I L, Macovei R Al, Caragea G, Ionica M and Cioca G. Rabdomyolysis in a venlafaxine poisoning case [abstract]. Toxicology Letters. 2008;180:S1, Page S129

Author Kai Knudsen

Anesthesia department, Sahlgrenska University Hospital, Gothenburg

Published with permission from Internetmedicin AB


Local Anaesthetics – Toxic Reactions (LAST)


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Local anesthetics are used to give patients pain relief in a range of surgical procedures and medical examinations. They are also used in dental practice, veterinary surgery and in the treatment of acute or chronic severe pain.

Local anesthesia is usually administered as an injection fluid but may also be given in ointment, gel or in sprays. Injections are performed by infiltration locally with syringe and injection needle or through peripheral nerve blocks, e.g. epidural, spinal or plexus blockade. Blocks are either administered as a single dose (bolus dose) or via repeated doses or in continuous infusion of a local anesthetic via catheter. It is common for epidural blocks to be given as a combination of local anesthetics and opioids.

A toxic reaction may occur unexpectedly and suddenly after an injection of local anesthetic agents with a dramatic influence on the patient’s condition, in pronounced cases the reaction can be life threatening. In modern English-language literature, toxic reactions triggered by local anesthetic systemic toxicity are called LAST. Dominant symptoms in a toxic reaction are CNS symptoms and cardiovascular symptoms, in particular cases of cardiovascular collapse with a risk of sudden death. Prior to major blocks (regional anesthesia), an intravenous peripheral venous catheter (PVC) must always be inserted on the patient for intravenous treatment. Access to anesthesia equipment and possibilities for artificial respiration and life-saving efforts must also be available. The same applies always when more than 20 ml of local anesthetic is administered.

Toxic reactions are distinguished from allergic reactions, vasovagal reactions with fainting and side effects of adrenaline supplements. Vasovagal reactions with pulse and blood pressure drop occur easily in painful injections – especially in young, nervous, irritated, distressed or obese individuals. Genuine allergic reaction to local anesthetic agents is extremely rare and is often confused with other unpleasant reactions, such as fainting, but allergic reaction to additives (carriers) in local anesthetic agents occurs. Referral to allergologists should be written in the event of a suspected true allergic reaction and a skin test should be carried out under supervision, preferably in an operating department. Carefulness with the term “Cave” shall apply to medical records.

In addition to system toxic reactions, it should be noted that in high doses, prilocaine (Prilocaine, EMLA) may cause methemoglobinemia with impaired oxygen transport capacity in the blood. In methemoglobinemia, the patient becomes cyanotic or grayish and the blood gets a chocolate brown color. Methemoglobinemia over 25% is considered to be life threatening and should be treated with the antidote methylene blue (methylthionine) given i.v. (1-2 mg/kg). Even when using Prilocaine in cream form, EMLA, the reaction may occur. Excessive lubrication with EMLA cream, for example in case of skin burns, especially on toddlers, should be avoided. Methemoglobinemia has also occurred after overdose with local anesthesia in the bladder (tampon).

PHARMACOLOGY

Local anesthetics are divided into two groups; amino amides and amino esters. Esters generally have higher toxicity than amino amides and all preparations have been deregistered in Sweden but are found in many other countries. The present preparations in Sweden, all of which are of amide type, are Mepivacaine, Lidocaine, Prilocaine, Ropivacaine, Levobupivacaine and Bupivacaine. The preparations are present in different concentrations, usually half (5 mg/ml) or one-percent solution (10 mg/ml) with or without adrenaline additive. Nesacain (chloroprocaine) occurs in single clinics as licensing agent (rapid action).

Local anesthetic agents are relatively fat soluble, absorbed in the tissues are related to local blood flow. The agents readily cross the blood brain barrier, and central nervous effects and system toxic effects usually occur within a few minutes after an intravenous injection. Metabolism occurs mainly in the liver. Some drugs metabolized in the liver delay the degradation of local anesthetics, such as antidepressant drugs. Drug interactions can affect system toxicity.

Different local anesthetic agents have different properties of system toxicity. Mepivacaine, lidocaine and prilocaine can be categorized as low toxicity drugs, ropivacaine and levobupivacaine as medium-toxic drugs and bupivacaine as a high toxicity agent.

The circulation effect caused by bupivacaine is more pronounced and more difficult to treat compared to other local anesthetics. When CNS symptoms occur, the cardiac effect of toxic reaction of bupivacaine is more potent than those of ropivacaine.

The risk of a toxic reaction becomes particularly high if bolus doses are given on top of a continuous infusion that goes into an infusion pump. Particularly sensitive is the continuous infusion of bupivacaine, which has a relatively long half-life. Extra bolus doses for a patient who is continuously injecting bupivacaine must be administered with extreme caution and preferably with other drugs with lower toxicity, such as lidocaine or mepivacaine. The toxicity of different local anesthetics given simultaneously is additive.

The absorption of local anesthetic agents (i.v.) in the nerve blockade varies with the type of blockade. At most, it is at intercostal blockade followed by caudal block, epidural block, plexus block and femoral block. Therefore, great caution should be observed when placing an intercostal block or caudal block. Infraclavicular block is more dangerous than axillary plexus block.

Maximum Doses of Local Anesthetic Agents

 Mepivacaine (Carbocaine®)Lidocaine (Xylocaine®)Prilocaine (Citanest®)Ropivacaine (Naropin®)Levobupivacaine (Chirocaine®)Bupivacaine (Marcaine®)
Maximum dose singel blockade (4 hours)400 mg400 mg400 mg300 mg150 mg150 mg
Maximum dose mg/kg5 mg4 mg5 mg3 mg2 mg2 mg
Maximum daily dose1000 mg1200 mg1200 mg800 mg400 mg400 mg

Maximum dose of local anesthetics to children

Dose in ml according to body weight
Body weight (kg)Bupivacaine 2,5 mg/mlBupivacaine 2,5 mg/ml + adrenalinBupivacaine 5 mg/mlBupivacaine 5 mg/ml + adrenalinLidocaine 10 mg/mlLidocaine 10 mg/ml + adrenalinMepivacaine 5 mg/mlMepivacaine 5 mg/ml + adrenalinVikt (kg)
108,0 ml12,0 ml--5 ml7,0 ml10 ml14,0 ml10
129,6 ml14,4 ml--6 ml8,4 ml12 ml16,8 ml12
14--5,6 ml8,4 ml7 ml9,8 ml14 ml19,6 ml14
16--6,4 ml9,6 ml8 ml11,2 ml16 ml22,4 ml16
18--7,2 ml10,8 ml9 ml12,6 ml18 ml25,2 ml18
20--8,0 ml12,0 ml10 ml14,0 ml20 ml28,0 ml20
22--8,8 ml13,2 ml11 ml15,4 ml22 ml30,8 ml22
24--9,6 ml14,4 ml12 ml16,8 ml24 ml33,6 ml24
26--10,4 ml15,6 ml13 ml18,2 ml26 ml36,4 ml26
28--11,2 ml16,8 ml14 ml19,6 ml28 ml39,2 ml28
30--12,0 ml18,0 ml15 ml21,0 ml30 ml42,0 ml30
32--12,8 ml19,2 ml16 ml22,4 ml32 ml44,8 ml32
34--13,6 ml20,4 ml17 ml23,8 ml34 ml47,6 ml34
36--14,4 ml21,6 ml18 ml25,2 ml36 ml50,4 ml36
38--15,2 ml22,8 ml19 ml26,6 ml38 ml53,2 ml38
40--16,0 ml24,0 ml20 ml28,0 ml40 ml56,0 ml40

Administration of Local Anaesthetics

High concentrations of local anesthetic agents in the bloodstream may occur due to involuntary intravascular injection, overdose or unusually rapid absorption from rich vascularized tissue. Rapid absorption occurs during infiltration anesthesia, especially if the injection occurs in the face around the oral cavity, nose or throat. Absorption increases with peripheral vasodilatation and high cardiac output with fast pulse.

Central blocks (face, throat, scalp, above and below the clavicle) cause greater risk of toxic reaction than peripheral blocks.

In epidural blocks, a toxic reaction occurs more easily if the injection occurs in a vein (epidural vein). The epidural space is richly vascularized and an epidural catheter may accidentally penetrate or perforate a vein. If local anesthetic is given in an epidural vein, it circulates into the heart within one minute, which can cause a serious toxic reaction with sudden circulatory arrest. In the case of bloody aspiration in an epidural catheter, the catheter should be replaced. Injection of a bolus dose of local anesthetic epidurally should therefore always be preceded by an aspiration test for blood and administration of a test dose, which may detect excessive uptake in system circulation. Addition of adrenaline in the test dose may facilitate the detection of an intravenous injection by responding to the patient with rapid heart rate (tachycardia). Adrenaline is usually not used in the majority of epidurally administered local anesthetics (8-14 ml) but only in the test dose (4 ml).

Toxic reactions are due to high plasma concentrations, usually short term. Adrenaline administration in local anesthetic agents causes local vasoconstriction, which inhibits absorption and reduces the risk of system toxic reaction in properly established epidurals. As a rule, therefore, higher doses of local anesthetic agents with adrenaline are tolerated better than local anesthetics without adrenaline.

SYMPTOMS of Toxicity

At high concentrations of local anesthetic agents in the blood, mainly CNS and cardiovascular systems are affected by system toxicity. All amide-type local anesthetic agents cause high-dose similar CNS symptoms, while the cardiovascular effects differ between different drugs, both quantitatively and qualitatively.

When administering local anesthetics in high doses, patients must always be monitored carefully. A common conversation can often reveal a systemic toxic reaction by suddenly getting the patient unclear, somnolent, slow talking or obnoxious speech. Patients who have just received a blockade, such as an axillary plexus anesthesia, should therefore never be left alone in anticipation of the blockade’s effects.

CNS toxicity occurs gradually with symptoms and reactions of increasing severity. Common initial symptoms are stiffness in mouth and tongue, making it harder to speak (perioral anesthesia and stiffness, slurred speech). Tinnitus and acute hypersensitivity (hyperacusia) may also occur early. Symptoms usually occur in the order of drowsiness, paresthesia in the tongue and mouth, tinnitus, muscle seizures, seizures, coma, respiratory distress and eventually cardiac arrest. Observe the difficulty of detecting the initial symptoms of an anesthetized patient!

CNS symptoms indicate that a cardiovascular reaction is imminent, so the immediate release of local anesthetic agents must be discontinued immediately.

Common CNS symptoms of toxic reaction of local anesthetic agents

  • Feeling drunk
  • Perioral paresthesia
  • Drowsiness in the tongue
  • Hyperacusia, hearing hallucinations
  • Tinnitus
  • Visual disturbances
  • Difficulty to articulate
  • Slow, slurred speech
  • Twitching
  • Difficulties to fix your eyes
  • Tremor
  • Generalized seizures
  • Unconsciousness

Cardiovascular Symptoms

If the patient is sedated with drugs or anesthetized, it may be difficult to detect early signs of CNS toxicity due to local anesthetics. In these patients, cardiovascular symptoms may be the first alarming signs of a toxic reaction.

A cardiovascular reaction often results in tachycardia. Thereafter, blood pressure drops, cardiac arrhythmias of various kinds, broad-range QRS complexes, bradycardia, repeated short-term asystoles and finally cardiac arrest follow. The course of a toxic reaction with cardiovascular symptoms may be rapid.

In an anesthetized patient, bradycardia and irregular rhythm (skipped strokes – sinus arrest) may be the first symptom of a toxic reaction followed by blood pressure drop and asystole.

Metabolic symptoms of a toxic reaction are oxygen deficiency, hypercapnea, metabolic acidosis and hypercalcaemia. Metabolic acidosis in itself increases the risk of a toxic reaction because a larger fraction of the drug circulates freely in plasma and affects the heart.

Acute Care

In case of a toxic reaction, action must be taken immediately. Weakness, breathing and hemodynamics can change rapidly. Seizures, psychomotor disorders, vomiting and nausea are relatively common. The treatment is essentially symptomatic. Usually, the toxic symptoms are rapidly transient within a few minutes. Initial measures mean that vital functions regarding breathing and circulation are ensured. Often it is enough to give oxygen and possibly some anticonvulsants like diazepam.

Emergency measures (see headings below for details)

  • Cancel the supply of local anesthetic agents immediately
  • Put the patient down in the supine position with a slightly raised head end
  • Give oxygen (always!) via breathing mask (Ruben blow)
  • Careful monitoring of alertness and breathing
  • Support breathing and circulation, avoid hypoxia and hypercapnia
  • If required: assisted ventilation, mask ventilation or intubation
  • If seizures do not stop spontaneously within 15-20 seconds, thiopentone (Pentothal Sodium) is given 1-3 mg/kg i.v. (50-100 mg) or diazepam 0.1 mg/kg i.v. (5-10 mg, slightly slower)
  • Alternatively to thiopentone, small doses of propofol are given 10-60 mg slowly intravenously. Risk of blood pressure drop.
  • Injection of muscle relaxants, e.g. suxametonium 0.5 mg/kg should be given in case of difficulty in ventilating the patient.
  • In the case of hypotension/bradycardia, a vasopressor is given, e.g. ephedrine 5-10 mg i.v. (may be repeated after 2-3 minutes) or adrenaline 0.05-0.1 mg i.v. (repeated doses 0.1 mg/ml). Even phenylephrine 0.1-0.2 mg IV can be tested.
  • Atropine (atropine) 0.5-1 mg i.v. given in bradycardia.
  • Sodium bicarbonate (50-100 ml, 60-120 mmol) is given at acidosis on liberal indication. Seek for positive Base Excess (BE).
  • Insert an artery needle and control blood gases
  • Hypertonic saline should be given in broad-scale QRS complexes (200 mmol Sodium fast i.v.)
  • In case of circulatory arrest, cardiac pulmonary resuscitation should be performed immediately and intravenous lipid therapy (ILE) should be tested.
  • Give a bolus of a 20% lipid emulsion (Intralipid), 1.5 ml/kg i.v. all 100 ml fast intravenously.
    • Start an infusion with a lipid emulsion of 0.25 ml/kg/min for 10 minutes, while cardiovascular rescue is performed, all. 100 ml intravenously.
    • Bolus doses can be repeated every 5 minutes, two or three times if necessary, 1.5 ml/kg Intralipid.
    • More than 12 ml/kg lipid emulsion should not be given in total (840 ml to 70 kg patient). Stop the infusion after stabilized circulation.
  • Blood sampling: arterial blood gas analysis with acid-base status, frequent electrolyte controls (routine status), B-glucose
  • Continued treatment is managed according to the patient’s condition
  • In severe arrhythmias, amiodarone (Cordarone) may be used
  • Avoid calcium blockers and beta blockers in treatment
  • Long-term cardiopulmonary resuscitation may be required in the toxic reaction of bupivacaine
  • If the patient is not responding to lipids and vasopressor treatment, treatment with an extracorporeal system (arteriovenous ECMO) should be initiated if possible. Since such treatment is usually started with delay, it may be wise to contact the nearest unit with resources for extracorporeal treatment. Geographical reasons can make this treatment impossible.

Free airway

  • Supine position with heightened head end for optimal intubation and ventilation position
  • Assisted ventilation
  • Jaw lift, nasal tube or oropharyngeal airway advice for mechanical ventilation
  • Endotracheal intubation, in case of emergency a laryngeal mask
  • Oxygen
  • Pulse Oximeter
  • Prevent and avoid aspiration

Venous access

  • Peripheral venous catheter (PVC), at unconsciousness at least two
  • Arterial catheter, unconsciousness or circulatory effects
  • Central venous catheter (CVC), unconsciousness or circulatory effect

Circulatory monitoring

  • ECG with arrhythmia monitoring, continuously and on paper
  • Invasive monitoring, continuous arterial pressure and central venous pressure (CVP) in case of severe circulatory failure
  • Pulse Oximeter
  • Urinary bladder catherization with urinary output

Lipid treatment (ILE)

Several animal experimental studies and case studies in humans have shown that rapid delivery of lipids intravenously (ILE) in circulatory collapse following overdose with bupivacaine increases survival. The mechanism is not yet fully understood, it is believed that the lipids bind a part of the free fraction of the drug in plasma, whereby local anesthetic agents diffuse out of the myocardium and the toxicity is reduced (“sink theory”). You get a diffusion gradient from cardiac cells into the bloodstream, which reduces cardiac toxicity. Another theory is that the fat constitutes a nutrient substrate for the heart with positive effects. What was previously called the “sink theory” has now been replaced by “shuttle theory”. Lipids are thought to change the distribution of local anesthetic agents in various compartments in a favorable manner. ILE also causes a vasoconstriction that causes blood pressure to rise even when common vasopressors such as adrenaline do not work.

Further studies on humans are needed to confirm these data, but studies are so convincing that several national specialist associations in anesthesia recommend this treatment in the event of cardiovascular collapse, especially in the case of overdose with bupivacaine. The concept is supported by several case reports on humans. However, data on the use of ILE on other poisons with circulation collapse are more contradictory.

Treatment of general seizures

Despite a certain respiratory depression effect, diazepam is a well-proven preparation for general seizures in the treatment of a toxic reaction. Appropriate starting dose is 5-10 mg i.v. Diazepam is then given in the dose of 5 mg x 3, plus if necessary.

Check ECG and ST depression! If diazepam is not sufficient, one can use thiopental (Pentothal Sodium) or propofol (Diprivan). Tiopental is given intravenously in small doses, 50-100 mg. Propofol should also be given in small doses, 20 mg i.v. or in continuous infusion (20 mg/ml 5-10 ml/hour). Observe the risk of blood pressure drop.

ICD-10

Local anesthetics T41.3

References

  1. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology. 1979; 51: 285-287.
  2. Di Gregorio G, Neal JM, Rosenquist RW, Weinberg GL. Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979-2009. Reg Anesth Pain Med. 2010: 35: 179-185.
  3. Scott DB, Lee A, Fagan D, Bowler GM, Bloomfield P, Lundh R. Acute Toxicity or Ropivacaine Compared to That of Bupivacaine Anesth Analg. 1989 Nov; 69 (5): 563-9.
  4. Knudsen K, Beckman Suurküla M, Blomberg S, Sjövall J, & Edvardsson N. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. British Journal of Anaesthesia, 1997; 5: 507-514.
  5. Corcoran W, Butterworth J, Weller RS, et al. Local anesthetic-induced cardiac toxicity: a survey of contemporary practice strategies among academic anesthesiology departments. Anesth Analg. 2006; 103: 1322-1326.
  6. Mayer E. The toxic effects following the use of local anesthetics. JAMA. 1924; 82: 876-885.
  7. Moore DC, Bridenbaugh LD. Oxygen: the antidote for systemic toxic reactions from local anesthetic drugs. JAMA., 1960; 174: 102-107.
  8. Prentice JE. Cardiac arrest following caudal anesthesia. Anesthesiology. 1979; 50: 51-53.

Author

Kai Knudsen

Department of Anesthesia and Intensive Care, Sahlgrenska University Hospital, Gothenburg

Published with permission from Internetmedicin AB

Publicerat med tillstånd av Internetmedicin AB


Cannabis – Marijuana


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


It is estimated that 147 million people worldwide use cannabis. Most commonly, use appears in New Zealand, Australia and the United States. Cannabis is also widely used in Europe where 14.6 million, or 11.2 percent of all young adults (15-34 years), have used cannabis sometime in recent years.

Cannabis is the most widely used drug among young people around the world. Essentially, cannabis is a juvenile drug in the age group 15-25 years, but addiction also occurs higher in the ages. In Sweden, 50 percent of those who seek help for cannabis abuse are under 20 years of age. Eighty percent (80%) of all seizures of drugs in the EU are cannabis. Two thirds of these seizures are captured in Spain and England.

Cannabis is usually consumed by smoking, either as hashis (cannabisharts) or marijuana. In recent years, supply has increased significantly on marijuana in the EU and in Sweden.

Acute cannabis poisoning does not usually require care in an emergency medicine department but can be administered in a psychiatric clinic or in dependence medicine, as well as withdrawal symptoms and other negative symptoms associated with addiction. Cannabis is commonly used in combination with other drugs. Cannabis use is also common among heavy drug addicts of heroin or amphetamine. Use of cannabis is categorized as heavy abuse when used daily or virtually daily (20 days or more per month).

The treatment of acute cannabis poisoning is directed by other drugs that have been taken simultaneously, but is mainly symptomatic. The most important issue about acute cannabis poisoning is careful monitoring of alertness, breathing, mental functions and circulation, as well as conducting the patient to the correct level of care. Many patients with cannabis abuse first need medical treatment and then assessment of psychiatric health, referral to dependence clinic and further to social services.

The prognosis for acute cannabis poisoning is usually good except for severe mixed drug toxicity.

CANNABIS SATIVA

Cannabis harvested from the plant Cannabis Sativa (Indian hemp) or from the plant Cannabis Indica or a blend of these two. Cannabis plants are grown mainly in North Africa (Morocco, Algeria), but can be grown in many other countries, even in scandinavian countries (indoors and outdoors). Market share for domestically produced, powerful marijuana has increased in recent years, and data now indicates that imported cannabis products has also become more powerful. Cannabis is included in hashish, marijuana and hash oil, all of which are used as intoxicants. Hashish has been the most common cannabis preparation in Sweden for a long time, accounting for about 85% of the market in 2011, but marijuana has become more prevalent in recent years. Since 2013, marijuana is more common than hashish in Europe. Among Swedish schoolars, the use of marijuana is more common than hashish. Marijuana is produced from cultivated dried flowers and top shoots while cannabis resin consists of the stem parts of the cannabis plant (female plant), compressed with plant harts. Hashish is usually mixed with regular tobacco while marijuana is mostly smoked without tobacco. Cannabis is usually smoked in joints, or in a pipe (hollow), but can also be eaten in cakes, candies or consumed in beverages, for example in tea. All cannabis consumption is illegal in most European countries. Common nickname of cannabis is “Brown, Green, Grass, Weed, Ganja, Braja, Smoke, Joint, Goose, Spliff” etc. One gram of marijuana on the street costs about 10 USD, 2.5 g costs about 30 USD. In a roll cigarette (joint), 200-400 mg cannabis is usually mixed with tobacco when you smoke alone or together with others. In a pipe (hollow), usually 700 mg is mixed at a cost of about 10 USD. The price for marijuana is about the same as for hash. Intense cannabis users usually consume more than 2 g per day.

The most psychoactive substance in cannabis is delta-9-tetrahydrocannabinol (THC) that provides a relaxing and euphoric substance. Other active cannabinoids are delta-9-tetrahydrocannabivarin, delta-8-tetrahydrocannabinol, cannabigerol, cannabinol, cannabichromium and cannabidiol. THC is considered to be psychotomimetic whereas cannabidiol is considered antipsychotic. There are a variety of cannabinoids (at least 60-80) and it is not entirely clear who are psychologically active. The level of THC in marijuana is usually lower than in cannabis, about 5-10% in marijuana against 7-14% active substance in hashish. A variant of cannabis called skunk is stronger and contains 6-15% THC. Skunk is considered to be extremely strong and has been shown to cause damage to the white substance in the brain near the corpus callosum. The concentration of THC has increased in recent years, preparations with levels of THC up to 30% have been seized, but usually it is not more than 14%. One variant of the cannabis plant called “sensimilla” contains no seeds and therefore contains extra high levels of THC. Cannabis, like opium, is a drug that has been used for a long time in some cultures as tranquilizing drug, for anxiety disorder, as an analgesic and mood enhancing agent. The use of cannabis has increased worldwide over recent years. Cannabis is considered to be moderately addictive. Dependence is present when the user continues to use the drug regularly despite behavioral, cognitive, perceptual and emotionally negative symptoms. Of all who use cannabis, approximately 9% develop an addiction. Of those who start using cannabis regularly during high school, approximately every sixth (16.7%) develops an addiction. Of those who are daily users (20 days per month or more) before age 17, 50-60% develops an addiction. There is robust scientific evidence that cannabis increases the risk of mental illness but to what extent is it controversial. Usually, the risk is estimated as “twice as big” as without cannabis use.

SYMPTOMS of Cannabis abuse

Smoking of cannabis gives the user a comfortable feeling of relaxation, calm, pain relief, peace of mind and joyful excitement. In high doses, perception may be enhanced and altered; experiencing increased and changed perception, above all, of sound and light. Cannabis is also a pain reliever and to some extent convulsive. In some parts of the world, cannabinols are used for medical purposes (“medical cannabis”) under regulated forms as analgesics, including multiple sclerosis (MS) and chronic disabilities with muscular contractures and spasticity. Medical studies have shown that cannabis does not help to improve MS disease. Research is ongoing in the field, also regarding effects on diabetes. What is meant by medical cannabis varies between countries and between different states in the United States, several preparations have been defined as medical cannabis.

Symptoms of cannabis abuse:

  • Drunkenness, excitement
  • Freakiness, cheerfulness, “hazy and giggly”, smiling
  • Talkative, more socially active
  • Ixoid (adhering) in speech and thoughts
  • Grandiose in thoughts
  • Red-eyed sclerae, shiny eyes
  • Wide pupils, hanging eyelids
  • Dry mouth and throat
  • Candy craving
  • Slow reflexes, relaxed muscles, (low tone)
  • Fumblingness, sloppy, floppy
  • Slurred speech
  • Heart palpitation, palpitations (tachycardia)
  • Sleepiness, fatigue, drowsiness
  • Inconsistent in speech and thoughts
  • Passivity, introversy, withdrawn
  • Anxiety attacks, panic attacks
  • Paranoid thoughts
  • Delusions, hallucinations

Abstinence – Withdrawal

Cannabis may cause withdrawal symptoms, such as:

  • Irritability
  • Blackouts
  • Concentration difficulties
  • Insomnia
  • Nightmares
  • Derealisation
  • Anxiety
  • Depression

Hallucinations and psychotic symptoms occur in more severe cases, even genuine psychosis occur especially after intensive use or use of very strong preparations. Cannabis is usually calming but aggressive breakthroughs with psychotic symptoms occur.

Addiction

Mental effects

People with cannabis abuse have a higher degree of psychiatric comorbidity compared with the normal population (higher degree of mental ill health). There is a higher incidence of depression, dysthymia, mania, hypomania, panic disorder, agoraphobia, social phobias, other specific phobias and general anxiety disorder. Contemporary abuse of other substances is common. Abuse of cannabis can lead to withdrawal symptoms like anxiety, confusion, delusions and hallucinations. In high doses and especially after long-term abuse, other mental symptoms may develop as:

  • Depressions
  • Apathy, weakness
  • Memory problems
  • Mood swings, numbness, anxiety
  • Amotivation syndrome, insomnia, shiftlessness
  • Personality change, increased inwardness (introversy), boundness, silence
  • Changed reality perception
  • Cognitive failure
  • Paranoid ideas
  • Psychotic symptoms

The personality change may persist if the user continues to smoke cannabis after developing the primary psychosis. Psychotic symptoms may occur in sensitive individuals soon after a few weeks of intensive abuse or use of stronger preparations commonly called acute cannabis psychosis. If there is a connection to cannabis at first-rate disease in psychiatric disease, this worse forecast predicts more days in hospitals and more entries. Some users risk over time, after months of intensive use to develop impaired cognitive function with poor learning ability, short-term memory, executive functions and simultaneous capacity. Personality change, as well as changed reality, with “schizophreniform symptoms” may occur. These symptoms usually do not occur until after several years of regular use. An Australian study has reported poor intellectual development among those who used cannabis before age 17. A Swedish study has shown 40% increased mortality among those using cannabis in teens compared with the normal population (OR 1.4).

The risk of developing schizophreniform symptoms is significantly higher for those who use the drug daily (double risk) compared to those who smoke only a few times. The risk is higher for those who started smoking in young years compared with those who started later (after 18 years of age). The risks of developing acute psychosis, personality change and depression follow the same pattern. Girls appear to be more sensitive than boys, but the use is much more common among boys.

Differential diagnosis between Cannabis Induced Psychosis (CIP) and Primary Psychosis (PP)

The following factors are more common in cannabis-induced psychosis (CIP) compared to psychosis caused by schizophrenia (primary psychosis – PP): male sex, expansiveness in emotions and ideas, derealisation or depersonalisation, visual hallucinations and altered sensory. Time of last drug intake can indicate if the patient’s psychotic symptoms are due to cannabis poisoning or withdrawal symptoms. Premorbid personality disorder is more common in underlying schizophrenia disease. Note that 25% prevalence of positive cannabis urinary toxicology has been reported in schizophrenia. It is important to have meticulous history. Carefully understand the difference between CIP and cannabis intoxication.

Characteristics of cannabis-induced psychosis (CIP):

  • Symptoms occur during or after heavy substance abuse or after increasing the strength of cannabis
  • A positive toxicology screening can provide a clear time relationship
  • Antipsychotic drugs do not always improve the symptoms
  • Often associated with visual illusions and paranoid ideas
  • The patient is more aware of symptomatology, has more insight into the disease
  • Thoughts are more organized and sequential compared to PP
  • It is common for heavy use of cannabis in the last month
  • Symptoms decrease with reduced drug use
  • Sudden onset of mood and paranoid symptoms within 1 week after use but as early as 24 hours after use.
  • More mood-related symptoms compared to primary psychosis (more anxiety)

Characteristics of primary psychiatric psychosis (PP):

  • The symptoms usually occur before or without heavy substance abuse
  • Antipsychotic drugs significantly improve the symptoms
  • Combined with delusions, hallucinations and thought errors
  • The symptom persists despite drug failure
  • Less insight into the psychotic state
  • Disorganized thoughts (eg loose associations, loose or even numbers)
  • More mood stable compared to CIP

Abuse of Cannabis can lead to:

  • Impulsive acts of violence
  • Suicide acts
  • Changed perception of time
  • Impaired ability to “understand the world”
  • Loneliness, social isolation, introversy
  • Personality change, schizophreniform symptoms

Teenagers may have delayed identity development and late personal maturity due to cannabis abuse. The typical character of teenage uprising can last for many years. Psychomotor features that require simultaneous capacity can also deteriorate. The ability to drive a car or to perform complicated tasks is deteriorating.

Physical effects

Abuse of cannabis has a lower degree of glucose metabolism in the brain, especially in the cerebellum. Cannabis smoking means an increased exposure to tar (50 percent more than in cigarettes), which increases the risk of cough and bronchitis, both acute and chronic, as well as for chronic lung disease. There is an increased risk of lung cancer and a number of other cancers and increased risk of cardiovascular disease. Fertility impairment may occur in cannabis abuse. In pregnancy there is an increased risk of growth inhibition in the fetus. Nor can it be excluded that there is an increased risk of malformations on the fetus, for damage to its mental functions and the risk of acute non-lymphatic leukemia. Cannabis is often detected in various acute drug poisoning. In drug-related deaths, cannabis affects are common, but rarely cause death due to overdose.

CLINICAL INVESTIGATION

  • Drug Screening (urine sample, U-tox)
  • Several urine samples for tetrahydrocannabinol (THC)
  • Control of electrolytes
  • Temperature Control
  • Lung X-ray on broad indications
  • Routine tests in blood
  • Haemoglobin
  • Na, K, Calcium
  • Liver enzyme parameters
  • CRP, SR
  • WBC, thrombocyte count
  • Creatinine
  • PK, APT
  • Psychological Assessment
  • Counselor contact
  • Possible referral to dependency clinic
  • Assess what type of cannabis has been used
  • Assess how many grams are consumed per week
  • Estimate how much money is spent on cannabis consumption per week

TREATMENT

There is no specific pharmacological treatment for cannabis addiction. Rimonabant is a type of antagonist, a competitive cannabinoid receptor agonist (CB-1 receptor) that blocks the effects of THC and has shown positive results in some studies to reduce acute physiological problems associated with cannabis smoking. Rimonabant, however, is unregistered in Sweden and has no place in treatment.

Therefore, treatment is mainly symptomatic in combination with psychosocial support therapy. Treatment can usually be done in outpatient care, but end-care is required in case of acute cannabis poisoning and acute psychosis. The primary treatment is total abstinence from continued cannabis consumption. Cannabis may cause severe withdrawal symptoms after intensive use, usually abstinence for about a week. Pharmacological treatment because of anxiety, withdrawal and anxiety status usually needs to continue for a long time after cannabis abuse. Contact with psychiatrist or psychologist with special knowledge about the effects of cannabis is important.

The treatment focuses on the negative effects of abuse on thought function, motivation and cognitive functions. Disease insight is usually low with poor motivation for treatment and abstinence. Psychiatric comorbidity is common. The investigation needs to assess whether psychotic symptoms or increased suicidality are present. Providing depression and psychotic symptoms is the risk of suicide acts. The outpatient treatment is individualized and based on frequent contacts with psychiatrists or psychologists, as well as regular checks of urine samples with analysis of THC. Cannabis can induce depressive reactions and psychoses. The risk of deep depression is increased threefold among cannabis users compared to non-cannabis users. Initially, it is common with a memory disorder, low disease insight and poor motivation for drug-freeness. Social aspects must also be evaluated in the patient’s treatment and the curator is connected. Psychosocial treatment for those with less problems focuses on short-term treatment (3-6 visits in outpatient care) while patients with more severe problems receive a longer treatment program, at least 14 visits to a psychologist or curator for a four-month period. In some cases, support for family and related parties may also be justified. Cannabis users have higher levels of social dependence, higher unemployment and poorer education than the normal population.

Pharmacological Treatment

The treatment of acute cannabis intoxication focuses on immediate abstinence from cannabis. If necessary, parenteral fluid is given, severe dehydration occurs. Also substitute electrolytes. Give the patient a quiet, dark room and rest, food and sleep. In the initial stage, pharmacological treatment of withdrawal symptoms is often necessary. The pharmacological treatment is gradually stepped out for 3-6 months while support therapy is in place. Abstinence treatment can be performed with, for example, an oxazepam schedule (oxazepam in gradual escalating dose for 4-7 days. The heavy oxazepam schedule involves 30 mg x 4 the first day, followed by gradual escalation. The abbreviated symptoms should be followed, but if the withdrawal symptoms are pronounced as after a long period of intensive abuse, the heavy schedule can be followed. Studies have been done with lithium against withdrawal symptoms, as well as acetylcysteine, buspirone, lofexidin (clonidine-like) and cannabinol.

  • Insert at least one PVC. Take HgB, WBC, platelets and screening of the urine.
  • If necessary, drop, for example, Ringer acetate or 1000 ml buffered glucose 5% per day.
  • Neuroleptics of the type olanzapine (Zyprexa) 5-10 mg x 1-2 (sedating) may be used, such as risperidone (Risperdal) 1 mg x 2 or haloperidol (Haldol) 4 mg x 1.
  • Antihistamines as an alternative: hydroxizin (Atarax) 25-50 mg by night.
  • Oxazepam (Oxascand) 15 mg, according to schedule, “light” or “heavy oxascand schedule”.
  • Nitrazepam (Nitrazepam) 5-10 mg to the night for 3 days.
  • Mirtazapine (Remeron) 30 mg to the night.
  • Acetylcysteine ​​may be considered. N-acetylcysteine ​​is an antioxidant that is a prodrug to the naturally occurring amino acid cysteine. It is used as anti-mucous drug and is sold prescription free in many countries, including in Sweden. The mechanism of action for cannabis addiction is not known.

Supportive Measures

Identify possible cognitive impairment, psychotic symptoms, the occurrence of schizophreniform symptoms and depression, and assess suicidality. Offer different types of support:

  • Psychosocial supportive efforts
  • Motivational improving therapy (MI) or Contingency management (CM)
  • Supportive social assistance for drug-related shortcomings
  • Clinical investigation and supportive measures for drug-related memory losses
  • Motivate total abstinence (MI)

Note that the deterioration of cognitive functions may initially be subtle and must be valued by structured methods. In case of cannabis abuse or addiction, Contingency Management (CoM), a behavioral therapeutic method in addition to Cognitive Behavioral Therapy (CBT) or relapse prevention (OPP) and motivational treatment (MET), provides better results.

  • A small effect on cannabis use compared to CBT or OPP only with MET during treatment or at end of treatment (moderately strong scientific basis).
  • A small effect on cannabis use compared to CBT or OPP with MET 6-12 months follow-up (moderately strong scientific basis).

ICD-10

  • Cannabis and its derivatives T40.7
  • Mental disorders and behavioral disorders caused by cannabis, harmful use F12.1
  • Mental disorders and behavioral disorders caused by cannabis, psychotic disorder F12.5

References

  1. WHO statistics Internet
  2. Drogutvecklingen i Sverige 2017, Rapport nr 164, Centralförbundet för alkohol- och narkotikautveckling, Stockholm 2017.
  3. Skolelevers drogvanor 2016, Rapport nr 161, Anna Englund CAN 2016.
  4. Narkotikan i Sverige: Metoder för förebyggande arbete en kunskapsöversikt Sven Andréasson (red.) Statens folkhälsoinstitut, Östersund, R 2008:23 ISSN 1651-8624 ISBN 978-91-7257-573-8
  5. Moore T et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370: 319-28
  6. D’Elia G, Perris C, Persson G. Psykoser i anslutning till cannabismissbruk. Läkartidningen 67;32:1970.
  7. Areseneault L et al. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 2002;325:1212-3. Länk
  8. Patton GC. Cannabis use and mental health in young people: cohort study. BMJ 2002;325:1195-8. Länk
  9. Editorial. Cannabis and mental health. BMJ 2002;325:1183-4
  10. Zammit S. et al. Self reported cannabis use as a risk factor for schizofrenia in Swedish conscripts of 1969: historical cohort study. BMJ 2002;325:1199-201
  11. Mass R et al. Relationship between Cannabis use, schizotypal traits, and cognitive function in healthy subjects. Psychopathology 2001;34:209-214. Länk
  12. Fletcher JM et al. Cognitive correlates of long-term cannabis use in Costa Rican men. Arch Gen Psychiatry 1996;53:1051-7. Länk
  13. Ashton CH. Adverse effects of cannabis and cannabinoids. Br J Anaesth 1999;83:637-49. Länk
  14. Volkow, ND et al. Psychiatry research: Neuroimaging, 67, pp 29-38, 1996.
  15. Fergusson and Boden, Cannabis use and later life outcomes are dose dependent. Addiction, 103: 969-976, 2008. Länk
  16. Gray, KM, Carpenter, MJ, Baker, NL, DeSantis, SM, Kryway, E, Hartwell, KJ, et al. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. The American journal of psychiatry. 2012; 169(8):805-12. Länk
  17. Manrique-Garcia E, et al. Cannabis, Psychosis, and Mortality: A Cohort Study of 50,373 Swedish Men. Am J Psychiatry 2016; 00:1–9; doi: 10.1176/appi.ajp.2016.14050637. Länk

Author

Kai Knudsen

Department of Anesthesia and Intensive Care, Sahlgrenska University Hospital, Gothenburg

Published with permission from Internetmedicin AB


Heroin and other Opioids


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Opioids

Among 185 million drug users worldwide about 26-36 million are using opioids as the main drug. In Europe, 1.3 million people are estimated to abuse opioids (0.4% of the population). Of all drug users, 13-26 million are estimated to use heroin as the main drug. Opioids include opiates naturally extracted from opium and synthetic analogues. Abuse has increased in Asia and Africa, while it has been stable or decreased slightly in Europe in recent years. In Europe, abuse has been highest in Scotland, England and France, which is usually associated with metropolitan regions. The relationship between men and women who regularly uses opioids is around 4:1.

About 44% of opioid users are intravenous addicts. Nearly half of all who receive treatment for drug addiction have heroin as the main drug. Heroin abuse in the EU is stable and slightly downward in recent years. The number of deaths related to heroin generally decreases, but deaths related to synthetic opioids increase. Heroin constitutes 4% of all seizures of illegal drugs while cannabis accounts for 80%. Heroin abuse in the EU is stable and slightly downward in recent years.

The number of deaths related to heroin is generally reduced, but deaths related to synthetic opioids increase and in Sweden these have increased markedly in recent years. In the National Board of Death’s register, 765 drug-related deaths were registered in 2014. An increase of 30 percent compared with the previous year. The registry records deaths where both legal drugs and illegal drugs such as heroin, cocaine and amphetamine were the cause of death or contributory cause of death. The so-called Toxicology Registry at the Karolinska Institute records only deaths where one or more drug-based preparations, legally or illegally, are judged to be the dominant or contributory cause of forensic autopsy.

Opioids were considered to cause death or being contributory cause of death according to the Toxicology register in the following number of cases in 2014; morphine 53 (28), Methadone 104 (10), buprenorphine 84 (14), fentanyl 47 (5) and oxycodone 42 (4). By comparison, it can be mentioned that deaths related to heroin are generally at the same level in 2014 as 1994. The most common illegal drug among opioid users is heroin. It is estimated that in Sweden there are between 8000 and 13,000 heroin abusers among 29,000 heavy addicts. The number of new addicts in Europe is approximately 41,000 per year. Opioids are administered mainly intravenously but may also be taken orally, transdermally in patches or by inhalation (smoke heroin). The drugs that are inhaled are opium and smoke heroin but also fentanyl. Smoke heroin is a brownish heroin base, also known as “Brown Sugar” (free base). Opioids are used as potent analgesics in the health care industry, especially for the treatment of severe acute pain but also chronic pain in severe conditions. Among drug-related deaths, opioids are present in 90% of cases. The medical use of opioids has increased significantly over the past ten years.Opioids are considered to be the drugs that have the strongest addictive effect. Among those receiving treatment for drug dependence worldwide, opiate addiction is the most common cause (50-85% of patients).

Common opiates are:

  • Heroin
  • Morphine
  • Hydromorphone
  • Raw opium
  • Codeine
  • Ethyl morphine
  • Buprenorphine

Common opioids are:

  • Ketobemidone
  • Oxycodone
  • Fentanyl
  • Petidin (meperidine)
  • Methadone
  • Tramadol
  • Dextropropoxyphene

Acute overdose is usually caused by heroin, fentanyl, buprenorphine or methadone. Serious cases and deaths in the overdose of dextropropoxifen were common in the past, but have decreased significantly after most preparations have been deregistered. A significant abuse of oxycodone has been reported, especially from the United States, from 2000 onward. In 2010, approximately 16,000 deaths were reported with oxycodone involved! In Sweden there is a significant abuse of Tramadol and buprenorphine. Still, more than 100 people die annually in Sweden due to acute heroin overdose. Of the deaths 90 percent are older than 25 years. About 80 percent of deaths are among men.

HEROIN

Heroin (diacetylmorphine) is the opioid that is primarily associated with drug addiction and illegal drug abuse. The most common is the brown form of heroin, which usually originates in Afghanistan, less common is the white form (hydrochloride salt), which usually originates in Southeast Asia. Brown heroin costs on the street usually between 30 and 70 USD/g. Purity is between 10-20%.

Heroin has pain relieving, sedative and anxiety-inducing properties. It is metabolized to morphine in the liver and is excreted mainly via the urine. The drug can be smoked, sniffed or injected; injections are the most common (44%).

Dosage

A normal dose heroin in addiction is around 15-50 mg intravenously. An overdose is seen when taken over 100 mg, severe ingestion at intake above 300 mg or more. The effects and tolerances vary considerably between different individuals. Note that heroin has a relatively short half-life of 2-3 hours versus 16-60 hours for methadone.

Methadone is usually taken in oral solution or as tablets but is also used in injection. In the treatment of heroin addiction, a normal dose methadone is 60-130 mg, which is dosed in oral solution once a day.

A capsule or bag of heroin usually contains 250 mg of 30-percent heroin when purchased on the street (a so-called “cab”). Heroin is produced from opium, mainly cultivated in Far East Asia, especially in Afghanistan. Even raw opium is abused and imported into several European countries. Raw opium is mostly abused by smoking. An increasing proportion of addicts smoke heroin (diacetylmorphine, freebase) instead of injecting it, but many smokers eventually pass into injection abuse.

Heroin is well known to provide rapid and powerful addiction development with increased tolerance and moderate or severe withdrawal symptoms upon discontinuation.

An overdose of opioids is characterized by:

  • Decreased consciousness, somnolence
  • Small pupils
  • Tiredness, tranquility
  • Slurred speech
  • Feeling cold, freezing
  • Anesthesia
  • Coma
  • Muscular rigidity (stiffness)
  • Urinary retention
  • Respiratory depression, respiratory failure
  • Hypoxia, cyanosis, gray-colored skin color
  • Bradycardia
  • Hypotension
  • Cardiovascular collapse

Life-threatening overdose may occur after injection as well as after smoking but is much more common after injections. Respiratory depression is the most serious symptom of overdose which can quickly become life-threatening. Alert patients usually have no respiratory depression but the vigilance can change rapidly.

Withdrawal symptoms

  • Chills
  • Faint tremor
  • Sweating
  • Palpitation
  • Shakes
  • Uneasiness
  • Concern
  • Agitation
  • Aggressiveness
  • Unstable temperament
  • Messiness
  • Violence

Sometimes the withdrawal symptoms are described as flu-like. These symptoms may occur as soon as 4-6 hours after the last intake.

Health risks

An intravenous drug abuse of heroin is characterized by high risk of contagious diseases (HIV, hepatitis B and C) and acute overdose. Abuse is associated with significant criminality and asocial life style. It has been reported that 66% of all heroin abusers at one time had a life-threatening overdose, 34% had attempted suicide.

White heroin (diacetylmorphine hydrochloride) has become more pure in the last ten years, i.e. an all-new “better” product worldwide. This speaks for a more controlled and refined production. The addict himself never really knows what concentration of heroin is injected during use. Concentration and dose can vary significantly between different heroin preparations, which explains many overdoses and deaths.

Another reason for overdose is reduced tolerance. Decreased tolerance develops within a few weeks after heroin abstinence. The craving after the drug can still be strong, but the tolerated amount significantly less than before. Many overdoses are therefore taking place among people who have recently been released from a detention center with forced abstinence.

Heroin addiction is a common cause of drug-related deaths, estimated between 100 and 200 cases occur annually in Sweden (Death registry). Of these, 40-60 cases are estimated to be due to acute overdose. In the case of overdose and abuse of heroin, there is a common occurrence of other potentially fatal diseases such as hepatitis B and C, acute hepatic failure, pneumonia, acute fasciitis, abscesses, cardiac failure, sepsis, myocarditis, DIC, ARDS, etc. New studies suggest that the most common cause of death in this group of addicts are trauma, usually drug-related trauma. In total, the number of drug-related deaths has fallen in the EU from about 7700 in 2009 to 6500 in 2011.

Methadone

Methadone is a pure opioid with soothing, analgesic, anxiolytic and sedative properties. Methadone has been used for the detoxification of heroin addiction since the 1960s, but has its strong opioid properties due to its own opioid potential. About 2,500 patients in Sweden with opioid dependence are included in different substitution programs and medicate with either methadone or buprenorphine.

Methadone is considered to have a better effect as substitution medicine on heavier and more recent heroin addicts compared to buprenorphine (Subutex). The effect sought by methadone is to block the craving of heroin as well as to prevent new heroin intake. Methadone treatment has helped more patients to work, more goes back to studies, and more maintain social structures within family and cohabitation.

Methadone is usually taken as tablets or in oral solution but is also available in the form of injection. In the treatment of heroin abuse, a normal dose of methadone is 60-130 mg, which is dosed in oral solution once a day. A normal dose for treatment of pain states is 5-10 mg 4-6 times daily in tablet form, the daily dose should not exceed 100 mg. Methadone in overdose may cause nausea and vomiting, severe respiratory depression and severe cardiac symptoms with dangerous arrhythmias (Torsade de Pointes arrhythmias, prolonged QT interval).

Methadone has significantly longer half-life compared with heroin, 16-60 hours, versus 2-3 hours for heroin, which means that the effect lasts significantly longer and covers all hours of the day. Side effects associated with methadone treatment include weight gain and impotence, and decreased libido. When treated with antidote naloxone hydrochloride (Naloxone) after overdose of methadone, the risk is significant that the effect becomes short-lived and transient. The sedative and respiratory depression effects of methadone may therefore come back after a period of awakening and cause serious symptoms. The number of deaths after overdose with methadone has increased in recent years in the 21st century.

Oxycodone

Oxycodone shows affinity to kappa, my- and delta-opioid receptors in the brain and spinal cord. It acts to these receptors as an opioid agonist without antagonistic effect. The therapeutic effect is predominantly analgesic and sedative. The absolute bioavailability of oxycodone is 60-87% after oral administration, and peak plasma concentrations are reached after approximately 1 to 1.5 hours. At steady state, the plasma elimination half-life is approximately 3 hours. Oxycodone and its metabolites are excreted via urine.

The prescription and consumption of oxycodone has increased markedly in recent years as well as the addiction problem. In 2014, approximately 250,000 prescriptions were prescribed for less than 50,000 in 2006. Oxycodone has been assessed as the cause or contributory cause of 42 deaths in 2014 in Sweden against only 4 cases in 2006. Oxycodone is sold as a fast-acting drug (OxyNorm) or as a depot preparation (OxyContin, Targinic). OxyNorm is available as capsules or injection solutions. Targinic is a combination preparation containing both oxycodone and naloxone in a ratio of 2:1. Oxicodone is also available in injection with approximately the same potential as morphine. Oral preparation of oxycodone is approximately twice as potent as oral morphine (higher bioavailability).

Fentanyl (Fentanyl, Durogesic, Matrifen)

Fentanyl is a potent opioid routinely used in conjunction with surgery and anesthesia. Fentanyl is approximately 100 times as potent as morphine, but the oral bioavailability is significantly lower (<2%). Fentanyl may be abused; it can be inhaled, swallowed, insufflated or injected. An increasing problem in recent years has been the abuse of fentanyl from various patches commonly used for transdermal pain management. These patches usually secrete 25, 50, 75 or 100 μg fentanyl per hour. When the patches are used for abuse, the fentanyl is scrapped to extract it from the patch for inhalation. Most common is smoking it, for example, in a sliced ​​light bulb used as a kind of container. Seizures have also been made of fentanyl in spray form. Fentanyl is easy to overdose and a number of deaths have occurred in Sweden in recent years. In Estonia and several other countries, fentanyl-related deaths are greater than the number of heroin-related. Fentanyl is available in many different chemical varieties with different potency. Some potent variants are carfentanil, alfentanil, remifentanil, furanylfentanyl, 4-fluorobutyrentanyl, 4-methoxybutyrentanyl (4-MeO-BF) and acetylfentanyl. Most are significantly more powerful than morphine, 100-1000 times stronger, because fentanyl is usually dosed in micrograms and morphine in milligrams.

Desomorphine (“Crocodile”)

A simple variant of opioid is desomorphine manufactured by addicts in Russia under the name “Crocodile”. Desomorphine is manufactured from codeine that can be purchased without prescription in pharmacies. Desomorphine has sedative and analgesic properties and is more potent than morphine. In the manufacture, codeine, iodine and phosphorus are used which have given a compound that is heavily contaminated and very unclean. Injections of desomorphine have given severe skin infections, wounds, dermatitis, fasciitis and necrosis. Abuse has led to extensive scarring and amputations of extremities. Several deaths have occurred and abusers of desomorphine usually have short survival (<1 year). The hose name Crocodile has also been used for the synthetic opioid 3-methylphentanyl which is also used most in Russia.

SYMPTOMS OF ABUSE 

Mental effects

Opioid effects cause drowsiness, relaxation, pain relief, anxiety disorder and mental depression. Regular use may lead to concentration difficulties and increased risk of traumatic injury due to decreased attention. Movements and reflexes become sluggish and slow as well as speech, even breathing can be slow. The voice may be low and dull under the opioid effect. There is a risk of chronic misery due to abuse and the personality becomes flattened.

Physiological effects

  • Mios (small pupils)
  • Impaired intestinal function (constipation, paralytic ileus)
  • Renal impairment, urinary retention
  • Nausea, vomiting
  • Itching (with tearing ulcer)
  • Neurological damage, numbness and numbness
  • Complications in pregnancy

Heroin addiction can lead to impaired immune system and opportunistic infections. Abusers have an increased incidence of infectious diseases, including hepatitis B and C, HIV, wound infections (S. aureus), skin infections, tetanus, botulism, endocarditis and sepsis. The risk increases for bronchitis, pneumonia and other lung diseases. Note that renal impairment (creatinine clearance <60 ml/min) increases the plasma concentration of oxycodone by 50%. Stick marks on the arms and legs as well as thrombophlebitis are seen in intravenous abuse. Poor dental status with severe caries, impaired hygiene, loss of appetite and cachexia are common.

CLINICAL INVESTIGATION

  • Drug screening and intoxication samples
  • Pupil controls
  • Severe urine tests for opioids (U-tox)
  • Check electrolyte status
  • Check infection parameters
    • Hepatitis serology
    • HIV test
  • X-ray chest and lungs
  • Cultivation of blood, sputum and urine
  • Routine tests, blood samples
    • Hgb
    • CRP, SR, Temperature
    • Liver enzyme parameters
    • WBC, TPC
    • Creatinine
    • PK, APT
    • Ethanol in serum (BAL)
    • Myoglobin in serum

Patients in poor condition should be examined with the ultrasound of the heart (UCG) with the question: heart failure (cardiomyopathy), heart valve vitium. In poor dental status, the patient should receive a referral for dental care. The clinical investigation includes psychological assessment and contact with the curator and social services. The application for social services must always be issued in case of life-threatening overdose or life-threatening addiction.

TREATMENT 

Treatment in case of acute overdose Start life-saving measures according to CPR principles for life-threatening overdose and provide antidote naloxone in case of respiratory depression. Acute poisoning with heroin is often part of a mixed drug overdose with other drugs, alcohol, especially benzodiazepines. Make a drug screening on urine samples. 65% of heroin users in a Norwegian study had ever overdosed heroin. Respiratory rate below 10 per minute or saturation below 90% indicates overdose and need for naloxone.

The treatment is controlled according to the means taken, but is mainly symptomatic.

Antidote

Naloxone (naloxone hydrochloride) has a central place in treatment and should be given intravenously (0.4 mg) as well as intramuscularly (0.8 mg). Higher doses may need to be given. Note that the antidote has a shorter half-life than the intake of heroin. After treatment with antidote, the patient should be monitored for 2 hours due to the risk of new severe respiratory depression. The necessity of this monitoring is scientifically controversial. Several recent studies from Norway (F Heyerdal et al) have shown that patients who are discharged directly from the ambulance after life-saving measures do not have increased mortality compared with hospital-treated cases. Currently, nasal administration of naloxone is being investigated as life-saving treatment given by related persons in connection with life-threatening overdose.

The most important treatment is careful monitoring of vigilance, breathing (oxygen saturation/respiratory rate) and circulation, as well as transferring the patient to a department where vital life functions can be ensured.

  • Secure free airway, provide assisted breathing and oxygen if necessary
  • Monitor patient in hospital for at least 2 hours
  • Insert at least one venous cannula. Check Hgb, WBC, CRP, platelets, liver status and drug marks.
  • Intravenous fluid supply of isotonic crystalloid solutions, for example Ringer-Acetate. Note the risk of pulmonary edema.
  • Check ECG
  • In case of unconsciousness, intubation and controlled ventilation.
  • X-ray of the lungs with the issue of edema (heroin lung) or pulmonary infection should be performed on liberal indications.

Pharmacological treatment:

  • Naloxone hydrochloride (Naloxone) 0.4 mg intravenously as antidote, possibly more. The dose may be repeated every 3-4 minutes until normal breathing occurs and the patient wakes up. Thereafter, the double intravenous dose is given intramuscularly, usually 0.8 mg. The effect of naloxone may be delayed in mixed oral toxicity, mainly with benzodiazepines or if anoxic brain injury has occurred. The intravenous dose has effect after 30-60 seconds and lasts for 45-60 minutes. The intramuscular dose has effect after approximately 10 minutes and lasts for 2-3 hours.
  • Flumazenil (Lanexat) 0.1-0.3 mg/min intravenously may be tested in combination with opiates and benzodiazepines. Adults are usually given 0.3 mg intravenously, and then repeat the dose at one minute intervals until effect is obtained. Often, 2-3 doses and a total dose of 2 mg are sufficient. The maximum dose for adults is 2-5 mg. Flumazenil is not a first aid in suspected opioid poisoning.
  • Inotropic treatment at circulation failure; Dopamine (Abbodop) in continuous infusion 2-10 μg/kg/min or noradrenaline (Noradrenaline) 0.05-0.15 μg/kg/min.

During treatment with naloxone sudden awakening occurs with anxiety, pain and aggressiveness. The patient may then run out and deviate from the hospital. Lung edema also occurs after administration of naloxone due to sympathetic activation and blood pressure increase, but may also be a consequence of overdose with heroin itself.

Many patients need a psychiatric assessment after acute treatment, as well as referral to dependent medical clinic and social services. The prognosis for acute heroin poisoning is usually good if the patient has not already received anoxic brain damage due to oxygen deficiency.

Weaning

Weaning addiction usually requires outpatient treatment in a dependency medicine clinic. Studies on withdrawal treatment indicate that more patients complete treatment (retention) if this occurs in primary care rather than in outpatient care. Such treatment is usually elective with scheduled insertion of substitution therapy according to specific treatment protocols. A dedicated care and treatment plan for each patient must be established. The patient first receives a medical withdrawal treatment and then a medical substitution treatment. In parallel, psychosocial supportive therapy is given (CBT; MI; Contingency Therapy). Patients are normally called to an assessment interview before withdrawal treatment. After a period of hospital care (3-6 months), some patients may continue the withdrawal treatment with maintenance treatment in outpatient care, but the risk of recurrence is significant.

Substitution Therapy

Some addiction clinics substitute the heroin with lighter opiates such as codeine, but not without difficulty. More clinics instead use pure opiates such as methadone (Methadone) in the substitution treatment or partial agonists such as buprenorphine (Subutex) or buprenorphine in combination with naloxone (Suboxone). Methadone is not significantly better than buprenorphine. The introduction of buprenorphine has made it possible for more patients to be drug-free compared to Methadone, but both Methadone and buprenorphine give a significant risk of opioid dependence. Many patients receive prolonged substitution treatment under controlled forms, initially available and after a few weeks (months) outpatients with daily subcutaneous injection.

New and younger addicts are getting Subutex more often, while older and heavier addicts are often given methadone. A new drug, Suboxone (buprenorphine plus naloxone), has been introduced in treatment with a lower risk of side effects and intravenous abuse compared to Subutex. Substitution treatment has enabled more patients to work socially with marital relationships and studies or work compared with untreated controls. Anti-sympathetic stimulant agents have also been used in the treatment of opioid abstinence such as clonidine (Catapresan) and dexmedetomidine (Dexdor).

Needle exchange programs

At some clinics, intravenous addicts allow replacement of syringes to new sterile in a so-called needle replacement program. This program is an attempt to reduce the risk of criminal activities and infectious diseases as well as being able to follow the patients carefully (“Harm reduction program”). Attempts are also made with hepatitis vaccinations and treatment. These addicts should be introduced to the use of nasal naloxone in case of overdose. The risk of premature death is significant among intravenous addicts (20-50 times normal). Intravenous heroin abusers have often gone a long time in their addiction; most are between 30 and 40 years old and have extremely low quality of life with significant social and marginalized life. A certain spontaneous healing occurs after 10 years of abuse or more.

Psychosocial treatment

  • Psychosocial treatment for opioid abuse and addiction has some effect on the extent of abuse.
  • The psychosocial treatment should have a clear structure, focus on the abuse and be long enough to give effect.
  • A dedicated care and treatment plan must be established.
  • Psychosocial treatment is usually given in parallel with abstinence treatment.
  • No single psychosocial treatment method seems superior to anyone else.
  • Psychotherapy such as family therapy, dynamic and cognitive therapy appears to be effective in maintaining patients in treatment programs.

ICD-10

  • Mental disorders and behavioral disorders caused by opiates, acute infections F11.0
  • Mental disorders and behavioral disorders caused by opiates, harmful use F11.1
  • Mental disorders and behavioral disorders caused by opiates, depression syndrome F11.2
  • Mental disorders and behavioral disorders caused by opiates, abstinence F11.3
  • Heroin T40.1
  • Other opiates T40.2
  • Methadone T40.3
  • Other synthetic drugs T40.4
  • F11 Mental disorders and behavioral disorders caused by opiates

References

1.      Drug development in Sweden 2011, Report No. 130, Central Federation for Alcohol and Drug Development, Stockholm 2012.

2.      Annual report EMCDDA The situation in the field of drugs in Europe 2011.

3.      Pre-Hospital Treatment of Acute Poisonings in Oslo: A One-Year Observational Study. F Heyerdahl, KE Hovda, MA Bjornaas, AK Nore, JC Figueiredo, O Ekeberg, D Jacobsen BMC Emergency Medicine 2008, 8:15.

4.      Steentoft A, Teige B, Ceder G, Vuori E, Kristinsson J, Simonsen KW, Holmgren P, Wethe G, Kaa E: Fatal poisoning in drug addicts in the Nordic countries. Forensic Sci Int 2001, 123: 63-69.

5.      Traces KA: Acute heroin overdose. Ann Intern With 1999,130: 584-590.

6.      Boyd JJ, Kuisma MJ, Alaspaa AO, Vuori E, Repo JV, Randell TT: Recurrent opioid toxicity after pre-hospital care of presumed heroin overdose patients. Acta Anaesthesiol Scand 2006,50: 1266-1270.

7.      Buajordet I, Naess AC, Jacobsen D, Brors O: Adverse events after naloxone treatment of episodes of suspected acute opioid overdose. Eur J Emerg With 2004, 11: 19-23.

8.      Spores KA, Dorn E: Heroin-related noncardiogenic pulmonary edema: a case series. Chest 2001, 120: 1628-1632.

9.      Warner-Smith, M, Darke S, Lynskey M, Hall W. Heroin overdose. Addiction 2001; 96 (8) 1113-1125

10.  Bach, Peter B .; Lantos, John. “Methadone dosage, heroin affordability, and the severity of addiction.” American Journal of Public Health. 1999, May. 89 (5): 662-665.

11.  Cook, Stephane; Moeschler, Olivier; Michaud, Katarzyna; Yersin, Bertrand. “Acute opiate overdose: Characteristics of 190 consecutive cases.” Addiction. 1998, 93 (10): 1559-1565.

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13.  Fugelstad A; Ågren G; Romelsjö A. “Changes in mortality, arrests, and hospitalizations in nonvoluntarily treated heroin addicts in relation to methadone treatment.” Substance Use and Misuse. 1998. 33 (14): 2803-2817.

Author

Kai Knudsen

Anesthesia Clinic, Sahlgrenska Hospital, Gothenburg Published with permission from Internetmedicin AB


Ecstasy


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Increased interest in hallucinogenic drugs can be seen among young people in recent decades, all over Europe. Ecstasy (MDMA) is an addictive drug that became popular in the 1990s as dance and party drug. Ecstasy is classified as an illegal drug and every use is illegal.

New psychoactive substances (NPS) include drugs such as ecstasy (MDMA), phenethylamines, katinones, synthetic cannabinoids (Spice), tryptamines and several other new hallucinogens. The drugs are also called “Designer Drugs, Legal Highs, and Smart Drugs.” Ecstasy has long been the most common and can be compared to as a reference substance. Most of these substances can be classified as substituted amphetamine derivatives. These agents have all pharmacological effects similar to amphetamine. The majority have been classified as illegal drugs according to The Controlled Substances Act (CSA), category I, but some are classified as hazardous products.

Benzylpiperazine (BZP), dextromethorphane (DXM), mephedrone, methedrone, nafyron, etc. may also be included under the term “New Psychoactive Substances (NPS)”. These drugs are all related to amphetamine with varying degrees of euphoric and hallucinogenic effects.

Acute poisoning with NPS and alcohol and various drugs, especially benzodiazepines, is not uncommon among mixed-use adolescents. Poisoning with hallucinogenic fungi and different gases, eg nitrous oxide, occurs among the same group of users.

This overview mainly deals with poisoning with ecstasy. Multiple variants of ecstasy (MDMA, MMDA, MDE, MDA, PFMPP) are sold over the internet as well as on the black market.

Ecstasy

Ecstasy (3,4-methylenedioxymethamphetamine – MDMA) is a central stimulant amphetamine-like agent that has become a common party drug in Europe in the 1990s. Ecstasy is classified as a drug according to The Controlled Substances Act (CSA), category I. Ecstasy was already synthesized by Merck in Germany in 1912. MDMA was first used as a psychotherapeutic aid in the 60’s in the United States through its “entactogenic” (empathy-seeking “trustworthy”) characteristics and later developed into a so-called party drug around Europe, such as England and Germany. Music events with mainly electronic dance music (“techno, psychtrance”).

In Sweden, Ecstasy was first found in 1986 and became drug-classified during the following year. The use of young people in Sweden increased sharply in the late 1990s, but has decreased significantly in recent years. The drug is used sporadically by adolescents between the ages of 15 and 25 in connection with parties and intensive dancing. Ecstasy is used more often by boys than by girls. In the drug survey in 2014 among Swedish schoolchildren, two percent reported that they tested ecstasy in upper secondary school’s grade 2 against 3 percent in 2006. Of those who tested drugs in grade 2, 12 percent reported that they tested ecstasy in 2013. Only a few abusers demand treatment for ecstasy-related problems. Ecstasy is more common in metropolitan areas and major cities.

Content and appearance

Ecstasy is a central stimulant with slightly weaker physiological, but more euphoric, hallucinogenic (psychotropic) and entactogenic effects compared with amphetamine. You get an increased sensory perception. There are several different substituted amphetamines with similar effects to ecstasy, for example:

  • MDEA/MDE (methylenedioxyethylamphetamine) “Eve”
  • MDA (methylenedioxyamphetamine) “Sally, SASS, Sassafras”
  • TFMPP (trifluoromethylphenylpiperazine) “Legal X”
  • MBDB (methyl-benzodoxol-butanamine) “Eden, Methyl-J”
  • PMA (para-methoxyamphetamine) “Dr Death”
  • PMMA (para-methoxy-methamphetamine) “Superman”

The drugs have many different popular names among the users, such as “XTC, Love and Kissing Pills, Adam, Eve, Eden, E, Mandy, Molly, Superman and X”.

Ecstasy is usually sold as colorful tablets taken orally with different appearance in the strength of 50-100 mg. Content and strength may vary between different tablets and are rarely known to the user. The effect is therefore hard to predict. The tablets are often stamped with a logo, such as a Smiley, Mitsubishi brand, Superman logo, Mercedes star or similar. In the illegal market, a tablet costs about 10 USD. Ecstasy in powder form can also be snorted, inhaled or dissolved and injected which is unusual. One tablet costs between 6-20 USD/pc.

Analyzes of the contents of various ecstasy tablets have shown the presence of a variety of chemical substances such as MDMA, MDEA, MDA, MDB etc. This allows the user to experience varying effects between different tablets of the same appearance. Party drugs are imported from Russia, Poland, Germany and Holland, among others.

The majority of party drugs can be analyzed in blood and urine in suspicion of drug impact in extended analysis. Rapid tests of urine samples are available for drug screening, but these only take the most common preparations such as ecstasy. MDMA can usually be detected in the urine up to 2-4 days after ingestion.

Molecular structure

Symptoms of Abuse

The effects of ecstasy and similar substances are characterized by euphoria, social empathy, openness and increased mental and physical energy. Well-being increases and a positive sense of lust occurs within 1 to 3 hours after ingestion. Self-confidence is increasing and you get an experience that all problems disappear. The drugs give an increased sense of communication, understanding and empathy. You experience increased trust and intimacy to other people in the environment. Odor, vision and hearing and perception are amplified. The pupils widen (mydriasis).

The central nervous effect is mainly caused by serotonin infiltration in the central parts of the brain, primarily the limbic system and hippocampus, but after prolonged use, serotonergic depots are depleted and patients may develop negative mental symptoms, depression and sometimes psychosis.

Examples of negative effects

  • Uncontrollable thoughts
  • Unstable temperament
  • Hyperactivity and hypomania
  • Anxiety, restlessness, anxiety, irritability
  • Decreased self-control, unstable behavior
  • Unlimited sexual activity
  • Increased appetite, sweating (but also loss of appetite and anorexia)
  • Headache
  • Psychosis-like reactions, hallucinations

The drug user eventually becomes exhausted, irritated and depressed after repeated intake. The patient’s drowsiness can be difficult and long-lasting. Experimental animal data indicate that damage to dopamine pathways and, above all, serotonin pathways is morphological and partly irreversible. Even general seizures occur.

Symptoms that may occur after a few months of abuse are:

  • Fatigue, numbness, depression
  • Insomnia
  • Stereotype behavior, tics
  • Visual tinnitus
  • Depression
  • Paranoia
  • Anxiety
  • Mutism
  • Catatonic behaviour

Treatment with antidepressant drugs (SSRIs) for depression is less effective than normal after abuse of ecstasy. The user is affected by a renewed intake of ecstasy. In the case of long-term abuse, many patients develop a cognitive dysfunction – memory and learning ability are significantly impaired.

Symptoms of acute overdose

A normal addiction dose is estimated at 100 mg orally, common variations are 50-250 mg. Mild overdose is 250-500 mg, moderate overdose 500-1000 mg and excessive overdose over 1000 mg.

In acute overdose of ecstasy and other central stimulant party drugs, widened pupils, hyperactivity, excitation, excitement, increased sweating, restlessness and agitation are noted. The patient can behave unnaturally and have a psychomotor disorder with involuntary movements. Tachycardia, palpitations and tremors may occur, as well as hypertension and chest pain. Aggressiveness occurs, as well as confusion and hallucinations. In a study of acute poisoning with NPS, psychosis was reported in 6% of patients. There is a risk that the patient may suffer from muscle rigidity, muscle twitching, spasms and seizures, and hyperthermia. The risk of hyperthermia is significant and can be very serious and life threatening. Ecstasy is metabolized in the liver via CYP2D6.

In case of acute overdose, the patient is at risk of:

  • Water intoxication with hyponatremia
  • Acute Confusion
  • Cardiac arrhythmias
  • Myoclonal seizures
  • Hyperthermia (fever)
  • Serotonin syndrome
  • Hepatic failure
  • Acute kidney injury

Water intoxication

May occur after ingestion of a couple of ecstasy tablets and excessive intake of water; Girls are more sensitive than boys. Water intoxication with pronounced hyponatremia (S-Na <120 mmol/l) may lead to brain edema, headache, blurred vision, seizures and coma. Individual deaths have been reported in Sweden and several cases in England and Europe.

Heat Stroke

May occur after intake of ecstasy and prolonged dance or stay in a warm environment (night club environment). The patient is at risk of developing hyperthermia with muscular rigidity, seizures and rhabdomyolysis. Poor intake of drink increases the risk of hyperthermia. Hyperthermia is often one of the symptoms of a “Serotonergic Syndrome” (see below) and can lead to hyperkalemia, cardiac arrhythmias, coma and multiple organ failure. Hyperthermia is probably due to a dominance of serotonin in hypothalamus and striatum with a down-regulation of dopamine.Body temperature above 41 degrees of Celsius is dangerous and over 42 degrees C is directly life threatening, such a strong hyperthermia requires immediate disposal with active sedation and cooling. Hyperthermia can be pronounced and prolonged, especially after ingestion of PMA or PMMA. Isolated cases with hepatic failure and renal failure are also described. Probably renal failure occurs secondary to rhabdomyolysis and myoglobin precipitation in the kidneys. Always check myoglobin in serum. CT brain scan or MRI scan should be performed if pronounced hyponatremia occurs (S-Na <120 mmol/L), to exclude brain edema, or in focal neurological symptoms. Morphological damage to serotonergic pathways can be detected by a PET camera (f-MRI). Other serious symptoms that may develop are impaired coagulation, DIC (disseminated intravascular coagulation) and respiratory failure with risk of pulmonary edema. Seizures and coma may occur. There is also a risk of cerebral hemorrhage, pulmonary embolism and cardiovascular collapse.

Serotonin syndrome

Serotonin syndrome refers to an over activity in the serotonergic system of the brain. It is a serious condition that may occur in the overdose of different NPS, often in combination with antidepressant drugs or analgesics. At worst, it leads to multiple organ failure and death. Serotonin syndrome usually occurs with fever (hypertension) and these cases should be treated in an intensive care unit.

Symptoms of serotonin syndrome include:

  • Involuntary movements (“Psychomotor restlessness”)
  • Tremor
  • Sweating
  • Enlarged pupils
  • Concern
  • Agitation
  • Confusion
  • Diarrhea
  • Clonus (easily resolved extremity reflexes), mainly lower extremities
  • Tachycardia
  • Rigidity
  • Hyperthermia

TREATMENT

The clinical treatment of acute overdose with central stimulant amphetamine analogues is essentially symptomatic and similar to most substances.

Specific antidotes are missing.

Most importantly, careful monitoring of:

  • Alertness
  • Breath
  • Circulation
  • Temperature
  • Mental functions

It is important to direct the patient to the right medical department so that vital life functions can be secured urgently. In the aftermath, drug abuse should be treated; assessment of psychiatrists and referral to dependence clinic and social services is often relevant. The application for social services must always be done in case of life-threatening addiction.

The prognosis for poisoning with party drugs is usually good unless serious complications are already granted before arrival at the hospital. Screening with drug stitches can sometimes, but not always, provide information about which drugs have been taken. Negative screening does not exclude poisoning with party drugs.

Treatment of acute overdose

Check heart rate, blood pressure, temperature and mental functions regularly. Invasive blood pressure measurement should be performed in case of severe blood pressure increase in moderate or severe intoxication. Place the patient in a quiet and dark room at mild to moderate poisoning and let him or her eat, sleep and rest (sleep morning). Treat anxiety and agitation as needed. Observe the risk of hyperthermia. Rehydrate with crystalloid liquids and check electrolytes in serum. Do drug screening of urine samples or plasma.

Suggestion of pharmacological treatment in case of anxiety or agitation:

  • Diazepam 5-20 mg 3 times daily or oxazepam 15-50 mg 3 times daily
  • Nitrazepam 5-10 mg to the night of sleep
  • Droperidol 10 mg im x 1.
  • Olanzapine 10 mg x 2 alt risperidone 1 mg x 2
  • Midazolam 2-5 mg i.v. in the event of anxiety and restlessness
  • Propofol i.v. for sedation in an intensive care department
  • Dexmedetomidine in severe restlessness in an intensive care unit
  • Symptomatic treatment in general
  • Caution with beta blockers

CT scan of brain in profound hypertension or neurological symptoms, such as cerebral edema or stroke. Check myoglobin in serum to see if rhabdomyolysis is present. Forced alkaline diuresis may be needed with crystalloid solutions, sodium bicarbonate and furosemide (10-40 mg/h).

In hyperthermia, active cooling and sedation may be required:

  • 1-2 liters cold saline intravenously
  • Diazepam 5-20 mg i.v. for sedation
  • External cooling with cooling sheet or similar
  • In extreme hyperthermia, cooling can be instituted extracorporeally through ECMO

In case of serotonin syndrome, treatment with any of the following medicines may be given:

  • Cyproheptadin – 8 mg x 3 orally (license preparation, antihistamine) alt.
  • Chloroprotixene 25 mg x 3
  • Risperidone 2 mg x 3

In case of severe hypertension (> 200 mm Hg) is it important with invasive blood pressure monitoring with arterial catheters:

  • Infusion of glyceryl nitrate (Nitroglycerin®) 0.2-0.5 μg/kg/min
  • Infusion of magnesium sulfate, 20 mmol in 100 ml NaCl for 20 minutes followed by 20 mmol for 20 hours
  • Beta-blockers with caution, eg metoprolol (2-5 mg iv) or labetalol (10-20 mg iv)
  • Alfa-blocker with caution, such as doxazosin (Alfadil®), labetalol (Trandate®)

ICD-10

  • F16.0 Mental disorders and behavioral disorders caused by hallucinogens, acute intoxication
  • F16.1 Mental disorders and behavioral disorders caused by hallucinogens, harmful use
  • F14.2 Mental disorders and behavioral disorders caused by cocaine, depression syndrome
  • T43.6 Psychostimulants with substance abuse
  • T40.6 Other and non-specified narcotic drugs
  • F15.1 Mental disorders and behavioral disorders caused by other stimulants, including caffeine, harmful use
  • F15.0 Mental disorders and behavioral disorders caused by other stimulants, including caffeine, acute intoxication

References

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  2. Ecstasy, the serotonin syndrome, and neuroleptic malignant syndrome – a possible link? JAMA feb 17, 1993, Vol 269, no 7.
  3. Skolelevers drogvanor 2013. Kunskapskällaren 2013, rapport 2013:1. Göteborgs Stad, Social resursförvaltning.
  4. Årsrapport EMCDDA Situationen på narkotikaområdet i Europa 2006. ISSN:1609-6207.
  5. Piper BJ. A developmental comparison of the neurobehavioral effects of ecstasy (MDMA). Neurotoxicol Teratol. 2007 Mar-Apr;29(2):288-300.
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  7. Montoya AG et al. Long-term neuropsychiatric consequences of “ecstasy” (MDMA): a review. Harv Rev Psychiatry 2002 10(4):212-20.
  8. Karlsen SN, Spigset O, Slördal L. The dark side of ecstasy: neuropsychiatric symptoms after exposure to 3,4-methylenedioxymethamphetamine. Basic Clin Pharmacol Toxicol. 2008;102(1):15-24.
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  10. Bråbäck L, Humble M. [Young woman dies of water intoxication after taking one tablet of ecstasy. Today’s drug panorama calls for increased vigilance in health care] Läkartidningen 2001;98(8):817-9.
  11. Parrott AC. Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol Biochem Behav. 2002;71(4):837-44.
  12. Stolaroff MJ, Wells CW. Preliminary results with new psychoactive agents 2C-T-2 and 2C-T-7. Yearbook for Ethnomedicine 1993:99-117.
  13. Balíková M. Nonfatal and fatal DOB (2,5-dimethoxy-4-bromoamphetamine) overdose. Forensic Sci Int. (2005) 153, 85–91.
  14. Bowen JS, Davis GB, Kearney TE, Bardin J. Diffuse vascular spasm associated with 4-bromo-2,5-dimethoxyamphetamine ingestion. JAMA. 1983;249(11):1477-9.
  15. Rammer L, Holmgren P, Sandler H. Fatal intoxication by dextromethorphan: A report on two cases. Forensic Sci Int. 1988;37(4):233-6.

Published with permission from Internetmedicin AB


Amphetamine


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Globally, there are about 185 million drug users. Of these, approximately 34 million use amphetamines as primary drug. Amphetamine abuse is relatively common in Sweden and other Scandinavian countries compared to other countries in Europe. It is estimated that between 10,000 and 25,000 people use amphetamine in Sweden. Of these, approximately 8,000 users have amphetamines as their primary drug, about 32% of those with severe addiction. Of the intravenous drug users in Sweden, it is estimated that the majority, about 60-70 percent, use amphetamines and the remainder uses heroin.

Injecting drugs in itself significantly increases the risk of medical complications such as infectious diseases and thrombosis. The mortality rate among amphetamine users is approximately 2% annually.

Amphetamine users have increased mortality compared to normal population, but lower compared to opiate drug users. Amphetamine is the drug in Sweden, which usually causes most frequent police interventions in society, about 7,000 seizures are made annually. In other words, the use of central stimulants is an extensive medical and social problem. Among the central stimulants, amphetamine, dexamphetamine, methamphetamine and methylphenidate are primarily used.

Many so-called new psychoactive substances (NPS) are derivatives of amphetamine and have similar central stimulatory effects. Several closely related agents are classified as phenethylamines or synthetic catinones. Even cocaine and ecstasy are central stimulants but are usually classified in a separate category of addictive drugs. Damage due to amphetamine is a relatively common problem in our medical and surgical emergency services and in drug addiction while isolated amphetamine intoxication is relatively unusual. Amphetamines are usually classified as illicit drugs or in some cases as hazardous to health.

Different central stimulants

  • Lisdexamphetamine (Elvanse®, Elvanse Adult®)
  • Methylphenidate (Concerta®, Ritalin®, Methylphenidate Sandoz®)
  • Dexamphetamine sulfate (Metamina®, Attentin®) (licensing agent)
  • Modafinil (Modiodal®)
  • Amphetamine (Amphetamine Recip®, Adderal XR®)

In other countries, a wide range of other amphetamine preparations are available, for example amphetamine sulphate (Amphetamine), dextroamphetamine (Dexedrine®), fenmetralin (Fenmetrazine®) and fentermine (Mirapront®). Of all patients treated for addiction in Sweden, approximately half use amphetamines regularly. Most people with amphetamine abuse have a mixed drug use with other illicit drugs, not seldom cannabis and benzodiazepines. Legal use of central stimulant drugs has increased significantly in recent years, mainly methylphenidate (Concerta® and Ritalin®), but lisdexamfetamine (Elvanse®) has also been significantly increased, both in children, adolescents and adults. Only Ritalin® and Elvanse® are approved for primary use in adults.

AMPHETAMINE

Amphetamine is a central stimulant that, after ingestion, provides increased energy, increased activity, increased stamina and elevated vigilance, the appetite decreases. It is the oldest, most well known and most abusive drug of all different central stimulants. Among all drug users in Sweden, about 4% have reported that they once tried amphetamine.

Amphetamine is chemically produced and is a white powder, sometimes with a slight shift to yellow, brown or gray. As a rule, amphetamine is injected, but it can also be swallowed or dissolved in a beverage (“bombing”). Between 40 and 80% of users indicate that they inject amphetamine. A dose of amphetamine usually has clinical effect for one to two hours, sometimes longer. Some common username on amphetamine is “Jack”, “Up Jacket,” “Watched”, “White”, “Dose” and “Speed”. Bags containing powder, capsules or tablets are sold illegally.

Normal dose at nasal, oral or intravenous intake is usually about 100-200 mg.

Methamphetamine

Metamphetamine is an amphetamine variant that has become popular in recent years. Some common names are “Meth”, “Speed” and “Yaba”. In Sweden, it is often called “Metatjack”, for example. The drug is smuggled to Sweden from, among other countries, Thailand and is described as providing more intensive euphoria with stronger perception than amphetamine (more psychotropic). Methamphetamine has become more common in in recent years and now accounts for about 20 percent of amphetamine use.

Methamphetamine is usually sold as a white powder in capsules, but it also occurs in crystalline form, commonly called “Ice” because the crystals resemble small ice cubes or coarse salts. Ice is usually transparent. Some other nicknames are “Los Angeles Glass”, “Glass” and “Crystal”.

Ice gives a stronger intoxication than usual amphetamine with a sense of intense excitement and energy. Methamphetamine has a longer half-life compared to usual amphetamine. The effect lasts longer than 24 hours. With repeated intake, the effect may last for several days. Abuse of methamphetamine is relatively extensive in the United States, Japan, South Africa, Southeast Asia (Thailand) and Australia. Metamphetamine is also used intravenously. Normal dosage is 10-30 mg, strong dose is 30-60 mg and very strong dose is 40-150 mg.

SYMPTOMS AND CLINICAL EFFECTS

The classic effect of amphetamine consists of a short-term euphoric effect with increased vigilance, self-confidence, increased energy, hyperactivity and heightened mood followed by a prolonged dysphoric period. During euphoria, wisdom and self-esteem increase, an increase in self-esteem appears and one becomes expansive in speech and thought, which can be perceived as hyperactivity and hypomania. Increased mental and physical energy, thought retention, increased impulsivity, increased appetite, increased sexual desire, increased mood, increased concentration and hypomania. Clinical symptoms of the effect of amphetamine may be large pupils, stare glance, hyperactivity, strange behavior, tics, flushing, dyspnea, itching, monotonous movements, tactile hallucinations, chewing, difficulty in stagnation and intense behavior; one gets “speeded”. Euphoria occurs as a result of increased release of several central nervous system (CNS) catecholamines, mainly dopamine and norepinephrine. Amphetamine gives up to 1000% increase in dopamine level in the nucleus accumbens compared to 150% for cannabis in animal studies. Subsequently, tolerance increases, with the risk of hallucinations and delusions. Amphetamine is therefore usually abused with a few hours interval for a few days or up to a week. After this, the addict needs to recover – sleep and rest. The abuse is often periodic and often includes other drugs.

Common symptoms after a long time of abuse are:

  • Concern
  • Anxiety
  • Irritability, aggressiveness
  • Hallucinations
  • Depression
  • Paranoid delusions

Paranoia usually disappears after a time of withdrawal.

Effects of addiction

Symptoms of abuse of amphetamine include hyperactivity with excitation and psycho motor anxiety. The affected person may over time have a characteristic springy, bouncing walk and suffer from involuntary, strange and dull movements (choreo athetosis). Additional symptoms/clinical signs of intoxication:

  • Big pupils
  • Tactile hallucinations, tingling
  • Itching
  • Monotonous movements
  • Chewing
  • Tics

Physiological effects

Pulse and blood pressure increase – the increase is dose dependent and can cause high blood pressure and tachycardia at high doses. It is not uncommon for amphetamine users to get intracerebral hemorrhage (ICH) – systolic blood pressure over 250 mm Hg has been measured. The bleeding (ICH) that occurs in the CNS is often punctured, making it difficult to evacuate the blood surgically. In the case of CT scan with angiography it may be difficult to detect a bleeding source. Instead, treatment is often conservative with invasive blood pressure control. An increased risk exists for the development of cerebral aneurysm that can burst and cause severe subarachnoid bleeding.

Hematoma is eventually resorbed, but neurological damage of varying degrees can persist.

Amphetamine abuse may eventually lead to thromboembolic complications with cardiovascular and vessel damage with increased risk of aortic aneurysm and vascular dissection, and heart failure (dilated cardiomyopathy).

Other physiological effects are reduced convulsion threshold, weight loss, impaired dental status with strong caries and dry mucous membranes, vitamin deficiency, and impaired immune system. Amphetamine abuse can also lead to increased risk of:

  • Miscarriage during pregnancy
  • Fetal injury with increased perinatal mortality
  • Hepatitis B and C, HIV
  • Liver cirrhosis
  • Stroke
  • Damaged heart valves (endocarditis)

Mental effects

Abuse of central stimulants can give psychological health issue in the form of hyperactivity, hypomania, distantness, anxiety, restlessness, anxiety, unstable temper and increased aggressiveness, both outward and inward.

Other mental symptoms and effects that abuse can lead to are:

  • Racing
  • Increased impulsivity
  • Manic episodes
  • Decreased self-control, disinhibited behavior
  • Increased appetite, sweating (but also loss of appetite)
  • Panic attacks, phobias
  • Compulsive behavior (forced and compulsive)
  • Psychosis-like reactions
  • Tics
  • Skin rash, tactile hallucinations (“Meth Bugs”)
  • Increased suicidality
  • Depression, malaise and suicide attempts

Acute overdose

In case of overdose, the addict receives a strong sympathetic boost with hypertension, tachycardia, sweating, rigidity and hyperthermia. Psychic symptoms listed below are commonplace.

Toxicity

Moderate overdose occurs at intake above 200 mg amphetamine, high overdose over 500 mg and life threatening overdose over 1000 mg (lower doses of methamphetamine). Normal intake is 100-200 mg per time. Intake of 500 mg may lead to:

  • Confusion
  • Anxiety attacks
  • Psychomotor anxiety
  • Aggressiveness
  • Acute psychosis
  • Kidney failure
  • Liver failure
  • Hyperthermia
  • Cardiovascular collapse

Hyperthermia can cause rhabdomyolysis and metabolic acidosis with potassium release and risk of cardiac arrhythmias. General seizures, hypotension and metabolic acidosis may occur suddenly.

TREATMENT

Amphetamine has a moderately addictive effect. In a study in adolescents 11% developed dependence of those who tried amphetamine. Tolerance development is described as well as strong psychological dependence. Dependence’s pathophysiology appears to involve the brain’s dopamine system. In both animal models and human PET studies, decreased mesolimbic dopamine levels have been demonstrated following amphetamine intake, changes that have also been associated with severity of withdrawal symptoms. The treatment of abuse is mainly symptomatic and therapeutically focused with the aim of absolute withdrawal. Attempts have been made with medical substitution treatment.

As far as drug treatment of dependence is concerned, there is insufficient scientific evidence to draw some safe conclusions on effective treatment. The proportion of intravenous addicts has decreased during substitution treatment. There is only limited evidence that substitution treatment in amphetamine dependence has positive effects with regard to addiction, withdrawal symptoms and drug withdrawal.

  • There are newer studies suggesting that treatment with dextroamphetamine (Dexedrine®), methylphenidate (Concerta®) and disulfiram (Antabus®) has an effect on central stimulants, especially in cocaine abuse. Lisdexamfetamine appears to reduce the risk of addiction compared to dexamfetamine but possibly this is only a dose question. Other studies are taking place with opioid antagonists.
  • There is ongoing studies of treatment with baclofen (Lioresal®) and naltrexone (Naltrexon Vitaflo®).
  • Treatment with benzodiazepines is the first choice in treating sleep disorders, and anxiety disorder.
  • Psychosis can be treated with neuroleptic drugs, for example, olanzapine (Zyprexa®), risperidone (Risperdal®) or zuclopentixol (Cisordinol®).
  • Caution is advised with high dose neuroleptics (levomepromazin) due to the risk of hemodynamic instability and reduced convulsion threshold.

Psychosocial treatment

Treatment in the form of learning and behavioral therapeutic methods has shown positive effects in the use of amphetamine, especially during the first six months of treatment. Only psychotherapy as a treatment method has resulted in increased retention in structured treatment programs compared with other interventions (higher retention rate).

Acute treatment

The treatment of acute overdose of central stimulants is controlled by the substances taken, but is mainly symptomatic. It is important to direct the patient to the correct level of care so that vital life support can be ensured. After acute treatment, many patients require assessment of psychiatry and referral to dependence clinic and social services.

In acute care of confusion abusers, regular monitoring of mental status and vital functions such as heart rate, blood pressure and temperature is important. Place the patient in a quiet and dark room and let him/her eat, sleep and rest (sleep morning). In case of severe hypertension (systolic blood pressure above 200 mmHg), invasive blood pressure measurement via an arterial line should be used. Rehydrate with crystalloid fluids and check electrolytes in serum.

Benzodiazepines should be given to control anxiety and to prevent or treat general seizures. In the case of oral overdose of amphetamine, activated charcoal and gastric emptying should be considered in the same way as in other poisoning conditions, i.e. it is generally recommended for serious poisoning only up to one hour after ingestion.

Increased blood acidity enhances the elimination of amphetamine, but is not generally recommended as it is unfavorable in rhabdomyolysis at the same time. Be liberal with echocardiography (UCG) to diagnose possible valve problems and cardiomyopathy. In neurological symptoms, a CT brain scan should be made and in the case of intracranial bleeding, cerebral angiography should be performed.

Pharmacological treatment:

  • Diazepam (Stesolid®) 5-20 mg 3-4 times daily against anxiety/irritability or oxazepam (Sobril®) 15-50 mg 4-6 times daily.
  • Nitrazepam (Apodorm®) 5-10 mg to the night of sleep.
  • Risperidone (Risperdal®) 1 mg 2 times daily, alternatively:
  • Olanzapine (Zyprexa®) 10-20 mg x 2, alternatively:
  • Haloperidol (Haldol®) 5 mg 1-2 times daily (avoid high dose neuroleptics) alternatively oral solution 1-2 mg, no more than 4 hours against psychotic symptoms. If oral treatment is not possible, Haldol can be given i.m. 2.5-5 mg x 4 alternatively zuclopentixol (Cisordinol-Acutard®) 100-150 mg i.m.
  • Midazolam (Dormicum®) 2-5 mg intravenously in the event of anxiety and restlessness.
  • Dexmedetomidine (Dexdor®) by continous infusion if treatment is given in an intensive care unit.
  • At heart palpitations and moderate hypertonia beta-blocker may be used – propranolol (Inderal®) 40 mg x 3 or metoprolol (Seloken®) 50 mg x 3.
  • Symptomatic treatment in general.

Severe hypertension

In case of pronounced hypertension (> 200 mm Hg), blood pressure should be monitored invasively.

Treatment of high blood pressure must be done with caution. Beta-blockers given intravenously have been described to give paradoxical effects on the toxic effects of cocaine and amphetamine. High blood pressure should therefore be treated primarily with vasodilators such as nitroglycerin. Magnesium sulphate is a mild vasodilator that works well in the treatment of sympathomimetic states and can be tested in amphetamine toxicity.

  • Infusion of glyceryl nitrate (Nitroglycerin®) 0.2-0.5 μg/kg/min.
  • Infusion of magnesium sulfate: 20 mmoles in 100 ml Sodium Chloride for 20 minutes followed by another 20 mmol for 20 hours.
  • Clonidine (Catapress®) can be tested in continuous infusion, 0.25-0.5 μg/kg/h alternatively dexmedetomidine (Dexdor®). Clonidine can also be given orally 75-150 microg x 3.
  • Caution with beta blocker intravenously
  • CT brain in hypertonic crisis or neurological symptoms

Hyperthermia

Sedation and cooling in hyperthermia is important. Active treatment may be required.

Sedation is achieved primarily with benzodiazepines, such as midazolam (Dormicum® 1 mg/ml) or diazepam (Stesolid® 5 mg/ml) intravenously, second choice may be propofol (Diprivan® 20 mg/ml).

Active cooling may be accomplished by intravenous delivery of 1-2 liters of cold saline (from the refrigerator).

Prognosis

The prognosis for acute poisoning with central stimulants is usually good if the patient has not already experienced complications in the form of cerebral hemorrhage, serotonin syndrome or cardiovascular collapse. A “sympathetic or serotonin syndrome” may develop in the event of overdose with amphetamine with multiple organ failure as a consequence in severe cases. Every year about 100 people in Sweden die in drug-related deaths due to amphetamine.

About half of all deaths due to amphetamine abuse depend on cardiovascular collapse, the rest dies differently; through accidents, trauma, suicide, severe infections, dilated cardiomyopathy, pulmonary embolism, myocardial infarction, other injuries, etc.

ICD-10

  • F 15.1 Mental disorders and behavioral disorders caused by other stimulants, including caffeine, harmful use
  • T43.6 Psychostimulants with substance abuse
  • X60-X69 Intentional self-destructive action through poisoning
  • Y10-Y19 Poison with obscure intention

References

  1. WHO Statistics Internet, 2018
  2. Drug development in Sweden 2007, Report No. 107, Central Federation for Alcohol and Drug Development, Stockholm 2007.
  3. Lan KC, Lin YF, Yu FC, Lin CS, Chu P. Clinical manifestations and prognostic features of acute methamphetamine intoxication. J Formos Med Assoc 1998; 97 (8): 528-33
  4. Robertsen A, Kowalczyk M, Gabrielsen AM, Jacobsen D. Amphetamine Poisoning. Tidsskr Nor Laegeforen. , 1998; 20; 118 (28): 4340-3
  5. Brown JM, Hanson GR, Fleckenstein AE. Methamphetamine rapidly decreases vesicular dopamine uptake. J Neurochem 2000; 74 (5): 2221-3
  6. Anglin MD, Burke C, Perrochet B, Stamper E, Dawud-Noursi S. History of the methamphetamine problem. J Psychoactive Drugs 2000; 32 (2): 137-41
  7. Yui K, Goto K, Ikemoto S, Ishiguro T, Kamata Y. Increased sensitivity to stress in spontaneous recurrence or methamphetamine psychosis: noradrenergic hyperactivity with contribution from dopaminergic hyperactivity. J Clin Psychopharmacol 2000; 20 (2): 165-74
  8. Abraham HD, Fava M. Order of onset of drug abuse and depression in a sample of depressed outpatients. Compr Psychiatry 1999; 40 (1): 44-50
  9. Xu JH, Shen H, Zhang YP. Amphetamine-induced rage response in mice and its mechanism. Yao Xue Xue Bao 1992; 27 (8): 566-71
  10. Silverstone T. Appetite suppressants. A review. Drugs 1992; 43 (6): 820-36
  11. Baucum AJ 2nd, Rau KS, Riddle EL, Hanson GR, Fleckenstein AE. Methamphetamine increases dopamine transporter higher molecular weight complex formation via a dopamine and hyperthermia-associated mechanism. Neurosci. , 2004; 24 (13): 3436-43
  12. Volkow ND, et al. Effects of dopamine and serotonin releasing agents on methamphetamine discrimination and self-administration in rats. Psychopharmacology (Berl). , 1999; 141 (3): 287-96
  13. Horrigan JP, Barnhill LJ. Low-dose amphetamine salts and adult attention deficit/hyperactivity disorder. J Clin Psychiatry 2000; 61 (6): 414-7
  14. Pelham WE, et al. Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings. Pediatrics 2001; 107 (6): E105
  15. Roffman JL, Raskin LA. Stereotyped behavior: effects of d-amphetamine and methylphenidate in the young rat. Pharmacol Biochem Behav 1997; 58 (4): 1095-102
  16. Ellinwood, E.H. Amphetamine Psychosis. I. Description of the individuals and processes. Journal of Nervous and Mental Disease. 1967; 144, 273-283
  17. Shoptaw SJ, Kao U, Ling WW. Treatment for amphetamine psychosis. Cochrane Database Syst Rev 2008; (4): CD003026
  18. N Buxton and N S McConachie. Amphetamine abuse and intracranial haemorrhage. J R Soc Med. 2000; 93 (9): 472-477
  19. Goodman, SJ; Becker, DP. Intracranial hemorrhage associated with amphetamine abuse. JAMA. 1970; 212 (3): 480-480
  20. Borbély A A, Baumann I R and Waser P G. Amphetamine and Thermoregulation: Studies in the unrestrained and curarized rat. 1974; 281 (4): 327-40
  21. Callaway CW, Clark RF. Hyperthermia in psychostimulant overdose. Ann Emerg With 1994; 24 (1): 68-76
  22. Bloniecki Kallio V, Guterstam J, Franck J. Substitution therapy is being tested against amphetamine dependence. Pharmacy 2016; 113: DSU6.

Author

Kai Knudsen

Department of Anesthesia and Intensive Care,

Sahlgrenska University Hospital, Gothenburg, Sweden

Published with permission from Internetmedicin AB


Cocaine – Abuse and Overdose


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Cocaine is a myth-induced central stimulant drug with a strong euphoric effect that is considered to be rapidly addictive. Cocaine is extracted from Coca leaves from the bush plant Erythroxylum coca. Cocaine preparations are classified as a central stimulant drug in a separate pharmacological entity different from the amphetamine group. Cocaine is an alkaloid with the chemical name benzoyl methyl ecgonine. The drug gives a strong euphoric intoxication and is considered to be strongly addictive.

The cocaine preparations can be divided into cocaine powder (a hydrochloride salt) which most often is sniffed or injected and crack (free base) which is normally inhaled. Ecgonine is a type of local anesthetic agent with strong vasoconstrictor effects, therefore cocaine has similar effects and is sometimes used as a local anesthetic in some medical settings such as eyes and nasal surgery.

The production, distribution, and sale of cocaine products is restricted (and illegal in most contexts) in most countries as regulated by the Single Convention on Narcotic Drugs, and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.

In 2014, about 78,000 seizures of cocaine were reported in the EU, which meant that 62.6 tonnes of cocaine were confiscated. The number of seizures has fallen slightly from 2008 to 2013. Cocaine is most common in southern and western Europe.

Today, cocaine is primarily known as a widespread party drug, and is therefore relatively common in the club and nightclub environment in the big cities, especially in the United States, Great Britain and southern Europe. 2.4 million people, or 1.9 percent of all young adults (15-34 years), have used cocaine in the last year in the EU. Cocaine accounts for 10% of all seizures of drugs where cannabis accounts for more than 80%. Nineteen EU countries reported cocaine-related deaths in 2013 with more than 800 cases in total. Seventy percent of all who receive treatment for cocaine dependence come from Spain, Great Britain and Italy. Cocaine takes second place among seized drugs after cannabis. One gram of cocaine usually costs between 52 and 72 Euro. The purity varies between 36% and 50%.

About twice as many men as women use cocaine, which is most common in the age group 18-25 years. At the age of 20, it is more common for women than men, young women are often invited by male acquaintances. Today, cocaine is likely to be more common among young people in Sweden than in the 1990s, but it is still significantly more uncommon than cannabis and amphetamine. Among adults, less than 0.5% say they have tested cocaine sometime in the past year.

In the United States, cocaine is much more common than in Sweden. It is estimated that about 50 million Americans used cocaine at some point and that 6 million use it regularly. Cocaine is the second most common drug after marijuana in the United States and the drug that causes the most visits to hospital emergency services after alcohol and tobacco. Of the patients who made emergency visits, 40% complained of chest pain caused by cardiovascular symptoms.

Cocaine Hydrochloride

Cocaine extracted from Coca leaves (Erythroxylum coca). The cocoa plant grows in South America and is produced almost exclusively in Colombia, Peru and Bolivia. Coca leaves are crushed and pressed together with solvents. This stewed primary product is called coca paste. Cocaine hydrochloride is prepared from coca paste by the addition of hydrochloric acid while heating.

Chewing of coca leaves is a relatively common habit in the Andes, which gives a moderate central stimulant effect. When chewing it takes about half an hour before the effect is noticeable and after two hours, maximum uplifting and hunger dampening effects are reached. Coca leaflet contains about 0.5% cocaine and by chewing the leaves with basic ashes, the cocaine is dissolved in low doses.

Cocaine is usually produced in primitive plants in the jungle and is then smuggled through Mexico, mainly to the United States, Canada and Europe. It is sold as a white powder in the form of cocaine hydrochloride which is sniffed, smoked or injected. Mexico has been exposed to significant crime in the context of smuggling and trafficking in cocaine – the so-called cocaine war. Cocaine was widely used in the United States in the late 1800s, and was completely banned in 1915.

In the first place, cocaine is consumed by snorting through a tube or a rolled note, but cocaine can also be injected intravenously. Cocaine is rapidly absorbed in the veins of the nasal mucosa and provides a rapid onset and a relatively short-term intoxication. Cocaine hydrochloride is rapidly metabolized to two inactive metabolites called benzoylecgonine and ecgonine methyl ester. Benzoylecgonine metabolite  has a longer half-life (3-10 h) compared to cocaine (1-2 h). Benzoylecgonine is the substance that is usually detected when sampling for cocaine intake.

Some common street names on cocaine among users include Snow Flake, Girl, Lady, Pimps Drug, Speed ​​Ball (with heroin), Blow, Nose Candy, Liquid Lady, and more.

Crack

By boiling cocaine hydrochloride with bicarbonate, cocaine base is extracted into crystallized free form, known as “Crack”. Crack is fat-soluble and rapidly absorbed into lung capillaries when smoke. It appears in grayish or yellowish lumps with a porous surface and greasy texture that can be smoked after heating. Crack is mostly used by marginalized addicts.

Crack is considered to give a very intensive but short-term intoxication. Cocaine base is absorbed by smoking in the lung capillaries endothelium and gives a high within 6-8 seconds

Synthetic Cocaine

Different variants of synthetic drug drugs similar to cocaine have begun to appear on the market in recent years. Some of these are dimethocaine and camfetamine. The drugs have different usernames or serial names, such as “syntecaine”. The drugs have also been called “legal cocaine”. Several of these drugs called cocaine have been found to contain other synthetic psychoactive substances than cocaine, for example, synthetic cannabinoids have been detected.

SYMPTOMS

Effects of addiction

The effect of cocaine is short-lived (20-40 min) after “snorting” and the drug needs to be taken repeatedly to keep the high. The euphoric state occurs 3-5 minutes after sniffing and the maximum concentration in the brain occurs after about 4 minutes. Euphoria is as strongest during the initial phase of the rush. The effect occurs most rapidly upon inhalation, then intravenous administration, nasal and last oral administration. You usually become spicy, happy, energetic and “upward” (euphoric) of the intoxication.

Cocaine primarily stimulates dopamine receptors, as well as noradrenaline and serotonin receptors with increased release of catecholamines as a consequence.

Cocaine rush is described as leading to increased:

  • Vitality
  • Euphoria
  • Mind sharpness
  • Energy and endurance

Acute cocaine poisoning is a rarity in Sweden and the direct effects of cocaine rush rarely cause hospital visits. Emergency hospital visits are more often the result of complications of abuse, overdose or joint poisoning.

Mental effects

In addition to the above effects, hyperactivity and hypomania also occur. Appetites may increase, leading to overeating, but also loss of appetite and anorexia. Insomnia, anxiety, restlessness, anxiety, irritability are other adverse effects that the drug may cause, as well as:

  • Thought escape, unstable temperament
  • Decreased self-control, uncontrolled behavior
  • Increased unrestrained sexual activity
  • Psychosis-like reactions
  • Self-centered thinking, paranoid ideas
  • Pseudo hallucinations (Magan’s sign), auditory hallucinations
  • Depression, depressed mood
  • Acts of suicide

Physiological effects

Sympathetic overdrive in cocaine intake may lead to hypertension, tachycardia and palpitations (tachycardia). The drug blocks the rapid sodium channels in the myocytes of the heart, resulting in increased calcium concentration and decreased magnesium concentration intracellularly and increased cardiac stress. Brugadas syndrome can be seen on ECG in the form of a J-wave with elevated early ST waves.

Cocaine has a strong vasoconstrictor effect that can cause serious cardiovascular complications due to ischemia in the the esophagus, brain and heart. Heart and vascular damage may eventually lead to heart failure, cardiomyopathy and myocarditis. Insufficient oxygen supply for a long time in the brain can cause memory disorder, occasionally severe memory disorder leading to an Alzheimer-like condition. Cocaine affects the components of the blood and induces platelet aggregation. Thrombocytopenia and increased atherogenesis may also be at risk of severe thromboembolic complications. There is a risk of renal failure due to rhabdomyolysis and in rare cases severe liver failure. Most deaths due to cocaine abuse is due to cardiovascular collapse.

Cocaine can also cause rupture of the blood vessels in the brain due to vasospasm, hypertension and micro-infarction with cerebral hemorrhage or stroke. In the United States, stroke due to cocaine abuse is not uncommon, even aortic dissection has been described. Sudden death is not completely uncommon among cocaine addicts, it is often preceded by Brugada’s syndrome.

Other physiological signs:

  • Tremor
  • Seizures
  • Hyperemia and wounds in the nasal mucosa
  • Inhibited immune system
  • Multiple skin ulcers

Acute overdose

A normal dose of cocaine is around 25-100 mg. Moderate overdose occurs at intake above 500 mg, excessive overdose at intake above 1000 mg and life-threatening overdose at intake above 3 000 mg. No real antidote exists. The most common symptoms after overdose are palpitations, intense sweating and seizures.

Life-threatening overdose is seen primarily among those who smuggle cocaine through bodily packers, or among those who swallow drugs to avoid being stunned by the body stuffers.

In case of acute overdose, the patient may develop severe sympathy boosts with hypertension, tachycardia, cold sweating, rigidity and hyperthermia (heat stroke). It is not uncommon with excitation, psychomotor disturbance, agitation and psychotic symptoms.

Intake of 500 mg may lead to:

  • Confusion
  • Psychomotor disorder
  • Aggressiveness
  • Psychosis
  • Mania
  • Cardiovascular collapse
  • Rhabdomyolysis
  • Kidney failure
  • Liver failure

Hyperthermia can cause rhabdomyolysis and metabolic acidosis with potassium release and risk of cardiac arrhythmias (broad-range QRS complexes on ECG). General cramps, hypotension and acid deficiency may occur suddenly.

Other symptoms of cocaine intake:

  • Big pupils (mydriasis)
  • Hyperactivity, excitation
  • Tremor
  • Breast pain, ECG changes

Neurological withdrawal symptoms may occur. There is a risk that the patient may suffer from brain edema and pulmonary edema with respiratory distress, as well as cardiovascular collapse and coma.

Clinical investigation

In acute care of abusers, cocaine screening is necessary as well as control of pulse, blood pressure, ECG and body temperature. Cocaine is included in most screening tests for drugs. Cocaine has a number of active metabolites: norcocaine, benzoylecgonine and ecgonine methyl ester. In addition, when consuming alcohol, cocaethylene can be formed. In the analysis of the incidence of cocaine abuse, it is primarily the metabolite benzoylecgonin which is measured.

Cocaine toxicity can be verified by HCMS following a simple drug screening of urine samples.

In case of acute toxicity, adequate patient monitoring is important, especially of:

  • Alertness
  • Breathing
  • Circulation
  • Mental functions
  • Body temperature
  • Renal function

See also “Treatment” below.

CT brain is performed at very high blood pressure or neurological symptoms.

Treatment of addiction

Cocaine has a significant addictive effect, physical tolerance development is described as well as a strong psychological dependency. The treatment of abuse is mainly symptomatic and therapeutically oriented. Regarding pharmacological treatment, there is insufficient scientific evidence to draw some safe conclusions on the effectiveness of different preparations.

  • Treatment with benzodiazepines is the first choice in treating sleep disorders, anxiety and anxiety.
  • Treatment with antidepressant drugs appears to have a positive effect on restoration in therapeutically oriented treatment compared to placebo
  • Some recent studies suggest that treatment with dextroamphetamine (Dexedrin) and disulfiram (Antabus) has an inhibitory effect on cocaine abuse. Studies are underway with modafinil treatment (Modafinil) which is a central stimulant of non-amphetamine type.
  • Treatment with baclofen (Lioresal) and naltrexone (Naltrexon) is doubtful but have been suggested
  • Psychotic symptoms can be treated with haloperidol (Haldol), risperidone (Risperdal) or olanzapine (Zyprexa).
  • Caution is advised with high dose neuroleptics (levomepromazine) due to the risk of hemodynamic instability and reduced convulsion threshold.

In the field of psychosocial treatment, learning and behavioral therapeutic methods have shown positive effects, especially during the first six months. It has been shown that psychotherapy as a treatment method has resulted in increased retention in psychiatric treatment programs compared with other psychosocial interventions.

General care of poisoning

Mixed poisoning with cocaine, alcohol and drugs (especially benzodiazepines and opioids) are common. The treatment is controlled by the different substances taken but is mainly symptomatic. There is no real antidote to cocaine. Concomitant intake of alcohol, which is common, can increase toxicity by forming ethylbenzoylcgonin, commonly called cocaethylene and delay the intoxication.

Most importantly, careful monitoring of alertness, breathing, circulation, mental functions and controlling the patient is at the correct level of care so that vital life functions can be safeguarded in the acute phase.

When taken over 3 g of cocaine, the risk is associated with life-threatening cardiac arrhythmias, and the patient must then be cared for in a department with adequate cardiac monitoring and the ability to quickly respond to ventricular fibrillation. Check ECG and carefully observe the presence of increased QRS complexes or prolonged QT time that increases the risk of ventricular arrhythmias.

Many cases result from the emergency phase assessment of psychiatry and referral to dependence clinic and social services.

The prognosis for acute cocaine poisoning is usually good if the patient has not received ventricular cardiac arrhythmias before arrival at the hospital or other severe complications.

Treatment in case of acute overdose

In case of oral cocaine ingestion, activated charcoal and gastric emptying should be considered in the same way as with other poisoning conditions, ie it is generally recommended for serious poisoning up to one hour after ingestion.

Rehydrate the patient with crystalloid fluids. Check heart rate, blood pressure and temperature regularly. Institute invasive blood pressure measurement in severe hypertension via an arterial line. Check electrolytes in serum.

Treat metabolic acidosis with sodium bicarbonate until base excess is positive in blood gas analysis. In the presence of ventricular arrhythmias, try lidocaine (Xylocard). Even magnesium sulphate intravenously can be tested.

In case of mild to moderate poisoning, place the patient in a quiet and dark room. Ordinate sleep, food and rest (sleep morning). Benzodiazepines are used as a first-aid kit in anxiety states, and to prevent or treat general seizures.

  • Inset at least one peripheral venous catheter. Take hemoglobin, white blood cell count, platelets and drug screening.
  • If necessary, give an intravenous drip, for example, Ringer’s Acetate. Rehydrate the patient until satisfactory urinary output.
  • Check regularly alertness, heart rate, blood pressure and body temperature.
  • Diazepam (Stesolid) 5-20 mg may be given 3 times daily
  • Alternatively, oxazepam 15-50 mg 3 times daily
  • Zopiclone (Imovane) 7.5 mg by night or nitrazepam 5-10 mg by night of sleep
  • Haloperidol (Haldol) 5 mg 1-2 times daily (avoid high dose neuroleptics) or as an oral solution 1-2 mg. If oral treatment is not possible, haloperidol may be administered intramuscularly 2.5-5 mg x 4.
  • Alternatively, zuklopentixol (Cisordinol-Acutard) 100-150 mg may be given intramuscularly (50 mg/ml, 2-3 ml).
  • Droperidol 10 mg i m.
  • Midazolam (Dormicum) 2-5 mg intravenously or orally in motor anxiety and restlessness (1 mg/ml).

Hypertension and hyperthermia

Treatment of high blood pressure and tachycardia in cocaine toxicity must be given with caution. High blood pressure should primarily be treated with vasodilators such as glyceryl nitrate or magnesium. Magnesium sulphate is a mild vasodilator that can be tried in coca toxicity.

  • In severe hypertension (> 200 mm Hg) intravenous blood pressure control
  • Infusion of glyceryl nitrate (Nitroglycerin) 0.2-0.5 μg/kg/min
  • Infusion of magnesium sulfate 20 mmol in 100 ml Sodium Chloride for 20 minutes followed by 20 mmol for 20 hours
  • Avoid beta blockers intravenously – it has been described to give paradoxical and irreversible effects

In case of hyperthermia, sedation and cooling are important:

  • 1-2 liters of cold saline intravenously
  • Inj. diazepam (Stesolid) 5-20 mg i.v., alternatively midazolam (Dormicum) 2-5 mg i.v.

ICD-10

  • Mental disorders and behavioral disorders caused by cocaine, acute infections F14.0
  • Mental disorders and behavioral disorders caused by cocaine, harmful use F14.1
  • Mental disorders and behavioral disorders caused by cocaine, depression syndrome F14.2
  • Cocaine T40.5

References

  1. Drug development in Sweden 2007, Report no. 107, Central Association for Alcohol and Drug Development, Stockholm 2007.
  2. Annual report EMCDDA The situation in the drugs area in Europe 2016. ISSN: 1609-6207
  3. Kelly BC, Parsons JT. Predictors and comparisons of polydrug and non-polydrug use in club subcultures. Am J Drug Alcohol Abuse. 2008: 34 (6): 774-81.
  4. Wood DM, Dargan PI, Hoffman RS. Management of cocaine-induced cardiac arrhythmias due to cardiac ion channel dysfunction. Clin Toxicology. 2008, Sep 24: 1-10.
  5. Characteristics of primary amphetamine users in Sweden: a criminal justice population examined with the Addiction Severity Index. Håkansson A, Schlyter F, Berglund M. Eur Addict Res. 2009: 15 (1): 10-8.
  6. Maurer, HH .; Sauer, C; Theobald, DS. Toxicokinetics of Drugs of Abuse: Current Knowledge of the Isoenzymes Involved in the Human Metabolism or Tetrahydrocannabinol, Cocaine, Heroin, Morphine, and Codeine. Therapeutic Drug Monitoring. 28 (3): 447-453, June 2006.
  7. Death of a female cocaine user due to the serotonin syndrome following moclobemide-venlafaxine overdose. Kłys M, Kowalski P, Rojek S, Gross A. Forensic Sci Int. 2009 Jan 6. (Epub).
  8. Wu S, Pearl-Davis MS, Manini AF, Hoffman RS. Use of antipsychotics to treat cocaine toxicity? Acad Emerg Med. 2008 Jan; 15 (1): 105.
  9. Fareed FN, Chan G, Hoffman RS. Death temporally related to the use of a Beta adrenergic receptor antagonist in cocaine associated myocardial infarction. J With Toxicol. 2007 Dec; 3 (4): 169-72.
  10. Billman GE. Cocaine: a review of its toxic action on cardiac function. Crit Rev Toxicol. 1995; 25 (2): 113-32.
  11. Robledo-Carmona J, Ortega-Jimenez M, Garcia-Pinilla J, Cabra B, the Teresa E. Severe Cardiomyopathy Associated to Cocaine Abuse. Int J Cardiol. 2006; 112: 130-131.
  12. Serper M R; Bergman A; Copersino M L; Chou J C; Richarm D; Cancro R. Learning and memory impairment in cocaine-dependent and comorbid schizophrenic patients. Psychiatry research 2000; 93 (1): 21-32.
  13. Pani, PP, Trogu, E, Vecchi, S, Amato, L. Antidepressants for cocaine dependence and problematic cocaine use. The Cochrane database of systematic reviews. in 2011; (12): CD002950.

Published with permission by Internetmedicin AB


Spice – Synthetic Cannabinoids


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Interest among young people for the consumption of cannabis and cannabis-like substances has increased significantly in recent years. Some of the cannabis-like drugs are semisynthetic herbal preparations, known as “Spice”. Spice consists of Indian spices mixed with different synthetic cannabinoids. Spice is usually smoked in a similar way to marijuana, usually in roll cigarettes, but you can also take synthetic cannabinoids in other ways, for example by swallowing or by injections.

The effects of synthetic cannabinoids are similar to cannabis effects, but these substances often give more hyperactivity and have more central stimulant effects than natural cannabis. Most synthetic cannabinoids are manufactured in China and then shipped to Europe with legitimate transport and distribution networks. During the first half of 2013, eighteen countries reported more than 1800 seizures of synthetic cannabinoids. The largest herds were reported from Spain (20 kg) and Finland (7 kg). In an English study from 179 cases of that sought an emergency care due to drug effects, synthetic cannabinoids were detected in 10% of cases. Of these, only 50% admitted taking these substances.

The use of Spice has become more common in recent years among young people in Sweden until 2015. In 2012 and 2013, questioning about Spice to the Swedish Poison Information Center in Stockholm were the most common case of different types of drugs purchased on the internet. Among illegal seizures made by Customs and Police in 2012, Spice was 4%. During the latter part of 2014, a number of young people collapsed after smoking Spice and demanded intensive care around Sweden. The number of seizures by police and the customs system has increased dramatically by the end of 2014 but has fallen significantly after 2015. Abuse therefore appears to have decreased significantly since 2015, although it has not completely disappeared. Several varieties of Spice have been narcotics in recent years.

The purchase of Spice is usually via the internet via various websites or abroad in the so-called “Head Shops”. Delivery comes by mail, often in small “zip bags”.

Spice has caused many serious incidences that have required intensive care and some cases of fatalities are described. A number of cases with fatal outcome have been under forensic investigation, most of which have been mixed poisoning, but single pure fatal spice intoxications are rare but have occurred. Reports on acute renal failure and reports of acute myocardial infarction have been published. The risk of emergency medical care after ingestion of synthetic cannabinoids appears to be significantly higher than natural cannabis, one study reported 30 times higher risk.

This overview deals with poisoning with Spice. At present, approximately 15 new substances are classified in Sweden each year and approximately 100 different substances are identified throughout Europe every year. The drugs are subsequently classified as either narcotic drugs or health hazardous drugs. Until such classification, the drugs can still be sold legally. Of the 81 new psychoactive substances reported in 2013 there were 29 synthetic cannabinoids.

SPICE

Spice consists of a mixture of about ten Indian indigenous herbs and spices with effects after intake similar to cannabis. These herbs are known as “Blue Lotus”, “Lions Tail” and “Indian Warrior”. The herbs themselves have weak psychotropic properties. The spice herbs are mixed with additives of synthetic psychoactive substances that have activity on the cannabinoid receptors of the brain. Spice tends to be addictive and in recent years several serious overdoses including a few deaths have been reported.

Some common variants of Spice are called:

  • Spice Silver, Spice Gold, Spice Diamond, Black Ice, Spice Arctic Synergy, Spice Tropical Synergy, Spice Egypt, Spice Yukatan Four, Boom, Double Dutch, Remix, Vegas, Earth Impact, etc.

By oral intake or injection, it is usually the raw material, that is, the synthetic cannabinols used in powder form. Effects and side effects after ingestion are cannabis-like with an euphoric, relaxing, comfortable rest. The psychoactive supplements in Spice are commonly called cannabinoids but are not genuine cannabinols, so the correct term instead would be “cannabinoid receptor agonists” or synthetic cannabinoids. In the preparation of dry matter of cannabinoids, acetone is often used because patients sometimes also smell acetone.

Because the substances bind to the same types of brain receptors (CB1 and CB2) as THC, they primarily give a cannabis-like substance that is perceived as euphoric and relaxing. The various cannabinoids usually refer to the chemical structural formula which is a difficult mixture of letters and numbers, for example CP 47,497. This term may also contain the initials after the chemist who developed the synthesis of the substance, such as in various variants of JWH.

Most cannabinoids are fat-soluble, small nonpolar molecules with 20-26 carbon atoms. Many are more potent on the CB1 receptor than THC and the active dose becomes relatively small, usually below 1 mg. Daily dose for an addict varies between 1-15 mg of active substance. Several cannabinoids have been drug-classified, for example, HU-210, JWH-018, JWH-073, and CP 47,497-C7 substances and several others are on their way. Most cannabinoids are weaker than THC, but some are stronger and some even much stronger, such as JWH-004, JWH-180, JWH-250, and CP 47,497-C6. Chemically, most of the cannabinoids in Spice belong to five different main groups, of which naphthoyl indoles are the most common, see Table.

NaftoylindolesCyclohexylphenoles – CPIndol-derivatives (bensoyl-indoles)DibensopuranesIndazol-derivativesOthers
JWH-007CP 47,497-C6AM-694,HU-2105F-AKB-48 (5F-APINACA)UR-144
JWH-015CP 47,497-C7AM-2233,HU-243AKB-48 (APINACA)5F-UR-144 (XLR-11)
JWH-018CP 47,497-C8STS-135HU-308SDB-001 (APICA)WIN 55,212-2
JWH-018 N-(5-kloro-pentyl) derivat)CP 47,497-C95F-PB-22CUMYL-5F-P7AICA,MAM-2201
JWH-019CP 55,940RCS-4CUMYL-5FPICAFUB-144
JWH-073ADB-CHMICAAPP-PINACA5F-AB-FUPPYCA
JWH-073 (metylderivat)M-CHMICSDB-0055F-ADB
JWH-081BB-22 (QUCHIC)SDB-006
JWH-098AB-FUBINACA5F-SDB-006
JWH-122MDMB-FUBICA5F-EMB-PINACA
JWH-1475F-AB-FUPPYCA5F-PY-PINACA
JWH-200AB-CHMFUPPYCAEMB-FUBINACA
JWH-203AM-22015C-AKB48 (5C-APINACA)
JWH-210APICA (SDB-001)AMB-FUBINACA (FUB-AMB)
JWH-2505-Fluoropentyl-3-pyridinoylindoleAMB-CHMINACA
JWH-3985F-PY-PICAADB-FUBINACA
CBL-018SDB-005MDMB-FUBICA
THJ-018CUMYL-5F-P7AICAADB-CHMINACA
AB-001 (JWH-018 adamantoyl derivat)CUMYL-5FPICAMDMB-CHMICA
JWH-018 adamantyl karboxamid (SDB-001, 2NE1, APICA)APP-CHMINACA
FUB-JWH-018AB-PINACA
5F-ADB-PINACA CUMYL-4CN-BINACA

Most of the cannabinoids are classified as narcotics and the list will be longer for each year. Among these substances may be mentioned:

  • CP 47,497 in several different subtypes (different cyclohexylphenols – CP)
  • JWH-015, -018, -019, -073, -081, -122, -203, -250 (different naphthoylindoles)
  • HU-210
  • 5F-AKB-48, 5F-PB-22, 5F-UR-144 and some variants of JWH-018 are classified as hazardous goods.
  • Some other recently reported substances are SDB-006, 5F-SDB-006 and FUB-PB-22 (2014).

Spice is difficult to find in routine blood sampling but can be detected in blood and urine through extended and targeted analysis. Special specific drug sticks are available for Spice. Spice and other synthetic cannabinoids can be difficult to detect through drug analyzes. Blood samples can detect more variants of Spice than urine samples. The right-wing laboratory in Linköping and the Department of Clinical Pharmacology, Karolinska University Hospital in Solna, can detect several different variants of Spice.

Immediately after the pleasant rush, negative symptoms may occur after consuming Spice. The negative symptoms after intake of Spice are characterized by:

  • Dry mouth
  • Panic feelings
  • Hunger feelings
  • Anxiety
  • Nausea, vomiting
  • Tiredness
  • Somnolence
  • Big pupils, red blood-stained eyelashes
  • Memory disorders
  • Elevated pulse, irregular pulse, even slow pulse
  • Increased blood pressure

In a clinical study conducted in the United States in 2012, tachycardia was presented in 37.5%, agitation in 21.8%, drowsiness in 17.9%, vomiting in 15.4%, 9.9% hallucinations, nausea in 9.8% , 9% confusion and high blood pressure in 8.5% of cases. Reports have come in recent years about more serious side effects such as acute renal failure, acute myocardial infarction (ischemic signs of ECG) and liver affect. Even single deaths and cases of grave neurological deficit have been reported, for example after ingestion of MDMB-CHMICA and ADB-CHIMINACA. In the case of renal failure, the substance 5F-UR-144 (XLR-11) has been common. In a German study (abstract EAPCCT congress, 2016) of 45 patients received after intake of AB-CHMINACA or MDMB-CHMICA, 29% showed general seizures, 25% aggressive behavior, 13% psychosis (including self-injury) and 13% syncope. As many as 16% (7 of 45) were assessed as life-threatening poisoning, which underlines the severity of Spice intoxications.

SYMPTOMS AND CLINICAL FINDINGS

In case of acute overdose of Spice, you will notice

  • Big, wide-eyed pupils
  • Red eye witness
  • Hyperactivity
  • Excitation
  • Excitement, restlessness and agitation.
  • Aggressive behavior
  • The patient can tease himself unnaturally and be psychologically worried.
  • He or she may suffer from tachycardia, palpitations and shaking, as well as high blood pressure and chest pain.
  • Confusion and hallucinations occur.
  • Syncope
  • There is a risk that the patient may suffer from muscle tension, muscle twitching, cramps and eventually collapse.

Overdose also involves a risk of:

  • Somnolence
  • Tachycardia
  • Disorientation
  • Acute Confusion – Acute Psychosis
  • Hyperglycemia
  • Hypokalemia
  • Hypertension
  • Nausea, vomiting
  • Amnesia can be long-term
  • Metabolic acidosis
  • Myoclonic general seizures, rhabdomyolysis
  • Kidney failure
  • Liver failure
  • Intermittent apneas
  • Cardiac arrhythmias, ECG changes

There is also a small risk of acute myocardial infarction and cardiovascular collapse.

TREATMENT

The treatment of acute overdose with Spice is mainly symptomatic. Specific antidotes are missing. It is important to direct the patient to hospital if the caretaker is so unclear that he or she cannot account for or have difficulty standing or walking so that vital life functions can be secured urgently. In the aftermath, drug abuse should be treated; assessment of psychiatrists and referral to dependence clinic and social services is often relevant. The application for social services (notification of concern ) must always be done in case of life-threatening addiction. One can also consider urgent notification. Most importantly, careful monitoring of:

  • Alertness
  • Breathing
  • Circulation
  • Temperature (risk of hyperthermia)
  • Mental functions

The prognosis for poisoning with Spice is usually good unless serious complications are already granted before arrival at the hospital. Screening with drug stitches can sometimes, but not always, provide useful information about which drugs have been taken. Negative screening does not exclude poisoning with Spice. It is important to work with updated urine stitches during drug screening.

In case of acute overdose, symptomatic treatment and supervision of vital parameters are important.

Therefore, make sure that:

  • Checks are regularly done for:
    • Pulse
    • Blood pressure
    • Temperature
    • Mental functions
  • Place the patient in a quiet place in case of mild to moderate poisoning and let him or her eat, sleep and rest (sleeping morning).
  • Treat anxiety and agitation (see below).
  • Observe the risk of hypokalaemia, rhabdomyolysis and hyperglycaemia.
  • Rehydrate with crystalloid fluids and check electrolytes in serum.
  • Do drug screening of urine samples or plasma.
  • Request a targeted analysis of urine samples with regard to Spice.

Pharmacological treatment in case of anxiety or agitation

  • Oxazepam (Sobril) 15-50 mg 3 times daily, alternatively diazepam (Stesolid) 5-20 mg 3 times daily
  • Nitrazepam (Nitrazepam) 5-10 mg to the night of sleep
  • Olanzapine (Zyprexa) 10 mg x 2 in psychotic symptoms
  • Dridol (Droperidol) 10 mg im. Provides good effect after about 20 minutes.
  • Haloperidol (Haldol) 5 mg 1-2 times daily (avoid high dose neuroleptics) alternatively oral solution 1-2 mg, no more than every 4 hours. If oral treatment is not possible, haloperidol can be administered i.m. 2.5-5 mg x 4. Alternatively to haldol, zuclopentixol (Cisordinol-Acutard) is 100-150 mg i.m.
  • Midazolam (Dormicum) 2-5 mg i.v. (1 mg/ml) in motor anxiety and anxiety. Can also be given perorally (10-15 mg) or intramuscularly 2-5 mg.
  • Propofol (Propofol) i.v. in severe anxiety in an intensive care department
  • Symptomatic treatment in general

Prognosis

The prognosis is usually good after taking Spice unless serious complications occur with rhabdomyolysis, hyperthermia or seizures. Particular attention should be paid to liver or kidney and rhabdomyolysis.

ICD-10

  • Mental disorders and behavioral disorders caused by hallucinogens, acute infections F16.0
  • Mental disorders and behavioral disorders caused by hallucinogens, harmful use F16.1
  • Psychostimulants with addiction risk T43.6
  • Mental disorders and behavioral disorders caused by multiple drugs in combination and other psychoactive substances F19

References

  1. Drug development in Sweden 2011, Report no. 130, Central Association for Alcohol and Drug Development, Stockholm 2012. Link
  2. School leader’s drug habits 2013. Kunskapskällaren 2013, report 2013: 1. Gothenburg City, Social resource management.
  3. Annual report EMCDDA The situation in the drug field in Europe 2012.
  4. EMCDDA; Action on new drugs briefing paper: Understanding the “Spice” phenomenon. 2009. Lisbon. Link
  5. EMCDDA; Perspectives on drugs: Synthetic cannabinoids in Europe, Lisbon. Link
  6. Centers for Disease Control and Prevention (2013), Acute kidney injury associated with synthetic cannabinoid use – Multiple States, Morbidity and mortality weekly report 62, pp. 93-8. Link
  7. Hurst, D., Loeffler, G., and McLay, R. (2011), Psychosis associated with synthetic cannabinoid agonists: a case series, American Journal of Psychiatry, 168, pp. 1119. Link
  8. Hermanns-Clausen, M., Kneisel, S., Szabo, B., and Auwärter, V. (), Acute toxicity due to confirmed consumption of synthetic cannabinoids: Addiction, 2013, 108, pp. 534-44. Link
  9. Uchiyama, N. et al. Chemical analysis of synthetic cannabinoids as designer drugs in herbal products, Forensic Science International, 2010, 198, pp. 31-8. Link
    Mixmag “The Mixmag / Guardian drug survey”, Mixmag (2012). Link
  10. Harris CR, Brown A. Synthetic cannabinoid intoxication: A case series and review. J Emerg Med. 2012; [Epub ahead of print] Link
  11. Hermanns-Clausen M, Kneisel S, Szabo B, et al. Acute toxicity due to confirmed consumption of synthetic cannabinoids: Clinical and laboratory findings. Addiction. 2012; [Epub ahead of print]
    Grotenhermen F. Pharmacokinetics and pharmacodynamics or cannabinoids. Clin Pharmacokinet. 2003; 42: 327-60. Link
  12. Drogutvecklingen i Sverige 2011, Rapport nr 130, Centralförbundet för alkohol- och narkotikautvecklingen, Stockholm 2012. Länk
  13. Skolelevers drogvanor 2013. Kunskapskällaren 2013, rapport 2013:1. Göteborgs Stad, Social resursförvaltning.
  14. Årsrapport EMCDDA Situationen på narkotikaområdet i Europa 2012.
  15. EMCDDA; Action on new drugs briefing paper: Understanding the “Spice” phenomenon. 2009. Lissabon. Länk
  16. EMCDDA; Perspectives on drugs: Synthetic cannabinoids in Europe, Lissabon. Länk
  17. Centers for Disease Control and Prevention (2013), Acute kidney injury associated with synthetic cannabinoid use — multiple States, Morbidity and mortality weekly report 62, pp. 93–8. Länk
  18. Hurst, D., Loeffler, G., and McLay, R. (2011), Psychosis associated with synthetic cannabinoid agonists: a case series, American Journal of Psychiatry, 168, pp. 1119. Länk
  19. Hermanns-Clausen, M., Kneisel, S., Szabo, B., and Auwärter, V. (), Acute toxicity due to the confirmed consumption of synthetic cannabinoids: clinical and laboratory findings Addiction, 2013, 108, pp. 534–44. Länk
  20. Uchiyama, N. et al. , Chemical analysis of synthetic cannabinoids as designer drugs in herbal products, Forensic Science International, 2010, 198, pp. 31–8. Länk
  21. Mixmag ‘The Mixmag/Guardian drug survey’, Mixmag (2012). Länk
  22. Harris CR, Brown A. Synthetic cannabinoid intoxication: A case series and review. J Emerg Med. 2012;[Epub ahead of print] Länk
  23. Hermanns-Clausen M, Kneisel S, Szabo B, et al. Acute toxicity due to the confirmed consumption of synthetic cannabinoids: Clinical and laboratory findings. Addiction. 2012;[Epub ahead of print]
  24. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42:327–60. Länk

Publicerat med tillstånd av Internetmedicin AB


New Psychoactive Substances (NPS)


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


The interest of young people for drugs purchased online has increased in recent years. These new drugs are commonly called new psychoactive substances (NPS) which are psychotropic drugs that can be purchased over the net. The drugs are similar to several established illicit drugs, usually they are central stimulants (amphetamine-like), opioid-like or cannabis-like. Several benzodiazepines that are not registered in Sweden can also be purchased online. Among NPS are different groups labeled as:

  • Synthetic cathinones (eg mefedron, metedron, nafyron)
  • Phenethylamines
  • Tryptamines
  • Piperazines
  • Opioids
  • Benzodiazepines
  • Several new hallucinogens
  • Synthetic cannabinoids (cannabis-like “spice”)

The NPS are also called “Research Chemicals (RC Drugs), Designer Drugs, Legal Highs or Smart Drugs.”

Most internet drugs have mainly amphetamine or cannabis-like effects but opiate-like and benzodiazepine-like drugs are also available. Many of the substances can be classified as substituted amphetamine derivatives or synthetic cannabinoids (SC). Most drugs are chemically related to phenethylamine, where alpha-methylphenethylamine is best known as amphetamine. Amphetamine analogues give the user increased energy and reduced appetite; Usually, the user feels good and upward and more focused. Excessive intake, on the other hand, provides a number of negative consequences with increased risk of psychosis. Some of the cannabis-like drugs are synthetic or herbal preparations, such as synthetic cannabinoids (“Spice”). The effects of these substances are similar to cannabis but produce relatively more hyperactivity due to some central stimulant effect.

The purchase of NPS is done different national or international websites. Delivery comes by regular mail or via a local pusher. NPS have given rise to many serious cases demanding intensive care and cases of fatal outcome are described.

Most new psychoactive substances are difficult to find in routine blood sampling but can be detected in blood and urine through extended and targeted chemical analysis. Rapid tests of urine samples are available for drug screening, but these often only detect the most common drugs, such as ecstasy, cocaine, cannabis and amphetamines, and risk losing the presence of NPS. Spice and other synthetic cannabinoids are more difficult to detect, but there are several new urine sticks available for detecting Spice and other illicit drugs.

This overview deals with poisoning with various new psychoactive substances. Currently, about 100 new substances are identified throughout Europe every year. A peak was noted in 2014 and 2015, after which the number of newly discovered substances has decreased slightly in number, both in Sweden and in Europe. The drugs are subsequently classified as either narcotic drugs or health hazard substances. Until such classification, the drugs can be sold legally. In total, more than 700 new substances have been reported and more than 400 have been discovered in the last 5 years.

SPICE

Spice is a mixture of several herbs and spices with additives of synthetic cannabinoids that produce psychotropic effects similar to cannabis. Spice is mixed with tobacco and smoked by pipes or cigarettes. The synthetic cannabinoids are often dissolved in acetone before spraying over a spice mixture that is then smoked. Substances have psychotropic properties and are called synthetic cannabinoids or, more correctly, cannabinoid receptor agonists. The effect in the CNS is mainly performed via CB1 receptors. Effects and side effects after ingestion are cannabis-like with an euphoric and stimulant effect.

The most common side effects are:

  • Dry mouth
  • Nausea, vomiting
  • Red eye whistle, eye sore
  • Memory disorders
  • Elevated heart rate
  • Increased blood pressure
  • Panic
  • Hunger
  • Anxiety
  • Hyperactivity
  • Psychomotor disorder
  • Confusion
  • Seizures (especially PB-22)
  • Kidney failure (especially XLR-11)

The synthetic cannabinoids have a complex chemical nomenclature (abbreviation plus order number) and in most cases the usernames are completely different. Most of the cannabinoids are drug-class and the list will be longer for each year. Among these substances may be mentioned:

  • CP 47,497 in several different subtypes (different cyclohexylphenols – CP)
  • JWH-015, -018, -019, -073, -081, -122, -203, -250 (different naphthoyl indoles)
  • HU-210
  • 5F-AKB-48, 5F-PB-22, 5F-UR-144 and some variants of JWH-018 are classified as hazardous goods.
  • Some other recently reported substances are SDB-006, 5F-SDB-006 and FUB-PB-22 (2014).
  • AB-CHMINACA, MBB-CHMINACA

Cathinones

The cathinones are a group of synthetic agents with weak central stimulant effects similar to the phenethylamines. Among the cathinones are some newer preparations like Mephedrone, MDPV, Methylone, Metedrone and Naphylone. The substances are present in powder, tablet and capsule form. Mephedrone has user names like “Crab” and “Subcoca”.

Cathinones are synthesized chemically from norephedrine and norpseudoephedrine. The effects are similar to the phenethylamines, i.e., central stimulation with a strong euphoric effect and increased socialization rate. Side effects may, for example, consist of:

  • Headache
  • Nausea
  • Dizziness
  • Abdominal cramps
  • Tachycardia, palpitations
  • Anxiety
  • Concern
  • Slurred speech
  • Confusion

Acute poisoning with confusion, cold sweating, fever, shaking, abrasive speech and psychotic symptoms have occurred. Individual cases of unconsciousness and death have been reported.

Mephedrone

Mephedrone (4-methyl methatinone) was rapidly spread among adolescents in Sweden 2009 and 2010. Mephedrone is highly euphoric and a fast-acting craving of the drug has been described.

Symptoms of overdose may be:

  • Hyperactivity
  • Racing
  • Increased energy
  • Mydriasis (dilated pupils)
  • Tachycardia
  • Hypertension
  • Increased risk of seizures
  • General seizures, respiratory arrest and single deaths have occurred.

Seizures of mephedrone in Sweden have come from China and Austria. The substance has a light scent of seafood, hence the hose name “Crab fish”. Mephedrone has been classified as a narcotic drug since 2009.

MDPV

MDPV is an abbreviation of 3,4-methylenedioxypyrovalerone. MDPV provides central stimulatory effects similar to amphetamine but with significantly more hallucinogenic effects. Like pyrovalerone, MDPV is likely to significantly increase the amount of several neurotransmitters in the brain, such as dopamine, norepinephrine and serotonin.

Some common usernames are “MDPV, MDPK, Sonic, Magic, Monkey Dust, Skutz”.

MDPV belongs to the group of cathinones and resembles pyrovalerone (4-methyl-α-pyrrolidino-valerophenone) listed in the 1971 Psychotropic Convention (Group IV). The presence of MDPV has increased dramatically in Sweden in recent years and seems to be one of the most common illicit drugs. MDPV has caused several deaths, mainly through drug-related trauma.

MDPV appears as powder, ampoules and tablets. For a normal to strong dose, the reported effects may last between 5 and 12 hours and the effects are described by users as strong euphoric effect. MDPV provides a strong stimulating sensation with unstable temperament, the experience varies greatly and switches quickly between pleasure and discomfort. Regular use of MDPV may be addictive and provide tolerance development (i.e. increasing dosage is required for continued efficacy). A so-called serotonin syndrome can occur that can last for up to a week. Serotonin syndrome refers to an overdrive of serotonin in the brain which affects vital functions throughout the organism. This condition usually requires intensive care.

A normal dose of MDPV is between five and ten milligrams. Among the negative effects is the high risk of acute psychosis with agitation and confusion. Patients can become violent and aggressive with powerful hallucinations and delusions. Other side effects listed are nausea, vomiting, anxiety, dizziness, dizziness, sweating, temperature increase, high heart rate, high blood pressure, visual hallucinations, cardiac arrhythmias and paranoia. Neurological symptoms such as involuntary tricky spastic movements may occur, e.g. dystonia and acatiasis. Several cases of acute poisoning with a messy and violent disposal have been described in emergency care and from the police force. High doses have been reported to cause severe anxiety attacks in inexperienced users and repeated intake can lead to addiction. Side effects are anxiety, panic attacks, self-destructive actions, depression, paranoid delusions and aggressiveness. Several cases of sudden impulsive suicide attempts and complete suicide have been observed. Impacted persons have been reported to be able to throw themselves through glass doors and into traffic in front of cars and buses. Repeated intake for a prolonged period has also been reported to give withdrawal symptoms similar to those of methamphetamine.

5-IT

5-IT (5-(2-Aminopropyl) Indole or 2-(1H-indol-5-yl)-1-methylethylamine) is an indole and an isomer of alpha-methyltryptamine (AMT). The compound is chemically related to phenethylamine derivatives such as 5-APB, 6-APB.

5-IT mainly has central stimulatory rather than psychedelic effects. It is noted that “at 20 mg orally, the substance causes increased heart rate, anorexia, urine excretion and some heat stroke for about twelve hours.” In different discussion forums, the effective dose is described around 100-250 mg.

Acute overdose with 5-IT has been described to give rise to symptoms similar to those associated with other central stimulants; anxiety, agitation, and hyperthermia.

Phenethylamines

Phenethylamines (PEA) are chemical derivatives of amphetamine with closely related properties. Phenethylamine is actually the basic chemical structure of amphetamine. There are at least one-fifty different phenethylamines; everyone is not classified as narcotics. Some are instead classified as hazardous goods, which prohibits possession unless professional handling can be substantiated.

The effect on intake is an increased release in varying degrees of dopamine, serotonin and norepinephrine. The drugs generally have psychotropic, i.e. hallucinogenic and energy-generating effects. The effect when using it resembles LSD and meskalin. Several of the phenethylamines affect the autonomic nervous system with the risk of blood pressure increase and peripheral vasoconstriction (amphetamine was originally used for its vasoconstrictive effects such as cold medicine, eg benzedrine).

Some examples of phenethylamines are:

  • BDB (benzodioxolylbutanamine)
  • 2C-B (bromodimethoxyphenethylamine)
  • 2C-T-2 (dimethoxyethylthiophenethylamine)
  • 2C-T-7 (dimethoxypropylthiophenethylamine)
  • DOC (4-chloro-2,5-dimethoxycloramphetamine)
  • MBDB (methylbenzodoxolbutanamine)
  • TMA-6 (2,4,6-trimethoxyamphetamine)
  • PMA (Para-Methoxy Amphetamine)
  • PMMA (Para-methoxy-methamphetamine)

2C-B is usually sold in the form of pink tablets. Some common snake names are Bromo, Venus and Eve. 2C-T-2 is similar to 2C-T-7, but does not have the same toxicity.

DOB (Dimethoxibromomethetamine)

DOB is a substituted amphetamine with stronger psychotropic activity than other phenethylamines. Usually, DOB appears as a white synthetic powder sold in capsules or tablets. The substance has also been found in soft tissues, so called “blotters”. DOB can also be “snorted”, that’s pulled through the nose. DOB has slow onset (about an hour) and gives a long lasting high. DOB has a strong vasoconstrictor effect. A common user name is “Golden Eagle”.

Bromo-Dragonfly

Bromo-Dragonfly (bromo-benzodifuranyl-isopropylamine) is a synthetic phenethylamine similar to DOB, LSD and amphetamine. The drug has a pronounced affinity for serotonin receptors. Bromo-Dragonfly occurs as a powder, “blotters”, fluid or tablets. Common user doses are 50-800 μg.

Bromo-Dragonfly is hallucinogenic, but also has effects similar to amphetamine. The drug is strongly vasoconstrictive and has caused pronounced vasoconstriction (pseudoergotism) leading to ischemia and amputation of the fingers and toes. Pseudoergotism has also occurred after taking DOI. Deaths after intake have occurred in Sweden. Common symptoms of overdose are psychomotor disorders and confusion.

MT-45

This substance is actually a piperazine but has effects similar to opioids with sedation, analgesia and respiratory depression. In 2013 and 2014, MT-45 was detected in twelve hospitalized poisoning cases. All cases were men aged 17-35 years. In eight of twelve cases, other drugs were also detected, most of which were new synthetic substances. In three cases, cannabis was also detected. In nine cases of twelve patients were unconscious at the encounter, a person died. In many cases, ototoxicity with impaired hearing developed. MT-45 has also caused depigmentation of hair and eyebrows and other body hair. It has also given rise to large flaming eczema skin changes as well as cataracts.

MDEA/MDE

Methylenedioxyethylamine is a derivative of phenethylamine which is ecstasyl-like with euphoric and empathogenic (“entactogenic”) properties. The drug increases the levels of serotonin, norepinephrine and dopamine. MDEA is often called “Eve”. Common doses are slightly higher compared to ecstasy, 100-200 mg for a high.

MDA

Methylenedioxyamphetamine is a derivative of amphetamine which is ecstasy-like with euphoric, empathogenic and hallucinogenic properties. MDA is also known as tenamphetamine. MDA is often called “Sally, SASS, or Sassafras”.

MBDB

Methyl benzodoxole-butanamine is a derivative of amphetamine which is ecstasy-like with mild euphoric and hallucinogenic properties. MBDB is often called “Eden or Methyl-J”. The drug appears to be slightly less potent compared with ecstasy (MDMA).

PMA

Para-methoxy-amphetamine is a derivative of amphetamine which is ecstasy-like with euphoric and hallucinogenic properties. PMA is also known as 4-methoxyamphetamine and has predominantly serotonergic effects. PMA has caused a number of deaths and is often called “Death or Dr. Death”. The drug can induce severe cardiac arrhythmias and is also a potent MAO inhibitor which can cause a pronounced serotonin syndrome with severe hypertension and severe hyperthermia.

PMMA

Para-methoxy-methamphetamine is a derivative of methamphetamine which is ecstasy-like with euphoric and hallucinogenic properties. PMMA is also called methyl-MA or 4-methoxy-methylamphetamine. In 2011, PMMA was detected in 12 deaths in Norway. The drug is often called “Superman or Superman-ecstasy“.

Tryptamines

Tryptamines are a group of synthetic drugs with LSD and measles-like effects. Tryptamins are more hallucinogenic than phenethylamines. Tryptamins are similar to structural serotonin. Among these are noted:

  • DiPT (diisopropyltryptamine)
  • 5-MeO-DiPT (5-methoxy-diisopropyltryptamine)
  • AMT (alpha-methyltryptamine)
  • DMT (n, n-dimethyltryptamine)
  • 5-MeO-AMT (5-methoxy-alpha-methyltryptamine)
  • 5-MeO-DMT (5-methoxy-DMT)
  • dimethyl-5-methoxytryptamine
  • DPT (dipropyltryptamine)

Typically, tryptamines are sold in the form of capsules or tablets and are taken orally. The substances can also be powdered or smoked. Psilocin and psilocybin, found in hallucinogenic fungi, can be classified as tryptamins.

Intake of tryptamins reinforces the senses, mainly hearing. An overdose causes, like other party drugs, symptoms such as:

  • Hyperactivity
  • Agitation
  • Confusion
  • Visual hallucinations

There is a risk of psychotic symptoms and general seizures. Tryptamines may cause severe blood pressure increase in case of overdose. They can also cause serious drug interactions.

Benzylpiperazin (BZP)

Benzylpiperazine is related to amphetamine and has similar effects to other party drugs. Piperazines were medically used in the 1970s as antidepressant drugs due to their serotonin enhancing effects. However, they did not have any positive long-term effects and were therefore removed from the pharmaceutical market. BZP has instead established itself as a party drug and a drug addiction among young people, especially in New Zealand and Australia. It is not drug-class and can be ordered home via the internet or purchased abroad.

BZP usually occurs in capsule form which is taken orally. Ruset lasts for six to eight hours. Overdose shows the same type of symptoms as when taking other amphetamine analogues, such as high blood pressure, tachycardia and psychomotor disorders.

TFMPP (trifluoromethylphenylpiperazine), has effects which, according to users, are instead entirely ecstacylic. TFMPP is often called “Legal X”.

Dextrometorphane (DXM)

Dextromethorphane (DXM) is a cough suppressant NMDA antagonist sold as non prescription drugs in some countries, including Denmark, Finland and the United States. DXM has opiate-like effects with sedative and dissociative properties. An increased use of DXM for intoxication has been reported among younger teens in Sweden. DXM at high doses has hallucinogenic effects. Acute poisoning with DXM and benzylpiperazine has until recently been relatively unusual in Sweden. However, in 1988, two DXM-related deaths were reported. In 2008, new deaths have been reported in Sweden.

Dextromethorphan is now drug-classified but can be ordered home via the internet or purchased abroad. DXM is sold abroad under drug names like Dexofan, Dexalon, Coricidin, Wick’s formula, Neo-Tussan, Resilience and Robitussin.

Some user names on the dextrometorphan are “DXM”, “Dex”, “Robo”, “Skittles”, “Syrup”, “Triple-C” and “Tussin”.

Symptoms of poisoning with DXM include:

  • Fever (hyperthermia)
  • Gastrointestinal symptoms
  • Itching
  • Somnolence
  • Respiratory failure
  • Dreamlike experiences
  • Feelings of isolation
  • Dissociation
  • Disorientation
  • Hyperesthesia
  • Ataxia

Increased suicidality occurs.

Benzodiazepines

Several different unregistered benzodiazepine preparations appear on the black market and are sold online. Flunitrazepam registered in Sweden (Flunitrazepam Mylan) is also illegally sold online. In the past, Rohypnol (flunitrazepam) was a commonly used drug in the illegal market. A relatively new benzodiazepine is phenazepam. It is a substance with a very long half-life, up to three days, which in case of overdose can produce very long-lasting effects. Memory disorder, coordination difficulties and disorientation have been described for up to one week after the intake of phenazepam. Fenazepam is imported into Sweden from mainly Russia.

Various unregistered benzodiazepine preparations available online:

  • Adinazolam
  • Bromazepam
  • Diklazepam
  • Desmetylflunitrazepam
  • Flubromazepam
  • Flubromazolam
  • Fludiazepam
  • Flurazepam
  • Flunitrazolam
  • Etizolam
  • Phenazepam
  • Camazepam
  • Clonazolam
  • Cloniprazepam
  • Loprazolam
  • Lorazepam
  • Lormetazepam
  • Meklonazolam
  • Meklonazolam
  • Norfludiazepam
  • Pyrazolam
  • Zapizolam

SYMPTOMS

Impact of NPS

The effect of most NPS such as cathinones, phenethylamines and various amphetamine analogues is euphoria, social empathy, openness and increased mental and physical energy. Well-being increases and a positive sense of lust occurs within 1-3 hours of intake. Self-confidence is increasing and you get an experience that all problems disappear. The drugs give an increased sense of communication, understanding and empathy with empathogenic or entactogenic effects. Odor, perception of hearing and perception is enhanced. The pupils widen (mydriasis). The central nervous effect is mainly caused by serotonin release in the central parts of the brain, primarily the limbic system, striatum and hippocampus. After prolonged use, the serotonergic depots are depleted and patients are at risk of developing negative mental symptoms, depression and psychosis.

Examples of negative effects:

  • Hyperactivity and hypomania
  • Thought escape, unstable temperament
  • Anxiety, restlessness, anxiety, irritability
  • Decreased self-control, distancelessness, unstable behavior
  • Boundless sexual activity
  • Increased appetite, sweating (but also loss of appetite and anorexia)
  • Headache
  • Psychosis-like reactions, hallucinations

The drug user eventually becomes exhausted, irritated and depressed after repeated intake. The humility can be difficult and long-lasting. Animal data suggest that damage to dopamine pathways and, above all, serotonin pathways is morphological and partly irreversible. Even general seizures occur.

Symptoms that may occur after a few months of abuse are:

  • Fatigue, irritability
  • Insomnia
  • Stereotypic behavior
  • Depression, suicidal thoughts, increased suicidality
  • Paranoia
  • Anxiety
  • Mutism
  • Catatonia

Acute Overdose

In acute overdose of NPS, large-scale pupils, hyperactivity, excitation, excitement, restlessness and agitation are noted. The patient can behave unnaturally and be psychologically worried. He or she may suffer from tachycardia, palpitations and tremors, as well as hypertension and chest pain. Confusion and hallucinations occur. There is a risk that the patient may suffer from muscle tension, rigidity, muscle twitching and seizures; Cramp in the jaw crotch (trismus) is common.

Overdose poses a risk of:

  • Water intoxication (acute hyponatraemia)
  • Cerebral edema
  • Acute confusion
  • Acute psychosis
  • Cardiac arrhythmias
  • Myoclonal seizures
  • Hyperthermia (fever)
  • Serotonin syndrome
  • Hepatic failure
  • Kidney failure

Heat stroke, rhabdomyolysis and serotonin syndrome may occur especially after ingestion of various synthetic cathinones or phenethylamines and long lasting dance or stay in a warm environment, as well as poor hydration. Hyperthermia may be accompanied by muscular rigidity, seizures and rhabdomyolysis. Hyperthermia is often one of the symptoms of a “serotonin syndrome” (see below) and can lead to hypercalcaemia, cardiac arrhythmias with heart failure, acidosis, coma and multiple organ failure. Other serious symptoms that may develop are impaired coagulation ability – DIC (disseminated intravasal coagulation) and respiratory failure with risk of pulmonary edema. There is also a risk of intracerebral bleeding and cardiovascular collapse.

Body temperature above 41 degrees is dangerous and above 42 degrees is directly life threatening – liver failure and renal failure have been described. Probably renal failure occurs secondary to rhabdomyolysis and deposition of myoglobin in kidneys. Kidney failure has also been reported after ingestion of some Spice varieties. CT or MRI brain should be performed to exclude brain edema if pronounced hyponatraemia occurs (S-Na <120 mmol/L), as well as in focal neurological symptoms. Morphological damage to serotonergic pathways can be detected by PET camera or functional MRI.

TREATMENT

General Care

The care of acute overdose with central stimulant drugs is generally symptomatic. Specific antidotes are missing.

Most importantly, careful monitoring of

  • Alertness
  • Breathing
  • Circulation
  • Temperature
  • Mental functions

It is important to steer the patient to the right medical department so that vital life functions can be secured urgently. In the aftermath, drug abuse should be treated; assessment of psychiatrists and referral to dependence clinic and social services is often relevant. The application for social services must always be done in case of life-threatening addiction.

The prognosis of poisoning with NPS is usually good unless serious complications are already granted before arrival at the hospital. Screening with drug stitches can sometimes, but not always, provide information about which drugs have been taken. Negative screening test does not exclude poisoning with any party drugs.

Treatment in case of acute overdose

Check heart rate, blood pressure, temperature and mental functions regularly. Invasive blood pressure measurement should be performed in case of severe blood pressure increase in moderate or severe intoxication. Place the patient in a quiet and dark room at mild to moderate poisoning and let him or her eat, sleep and rest (sleep morning). Treat anxiety and agitation (see below). Observe the risk of hyperthermia.

Rehydrate with crystalloid fluids and check electrolytes in serum. Do drug screening of urine samples or plasma. Request a targeted analysis of urine samples with regard to mesh drugs.

Pharmacological treatment in case of anxiety or agitation

  • Diazepam 5-20 mg 3 times daily, alternatively oxazepam (Sobril®) 15-50 mg 3-4 times daily
  • Midazolam 2-5 mg i.v. (1 mg/ml) in motor anxiety and anxiety
  • Olanzapine 10 mg x 2 alternatively Risperidone 1 mg x 2.
  • Droperidol 10 mg in x 1.
  • Haloperidol 5 mg 1-2 times daily or oral solution 1-2 mg, no more than 4 hours. If oral treatment is not possible, haloperidol can be administered i.m. 2.5-5 mg x 4. Propofol  i.v. in severe intimacy in an intensive care department
  • Dexmedetomidine in continuous infusion with severe concern in an intensive care unit
  • Symptomatic treatment in general
  • Caution with beta blockers

CT brain is performed at blood pressure or neurological symptoms, such as brain oedema or stroke. Check myoglobin in serum to see if rhabdomyolysis is present. Consider forced alkaline diures if so.

In hyperthermia, active cooling and sedation may be required:

  • 1-2 liters of cold saline i.v.
  • Diazepam 5-20 mg i.v.
  • External cooling with cooling blanquet or the like
  • In extreme hyperthermia, consider extracorporeal cooling through ECMO systems or the like

In case of serotonin syndrome, treatment with any of the following medicines may be given:

  • Cyproheptadin – 8 mg x 3 per os (license preparation, antihistamine)
  • Risperidone 2 mg x 3

In case of severe hypertension (> 200 mmHg) – invasive blood pressure control with arterial catheters:

  • Infusion of glyceryl trinitrate (Nitroglycerin®) 0.2-0.5 μg/kg/min
  • Infusion of magnesium sulfate (Addex-Magnesium) 20 mmol in 100 ml NaCl for 20 minutes followed by 20 mmol for 20 hours
  • Beta-blockers with caution, eg metoprolol, labetalol
  • Alfablocker with caution, such as doxazosin, labetalol

ICD-10

  • Mental disorders and behavioral disorders caused by hallucinogens, acute infections F16.0
  • Mental disorders and behavioral disorders caused by hallucinogens, harmful use F16.1
  • Mental disorders and behavioral disorders caused by cocaine, depression syndrome F14.2
  • Psychostimulants with addiction risk T43.6
  • T40.6 Other and non-specified narcotic drugs
  • F15.1 Mental disorders and behavioral disorders caused by other stimulants, including caffeine, harmful use
  • F15.0 Mental disorders and behavioral disorders caused by other stimulants, including caffeine, acute intoxication

References

  1. Drug Development in Sweden 2014, Report No. 144, Central Federation for Alcohol and Drug Development, Stockholm 2014.
  2. Gouzoulis-Mayfrank E. & Daumann J. Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage? Addiction 2006; 101: 3: 348-361
  3. Ecstasy, the serotonin syndrome, and neuroleptic malignant syndrome – a possible link? JAMA Feb 17, 1993, Vol 269, No. 7.
  4. Skolelevers drug habits 2013. Knowledge Source 2013, Report 2013: 1. Gothenburg City, Social Resource Management.
  5. Annual report EMCDDA The situation in the field of drugs in Europe 2012.
  6. EMCDDA; Action on new drugs briefing paper: Understanding the “Spice” phenomenon. 2009. Lisbon.
  7. Borek HA, Holstege CP. Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med. 2012 Christmas; 60 (1): 103-5.
  8. 8Jerry J, Collins G, Streem D. Synthetic legal intoxicating drugs: the emerging ‘incense’ and ‘bath salt’ phenomenon. Cleve Clin J Med. 2012 Apr; 79 (4): 258-64.
  9. Lindeman E, Hultén P, Ström S, Enlund M, Al-Saffar Y, Helander A. Increased abuse of the drug drug MDPV in Västmanland. Severe cases of poisoning have given healthcare major problems.
  10. Läkartidningen. 2012 Oct 24-Nov 6; 109 (43-44): 1954-7.
  11. Murray BL, Murphy CM, Beuhler MC. Death following recreational use of designer drug “bath salts” containing 3,4-Methylenedioxypyrovalerone (MDPV). J With Toxicol. 2012 Mar; 8 (1): 69-75.
  12. Penders TM, Gestring RE, Vilensky DA. Intoxication Delirium following Use of Synthetic Cathinone Derivatives. The American Journal of Drug and Alcohol Abuse. 2012: 38 (6) 616-617.
  13. Ross EA, Reisfield GM, Watson MC. Psychoactive “bath salts” intoxication with methylenedioxypyrovalerone. The American Journal of Medicine. September 2012, 125: (9) 854-858.
  14. Schneir AB, Cullen J. Ly, BT. “Spice” Girls: Synthetic Cannabinoid Intoxication. The Journal of Emergency Medicine 2011; 40 (3) 296-299.
  15. Wood DM, Davies S, Puchnarewicz M, et al. Recreational use of 4-methylmethcathinone (4-MMC) with associated sympathomimetic toxicity. J With Toxicol 2010; 6: 327-330.
  16. Wood DM, Greene SL, Dargan PI. Clinical pattern of toxicity associated with the novel synthetic cathinone mephedrone. Emerg Med J 2011; 28: 280-282.
  17. Piper BJ. A developmental comparison of the neurobehavioral effects of ecstasy (MDMA). Neurotoxicol Teratol. 2007 Mar-Apr; 29 (2): 288-300.
  18. Bankson MG, Cunningham KA. 3,4-Methylenedioxymethamphetamine (MDMA) as a unique model or serotonin receptor function and serotonin-dopamine interactions. J Pharmacol Exp Ther. 2001 Jun; 297 (3): 846-52.
  19. Montoya AG et al. Long-term neuropsychiatric consequences of “ecstasy” (MDMA): a review. Harv Rev Psychiatry 2002 10 (4): 212-20.
  20. Karlsen SN, Spigset O, Slördal L. The dark side of ecstasy: neuropsychiatric symptoms after exposure to 3,4-methylenedioxymethamphetamine. Basic Clin Pharmacol Toxicol. 2008: 102 (1): 15-24.
  21. Dar KJ, McBrien ME. MDMA-induced hyperthermia: report of a fatality and review of current therapy. Intensive Care With 1996; 22 (9): 995-6.
  22. Bråbäck L, Humble M. [Young woman dies of water intoxication after taking one tablet of ecstasy. Today’s drug panorama calls for increased vigilance in health care] Medical Journal 2001; 98 (8): 817-9.
  23. Parrott AC. Recreational Ecstasy / MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol Biochem Behav. 2002; 71 (4): 837-44.
  24. Stolaroff MJ, Wells CW. Preliminary results with new psychoactive agents 2C-T-2 and 2C-T-7. Yearbook for Ethnomedicine 1993: 99-117.
  25. Balíková M. Nonfatal and fatal DOB (2,5-dimethoxy-4-bromoamphetamine) overdose. Forensic Sci Int. (2005) 153, 85-91.
  26. Bowen JS, Davis GB, Kearney TE, Bardin J. Diffuse vascular spasm associated with 4-bromo-2,5-dimethoxyamphetamine ingestion. JAMA. 1983; 249 (11): 1477-9.
  27. Rammer L, Holmgren P, Sandler H. Fatal intoxication by dextromethorphan: A report on two cases. Forensic Sci Int. 1988; 37 (4): 233-6.

Published with permission from Internetmedicin AB


GHB


By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


GHB is a liquid chemical that is used as an intoxicant among many young people to get an alcohol-like strong jagg. The abuse of GHB has been global since the 1990s with dispersed endemic eruptions in various countries including the United States, Switzerland, Spain, Norway and Sweden. During 2014, GHB or GBL seizures were reported by 18 countries in Europe. The 1 243 seizures amounted to 176 kg and 544 liters of drug, where Belgium (40 per cent) and Norway (34 per cent) each accounted for more than one third of the seizures.

GHB is classified as a narcotic agent in Sweden and several other countries and forbidden to use freely since 2000. GHB abuse has been intense in some regions between 2000 and 2010 but has decreased significantly since then. Certainly, addiction still occurs to a lesser extent. Some nearby chemicals that are also abused as intoxicants are GBL and butandiol.

GHB as an abusive agent is usually taken in a translucent oral solution and is most used by caucasian men aged 20-30 years.

GHB (gamma hydroxybutyrate) is an organic acid and a derivative of carboxylic gamma butyric acid. In medical use, GHB is legally used as a drug for narcolepsy in some countries, even against alcoholic abstinence, especially for its strong sleep inducing properties. GHB is registered as a pharmaceutical drug in Sweden on the indication narcolepsy, the product name is Xyrem (sodium oxibate) 500 mg/ml. As an abusive agent, GHB is often termed “Oxybate” or “Sodium oxybate”. Common preparations include “Xyrem, Alcover, Anesthetic, Gamanest, Gioron, Somsanit”.

GHB is usually consumed in a translucent solution, slightly soggy or oily to the consistency. The solution is clear or straw yellow to the color. GHB smells a bit like solvent, much like linoleum carpet, and usually tastes a bit of salt.

Intake of 0.5-2 centiliter GHB (20-30% solution) gives a rest with a euphoric and relaxing effect, similar to a mixture of benzodiazepines and alcohol. The drug is absorbed most in liquid form but is also sold in crystalline form in capsules. The intoxication is boosted by alcohol and sleepers, and it is common for other illegal drugs to be taken at the same time as GHB. GHB has many nicknames, such as “Gobby”, “Liquid Ecstasy” and “Soap”.

Recipes for making GHB are available on the Internet and the drug can easily be made from chemicals in a standard kitchen. GHB can be cooked by GBL (gammabutyrolactone) and sodium hydroxide (caustic soda). Ready-mixed GHB in solution is usually consumed from a blank Sprite or Coca-Cola bottle (PET bottle). The finished solution is capsized (“cork”), a common drug addiction is one to two capsules (0.5-2 centiliter equivalent to about 2-4 g [200 mg/ml]) GHB. A dosing dose may vary between a few grams up to 18 grams.

In Gothenburg’s drug survey among school students in 2013, the proportion of young people who tested GHB has decreased in recent years. In 2013 it was 2% of those who tried any drugs. In 2014, 0.4% of boys and 0.1% of girls in grade 2 reported that they ever tried GHB. Abuse has fallen sharply in recent years. Many cases have presented as dramatic and severe acute cases with either unconsciousness, cramps and respiratory distress or with marked aggressiveness, general disorder and psychomotor irritability.

Pharmacology

GHB occurs naturally (endogenously) in the body as a substrate (precursor) of GABA in very small amounts and affects p. a vigilance and cramping threshold. GHB rapidly passes the blood brain barrier and causes a central nervous effect on predominantly monoaminergic synapses affecting dopamine and specific GHB receptors. GABA is a chemical transmitter substance for about 30% of all CNS cells. GABA is essentially a sedative signal in its functions and affects several other neurotransmitters, including dopamine. GHB binds mainly to specific GHB receptors that are excitatory as well as to GABAB receptors. GHB releases both dopamine and glutamate. Therapeutic serum concentrations of GHB are not fully known, but it is believed that around 100 mg/L gives an euphoric state and over 500 mg/L may produce a life-threatening condition. Large inter-individual differences occur.

Clinical effects

Intake of GHB produces clinical effects similar to a mixture of alcohol and benzodiazepines. The feeling of intoxication occurs 10-20 minutes after intake with maximal effect after 30-60 minutes, which gives a significantly slower turnout than alcohol. GHB causes intoxication, drowsiness and euphoria. In the high dose, unconsciousness and sometimes cramps and muscle twitching, both of the muscular jerks, “petit mal” and “grand mal” occur. It is common with anxiety, muscle twitches, involuntary movements, stubbornness and aggressiveness. Strange choreo-athetotic movements have been observed and documented.

  • GHB provides small amounts of euphoria and increased well-being but also increased self-esteem, sexual stimulation and reinforced male identity (“macho effect”, “reinforcement”).
  • Taking a moderate dose GHB gives an alcohol-like intoxication that is initially uplifting, relaxing and then heavily sedative.
  • GHB can give a sense of relaxation, calm, peacefulness, increased sensuality, mild excitement, positive kicking, “increased verbality” and muscle weakness.
  • Repeated intake of GHB over time can rapidly give rise to tolerance development with intake of increasing doses.
  • The risk of dependence and addiction is significant.
  • GHB can relatively quickly cause physical and mental dependency (within 3-6 months).
  • The drug usually leaves no hangover (rather you feel well the day after) and have low organ toxicity.

Side effects of GHB addiction may include

  • sleep discomfort
  • drowsiness
  • dizziness
  • memory loss
  • ataxia
  • stomach pains
  • choreoatethosis
  • mental depression
  • nausea, vomiting
  • impotence
  • blood pressure drop
  • headache

Abuse causes significant withdrawal symptoms.

Concentration of the solution and dosage

  • Regular dose is 0.5-4 centiliter (20-30% solution) with large individual differences and variations in solution strength.
  • A capsule of GHB gives an intoxication corresponding to about 2 cans of beer and last for about an hour.
  • Two capsules can lead to sleep within 20-30 minutes.
  • Three to four capsules can cause coma for 3-5 hours.
  • Five to six capsules can lead to deep coma (GCS < 6), respiratory depression, slow heart rate (bradycardia) with risk of seizures and sudden death.
  • Boys/men appear to tolerate higher doses compared to girls/women.
  • GHB induces significant tolerance development after 1-6 months of use.

The concentration of potable GHB varies considerably between different solutions. A common strength is 20-30% GHB in liquid form (source NFC). GHB has a narrow dose range (narrow therapeutic window), giving varying effects of intoxication from time to time, and is very easy to overdose. Large differences in individual tolerance occur and the above effects refer to an above user. An addict with tolerance tolerates a significantly greater amount for the corresponding symptoms.

Symptoms of overdose

  • drowsiness
  • inebriation
  • fast-acting sleepiness
  • fluctuating alertness (waking up/descending periodically is a relatively typical phenomenon)
  • absence periods (absenses)
  • nausea
  • vomiting
  • shake
  • dizziness
  • muscle spasms
  • ataxias
  • choreoatetoses
  • short-term unconsciousness
  • slow pulse (40-60 bpm)
  • motor restlessness
  • flattening
  • affectability, aggressiveness

A big overdose may give

  • fast-acting sleepiness
  • fluctuating alertness
  • unconsciousness, coma
  • small pupils, ophthalmoplegia
  • blood pressure fall
  • slow heart rate bradycardia
  • ECG, possibly AV block I-III or high QRS amplitudes
  • irregular pulse
  • slow and irregular breathing respiratory depression
  • general cramps
  • vomiting
  • risk of aspiration of gastric contents in the lungs
  • hypothermia
  • apnea
  • hypoxia
  • cardiopulmonary arrest

EMERGENCY CARE

The treatment for acute overdose is mainly symptomatic and no antidote is present. Vigilance and breathing may fluctuate. GHB poisoning usually has a pronounced dynamic process of rapid fluctuations in alertness. Seizures, muscular cramps, nausea and vomiting are relatively common. Insufficient breathing is supported by endotracheal intubation and respiratory support in an intensive care unit.

The most important thing in the treatment is:

  • careful monitoring of alertness, oxygen saturation and breathing
  • support of respiration and circulation when needed
  • treat hypoxia with oxygen
  • ensure free airway (nasal tube, orofaryngeal advice or endotracheal tube, intubation when needed)
  • treat blood pressure drops with intravenous fluid and, if necessary, antihypertensive drugs (ephedrine, norepinephrine)
  • Provide a reasonable degree of sedation if necessary
  • treat acute confusion and motor anxiety in a calm and safe way
  • Put the patient at the correct care level
  • conduct a follow-up investigation and treatment of addiction problems through psychiatry, dependency clinic and social services

Gastric lavage and installation of activated charcoal are of limited value and should be avoided.

Sleeping/comatous patient

If the patient is sleeping deeply and can not be awakened, he or she should be supervised in an intensive care unit (ICU) with readyness for intubation. If vital parameters are stable and the patient breathes calmly and regularly, monitoring is usually enough and the patient is allowed to sleep off. If the patient keeps the airway in the backrest and oxygenates well, it is usually not necessary to go to the ICU, but note that the awakening may deteriorate suddenly and dramatically.

Another reason for deep unconsciousness should be ruled out. Check electrolytes and an arterial blood gas. Perform CT scan with x-ray in case of doubt or in focal neurological symptoms.

In GHB poisoning, the patient is sleeping deeply for 1-5 hours. Longer unconsciousness than 6 hours usually depends on other causes, such as mixed poisoning with other drugs. The wake up usually takes place fast and the patient feels quickly restored. The patient can usually be discharged to the home.

If the patient is worried during the awakening phase, the patient should be sedated to prolong the sleep and provide a calmer awakening. The patient may be dosed with diazepam or midazolam 1-2 mg intravenously (1 mg/ml) or olanzapine (10-20 mg i m). In some cases, the condition passes into an emergency withdrawal phase that may be pronounced and require emergency withdrawal treatment.

Indications for treatment at the ICU

  • Significant alertness reduction
  • RLS 3 or higher value
  • GCS lower than 10
  • Significantly worried or confused patient
  • Sudden consciousness reduction
  • Inability to keep free airway
  • Cardiac arrhytmias or heart failure
  • Hypoxia (<90%)
  • Respiratory rate less than 10 or greater than 30 breaths per minute
  • Pulse below 50 or over 130 beats per minute
  • Systolic blood pressure below 90 mmHg despite fluid
  • General seizures
  • Pronounced metabolic acidosis

Drug screening and blood/urine sampling

Do a drug screening on the urine to detect joint poisoning and other possible causes of unconsciousness. Send urine or blood samples to clinical chemical laboratory for GHB analysis with GC-MS (gas chromatography mass spectrometry). GHB can also be analyzed by a new immunohistochemical analysis that can determine GHB poisoning on the day of the test. GHB is available on some quick screening for drug screening.

Agitated and restless patient

If the patient is agitated and restless, the patient may be sedated with midazolam (Dormicum 2-5 mg i.v.) or propofol i.v., which may be repeated. Even sedating psychotropic drugs have been successfully used in the acute phase, such as droperidol (Dridol) 10 mg i.m. or olanzapine 10-20 mg i.m. Heminevirin (clomethiazole) should be avoided completely.

Note that the alertness fluctuates and the patient can quickly become unconscious with insufficient breathing.

If the patient is heavily agitated and/or violent, one may be forced to fully sedate the patient and put him or her in the respirator. You can then start with midazolam (Dormicum) 5 mg i.v. and then give propofol 50-300 mg i.v. as needed until the patient is sleeping easily. These patients usually require continuous infusion of propofol for 5 to 8 hours in an intensive care unit. One then gives 100-400 mg per hour and controls the rate of infusion after the onset. The patient should be monitored in the ICU and the respiratory tract must be secured by endotracheal intubation and ventilator treatment. Then you can ease the sedation and extubate when the patient wakes calmly and peacefully.

Sedation of the patient with propofol intravenously should only occur if the situation is unsustainable with immediate danger to the patient’s life (emergency warn). This usually requires active involvement of anesthetic physicians and intubation with respiratory treatment for at least 4-6 hours. Consider the act on compulsory psychiatric care.

If the patient’s vigilance change, “typically for GHB overdose” does not change after 3-5 hours, another diagnosis should be considered. Check other toxicity tests, such as electrolytes (hyponatraemia), β-glucose, and an arterial blood gas. Consider X-ray with CT brain.

Agitated and restless patients should not be released from emergency care while they are still drug-affected because they can be violent and uncontrolled both against themselves, relatives and staff.

Withdrawal phase

If the patient exhibits abstinence with anxiety, hallucinations, shaking, nausea, headache or psychotic symptoms, acute detoxification may need to be performed. The patient should then be taken care of, preferably in a psychiatric department or at a dependency unit. Acute severe withdrawal can follow immediately on acute overdose.

The first day may require sedation with inj. midazolam or propofol. Then you can use diazepam tablet or tablet lorazepam. The patient usually needs high doses of diazepam for the first few days. The appropriate starting dose is 60 mg/day or more (Sic). When treated with Propofol, the patient should be treated in an intensive care unit (ICU).

Zuclopentixol (Cisordinol) can be given in the form of Cisordinol-Acutard 50 mg/ml 1 ml, alternatively, olanzapine (Zyprexa) 10 mg x 2 or more, alternatively risperidone (Risperdal) 1 mg x 2, is given if the patient has hallucinations or severe agitation.

If you need immediate effect, you can instead give haloperidol (5 mg/ml) one to one milliliter (2.5-5 mg) i.v. or i.m.

In a later phase, one may need to add an antidepressant, such as mirtazapine 30 mg x 1 or sertraline 50 mg x 1. Mirtazapine has a relatively strong sedation effect. Sertraline also has a sedative effect, especially at the beginning of a treatment or in high doses. Treatment with an antidepressant drug makes it possible to correct the sleep disorder that is common in long-term GHB addiction. Problems with sleep are those that often concern patients most. Many patients with GHB addiction develop a depression that may be pharmacologically demanding.

Note that caution should be exercised in the outpatient clinic prescription of large doses of benzodiazepines to GHB addicts while taking GHB together with benzodiazepines may be highly respiratory depressant. Flunitrazepam should be avoided completely.

FOLLOW-UP

A psychiatric and social follow-up of patients with established GHB addiction is important, as drug abuse, alcohol and drug abuse is common. A care and treatment plan should be established. Returning to psychiatry in dependent care or social services is desirable. Referral should always be written to the social services. Disapproval of suicidal thoughts and increased suicidality occur.

Abuse of central stimulants (amphetamine, cocaine, ecstasy) or alcohol is common among patients with GHB addiction as well as general social unrest. Cases with adolescents under the age of 18 should be reported to social authorities and child and adolescent psychiatric clinic. Even school healthcare may need to be connected.

In case of repeated acute overdosage, notification to the social services should be made urgently and care under the act on compulsory psychiatric care is immediately considered.

Persistent disabilities

A GHB overdose usually does not last but unless serious complications occur as respiratory aspiration, cramps, apnea or hypoxia. However, if respiratory arrest with hypoxia has occurred, severe disabilities may persist.

A transient sleep disorder with severe sleep difficulties for 3-4 weeks is common. A subsequent depression is also common.

Other side effects described are stomach ache and impotence. Dependence may require treatment for several months.

ICD-10

  • Mental disorders and behavioral disorders caused by sedatives and hypnotics, acute infections F13.0
  • Other psychotropic agents not classified elsewhere T43.8

Sick leave

Links to medical insurance decision support from the National Board of Health and Welfare:

F13 Mental disorders and behavioral disorders caused by sedatives and hypnotics

 

References

  1. Persson S-Å, Eriksson A, Hallgren N, Eklund A, Berkowicz A och Druid H. GHB – farlig, beroendeframkallande och svårkontrollerad ”partydrog”. Läkartidningen Nr 38 2001 Vol 98 4026-34.
  2. Engelsen J & Rolighed Christensen H; Gammahydroxybutyrat en endogen substans og et nyt rusmiddel. Ugeskr Laeger 199;161:6903-7.
  3. Liechti ME, Kupferschmidt H. Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL): analysis of overdose cases reported to the Swiss Toxicological Information Centre. Swiss Med Weekly. 2004 Sep 4;134 (35-36):534-7.
  4. Caldicott DG, Chow FY, Burns BJ, Felgate PD, Byard RW. Fatalities associated with the use of gamma-hydroxybutyrate and its analogues in Australasia. Med J Aust. 2004 Sep 20;181(6):310-3.
  5. Couper FJ, Thatcher JE, Logan BK. Suspected GHB overdoses in the emergency department. J Anal Toxicol. 2004 Sep;28(6):481-4
  6. Dyer, J.E., Roth, B., Hyma, B.A. Gamma-hydroxybutyrate withdrawal syndrome. Ann Emerg Med 2001;37:147-153.
  7. Knudsen, K., Greter, J., Verdicchio, M. High mortality rates among GHB abusers in Western Sweden. Clinical Toxicology 2008;46:187-192.
  8. Knudsen, K., Greter, J., Verdicchio, M., Cederquist, T. [GHB, GBL and butanediol poisonings–a serious problem in Western Sweden]. Lakartidningen 2005;102:3294-3296.
  9. Liechti, M.E., Kunz, I., Greminger, P., Speich, R., Kupferschmidt, H. Clinical features of gamma-hydroxybutyrate and gamma-butyrolactone toxicity and concomitant drug and alcohol use. Drug Alcohol Depend 2006;81:323-326.
  10. Skolelevers drogvanor, CAN rapport nr 146, Centralförbundet för alkohol- och narkotikautvecklingen, Stockholm 2014.
  11. Skolelevers drogvanor 2013. Kunskapskällaren 2013, rapport 2013:1. Göteborgs Stad, Social resursförvaltning.

Published with permission from Internetmedicin AB


Snake Bites – Envenomation

By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2019-01-24


Bites of poisonous snakes in Sweden comes mainly from the Scandinavian viper (Vipera berus) which is the only poisonous species that occurs naturally in this country. Snake envenomation occurs most commonly along the coasts, especially during summer time. About 70 patients per year are admitted to hospital in Sweden for care after snake envenomation. Adult Scandinavian viper grow around 60 cm long, are gray or light brown with a characteristic black zigzag pattern over the back but the snake can also be completely black or gray. Younger copies may also be reddish brown. Scandinavian viper can sometimes be confused with the smooth snake, however, this snake has a round pupil unlike the viper that has a vertical slit-shaped pupil. The smooth snake is usually bigger than the vipers and can be over one meter in length. The smooth snake usually has two yellow, white or oily yellow spots in the neck.

The Vipera berus poison contains a series of proteolytic enzymes (proteases, peptide hydrolases, hyaluronidase, phospholipids, phosphodiesterases, and L-amino acid oxidase) which mainly give local symptoms such as swelling, pain and bleeding but can also give general symptoms of dizziness, nausea, vomiting, respiratory distress and shock. The venom is hemorrhagic and necrotising but not neurotoxic. Scandinavian viper venom can cause pronounced focal necrosis with blisters, especially in the fingers and toes, but the reaction usually limits to moderate redness and swelling and a characteristic fang mark. The serpent’s teeth are about 4 mm long and cause a typical bite mark with 2 fang marks (6-9 mm). The venom can also lead to bleeding, thrombosis and a disseminated intravascular coagulation (DIC condition).

Venomous snakes are usually divided into viperidae and elapidae (poisonous snake). Among the viperidae are European vipers, including the Scandinavian viper and Russel’s viper. Among the elapida species are cobras, mambo, coral snakes, taipans and krait (Australia, Asia, Southeast Asia). Most elapidal venom produce neurotoxic effects, whereas viperidal venom mainly cause muscle decomposition and coagulation effects including disseminated intravascular coagulation (DIC). In Sweden, about 200 bites per year occur, which results in a single death every decade, the last known death case was in 2000. Throughout Europe, mortality is estimated at 30-50 people per year. The mortality of viper bites is as low as 1-2 per cent and decreases steadily.

A series of exotic snakes are found in both private and public terraries. Treatment of bites of tropical venom snakes is therefore not quite unusual in Sweden. Rules for permission to hold a poison in private ownership vary around the country and is determined by the regional health authority. It is estimated that no less than 120 different species of venomous snakes are found in Sweden.

Most of the tropical venom can cause life-threatening symptoms that may require treatment with a specific antidote. There are about twenty specific serum available in Sweden. These twenty different sera cover most of the different snakes in the country. Several sera are polyvalent, ie cover more than one kind of snake venom. On the other hand, snakes of the same species but different types, such as rattle snakes, may require treatment with different types of serum. Specific monovalent sera with fractionated antibodies have the best effect with least side effects. Serum with fractional antibodies produces significantly fewer allergic reactions compared to unfractionated serum (eg Zagreb serum). It is therefore important for treatment of snake bites to identify the snake so that the right kind of snake serum is used. Experts who can identify the snake are found at the Skansen aquarium in Stockholm and Universeum aquarium in Gothenburg.

Antivenom serum are usually available in larger hospitals, but accessibility may vary widely. Please note the best-before date. Regional Poisonos Information centres will help to request applicable sera. Pharmacy Scheele in Stockholm has a central stock of snake sera, and from here you can request serum if necessary. Any serum from the pharmacy Scheele can reach all healthcare institutions around Sweden within 4-6 hours of emergency care.

The mortality of tropical snakes varies between different countries and with different snakes. In Africa, Southeast Asia and India, mortality is significantly higher than in Europe, which is due to longer distances to medical treatment and poorer accessibility to relevant sera.

There are significantly more deaths in Asia compared to Australia where only 2-3 deaths per year take place.

Among the world’s most toxic snakes are king cobra, black mamba and Australian (brown) taipan. Sea snake venom can also be higly toxic. The toxicity between different variants of the same species can vary considerably, for example different cobra species. General symptoms become more pronounced when the bite site is more centrally located on the body, for example on the trunk and around the head. Older people and young children are generally more sensitive as well as asthma and allergy sufferers. Local symptoms are more pronounced on the extremities. The most common bite site are on the feet and hands. The risk of compartment syndrome increases at peripheral bites, for example in a hand or foot. It is more common for men to be bitten than women. In different studies, snake bites have been more than twice as common among men as among women. Snake bite is the most common in the age 20-50 years.

SYMPTOMS

The symptoms are usually local and/or general. General symptoms indicate serious poisoning. Approximately 25% of the hip-body bites give general symptoms and 75% only local symptoms in the form of redness, swelling and pain around the bite site. Bite of Swedish viper is similar to the bite of many exotic snakes, but most of the snake bites produces only local symptoms. In a Swedish study of 231 cases, the serious bite was 13% of all cases and 29% had moderate symptoms (Karlsson-Stiber, 2006).

Common symptoms of snake bites are pain followed by swelling and discoloration. The pain is often intensive and requires strong analgesics (morphine). Some tropical snakes like “asian krait” injecting a neurotoxic poison can cause severe paralysis including respiratory paralysis without significant local symptoms or pain.

Snake venom is mainly hemorrhagic, necrotic or neurotoxic. This varies with the nature of the snake but dominant symptoms are often a local swelling, pain, discoloration and in pronounced cases a necrotization of the tissue. Hemorrhagic toxin causes more extensive tissue damage with swelling, haemorrhage and necrotisation versus neurotoxin. The risk of developing a compartment syndrome is significant due to snake bite in the arms and lower legs. Neurotoxic venom (cobra, multiple-banded krait) may in the worst case result in complete paralysis with respiratory insufficiency and need for assisted ventilation and respiratory care.

Snake venom is spread mainly through the lymphatic tissue. Hemorrhagic snake toxicity affects blood clotting ability and may induce increased bleeding tendency and disseminated intravascular coagulation (DIC) (especially Russel viper). However, some snakes may cause bleeding disorder with thrombocytopenia without DIC. It is important to check the patient’s status regarding bleeding both clinically and in laboratory parameters. In the case of bites of highly toxic tropical snakes, both initial and initial samples of coagulation may be completely normal for complete 24-hour full thrombocytopenia and increased bleeding tendency. Check the bleeding effect of the oral mucosa, the eye and retroperitoneum, where major spontaneous bleeding may occur in clinical signs of bleeding (CT scan).

Swelling after a snake bite may vary considerably and progress for several days. Swelling that spreads over a larger joint, such as the elbow at the bite of the hand or the knee at the bite in the foot is a sign of serious bite and is an indication of serum treatment. The swelling itself can create a compartment syndrome in, for example, in a hand or a leg. The compartment syndrome may require surgical intervention with fasciotomy (preferably not) but the venue should be left alone in peace and not cut or dipped. On the other hand, the pressure in the tissue should be measured in compartment syndrome.

The discoloration often becomes hemorrhagic, red-blue or dark transient to black upon necrotization of the tissue. The necrotization includes skin, soft parts and deeper parts. Fingers may need to be amputated partially or completely. The discoloration and swelling can be extensive even without necrotising, sometimes over a whole leg and above the bonfire.

At the bite site there are usually but not always traces of two fangs with 0.5 to 2 c m distance. The distance between the teeth can provide guidance on what snake that bites and the size of the snake. There may be both one, two and three punctual or stamped marks (“fang marks”).

Local symptoms

  • Pain
  • Swelling
  • Discoloration (hemorrhagic, echymose)
  • Numbness
  • Paralysis, paralysis
  • Paresthesia
  • Necrosis
  • Bleeding
  • Compartment Syndrome

General symptoms

  • Nausea
  • Vomiting
  • Worry, strong fear
  • Anxiety, hyperventilation
  • Pain
  • Fainting
  • Heart valve, tachycardia
  • Hypotension (blood pressure drop)
  • Circulatory shock
  • Dyspnoea, bronchoconstriction, obstructivity
  • Allergic reaction
  • Coagulation effect, general DIC condition

Main recommendations and general measures

When an injured person comes in with a bite of a snake, this should be dealt with promptly.

In case of serious injury, inform the following persons immediately:

  • Responsible emergency doctor at the emergency room
  • Current back-up at emergency room
  • Anesthetic or intensive care personel

If possible, also contact:

  • Your local Poisons Information Center
  • Pharmacists providing the hospital’s antidote stock
  • Police or Emergency Services to catch snakes that came loose
  • Snake expert to identify the actual snake if unknown

Patient care

  • Ensure that all patients with snake bites enter hospitals and do not wait in the home even at mild bites.
  • The patient should be disposed of immediately and must not be left unattended. Even in a relatively unaffected person, severe symptoms may occur suddenly.
  • Responsible physician decides in consultation with ICU journals on insertion at ICU. In case of serum treatment, insertion and treatment is recommended in an intensive care unit.
  • Snake serum can be obtained urgently from Pharmacy Scheele in Stockholm with urgent air or taxi transport. Scheele usually handles a delivery within 3 hours. The Skansen aquarium in Stockholm and some other private terrariums provide some sera that are active in the bite of exotic snakes. Snakes are usually polyvalent, ie they are active against more than one type of snake. Check expiration date and durability. Certain sera are considered durable certain time even after the expiration date.

TREATMENT

General practice

  • Create peace and quiet for the patient. The patient should sit or lie, even during transport. Try to prevent the patient from panic. Give sedatives or analgesics if necessary. For example, diazepam (5-10 mg i.v.) in anxiety and anxiety or morphine/ketobemidone (Morphine) (5-10 mg i.v.) in pain and anxiety. The patient must not run on the way to a hospital.
  • Eventually compression bandages. In some countries, such as Australia, routinely, a firm elastic bandages over the limb extremity to prolong the resorption of the toxin and counteract the edema formation. The bandage is placed around the extremity, beginning distally and winding in the proximal direction. It counteracts the spread of the snake venom, as well as decreases the edema formation. The bandage must not be detrimental. The bandage is usually not removed until the patient has received a serum. The idea is that antibodies should be in the blood when the antigen (the snake venom) enters the system circulation. Compression bandage work better after bites of neurotoxic snakes than necrotizing hemorrhagic snakes. As a rule, it is therefore more applicable to bites of Australian or Asian snakes than European, African or American snakes. Better at the bite of elapidae than viperidae.
  • Immobilize the bit body part, in high position after winding. When bitten in the hand, the hand can be placed on top of a pillow or hung up in a mitella.
  • Leave the betting site intact.
  • Obtain specific snake serum in case of serious envenomation. Treatment should commence within 12 hours after the snakebite, preferably within 4 hours. In case of pronounced general effect, serum treatment should be initiated as soon as possible. Chock can develop within 30 minutes of the snake bite but is more common after 2-3 hours.
  • Tetanus protection is recommended but scientific evidence is very weak.
  • Antibiotic treatment is recommended only for symptoms of infection. Routine treatment with antibiotics is not required.
  • Exceptional comments from the patient like “it’s not so dangerous”, “I’m just fine” are common and should be ignored!

Avoid the following

  • Epidural. In case of pain in the leg, epidural should be avoided as there is an increased risk of general thrombosis/bleeding complications.
  • That the patient himself drives a car to a hospital
  • Do not suck, cut, cool, heat or diatrate the betting site.
  • That the patient runs or strives on the way to the hospital
  • Narrow dressing, avoid winding from top to bottom.
  • Hysteria and panic
  • Treatment with unclear or outdated antivenom in the bite of unidentified snakes.
  • Treatment with antivenom sera as only moderate local symptoms are present.

Treatment of mild bites

When only local redness and swelling are present.

The patient is treated at the emergency department and the Medical Emergency Department or equaI ICU. Patients belonging to any risk group, ie old, weak, young children, and asthmatics should be observed for at least 8 hours before discharge.

  • The patient is handled by the attending medical physician.
  • Insert at least one peripheral venous cannula. Take Hgb, wbc, platelets and urine sticks. If necessary, i v fluid, for example, Ringer’s Acetate.
  • Include all children and generally affected patients in hospitals for at least one day.
  • Unaffected patients should be observed for at least 6-8 hours.
  • Corticosteroids (Solu-Cortef, 100 mg x 1 i.v. or i.m.). Scientific evidence is insufficient for treatment with steroids in snake envenomation but is a well-proven routine and is recommended primarily in allergic symptoms, bronchospasm or after treatment with horse-based serum. Probably also beneficial in the event of a significant inflammatory reaction.
  • Antihistamine, for example Klemastin (1 mg i.v). Please note that treatment may be sedative. Scientific evidence for effect is weak.
  • Morphine/Ketobemidone (5-10 mg i.v.) in pain.

Check and follow blood samples, observe occurrence of:

  • Metabolic acidosis (arterial blood gas analysis)
  • Hemolysis (S-haptoglobin, LD), leukocytosis, thrombocytopenia
  • Rhabdomyolysis (serum myoglobin, CK)
  • Hb, wbc, TPC, CRP, PK/INR, APTT

Treatment of serious bites

Strong local reaction or clear systemic effect is present (cloudy consciousness, low blood pressure (systolic blood pressure < 90 mm Hg), high pulse rate, high respiratory rate).

Patients with prechock/shock are treated in an intensive care unit (ICU). Check the bleeding parameters carefully after arrival and after 12 and 24 hours.

  • Corticosteroids (100-200 mg i.v.).
  • Give antihistamine preparation (1 mg i.v. x 2). Please note that treatment may be sedative. Scientific evidence for effect is weak.
  • Give serum antivenom treatment, see instructions below.
  • Immobilization of a bit body part, preferably in high position. When biting your hand, raise your arm high in a mitella to a bedpost or the like.
  • Morphine/ketobemidone (5-10 mg i.v.) in pains. Note that the treatment itself may be sedating.
  • In case of allergic/anaphylactic reactions or bronchospasm, give adrenaline (1 mg/ml, 0.3-0.5 ml i.m. on the outside of the thigh).
  • In bronchospasm, administer beta-stimulant therapy inhalation, for example salbutamol or terbutaline.
  • In the event of a circulatory shock, adrenaline may be administered intravenously, 0.1-0.5 mg (0.1 mg/ml) i.v. titrated after blood pressure.
  • Provide adequate fluid substitution, such as Ringer acetate, or dextrane containing solutions. Provide volume substitution with balanced electrolyte solution and colloids, preferably in the form of dextran. However, do not give large amounts of dextran, as this may affect the blood’s coagulation ability.
  • If dextran is not administered, other thrombosis prophylaxis should be considered, such as dalteparin sodium in a low dose (2500-5000 units s.c.) or enoxaparine sodium 40 mg s.c. regardless of weight.
  • Inotropic support and other shock treatment are given on usual indications of circulatory failure, such as infusion noradrenaline.
  • Oxygen on breathing mask or via nasal catheter.
  • Check Hb, wbc, TPC, CRP, myoglobin, INR/APTT, FDP, S-haptoglobin, LD.
  • Thrombelastogram or ACT.

Antivenom Serum Treatment

Treatment should commence within 12 hours after the snakebite, preferably within 4 hours. In case of pronounced general symptoms, serum treatment should be initiated as soon as possible. Serum treatment is the antivenom treatment that works best for severe snake bites.

Serum treatment should be given when severe general symptoms are present or when significant progress of swelling and discoloration occurs, for example over a major joint (knee joint, elbow joint).

Indications for starting serum treatment are:

  • Circulatory effect not responding to initial fluid treatment
  • Unconsciousness or reduced alertness
  • Long-term or recurring gastrointestinal symptoms
  • Bronchospasm or dyspnea
  • Progress of local reaction in the limb, the swelling passes over a joint, for example the knee or elbow within 6 hours.

In case of doubt, the following factors support the indication of serum treatment:

  • Leukocytosis >15-20 x 109
  • Metabolic acidosis
  • Bite of very toxic snakes such as some cobras, black mamba or Australian taipan.
  • Hemolysis (high LD, low haptoglobin)
  • New ECG Changes:
  • arrhythmias
  • ST-T changes
  • Other ischemic signs
  • Coagulation disorders (thrombocytopenia, high PK/INR or high APTT)

Viper bites are usually treated with antidote Vipera Tab. 2 ampoules = 200 mg are dissolved in 10 ml of sterile water and diluted in 100 ml of NaCl (9 mg/ml) and given as an intravenous infusion for 30 minutes. The same dose is given to children as adults. A second, equal dose (200 mg) may be indicated in the event of recurrence of circulatory effects or in persistent gastrointestinal symptoms, in severe coagulopathy or haemolysis, as well as in continued progression of the local reaction with risk of involvement of the throat.

In case of serum treatment after bites of tropical snakes, follow the package leaflet carefully.

In case of doubt, consult your local Poison Information Center.

Follow-up after snake bite

One to two weeks after serum treatment, an allergic reaction may occur, such as serum sickness. Invite the patient to listen to symptoms such as fever, joint pain or fatigue. Serum disease should be treated with corticosteroids.

After severe bites or when serum is given to tropical snakes, an outpatient visit is recommended 1-2 weeks after printing. Then check SR, CRP, Hgb, TPC, Creatine and wbc. Reported fatigue and impaired general condition may occur long after the snakebite as well as remaining local symptoms such as swelling and numbness with paresthesia. Referral should be planned.

ICD-10

Toxic effect of snake toxicity T63.0

References

  1. Russell FE, Carlson RW, Wainschel J, Osborne AH. Snake venom poisoning in the United States. JAMA 1975; 233(4): 341.
  2. Karlson-Stiber C, Salomonsson H., Persson H. A nationwide study of Vipera Berus bites during one year – epidemiology and morbidity of 231 cases. Clinical Toxicology 44:25-30, 2006.
  3. Forks TP. Evaluation and treatment of poisonous snakebites. American Family Physician. 1994;50(1):126.
  4. Karlsson-Stiber C. Exotic snakes on the chop here too! Medical Journal 1996; 93 (48): 4393-4399
  5. Holmen C. Tropical snakes also risk in Sweden. Medical Journal 1996; 93 (48): 4409-4411
  6. Karlson-Stiber C, Persson H. Antivenom treatment in Vipera berus envenoming–report of 30 cases. J Intern Med. 1994;235(1):57-61.
  7. Persson H, Karlson-Stiber C. Huggormsbett – klinik och behandling. Läkartidningen 1995;92:2906-10.
  8. Karlson-Stiber C, Persson H, Heath A, Smith D, Al-Abdulla IH, Sjöström L. First clinical experiences with specific sheep Fab fragments in snake bite. Report of a multicentre study of Vibera berus envenoming. J Intern Med 1997;241:53-8.
  9. Cederholm I., Lennmarken C. Vipera berus Bites in Children—Experience of Early Antivenom Treatment. Acta Pædiatrica 1987;76(4):682 – 684
  10. Persson H. Envenoming by European vipers antivenom treatment–influence on morbidity. Przegl Lek. 2001;58(4):223-5.
  11. Harborne DJ. Emergency treatment of adder bites: case reports and literature review. Arch Emerg Med. 1993 Sep;10(3):239-43.
  12. Tanos PP, Isbister GK, Lalloo DG, Kirkpatrick CM, Duffull SB. A model for venom-induced consumptive coagulopathy in snake bite. Toxicon. 2008 Dec 1;52(7):769-80.
  13. Currie BJ, Canale E, Isbister GK. Effectiveness of pressure-immobilization first aid for snakebite requires further study. Emerg Med Australas. 2008 Jun;20(3):267-70.
  14. Kuruppu S, Smith AI, Isbister GK, Hodgson WC. Neurotoxins from Australo-Papuan elapids: a biochemical and pharmacological perspective. Crit Rev Toxicol. 2008;38(1):73-86.
  15. Whitehall JS, Yarlini, Arunthathy, Varan, Kaanthan, Isaivanan, Vanprasath. Snake bites in north east Sri Lanka. Rural Remote Health. 2007 Oct-Dec;7(4):751.
  16. Sutherland SK, Coulter AR, Harris RD. Rationalisation of first-aid measures for elapid snakebite Lancet 1979 Jan 27;1(8109):183-5.
  17. Currie BJ. Treatment of snakebite in Australia: the current evidence base and questions requiring collaborative multicentre prospective studies. Toxicon. 2006 Dec 1;48(7):941-56.

Mushroom Poisoning

By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2019-01-26


In the Scandinavian region, about 10,000 different fungi grow in nature, of which only one hundred are edible. Mushrooms grow not only in the soil but also on stumps and trees, on plants and other biological organisms and in many other places. The total number of species on earth is estimated to exceed one million. Mushrooms consist of rootlets, a mycelium and a fruit body. It is usually the fruit body that we call fungus and is the part that is eaten.

Mushroom poisoning usually occurs after ingestion of toxic fungus, which has been confused with edible fungus. In rare cases, poisoning occurs in other ways, for example, by smoking of hallucinogenic fungi or after inhalation of vapors in the presence of parboiling. Some common edible fungi are chanterelle, truffle mushroom, “penny bun” (Boletus edulis), and skiitake mushroom.

Estimately, 50-200 people seek medical care in Sweden for suspected fungal poisoning every year. Serious poisoning is unusual, but occasional serious cases occur annually. Deaths are very rare and occur sporadically.

Mushroom poisoning is most common during the mushroom season that is during autumn. Poisoning can, however, pop up all year round, for example, the False morel (Gyromitra esculenta) is a spring sponge. Funnel chanterelles (Cantharellus tubaeformis), sometimes confused with Deadly webcap (Cortinarius rubellus), grow mostly late in the fall. In case of poisoning, please call your local Poison Information Center for advice. Store current sponge for identification of fungus expert. In recent years, a number of cases of severe fungal poisoning have occurred among newly arrived immigrants, both in Sweden and other countries such as Germany and the United States. Inedible Swedish mushrooms have often been confused with edible fungi from their homeland.

Classification and diagnosis

In Sweden, a number of poisonous fungi grow among the most toxic ones:

  • Destroying angel (Amanita virosa) grows in coniferous forests, above all in spruce forest. May be confused with Scaly Wood Mushroom, Blushing Wood Mushroom or Pinewood Mushroom (Agaricus silvaticus)
  • Death cap (Amanita phalloides) grows in oak and beech forest. May be confused with Grass-green russula (Russula aeruginea)
  • Deadly skullcap (Galerina marginata) grows on rotten wood. May be confused with Sheathed woodtuft (Kuehneromyces mutabilis)
  • Deadly webcap (Cortinarius rubellus) grows in mossy spruce forest. May be confused with Funnel chanterelles (Cantharellus tubaeformis)
  • False morel (Gyromitra esculenta) grows in the woods, even in sandy fields. Can be confused with Black morel (morchella conica).

Toxic mushrooms are usually grouped according to the toxin they contain. The main groups of toxins are: cytotoxin, neurotoxin and gastrointestinal irritant toxin (see Table 1).

Cytotoxins

To the cytotoxins, the toxic substances include orellanine, amatoxin and gyromitrin. Cytotoxic fungi are, for example, False morel, Destroying angel, Death cap, Deadly skullcap and Deadly webcap. Destroying angel and Death cap (amatoxin) are most toxic and causes several serious poisonings, sometimes even deaths, every year. Deadly webcap are mainly causing renal injury by its toxin orellanine. Amatoxin and orellanine cause cell damage in above all in the liver, bowel and kidneys. The fungi also contain hemolysins that can cause haemorrhage with skin and bowel bleeding.

Ingestion of cytotoxic fungi is usually associated with longer latency between intake and symptom debut than neurotoxic and gastrointestinal fungi. The time between ingestion and the onset of symptoms can provide guidance on the type of poisoning that has occurred. Cytotoxic fungi generally give a latency of 8-24 hours from ingestion to symptom debut. In some cases, latency may be longer when symptoms are due to organ damage, symptoms may only start after 3-7 days.

Neurotoxins

For this toxin type, for example, the substances include muscarine, ibotenic acid, muscimol (also known as agarin or pantherine), muscazon, psilocybin and psilocin. Neurotoxic substances are found in Sloping head (clitocybe – genus agaricus), inocybe mushrooms, Psilocybe and Fly agaric mushrooms (red, brown, panther-stained). Among the most famous neurotoxic fungi should be mentioned Red agaric fungus that contains both muscimol, ibotenic acid, muscazone and muscarin, and Deadly skullcap containing muscarine. Deadly skullcap is also known as “Funeral bell” and “Deadly Galerina”. California fungi (Scleroderma cepa) can cause dizziness, vomiting and visual hallucinations.

Neurotoxic fungi primarily cause central nervous and sensory symptoms. Muscarine gives rise to cholinergic symptoms such as increased salivary secretion and bronchoconstriction, while ibotenic acid, muscimol and muscazone cause anticholinergic symptoms. The latency from ingestion to symptom development is generally shorter for neurotoxins than for cytotoxins; usually ½-2 hours, but sometimes longer. Red and Brown agaric fungus and Panther agaric fungus primarily give symptoms such as palpitations, big pupils and nausea. The levels of muscimol and ibotenic acid are as high in spring and summer. Muscarinergic fungi provide increased sweating, low heart rate and respiratory failure.

Fungi with hallucinogenic effects can be used as intoxicants in the same way as narcotic drugs. Most common are different fungi that contain psilocybin or psilocin. Some hallucinogenic fungi grow naturally in Sweden, for example, Red ascaris fungus and Liberty cap (Psilocybe semilanceata). Hallucinogenic mushrooms can be purchased online and delivered with regular mail. Some users take fungi while using other drugs, such as cannabis, LSD or ecstasy. Mushroom poisoning can cause acute psychosis with severe hallucinations and irrational behavior. Case descriptions are available with bizarre elements.

Gastrointestinal irritant toxins

There are a large number of gastrointestinal toxins among the fungi that most cause gastrointestinal symptoms. These are the most common mushroom poisonings. They occur, for example, in Livid entoloma, Livid agaric, Livid pinkgill, Leaden entoloma, and Lead poisoner (Entoloma sinuatum), yellow-staining mushroom or simply the yellow-stainer (Agaricus xanthoderma), Chestnut knight (Tricholoma albobrunneum) and the Sickener, emetic russula, or vomiting russula (Russula emetica). Symptoms consist of nausea, abdominal pain, stomach cramps, vomiting and diarrhea.

The latency from intake to symptom debut is generally short, 2-4 hours (i.e., significantly less time than for the cytotoxins) and the symptoms usually resolve within a day. Note that some neurotoxins also have gastrointestinal irritants, such as muscarinic and muscular zones.

Other fungi

A few toxins do not fall into any of the three main groups above. Most of these are coprin (and coprin-like toxins) that can cause an “antabus-like” reaction with “flush”, sweating, tachycardia and hypotension when consuming alcohol. Coprin is, for example, in common ink cap or inky cap (Coprinus atramentarius).

Brown roll-rim, common roll-rim, or poison pax (Paxillus involutus) may cause an allergic reaction after repeated ingestion. Ingestion of some Asian mushrooms like Shiitake (Lentinus edodes) may cause migratory erythema over the trunk and extremities 12 hours to 5 days after ingestion.

Symptoms of fungi poisoning, type of toxin and latency for different symptoms

Mushrooms NameLatin nameToxinSymptomsTime to symptoms
Death cap Amanita phalloidesAmatoxin, CyclopeptidesNausea, dizziness, stomach pain, vomiting, intense waterproof diarrhea, liver and kidney damage, general malaise, fatigue, fever, electrolyte disturbances, tachycardia, lowering of consciousness and blurred consciousness, confusion, anxiety, hyperglycemia, hypotension, bleeding in the intestine and skin4 – 24 hours
False death cap
Citron Amanita
Amanita citrina, Amanita mappaCytotoxinRed and Royal fly agaric: ½-2 hours for neurotoxic symptoms.
Destroying angel Amanita virosa
Fly agaricAmanita muscaria
Royal fly agaric or the king of Sweden AmanitaAmanita regalis
Panther cap and false blusherAmanita pantherina
Funeral bell
Deadly skullcap
Deadly Galerina
Galerina marginata
Brain mushroom
Turban fungus
Gyromitra esculentaGyromitrin, monomethylhydrazinNausea, stomach pain, vomiting, dizziness, fatigue, double vision, diarrhea, liver and kidney damage, hemolysis, seizures5 – 8 hours
False morel mushroom
Sneaky bishop's hat
Gyromitra ambiguaCytotoxin
Deadly webcapCortinarius rubellus, speciosissimusOrellaninThirst, fatigue, headache, chills, stomach pain, kidney pain, muscle pain (back pain), low urine output (initial polyuria), kidney failure, uremia, nausea, vomiting. May cause permanent kidney damage2 – 14 days
Fools webcapCortinarius orellanusCytotoxin
Certain inocybe genusInocybe-arter
Muscarinic (Neurotoxin)Nausea, vomiting, stomach ache, diarrhea, sweating, anxiety, anxiety, increased saliva and tear flow, miosis, bradycardia, rhinorrhea, bronchitis, bronchial obstruction (mainly increased cholinergic activity), dizziness, headache.30 minutes – 2 hours
Earthy inocybe
Inocybe geofylla
Muscarinic (Neurotoxin)30 minutes – 2 hours
Red-staining inocybe Inocybe erubescensMuscarinic (Neurotoxin)30 minutes – 2 hours
Top thread (?)
Inocybe fastigiata, Inocybe rimosaMuscarinic (Neurotoxin)30 minutes – 2 hours
Clouded agaric
Cloud funnel
Clitocybe nebularis Muscarinic (Neurotoxin)30 minutes – 2 hours
Ivory funnelClitocybe dealbata = Clitocybe agrestisMuscarinic (Neurotoxin)30 minutes – 2 hours
Frosty Funnel mushroomClitocybe phyllophilaMuscarinic (Neurotoxin)30 minutes – 2 hours
Bitter gilled mushroomsGymnopilus species
From gilled mushrooms
Family Hymenogastraceae
Hebeloma -species
Saprotrophic mushrooms Mycena -liberty cap
Fly agaricAmanita muscariasoxazole; ibotenic acid, muscimol, muscazone, muscarinConfusion, lowering of consciousness, anxiety, dizziness, affected time and space perception, hallucinations, mydriasis, dry mucous membranes, agitation, palpitations, rarely convulsions, nausea, vomiting, diarrhea (mainly increased anticholinergic activity)30 minutes – 2 hours
Royal fly agaric or the king of Sweden AmanitaAmanita regalisNeurotoxic
Panther cap and false blusherAmanita pantherinaNeurotoxic
Liberty capPsilocybe semilanceataPsilocybin, PsilocinAnxiety, anxiety, confusion, affected time and space perception, feeling of unreality, hallucinations, agitation, psychotic symptoms, tachycardia, palpitations. Usually, the intake of many fungi is required to produce serious symptoms.15 minutes – 2 hours
Small, black-spored, saprotrophic agaricsPanaeolus-speciesNeurotoxic
Banded mottlegill,
Weed Panaeolus or subbs
Panaeolus subbalteatusNeurotoxic
Fungal family StrophariaceaeGymnopilus-speciesNeurotoxic
Pluteus familyPluteus-speciesNeurotoxic
Knackers CrumpetPluteus salicinusNeurotoxic
Conocybe-familyConocybe-speciesNeurotoxic
Psilocybin, Psilocin
Yellow-staining mushroom
Yellow-stainer
Agaricus xantodermaGastrointestinal irritating toxinsNausea, stomach pain, abdominal cramps, vomiting, diarrhea, anxiety2-4 hours
Eastern Flat-topped AgaricusAgaricus placomycesEastern Flat-topped Agaricus may cause a so-called paxillus syndrome: an allergic reaction with immunohemolysis and DIC. May cause kidney failure and shock.
Satan's bolete or Devil's boletusBoletus satanas
Lurid boleteBoletus luridus
Suillellus luridus
Family of terrestrial pink-gilled mushroomsEntoloma-species
Livid entoloma, livid agaric, livid pinkgill, leaden entoloma, and lead poisonerEnteloma sinuatum
Family HymenogastraceaeHebeloma-species
Milk-capsLactarius-species
Brown roll-rim, common roll-rim, or poison paxPaxillus involutus
Some coral fungi
Family Gomphaceae
Ramaria-species
Some brittle gillsRussula-species
The sickener, emetic russula, or vomiting russulaRussula emetica
Earth ballsScleroderma-species
Some tricholoma species
Wood blewit
St George's mushroom
Tricholoma-species
White knightTricholoma album
Ashen knightTricholoma virgatum
Brown knightly mushroomTricholoma albobrunneum
Sulphur tuft, sulfur tuft or clustered woodloverHypholoma fasciculare
Common ink cap or inky capCoprinus atramentariusCoprin (antabuse-like)At the same time alcohol intake: nausea, headache, sweating, drop in blood pressure, chest pain, shortness of breath, anxiety, anxiety, flushing15 minutes – 7 days

Likelihood of confusion between edible and inedible fungi

Edible fungiFeatureMay be confused with inedible fungiFeature
Sheathed woodtuftOutstanding scales on the foot. Grows in clusters on stumps.Funeral bellClock shaped arched hat. Brown to tan. Beige to light brown discs.
Grass-green Russula, the tacky green Russula, or the green RussulaNo ring. Arched to widespread hat. White to brownish foot. White meat.Death CapArched widespread greenish hat. White to green-yellow discs under the hat. White greenish foot. Thin ring.
Field mushroom or, in North America, meadow mushroom.Gray-white or brown discs under the hat. Hemispherical or widespread hat.Destroying AngelWhite discs under the hat. White or yellow-brown hat, sack stocking at the base of the foot. Growing mainly in mossy spruce forest.
Yellowfoot, winter mushroom, or Funnel ChanterelleThin navel to funnel-shaped hat. The top is yellow-brown to brownish-black. Hollow foot that is brownish to yellow.Deadly webcapMaroon to yellowish-brown hat. Usually top hat but can be flattened. Maroon tall and firm foot. Yellow zigzag band on the foot.
ChanterelleYellow, ridges under the hat, do not have discs. Spicy taste and aroma. Irregular hat edge and ridges on the underside of the hat. Grows in coniferous and deciduous forest. Stuck in the consistency.False chanterelleThin tightly seated real sheets, finely felt hat top. Soft and clever in texture. Thin meat hat, hollow foot. Clear border between hat and foot.
Dove-coloured tricholomaDo not have ring or sock. White to cream white, lateral and sticky when wet. White discsDestroying angelWhite or yellow-brown hat, sack stocking at the base of the foot. White discs under the hat. Growing mainly in mossy spruce forest.
Scaly Wood Mushroom, Blushing Wood Mushroom or Pinewood MushroomGray-white or brown discs under the hat. Hemispherical or widespread hat. Characteristic gear band under the ring.Destroying angelWhite or yellow-brown hat, sack stocking at the base of the foot. White discs under the hat. Growing mainly in mossy spruce forest.
Parasol mushroomDark hat mountains. Brown-watered foot. Beautiful brownish hat. Dense white discs under the hat.Panther capHat like young hemisphere-shaped, gray-brown to olive brown with white grainy shelf remains (white dots).
Turban fungusBrown hat, crumpled like a brain. The hat edge is rolled into the foot.Black morelBeautifully wrapped hat with cavities. Top hat. White grainy foot.

Identification

In case of suspicion of acute mushroom poisoning, it is important to identify the fungus early. Without thorough knowledge of fungi, it is generally necessary to use a fungal expert for both macroscopic and microscopic identification. Contact information can be obtained from the Poison Information Center or the botanical institutions at universities around the country.

History is very important in acute care, especially regarding fungal identification and estimation of past time between fungal intake and symptom debut. The history should extend for a long time; As mentioned above, latency for some cytotoxins may be up to 2-3 weeks.

If a group of people have eaten the same portion, but only some have become ill, this does not exclude fungal poisoning. For example, spicy gift spiders are so poisonous that single copies are enough for the people who get bites themselves to fall sick while others remain healthy. The toxin in Deadly webcap is, like some other toxins, heat stable and can withstand both boiling and freezing.

Symptoms

Symptoms of fungal poisoning:

  • Stomachache
  • Abdominal cramping
  • Nausea
  • Vomiting
  • Diarrhea, often severe, may be blood-mixed
  • Grumble awareness, alertness reduction
  • Palpitations
  • Big pupils
  • Headache
  • General feeling of sickness, fatigue
  • Joint and muscular pain
  • Anxiety concern
  • Depression

Cytotoxin

  • Amatoxin-containing fungi cause abdominal pain, nausea, vomiting and profuse water-thin diarrhea (cholera-like) 6-12 hours after ingestion. These symptoms usually last up to 24 hours. After 2-3 days, symptoms of liver injury develop. This can progress to fulminant hepatic failure within 3-7 days.
  • The latency of poisoning with cytotoxin is longer than for the other toxins, usually 8-24 hours.
  • Symptoms may come asymptomatic (after 2 days up to several weeks) due to secondary organ injury with acute liver failure or uremia.
  • Poisoning with False morel can cause pyridoxine deficiency with CNS affection. Even mucous membranes, liver and kidneys can be affected and acute hemolysis may occur.

Neurotoxin

  • Nausea, intoxication, drowsiness, euphoria, confusion, clumsy consciousness, hallucinations, excitation, hyperreflexia and, in severe cases, general seizures.
  • Anxiety and numbness are commonplace.
  • Symptoms/signs of muscarinic effects such as; miosis, bradycardia, hyper/hypotension, flush, sweating, bronchoconstriction, increased salivation, bronchial fluid and pronounced pulmonary edema. Special intake of certain wire agaric and funnel agaric (Inocybe and Clitocybe genera), such as false champignon (Clitocybe rivulosa = fool’s funnel) and Clouded agaricus cloud funnel (Lepista nebularis) can give rise to this clinical picture.

Gastrointestinal toxin

  • Gastrointestinal symptoms, in pronounced cases persistent vomiting and diarrhea.
  • The symptoms are many times very troublesome, but fast transitory, usually within 24 hours.
  • In general, hospital care is rarely indicated if isolated intestinal tract symptomatology can be determined.
  • Some toxin, for example, in Livid entoloma, Livid agaric (Entoloma sinuatum), is exclusively irritant to the gastrointestinal tract, while some others, eg muscarine, are both neurotoxic and gastrointestinal.
  • It is important to keep in mind that gastrointestinal symptoms after fungal ingestion are not always an expression of acute fungal poisoning. Mushrooms are easily attacked by bacteria and parasites and, like other foods, can cause food poisoning. Many people are ill every year after ingestion of old or improperly treated sponges.

Coprin

  • Sweating
  • Flush
  • Hypotension

Treatment

  • Identification of the fungus (call expert)
  • All publicly treated patients should be treated in a hospital
  • Take Hb, Wbc, CRP, platelets, PK/INR, creatinine, liver enzymes and urine analysis. If necessary, intravenous fluid, for example, Ringer’s Acetate.
  • Adequate fluid supply, insert at least one PVC and provide abundant rehydration (2-3 liters of Ringer-Acetate) with a view to good diuresis.
  • Careful monitoring of fluid balance, electrolyte status, renal function and liver parameters. Correct electrolyte disturbances.
  • Gastric lavage may be possible. Performed at early disposal (within 6-8 hours after fungal intake, preferably within one hour). Should not be carried out in case of persistent vomiting.
  • Medical activated charcoal 50 g x 4 (10-25 g for children) can be given up to 2-3 days after ingestion of toxic fungus. Charcoal is given in repeated doses for a day.
  • Silibinin (Legalon Sil, Madaus/Schering-Plow license preparation) is given by poisoning with Death cap. Dosage: 20 mg/kg/day for 2 days divided into 4 doses (5 mg silibinin/kg per infusion). Infusion is given for 2 hours at 4 hours intervals. Silibinin is an extract from the plant Carduus marianus, Maria thistle, Milk Tart or St. Mary’s thistle (Milk thistle).
  • Benzylpenicillin (phenoxymethylpenicillin) in high dose (5 g x 4) for 3 days when poisoned with Death cap or Destroying Angel) unless silibinin is available
  • Acetylcysteine i.v. In case of poisoning with Death cap. Inhalation fluid acetylcysteine ​​200 mg/ml is given intravenously for 1 hour 150 mg/kg in 200 ml glucose 50 mg/ml. Then 50 mg/kg for 4 hours and then 100 mg/kg for the following 16 hours (mixed in the same glucose solution as above). In total, 300 mg/kg is given for 20 hours. There is some scientific support for acetylcysteine ​​to be administered for at least 48 hours when poisoned with amatoxin.
  • Antiemetics are given in nausea, such as ondansetron 4 mg x 1 or granisetron 1 mg x 1
  • Benzodiazepines in case of anxiety or convulsions (injection of diazepam) 5-10 mg i.v. vb)
  • Atropine (atropine), 1-2 mg i.v. in the case of cholinergic symptoms. Note that usual doses of 0.5-1 mg are usually insufficient. Sometimes more than 1-2 mg is required, the symptomatology controls. Avoid atropine when poisoning with isoxazole derivatives.
  • Acidosis correction, sodium bicarbonate buffer solution
  • In hemolysis, alkalinization of the urine with sodium bicarbonate
  • Pyridoxine Hydrochloride (Pyridoxine) at the poisoning of False morel. Dosage: 1.5-2 g per day (25 mg/kg) i.v. as a single dose or two-dose procedure depending on symptoms
  • Hemoperfusion (hemodialysis with charcoal filter), alternatively forced diuresis, may be considered early (within 36 hours) by poisoning with Deadly webcap.
  • Treatment of renal failure.
  • Treatment of hepatic failure, phytomenadione (Konakion) 10 mg x 2 i.v. Consider MARS treatment in acute liver failure. Consider liver transplantation in severe cases of liver failure.

Antidote at some mushroom poisoning

Mushrooms NameFirst antidoteSecond antidoteThird antidote
Destroying AngelActivated charcoalSilibininN-Acetylcysteine
Death CapActivated charcoalSilibininN-Acetylcysteine
Funeral bellActivated charcoalSilibininN-Acetylcysteine
False morelActivated charcoalPyridoxine
Mushroom-containing fungi (above all the species Inocybe and Clitocybe)Activated charcoalAtropin

Gastric lavage and activated charcoal administration are the main initial measures for mushroom poisoning, but must be given shortly after fungal intake for good effect (please see above for details). Charcoal is atoxic and harmless to drink for those who are not consciously minded.

Active antidotes are available for poisoning with white Death cap, Destroying Angel, False morel and muscarinic fungi (see Table 2 above).

Silibinin (Legalon Sil) is considered to prevent toxin uptake in the liver cells and reduces the risk of liver injury. Possibly the levels of glutathione in the liver may also increase. Acetylcysteine ​​should be administered in liver injury after poisoning with amatoxin-containing fungi. Side effects consist of warmth and flush. Benzylpenicillin also reduces the risk of liver damage and should be given if silibinin is not available in Death cap or Destroying Angel toxicity. Note that benzylpenicillin in high doses may cause general cramps. An alternative to benzylpenicillin is cefuroxime. The treatment in general is mainly symptomatic.

In case of poisoning with neurotoxic fungi (eg psilocybes), the patient should be cared for in a quiet room if possible. Confusion and other mental symptoms are symptomatically treated with sedatives and neuroleptics, such as olanzapine or droperidol.

Renal damage after fungal poisoning rarely leads to manifest renal failure with uremia treated with dialysis or renal transplantation. Acute liver damage can lead to fulminant hepatic failure with bad forecasting 3-7 days after ingestion of toxin. Fulminant liver cell injury after mushroom poisoning has been a case of acute liver transplantation. Acute hepatic failure after fungal poisoning is treated in the usual way but observe the possibility of antidote treatment. Treatment with dialysis and charcoal filters in a MARS system can be tested. Patients with kidney or liver damage after mushroom poisoning should be treated in an intensive care unit.

Fatalities due to fungal poisoning are very rare, but also occur among small children, usually secondary to acute liver failure.

Follow-up after severe mushroom poisoning should be planned with control of general health issues, liver function and renal function.

ICD-10

  • Toxic effect of contaminated fungus T62.0

Published with permission by Internetmedicin AB


Venomenous fish and fish poisoning

By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


MARIN TOXICOLOGY

A large number of fish, molluscs, anemones and other marine organisms can cause a toxic reaction in contact with humans. Approximately 1,700 of the sea’s approximately 27,000 known species are considered more or less toxic. There are more than all known poisonous vertebrates together. Poisoning of marine species can occur after ingestion of poisonous fish but can also occur after sting or touch, usually through toxins. The most common poisoning after ingestion of fish is scombroid poisoning, ciguate poisoning and fugu poisoning (bladder fish), of which fugu poisoning is the most serious with several deaths occurring.

It is becoming increasingly common for Swedes to dive or bathe in tropical waters and be exposed to various toxic marine species. Ingestion of toxic exotic fish has become more common in Europe through imports. Several cases of ciguate poisoning have occurred in Germany in recent years.

For information on other toxic marine animals and algae, please see treatment overview:Jellyfish, algae and poisonous marine animals

Greater weever (Trachinus draco)

Greater weever (“Weed dragon”) is an edible fish that occurs along the Swedish west coast right down to the danish Østersund, most commonly it is along the northern part of the west coast in Sweden.

Description

The Greater weever is narrow, looks compressed and usually becomes a few inches long. It is cartoon in shimmering green, yellow and black on a yellow-green bottom, the mouth is upward, the remote looks a bit slow.

On the back and the gill fins, the dorsal fin has toxic spines. It can inject a poison at stitches, mainly from the dorsal fins. The fish has two dorsal fins and it is the front that is toxic. The toxin is both hemorrhagic, neurotoxic and necrotizing. The weever does not attack, unlike, for example, Dragonfish, but only stands in self-defense.

External link to image on the removal from the Sea and Water Authority’s website

Risk of sting

The Greater weever comes towards the coast in the spring and is next to the beaches during the summer, when most stitches occur. The Greater weever lies hidden in the sand at the bottom where it lies and waits for the prey. It only has eyes and mouth visible.

  • The most common thing is that stitches arise in connection with fishermen clearing their yarns after catching remnants and happen to come against the poisonous spine with their fingers.
  • It is risky to be hooked off a Greater weever from a fishing hook as one can easily be stung. Please note that even the gill fins have toxic spine, not just the dorsal fins!
  • Stingin the foot can occur if you accidentally step on a Greater weever.

The poison of Greater weever is active even when the fish is dead after capture. A sting of Greater weever leads to a severe inflammation with pain, swelling and numbness.The greater weever is, despite its poison, a fine food fish (tastes in the style of sole) that can be purchased in the fish trade.

Small weever (Echiichtys vipera)

Along the west coast of Denmark in the Atlantic, there is a variant of weever call called small weever or minor weever . This fish is also found in the English Channel, the East Atlantic, along the west coast of France, in the Black Sea and the Mediterranean.

Echiichtys vipera is considered Europe’s most dangerous fish. The fish is about 15 cm long and sand colored. The dorsal fin with the toxic spine is completely black. The spines are so sharp that they can go through a wetsuit or a flip-flop sandal. The small weever toxin contains more serotonin than its larger relative, which is considered to explain why the pain becomes more pronounced when stung by this fish.

External link to photo on small weever

Symptoms

Common local symptoms are:

  • Intense pain
  • Swelling
  • Numbness
  • Paraesthesias
  • Skin discoloration

General symptoms may also occur, such as:

  • Nausea
  • General discomfort
  • Headache
  • Dizziness
  • Chills
  • Sweating
  • Drowsiness
  • General seizures (in rare cases)

The stitch is not normally life-threatening, but a bacterial infection may occur locally in affected skin and complicate the procedure.

Sensitivity loss after sting of small weever is usually transient, but can be lengthy and lasting in rare cases. The swelling can persist for a long time, usually up to one month, in some cases up to one year! However, the toxin does not remain more than 48 hours.

Treatment

  • The affected body part should be lowered into hot water (at least 40 degrees) immediately after the sting. Then the toxin (the protein is denatured) is inactivated and immediate and effective pain relief is achieved. The water should keep a temperature around 45 degrees and it is of course important that you do not scald your skin. The affected body part should be kept in the warm water until lasting pain relief has been achieved. Heating should last for at least 30 minutes, but up to one and a half hours may be needed. You can refill with hot water during treatment and preferably measure the temperature with a water thermometer.
  • Remnants of any toxins that may remain in the wound should be removed. If you have to, this should be done surgically. Hard to find spine can sometimes be found using ultrasound scans!
  • The affected body part should otherwise be left in peace and the wound kept clean.
  • Antibiotics are given only if secondary infection occurs, which is not unusual.

In the case of the following, medical care should be sought:

  • If general symptoms occur.
  • In case of troublesome prolonged pain.
  • If surgical removal of a toxic spine is required. Ultrasound!

REEF STONE FISH (Synanceia verrucosa)

Reef stone fish is a very poisonous fish spread in the tropical parts of the Indian Ocean and the Pacific Ocean. The stone fish grows 30-60 cm long and is a large-mouthed cheek-armored predator that lives on to lightly attack and eat small fish. The stone fish hurt people by stinging spines.

The stone fish belongs to the genus scorpionidae and is probably the most toxic of all fish. Several deaths are described, some already within one hour after the sting. Several different subspecies of synanceia are available, besides Synanceia verrucosa also for example Synanceia erosa and Synanceia trachynis in various sizes.

Features

The reef stone fish is a particularly ugly fish with well-developed camouflage. It makes it extremely difficult to discover in the sea even if you look exactly where the fish is located. The fish is often hidden in the sand with only mouth and eyes visible. The warty cover makes it completely similar to surrounding stones and algae on the bottom. The stone fish has 13 toxic spines on the dorsal fins as it immediately rise if you approach the fish, touch it or accidentally step on it. The poison is very complex and contains neurotoxins and myotoxins as well as proteins that cause a strong antigen response. Antiserum against stone fish is available for systemic treatment at general symptoms after sting.

External link to a picture of a stone fish

Symptoms

The toxin from the stone fish is very toxic and a stitch gives rise to immediate very severe pain.

Common symptoms are:

  • Intense pain
  • Swelling
  • Numbness
  • Paraesthesias
  • Skin discoloration

General symptoms may also occur, such as:

  • Nausea
  • General discomfort
  • Headache
  • Dizziness
  • Chills
  • Sweating
  • Drop in blood pressure and seizures (in rare cases)
  • Circulatory and respiratory depression, in pronounced cases

The toxin can be fatal with a serious illness within a few minutes. Deaths have occurred within one hour of the sting.

Treatment

  • Infected body part should immediately be immersed in hot water at stitches. Then the toxin (protein denatured) is inactivated. The water should keep a temperature around 45 degrees. The affected body part should be kept in the warm water for 30-90 minutes, until lasting pain relief is achieved.
  • Immunoglobulin for tetanus, 250 IU i.m. if tetanus protection is missing, otherwise tetanus vaccine s.c. (It is recommended, however, with doubtful scientific evidence, rigid cramps are described).
  • In pronounced general symptoms or shocks, treatment with specific immune serum is given to stone fish poisons.

DRAGONFISH (Pterois volitans)

Dragonfish is a beautiful zebra-like fish that lives among corals in the Indian Ocean and western Pacific Ocean. The Dragon fish can cause poisoning through stitches. It also occurs along the US east coast. In Sweden, the Dragon fish occurs only as aquarium fish.

The dragon fish belongs to the genus dragon head fish, a subgroup of the scorpion fish – Scorpenidae.

Features

The fish is up to 38 cm and can weigh up to one kilogram, but is usually slightly smaller. The dragon fish is a beautiful fish, transverse in brown and white, and is also called lion fish. The dragon fish chases fish and crabs at night and lies and hides among corals during the day. It has large pectoral fins, abdominal fins and a dorsal fin as it slowly moves like beautiful veils. Dragonfish have a toxin secreted from the first three dorsal fins. The toxin is primarily neurotoxic. Both local symptoms and general symptoms can be developed. The toxin contains inflammatory substances such as prostaglandins and thromboxane B2. The kite fish can attack and stab the attacker actively with their dorsal fins. Stitches are most common on the lower extremity. Injuries in Sweden are reported primarily from people who work with aquarium fish.

External link to picture on dragonfish, Wikipedia

Symptoms

The poison glands on the dragon fish are smaller than on the stone fish. The toxin is very toxic and a sting causes immediate severe pain. Common symptoms, in addition to the pain, are:

  • Swelling
  • Numbness
  • Paraesthesias
  • Skin discoloration

General symptoms may also occur, such as:

  • Nausea, vomiting
  • General discomfort
  • Headache
  • Dizziness
  • Chills
  • Sweating
  • Drowsiness
  • Circulatory and respiratory effects (in rare cases)

Deaths are very rare, but occur. The toxin is active even after the fish is dead, and can withstand freezing. Secondary infections are common after stitching.

Treatment

Infected body part should be immediately immersed in hot water. Then the toxin (protein denatured) is inactivated. The water should keep a temperature of at least 40 degrees, preferably between 45 and 50 degrees. One should keep the affected body part in the warm water for 30-90 minutes, until lasting pain relief is achieved. Look for ultrasonic toxins and surgically remove any residual spine.

Spotted trunk fish (Lactophrys bicaudalis)

The spotted trunk fish is a coral fish that secretes a ciguatera toxin when touched by glands on the back. The toxin is only dangerous if the fish is ingested, so there is no immediate danger to divers when touched. However, sharks can die as a result of eating a trunk fish. Even moray eels as well as many other coral fishes can be abundant in cigueter poisons when consumed.

SCOMBROTOXISM

Consumption of fish of the species scombroidae and scomberesocidae can give rise to a poisoning syndrome called scombrotoxism or scombroid poisoning. Usually the syndrome occurs after ingestion of different species of tuna or mackerel, eg Skipjack Tuna or Bonito. These fish are usually consumed in salads, including in the Mediterranean region.

Scombrotoxism occurs after eating fish contaminated with bacteria that release abundant amounts of histidine. The bacteria are of the species E. Coli, Proteus, Klebsiella or Aerobacter. In these bacteria, histamine and histamine-like substances (histidine) are produced by the enzyme histidine decarboxylase. Scombrotoxism is not an allergic reaction, but the symptomatology is similar.

Symptoms

Symptoms usually occur within one hour of consumption. The symptomatology is related to histamine release and consists of:

  • Sweating
  • Nausea
  • Vomiting
  • Diarrhea
  • Headache
  • Palpitation
  • Flush
  • Urticaria
  • Dizziness
  • Swelling of the face with swollen lips and swollen tongue (in rare cases)

Respiratory problems may occur with broncho-obstruction and hypotension. The symptoms are usually transient and transient within 8-10 hours.

Treatment

  • Treatment with antihistamines that block H1 and H2 receptors is recommended, eg cimetidine 400 mg x 2.
  • Cortisone is not indicated but can on the contrary prolong the course.
  • Serious procedures must be treated with intravenous fluid, antihistamines and adrenaline.

CIGUATERA POISONING

Poisoning can occur after consumption of fish belonging to the genus ciguatera. These fish are mainly found in the Caribbean and the West Indies. This includes Napoleon fish, Parrot fish, barracuda, tropical grouper, red snapper, amberjack, kingfish and other exotic fish that live around coral reefs. Ciguate poisoning is common in and around the Dominican Republic. Parrot fish can also contain tetrodotoxin which is significantly worse.

Ciguatera toxin comes from toxin-forming algae found in coral reefs and which have passed upwards in the food chain. The fish smells and tastes normal. The concentration of toxin is highest in the liver and intestines of the fish.

Symptoms

Common symptoms are:

  • Nausea
  • Vomiting
  • Diarrhea
  • General malaise, fatigue and sleepiness
  • Myalgia, nonton
  • Chills and sweating
  • Neurological loss symptoms (polyneuropathy), paresthesia, numbness and loss of sensation in the extremities, mainly the lower but also cranial nerve effects can occur
  • Pain, aches and muscle weakness
  • Metal taste in the mouth
  • Cold-touch pain, allodynia
  • Drop in blood pressure, bradycardia
  • Comes in pronounced cases

Gastrointestinal symptoms last for 1-2 days, other symptoms last up to one week. Neurological failure symptoms may be prolonged and occasionally persistent. You talk about chronic ciguate poisoning. This condition can cause allodynia and a chronic pain condition. Investigation with clinical neurophysiology can demonstrate impaired nerve conduction in affected extremities.

The diagnosis is made by history and the clinical picture. Analysis of ciguatera venom in humans is under development but is not yet an established method. However, fish residues can be analyzed and confirm the presence of ciguatera poison, This should be done if several people have been poisoned and the health authority should be connected.

Treatment

Essentially symptomatic with rest and if necessary intravenous fluid. Mannitol given intravenously (1 g/kg) has been shown in several case studies to have a good effect on neurological and muscular symptoms if treatment is given within 48 hours of onset. However, the scientific evidence for mannitol treatment is weak and the treatment has been questioned. Other specific treatment is missing. Antihistamines can help as well as common analgesic type paracetamol (Alvedon) against pain.

FUGU POISONING

In Japan and some other Asian countries, blowfish (Fugu) are consumed. Fugu being properly prepared is considered a delicacy. Some different species of blowfish are Takifugu rubripes, Lagocephalus and Sphoeroides. The blowfish live in the Pacific Ocean, the Red Sea and the Indian Ocean. The fish is mainly found around Japan, China, the Philippines and Taiwan, but is also found in the Caribbean and Mexico. The blowfish is also called knotty tetraodontite fish because it is knotty and has four powerful teeth. Poisoning occurs only after ingestion.

The fish has a potent poison, tetrodotoxin, which can cause very serious neuromuscular poisoning, even death. Tetrodotoxin is a neurotoxin that can cause paralysis. The toxin binds to sodium channels in peripheral neurons and blocks the neurotransmission. Ten milligrams are considered a lethal dose. It does not pass the blood-brain barrier, but mainly causes peripheral paralysis, including respiratory paralysis. Tetrodotoxin is also found in other marine species such as the blue-tailed octopus, Parrot fish and some frog species (Pilgrim frogs). The toxin is enriched in the fish’s intestines, mainly in the liver but also in the intestines, the gonads (the ovaries) and the skin. The meat of the blowfish is not toxic but the toxin is found throughout the fish.

From 1974 to 1983, 646 cases of Fugu poisoning were reported in Japan with 179 deaths. In severe poisoning, mortality has been estimated to be close to 50% in neuromuscular paralysis with respiratory insufficiency. The poisoned patient can develop total paralysis but still be alert and conscious close to death. Death usually occurs within 4-6 hours after ingestion, with a range of 20 minutes to 8 hours. Patients die through respiratory paralysis and asphyxia. When treated with artificial ventilation, mortality has been reduced to around 5%. No antidote exists. The poison is probably formed by various bacteria that the fish eats, eg Vibrio alginolyticus.

Symptoms

Common symptoms of Fugu poisoning are:

  • Anesthetic feeling around the mouth and lips
  • Increasing loss of sensation on the face, arms and legs
  • Feeling of numbness and feeling of absence (“lightheadness”)
  • Headache
  • Abdominal
  • Nausea
  • Diarrhea
  • Increasing neuromuscular paralysis
  • Hypoventilation
  • Hypoxia
  • Hyperkapné
  • Convulsions
  • Mental blunting
  • Arrhythmias
  • Cardiovascular collapse

Treatment

No specific antidote is available. The treatment is mainly symptomatic with a focus on artificial ventilation and follows general intensive care principles. Because neuromuscular paralysis is common, it is important to support breathing and insert mechanical ventilation and ventilator as quickly as possible. Treatment with intravenous fluid and cardiovascular (inotropic) drugs follows current intensive care principles.

STINGRAY

This beautiful fish has given rise to a number of dangerous poisons by stinging with the tail fins, usually by too close divers. The stingray is a cartilage fish and a freshwater fish that occurs in South America’s rivers. Also other sting rays living in salt water has caused damage to divers by mechanical trauma. Damage usually occurs when you accidentally step on a stingray, it usually does not attack people. A stitch can give rise to pain, swelling, soreness, and often secondary infections. Muscle cramps and general symptoms may occur. Stitching is usually not life threatening unless vital organs are damaged but serious hemorrhage may occur. Some of the fin can remain in the wound and should be surgically removed. Treatment can be tested with hot water (45 degrees for 30 minutes) as with other marine stitches of affected body part.

ICD-10

  • Fish poisoning caused by ciguatera T61.0
  • Fish poisoning caused by scombroid T61.1
  • Toxic effect of contact with fish T63.5

Published with permission from Internetmedicin AB


Jellyfish and algiers

By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2019-02-15


A large number of fish, molluscs, anemones and other marine organisms can trigger a toxic reaction in close contact with humans, usually by stinging. Approximately 1,700 of the ocean’s approximately 27,300 known species are considered more or less toxic. There are more than all known poisonous vertebrates together. Approximately 9,000 different marine species are called Cnidaria, called from the Greek “sting”. The cnidaria group includes jellyfish, coral animals and hydrates. All cnidaria animals are a type of predator living on capturing and eating prey.

It is estimated that at least 80,000 people each year suffer from various ailments caused by toxic sea animals. Most of these are skin irritation after contact with stinging cells (nematocysts) when an inflammatory toxin has been released.

This mEMO describes the most common toxic organisms, with the exception of fish, found in Scandinavian sea waters and some of them we can come into contact with at exotic latitudes. It is becoming increasingly common for European tourists to dive or bathe in tropical waters and be exposed to various toxic marine species. In the Mediterranean Sea there are a large number of jellyfish that have increased dramatically in number in recent years.

For more information on toxic fish, see also overview: Weever and other toxic fish

Cnidaria are divided into four classes: Anthozoa (Anthozoa), Jellyfish (Scyphozoa), Box jellyfish (Cubozoa) and Hydrozoes (Hydrozoa).

  • Anthozoa: Coral animals lacking in medusa form. Solitary or colony forming polyps.
  • Scyphozoa: Jellyfish, polyps in medusa form, ring jellyfish, lung jellyfish and disc jellyfish.
  • Cubozoa: Box jellyfish with several different subspecies.
  • Hydrozoa: A diverse and highly varied subgroup of Cnidaria animals. Colony formation, eg Portuguese Man of War.

JELLYFISH (Scyphozoa)

Jellyfish are free-swimming medusas, bell or plate-shaped with a wreath of tentacles under them. The mouth’s edges on the underside are extended to coin hoops or arms hanging (trawls) under the animal. A small number of different jellyfish occur naturally in Swedish seawater. The Common Jellyfish, Lion’s mane jellyfish and Blue Jellyfish all occur along the west coast, in the Kattegat and Skagerack Sea. The Compass jellyfish and the Barrel jellyfish can also be seen here. Of these, only the earmuff appears in the Baltic Sea.

In Scandinavian sea waters, it is mainly the Lion’s mane jellyfish that causes injuries to people, but also blue Fireman and compass jellyfish have nettle cells that can cause skin irritation. The jellyfish that occur in Sweden cause only local symptoms in the form of a burn-like skin irritation. In tropical countries, there are significantly more poisonous jellyfish that can cause general symptoms in addition to pronounced local symptoms.

Features

Jellyfish is a type of invertebrate, soft nettle animal that mainly consists of bound water with a jelly-like shell. The upper part of the jellyfish body constitutes the bell and during the bell several mouth arms and tentacles sit. From the bellformed body wire hangs and commutes a large number of burners.

Jellyfish swim through the rhythmic contraction of the bell, causing a propulsive jet, but essentially the jellyfish passively follow the water currents. The long tentacles trawl after the body and have the task of catching the prey caught, burned, disintegrated and digested into food.

The jellyfish occur mainly during the summer and autumn in Swedish seawater. Jellyfish live in two phases, first as polyps grown to the bottom and then as free swimming medusas. The free-swimming phase begins in the spring when the jellyfish buds off from its polyphase phase, then the jellyfish live in medusa form for about a year.

The Lion’s mane jellyfish is called in English for “Lion Man’s Man” – Lion’s mane jellyfish, which speaks describing the look. The largest Lion’s mane jellyfish found was 2.3 meters in diameter and 36.5 meters in length. Very large lion’s mane jellyfish jellyfish occur mostly in the open sea on the Atlantic, beside the coast they rarely become more than 50 cm in diameter. Normal size is about 20-30 cm in diameter. Lion’s mane jellyfish thrives in cold water. If the water temperature rises too much (over 20 degrees), the jellyfish draws on deeper and cooler water.

Classification

There are around 200 different types of jellyfish (Scyphozoa), of which around 14 species in Sweden. These are divided into four main groups:

Lion’s mane jellyfish (Cyanea capillata) and Blue Jellyfish (Cyanea lamarckii)

Common Jellyfish (Aurelia aurita)

The Compass Jellyfish (Chrysaora hysoscella)

The Barrel Jellyfish (Rhizostoma octopus)

Among the most poisonous species around the world are Portuguese Man o’ War (Man of War, Physalia physalis), Box Jellyfish (Chironex fleckeri) and Irukandji jellyfish (Carukia barnesi). Each year, these jellyfish cause a lot of sting with serious poisoning incidents, even deaths. See further information about the respective jellyfish below.

Portuguese warrior (Colonial siphonophore, class: Hydrozoa)

The Portuguese Man of War (Physalia physalis) has a wide spread in the tropical and warm seas, most commonly it is off Florida’s coast and southeast of the Gulf of Mexico. The Man of War jellyfish is not really a jellyfish, but a scyphozoa without jellyfish-like colonial organism (colony-forming cnidaria animals) and categorized as hydrozoa. It is also found along the coasts of Africa and a closely related species occurs in Australia (Physalia utriculus). The Man of War consists of a cluster of different organisms living in symbiosis. The upper part is gel-like and gas-filled, containing, among other things, carbon dioxide and nitrogen gas. The upper part acts as a sail that lies above the water surface and drives the windmill forward.

The Portuguese Man o’ War is probably the jellyfish that causes the most serious sting of all species, even deaths have occurred. Direct contact with the wires results in severe pain, severe fever and severe skin inflammation. The jellyfish is about 30 cm in diameter and floats around up on the surface with meter-long thick tentacles trailing far below the surface, the bell is partly above the water surface.

Box Jellyfish (class: Cubozoa)

The Australian Box jellyfish, (Chironex fleckeri), is a very dangerous jellyfish. The Box jellyfish has a transparent blue-haired cube-shaped clock. It is estimated that it has caused some sixty deaths, especially along the north and west coast of Australia. There are about 40 known subspecies, many of which are considerably smaller than the large Box jellyfish. The jellyfish can weigh up to 2 kg, the bell can be large as a salad bowl and the tentacles can be up to 2 m long. The cubic bell has four long tentacles richly covered with dangerous cnidaria cells.

The Box jellyfish moves relatively fast and the tentacles trawl in the water. Each tentacle contains several million cnidaria capsules (nematocysts) which can cause serious burns and very severe contact pain. In total, it is estimated to have no less than 5 billion nematocysts.

Irukandji jellyfish (class: Cubozoa)

Irukandji jellyfish (Carukia barnesi) is a dangerous small “stinger” that is considerably smaller than the box jellyfish with a bell big as a regular wristbell (about 2 cm in diameter). It occurs mostly in Australia, especially in northern Queensland. The Irukandji jellyfish is usually found in deeper waters, but can enter the beaches after storms. The jellyfish come in shoals or flocks.

Contact with the Irukandji jellyfish can cause more general symptoms with nausea, general affections and drowsiness. The toxin releases catecholamines, which are why pulse and blood pressure increase markedly, even cardiac arrhythmias, occur. The symptoms may debut 30 minutes after contact with an intense pain that slowly increases. The pain gradually becomes worse and worse and the affected body part swells significantly.

In the northern Mediterranean along the coasts of Spain, France and Italy, there are a large number of jellyfish that can cause different degrees of burn. Here is a brief description of some of them.

Mauve Stinger (Pelagia noctiluca)

Mauve stinger (Spanish: “Clavel de mar” – Sea carnation) are pink or bluish (violet) and transparent with multiple darker dots in the bell and tentacles. The bell is hemispherical with a diameter of 5-10 cm. It has 4 major central mouth arms and 16 peripheral tentacles. The dark red tentacles resemble octopus arms and are abundantly covered with cnidaria cells. The bell has illuminating cells that provide a fascinating light shine in the water at night or at contact. Mauve stingers provide a relatively heavy burn on contact with skin.

Mediterranean Jellyfish (Cotylorhiza tuberculata)

Mediterranean jellyfish is commonly referred to as “fried eggs” because they are simply similar to fried eggs (Q: “Aguacuajada” or “Huevo frito“). Mediterranean jellyfish is yellow with a flat compact bell with a central hemispherical round yellow protrusion with a diameter of 20-35 cm. Below the bell are 8 inverted mouth arms that give the jellyfish a compact look. The bottom of the plate with the mouth arms is whitish with dark or blue-black dots. The bell is divided into 16 lobes. Mediterranean jellyfish provide a light to moderate burn on skin contact.

Barrel Jellyfish (Rhizostoma pulmo)

The Barrel Jellyfish (Sp: “Aguamala“) is may found in Swedish and atlantic water. The jellyfish is large with a whiteish violet hemispherical clock with a blue border band. The bell can be up to one meter in diameter (90-100 cm). The bell has blue-violet lobes with no threads but with 8 compound mouth arms. The mouth arms form a whitish firm bottom. The Barrel Jellyfishs provide only a slight burn on skin contact.

Compass jellyfish (Chrysaora hysoscella)

Compass jellyfish occurs both in the Mediterranean and in northern seawater (Sp: Compases). It has a white to yellowish semi-transparent bell with a diameter up to 30 cm. The bell has darker centrifugal lines that make the look similar to a compass. Compass jellyfishes provide a relatively heavy burn on contact with skin.

Velella jellyfish (Velella velella)

Velella jellyfish is small, 1-5 cm thick or wide jellyfish that has a gelatinous body that it uses as a sail above the water surface to move (Spa: “Velero“). The seal is covered with a whitish skin. The bell is violet or bluish and semi-transparent. Around the body there is a blue-violet ring of relatively short threads. It is similar but is not to be confused with the much more dangerous Portuguese Man of War. The bidder sailor is harmless when in contact with skin.

“Water jellyfish – Crystal jellyfish” (Aequorea forskalea)

Crystal jellyfish are transparent blue-violet slightly-colored jellyfish. The body is hemispherical with centrifugal (radial) lines (channels) and a central clarification zone. In the clarification zone there is a triangular condensed area. The bell measures up to 15-30 cm in diameter. Underneath the bell hangs long thread-like tentacles. Crystal jellyfish are more common in the Atlantic than in the Mediterranean. These jellyfish do not cause burns on skin contact.

Toxicity

Jellyfish cause toxic injuries through contact with the human skin with their tentacles and burning threads. On the tentacles and the filaments are cnidaria cells with small blisters, nematocysts. In these nematocysts there are barbed wires which, upon skin contact, project through the skin like a harpoon and release a toxin. Nematocysts stick to thousands in the skin and may cause further reactions if the skin is rubbed or if the nematocysts are lysed. Early flushing of the skin is aimed at removing non-triggered nematocysts. The toxin released gives rise to an inflammatory reaction.

The jellyfish’s toxin is complex and contains a number of inflammation-promoting substances, including:

  • Bradykinin
  • Hemolysin
  • Serotonin
  • Histamine
  • Prostaglandins

Upon contact, a varying degree of skin inflammation occurs as in a burn. The toxin causes an increased influx across the cell membrane into various tissues of calcium, potassium and sodium which are non-sensitive to organic channel blockers. The reaction occurs through increased permeability across the cell membrane and not by formation of pores.

In Sweden, it is mainly the Lion’s mane jellyfish that gives rise to injuries but also the blue fireman jellyfish and the compass jellyfish have cnidaria cells with nematocysts that can cause skin irritation.

The Portuguese Man o’ War and the Australian Box jellyfish can cause very severe inflammation with long whiplash-like redness over the affected skin areas.

The toxin from the Box jellyfish is both neurotoxic, hemolytic and cardiotoxic. Skin contact with more than 1.2 meters of tentacles is considered to be life-threatening with regard to the Australian Box jellyfish.

The Portuguese Man o’ War has tentacles that can be more than 10 meters long, the tentacles can also come loose from the jellyfish and float freely in the water. The toxin is mainly neurotoxic and may cause respiratory paralysis. Tentacles are full of nematocysts. The inflammation can be so severe that permanent scars can occur with skin contractures as after burns. The toxin of the Irukandji jellyfish is also neurotoxic.

Symptom

Symptoms of contact with jellyfish are mainly local skin manifestations, such as:

  • Itching, often persistent
  • Redness
  • Swelling
  • Easy to moderate pain

In some cases, more general symptoms may occur, mainly:

  • General persistent itching
  • Severe pain
  • Nausea, vomiting
  • Drowsiness, somnolence

The Common jellyfish and the Barrel jellyfish only cause slight skin irritation.

Contact with the Box jellyfish can cause such a rapid inflammation that shortness of breath and respiratory arrest with shock can occur momentarily followed by cardiovascular collapse. Several cases have been described where immediate cardiac resuscitation next to the waterline has been life-saving.

The Box jellyfish and the Portuguese Man o’ War may cause after skin contact immediate, very severe pain and more general symptoms, such as:

  • Nausea
  • Chills
  • Muscle aches
  • Headache
  • Respiratory distress
  • Circulatory collapse

Treatment

In case of injury by jellyfish in Swedish sea waters, mainly Lion’s mane jellyfish (Cyanea capillata):

  • Rinse off the affected area with large amounts of seawater, though not with tap water. Take 3 buckets with sea water and rinse the skin. Salt water is recommended in the first place, as fresh water causes the nematocysts to burn in the filaments and thereby release more toxin. Avoid showering immediately after burn.
  • You can try to bathe affected skin with cooling balm. Avoid getting jellyfish on your hands. Avoid vinegar as this releases the burners.
  • Remnants of jellyfish tentacles can be scraped off, eg with a credit card. Tentacles can also be removed using a wide tape, for example, silver tape. However, one should not rub the skin as it can release toxins. Even shaving foam and razors can effectively remove jellyfish threads.
  • If symptoms persist, one can also try to lower affected body parts in hot water immersion therapy (40-45 degrees) (HWI) to neutralize toxins. One should try a hot bath for 30-60 minutes after flushing with salt water!
  • In case of contact with the eyes, rinse abundantly and prolonged with tap water or preferably physiological saline (at least 15 minutes).
  • Antihistamines per os, eg cetirizine 10 mg per os (not for children <6 years) or loratadine 10 mg x 1, for children under 2 years and less than 30 kg given 5 mg x 1. For children below 30 kg loratadine syrup (1 mg/ml) is recommended rather than tablets
  • The skin can be lubricated with cortisone cream such as Hydrocortisone or cold balm to suppress the inflammatory reaction and itching. You can also try acetylsalicylic acid in cream or ointment.
  • Ice cold pack or lidocaine cream over painful batches can alleviate the pain. Do not apply ice cubes (tap water) directly to the skin, instead apply the ice in a plastic bag.
  • Symptomatic treatment in general.
  • Vinegar, which is sometimes recommended for bathing the skin, has been shown to lyse nematocysts to a large extent and is therefore not recommended for stinging lion’s mane jellyfishes, but it is recommended when stitching after contact with some exotic jellyfish in other countries (scientifically low evidence).

When injuried by the Box jellyfish or Portuguese Man o’ War in foreign waters:

  • In case of damage by the Box jellyfish or Portuguese Man o’ War, one should immediately seek the nearest healthcare facility.
  • Box jellyfish can cause respiratory arrest and cardiac arrest.
  • The pain of contact with the Box jellyfish and the Portuguese Man o’ War can be extremely powerful and is very difficult to handle. Regional anesthesia is a possible way to block the pain with the help of peripheral blockades and local anesthetics.
  • When attacked by the Box jellyfish, it is recommended from some places to lubricate the skin richly with vinegar. Vinegar is reported to prevent lysis of burning threads but does not help against already occurring damage. Vinegar treatment is controversial and not scientifically proved.
  • You should lower affected body parts in hot water (hot water immersion therapy – 40-45 degrees) to neutralize toxins. You can try a hot bath for 30-60 minutes in case of widespread burns!
  • One should avoid rubbing the skin as well as applying alcohol over the skin.
  • There is an antidote to the Box jellyfish in the form of an immune serum developed using immunized sheep. Three ampoules of immune serum are given intravenously as soon as possible after attack of the Box jellyfish, if there are general symptoms or shock symptoms.

ALGAE

Algae apply photosynthesis, but are not plants but a type of microorganisms classified as phytoplankton. Toxic algae occur in Sweden mainly in sweet or brackish water, i.e. most in the Baltic Sea. These algae can produce toxic cyanobacteria that can cause acute poisoning. The toxin-producing algae cannot tolerate salt water and therefore do not exist along the Swedish west coast, or in the Kattegat or Skagerack sea area. There is an unverified hypothetical link between cyanobacteria and neurological diseases such as ALS, Alzheimer’s and Parkinson’s disease through increased formation of beta-N-methylamino-L-alanine (BMAA) and increased glutamate activity in the CNS. The connection is only hypothetical and some research in this field is ongoing.

Algae bloom

Algae blooms occur at sea, along the coast, in lakes and streams with stagnant water. Algae blooms mean a strong growth of toxin-forming algae, usually of the same species.

Algae blooms occur mainly in sunny and windless weather when the water is in imbalance, but also in eutrophication, primarily with phosphorus and nitrates. Plenty of sunlight is needed for algal blooms. The flow of toxin-producing algae occurs mainly at a water temperature between 15 and 23 degrees.

Algae amounts below 10,000 cells per ml of water are usually not categorized as algal blooms. In the case of extensive algal blooms, there are more than one million cells per milliliter of water.

Algae blooms can usually, but not always, be observed with the eye and nose. Sign of algal bloom:

  • The water becomes turbid with a marked color change. This can shift in yellow-green, blue-green, yellow-white, red-brown or rhubarb-like.
  • In general, the water volume is near-surface and not in depth.
  • The taste and aroma of the water can be affected; the water usually smells bad with a markedly repellent odor.

The algae can bloom throughout the year, but usually toxic algal blooms occur in July and August. However, they can take place right into November. Frequently, spring and autumn blooms are not toxin-producing and therefore harmless to humans.

Algae blooms can lead to the production of decay bacteria with subsequent oxygen deficiency in the water, which in turn can lead to fish death.

Exposure to toxic algae occurs mainly through baths, whereby contact takes place through the skin and mucous membranes, but also by swallowing of water.

Classification

Toxin-producing algae are blue-green algae, which are a variant of phytoplankton. In fact, the toxins are produced by bacteria (eubacteria), but classified as phytoplankton.

There are at least eight different types of toxin-producing algae in Sweden. Some of these are Microcystis aeruginosa, Anabaena sperica, Oscillatoria and Nodularia Spumigena (Cat sores).

The toxins are classified mainly in three different categories:

  • Neurotoxic toxins
  • Hepatotoxic toxins
  • Intestinal toxins

They can also cause skin and mucous membrane irritation in direct contact. In addition to purely toxic symptoms, they can cause allergic symptoms.

Symptoms

In the clinical picture after close contact, skin rashes and gastrointestinal disorders are usually included. Pronounced symptoms occur mainly if you swallow water through repeated colds or accidentally drinking contaminated water. The latter mainly affects animals, e.g. The symptoms usually occur within a few hours after bathing, rarely later than after 12 hours, and are usually transient within a few days. In pronounced cases, the symptoms can last for 2-3 days.

There is a risk of liver and kidney effects in the case of heavy exposure. An indication of strong exposure is general symptoms such as muscle pain and joint pain. Diagnosis is made by history and clinical picture. Even animals other than humans are at risk of becoming ill when in contact with toxic algae; Mostly dogs are at risk of serious symptoms after bathing among algae or by swallowing contaminated water. Common symptoms of poisoning with toxic algae:

  • Itching
  • Rash
  • Eye irritation
  • Nausea
  • Vomiting
  • Diarrhea
  • Stomach pain
  • Stomach cramps
  • Fever
  • Muscle pain
  • Joint pain (artralgia)
  • Runny nose
  • Asthma-like disorders, bronchial obstruction

Treatment

There is no specific treatment. The treatment is essentially symptomatic.

  • If bathed in poisonous algae, rinse the body thoroughly with shower water and then wash with soap and water all over the body.
  • In eye symptoms, rinse the eyes with running water.
  • If you have swallowed large amounts of water and experience general effects, you should visit a hospital. In hospitals, liver and kidney function should be checked with regular routine tests.
  • Dogs bathed in poisonous algae should initially drink plenty of fresh water.

SEA ANEMONES, CORALS AND CNIDARIA

It is increasingly common for Swedes to travel to tropical countries and dive or bathe in temperate, subtropical and tropical waters. Here you can encounter sea anemones, corals and cnidaria animals that can give rise to toxic reactions when in contact with nettle cells. One should therefore avoid taking or breaking corals and sea anemones.

In particular, these organisms cause local symptoms through their hives cells, but some of them can also give rise to general symptoms. The nettle cells release a toxin to allow the organism to paralyze its prey which it then consumes.

Classification

Anemones belong to the group of six-ray coral animals and are a type of polyp with tentacles. The skin irritating anemones belong to the strain Cnidaria which is a type of marine animal with toxin releasing nettle cells (nematocysts). Some toxic anemic and coral species are mentioned below. Click on the red marked external link for more images.

Actinodendron plumosum (pictured) is a toxic sea anemone, it has plenty of nematocysts that release an irritating toxin

Other highly burning anemones are Bolocera tuediae (pictured) and the Fire coral (Millepora dichotoma, picture). Stitches from the fire coral can cause pronounced burns with permanent scarring.

Treatment

The treatment is essentially symptomatic and resembles that of an attack by a jellyfish.

  • First rinse the damaged area with salt water.
  • Avoid heat and sun exposure.
  • Apply a corticosteroid cream or surface anesthetic containing lidocaine.
  • Antihistamine orally can suppress the inflammatory reaction, eg clemastine 1-2 mg p.o.

It is unusual with general symptoms.

PALYTOXIN

When handling saltwater aquariums, some implanted corals can release a toxin, a so-called palytoxin. The corals that are mainly prevalent are palythocorals and protopalythocorals, although some anemones also can release this toxin. Palytoxin is a potent toxin and has caused serious poisoning. One can be exposed to palytoxin via skin contact, eye contact, ingestion or inhalation. The toxin is a powerful vasoconstrictor and can cause vascular ischemia, including cardiac ischemia.

When handling these corals, the use of goggles, visors and long gloves is recommended to avoid splashing! The treatment is mainly symptomatic and supportive but one can try vasodilating treatment with eg papaverine or nitroglycerin. One should avoid boiling corals from such aquariums as the vapors may cause respiratory problems.

Symptoms of palytoxin poisoning may cause symptoms similar to local anesthetic drugs, but primarily give respiratory symptoms such as coughing and bronchoconstriction, gastrointestinal symptoms with nausea and vomiting and fever. Elongated obstructive distress have been described (1-3 months). Symptoms that may occur are:

  • Metal taste in the mouth
  • Tachycardia
  • Shortness of breath, cough
  • Bronkobstruktivitet
  • Fever
  • Chest pain
  • Hypotension
  • ECG changes
  • Muscle spasm
  • Severe pain
  • Vomiting
  • Seizures

When handling these corals, the use of goggles, visors and long gloves is recommended to avoid splashing! The treatment is mainly symptomatic and supportive but one can try vasodilating treatment with eg papaverine or nitroglycerin. One should avoid boiling corals from such aquariums as the vapors may cause respiratory problems.

CONIDAE (Conus geographus)

The conidae is a type of predator snail that lives on attacking and eating fish. The cone shell is large, has a cone-shaped spotted (leopard-like), hard and thick shell and can reach a length of 25 cm. It usually has a beautifully patterned shell that makes it attractive as a collector’s item and tourist attraction. It occurs mainly in the Pacific and Indian Ocean. The worm has a mouth arm that it can project as a harpoon from its shell and thus paralyze and catch the prey. Even people have been injured by contact with the cone-shaped shell.

The conidae injects a neurotoxic poison (conotoxin) that gives rise to pain, paresthesia and numbness, but also general symptoms such as muscle weakness, difficulty in coordination and impaired speech, hearing and vision. Even single deaths have been reported.

Bristle worms (Chloeia Flavia)

These little worms (aka fireworms) swim freely in tropical and warm waters and can cause burning pain in skin contact with divers. The fireworms belong to the group polychaete which contains a large number of different species. The worms have nettle cells that can give rise to local redness, pain and itching. The nematocytes can be removed with tape (silver tape) from affected skin. Then you should rinse off the skin, iron in vinegar and then apply a cortisone cream or a local anesthetic. Antihistamine can suppress the itch slightly.

Blue mussels

Blue mussel is a species in the mollusc class of mussels, (marine bivalve mollusks). The blue mussel is blue-black and normally oval shaped. It usually becomes about 6 centimeters long, but can be up to two decimeters. The edible muscle is yellow/yellow-white.

Blue mussel is extensively fished and grown on a large scale. Mussels are sold fresh, preserved or frozen. Blue mussels are a common food after cooking. They have the best taste in the spring.

Flowering phytoplankton that is toxin-producing can be found in blue mussels. These can then become unfit for food. A genus phytoplankton (Alexandrium) has been found in such quantities among blue mussels in Bohuslän that they can give rise to general disease symptoms.

It is extremely rare with poisoning from blue mussels. The toxin content usually rises in the autumn and is at its peak during the winter.

 

Symptoms

Symptoms of consumption of toxic blue mussels are mainly gastrointestinal:

  • Diarrhea
  • Nausea
  • Vomiting

Treatment

Normally you do not need to seek medical care, as the symptoms are relatively modest and quickly transient. In pronounced cases, fluid may need to be given intravenously. Otherwise, symptomatic treatment applies.

PSP “Paralytic Shellfish Poisoning”

More serious poisoning after consumption of blue mussels has occurred when the mussels are contaminated, including by Gonyulax catenella. The most common toxin that causes PSP is a saxitoxin. The Saxitoxin can be housed in mussels for several weeks or longer. The toxin is produced by microscopic algae filtered through blue mussel, eg after algal blooms. Other toxins that can give rise to poisoning symptoms are neosaxitone and gonya toxin. All toxins are essentially neurotoxic.

Initial symptoms are nausea and vomiting, but this toxin can also cause dizziness, coordination disorder, speech difficulties, dry mouth, swallowing difficulties, difficulty breathing, increasing muscle weakness and paralysis. There is also a drop in blood pressure, heart failure and cardiovascular collapse. Occasional deaths are reported. Children and immunosuppressed individuals are more sensitive to these toxins.

The treatment of PSP is essentially symptomatic. In severe cases, ventilator treatment in an intensive care unit may need to be addressed.

CSP (Ciguatera shellfish poisoning)

In French Polynesia, ciguatera-like symptoms have been reported after consumption of shellfish, including oysters.

Symptom

  • Nausea
  • Vomiting
  • Asthenia
  • Myalgia
  • Paresthesia
  • Dysaesthesias
  • Persistent hiccups

Treatment

Treatment is essentially symptomatic but mannitol intravenously has been tried as for ciguate poisoning.

ICD-10

  • Other fish and shellfish poisoning T61.2
  • Toxic effect of contact with other marine animals T63.6

Published with permission from Internetmedicin AB


Irritant Gas Exposure

By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2018-12-21


Poisoning after exposure to irritant gas usually occurs after fires, but can also occur after chemical accidents. Fire smoke can contain up to 60 different chemical substances that can irritate airways and bronchi, but essentially it is black soot that irritates the respiratory tract in connection with fire. In addition to harmful smoke in case of fire, the airways can be damaged by extreme heat, hot steam, toxic gases and hypoxia. Swollen eyebrows, eyelashes, nasal hair and beard, conjunctivitis, increased tear flow, light shading, facial burns, swelling of soot, edema in the throat and nasal passages are symptoms of inhalation injury. Larynx can swell heavily after thermal damage and soot can obstruct the airways purely mechanically. Soot can pluck the bronze tree again and give rise to shut-off airways with auto-PEEP. Other symptoms may include coughing, hoarseness, strife and obstructive breathing. If severe edema is present in the airways, the patient should be intubated acutely and cared for in an intensive care unit.

Irritant gases can cause tracheitis, bronchitis and bronchiolitis with hyperemia, bronchospasm, abundant mucus secretion and edema. In severe cases, an ARDS image may develop with increasing lung fibrillation. Inspection of pharynx and larynx prior to intubation should be done if soot and edema occur through thin fibrosis via the nose during easy sedation.

Gases can exert direct toxicity, such as cyanogen gas (blocking cellular respiration), carbon monoxide (blocking oxygen transport) or chlorine gas (mucosal irritation). Other gases can cause severe hypoxia by replacing the oxygen in the inhaled air, such as methane, carbon dioxide and butane gas.

Inhalation of black soot quickly gives rise to severe shortness of breath, respiratory irritation, edema and cough. Primary action when exposed to irritant gases, of course, will escape the exposure and breathe fresh air. If the exposure has been short-lived, most people quickly recover without having to seek medical care, but sensitive people may have persistent broncho-obstruction and respiratory irritation. Heavy exposure to fire smoke can cause serious symptoms that can cause long-lasting symptoms. In case of inhalation of fire smoke, it is primarily inhalation of carbon monoxide and hydrogen cyanide which causes severe poisoning symptoms.

Irritant gases

Highly soluble gases

The properties of easily soluble gases in water are that they dissolve easily in moist mucous membranes, for example in the upper respiratory tract and eyes. The easily soluble gases therefore give immediate symptoms.

Examples of readily soluble gases are:

  • Alkali
  • Ammonia
  • Phenacyl chloride
  • Hydrogen fluoride gas
  • Formaldehyde
  • Gaseous acids
  • Sulfur dioxide
  • Hydrogen chloride (hydrochloric acid)
  • Zinc chloride (in defense smoke grenades)

Medium soluble gases

Medium soluble gases produces both upper and lower respiratory tract symptoms.

Examples of medium soluble gases are:

  • Phenol
  • Sulfur dioxide

Low soluble gases

The properties of sparingly soluble gases in water are that the gases are difficult to dissolve in the moist mucous membranes. Thus, the gases reach the lower airways and all the way down to the lung vesicles. The sparingly soluble gases therefore provide delayed symptoms; from 30 minutes up to 48 hours after exposure, with risk of late pulmonary edema. The extent of the damage in the airways depends on the concentration of the gas, the time of the exposure and the solubility of the gas. Slightly soluble gases give more in-depth damage that is more likely to cause persistent but as bronchiolitis, granulation with fibrosis and ARDS. Phosgene and nitrous gases can cause modest initial symptoms that worsen gradually.

Examples of low soluble gases are:

  • Phosgene
  • Isocyanates
  • Chlorine
  • Chlorine dioxide
  • Mercury steam
  • Nitrogen dioxide
  • Nitrous gases
  • Hydrogen sulphide (hydrogen sulphide)
  • Orthochlorobenzalmalononitrile (tear gas)

Examples of irritant gases or chemicals

Tear gas

  • (CS gas) – used as incapacitating agents in connection with demonstrations and riots
  • Contains usually 2-chlorobenzene malonic acid dinitrile.

The substance is used as an aerosol dissolved in acetone. Tear gas is a strong respiratory tract irritant and causes severe burning and itching of the eyes and mucous membranes with abundant toes secretion. Tear gas usually gives no pronounced poisoning symptoms but occasional deaths have occurred. Instead, Swedish police use pepper sprays which contain capsaicin, which is a constituent of pepper fruit.

Acetone

  • Colorless, volatile, flammable liquid
  • Solvents in varnishes and plastics
  • May cause headaches and, in the worst case, unconsciousness

Acrylic nitrite

  • Colorless, toxic and highly flammable liquid
  • Converts to cyanide in the body
  • The symptoms are gradual over several hours
  • Available in plastics and nitrile rubber
  • Gives burning in the eyes, irritates the skin and can cause vomiting and headaches
  • Should be treated with the cyanide antidote sodium thiosulfate

Ammonia

  • Colorless gas at room temperature
  • Occurs in refrigeration plants and in the chemical industry
  • Irritating to eyes and airways in small quantities. May lead to suffocation at high levels.

Aniline

  • Colorless poisonous liquid is available in the refrigerator
  • Used in the manufacture of dyes, pharmaceuticals and antioxidants.
  • Blocks oxygen-carrying capacity of hemoglobin so that it cannot release oxygen or absorb carbon dioxide in the cells

Benzene

  • Colorless, highly flammable liquid
  • Solvent for fat
  • Carcinogenic, may affect the bone marrow

Benzopyrene

  • A group of aromatic hydrocarbons formed during incomplete combustion, for example in car engines
  • Highly carcinogenic and reproductive disorders

Hydrogen Cyanide

  • Colorless, volatile and extremely toxic liquid or gas. Smells bitter almond.
  • Has been used in executions in certain countries and in the production of methacrylate, amino acids and cyanide compounds.
  • Blocks the ability of cells to absorb oxygen.
  • Provides seizures, heart effects and unconsciousness.
  • High doses kill very quickly

Phenol

  • Highly corrosive and toxic substance that forms colorless crystals.
  • Manufacture of plastics, dyes, explosives, pharmaceuticals and detergents.
  • Several phenols can contribute to cancer. One gram has caused death.

Formaldehyde

  • Colorless gas extracted from methanol. Easily soluble in water.
  • Used in the manufacture of plastics, disinfectants and insecticides.
  • Respiratory tract irritation, damaging cilia. May be carcinogenic.

Cadmium

  • Silver-white, soft metal found in the earth’s crust. Very toxic.
  • Available in batteries and alloys.
  • May damage airways and lungs. May be carcinogenic.

Chlorine gas

  • Heavy mucous membrane irritation both in the eyes, mouth and throat and upper and lower respiratory tract
  • Converts to acid and gives rise to severe mucosal damage
  • Fatal in strong concentrations

Vinyl chloride

  • Colorless toxic gas.
  • Manufacture of PVC plastics
  • May be carcinogenic.

Isocyanates

  • Available in colors and plastics
  • May cause skin allergies
  • Evaporate and can form toxic gases at temperatures above 160 degrees
  • Was the subject that mainly caused more than 2000 deaths in connection with leakage from an industry in Bhopal in India in 1984.

SYMPTOMS after inhalation of irritant gas

Inhalation of fire smoke and other irritating gases usually causes severe respiratory irritation with persistent cough, shortness of breath, severe mucus secretion and airway obstruction (bronchospasm). Hypoxia, cyanosis and hypercapnia can follow. Other clinical symptoms may include agitation, anxiety, dyspnoea, anxiety, tachypnea, nasal congestion, wakefulness, unconsciousness and intercostal withdrawal. Note that some toxic gases can be toxic without being irritating in the airways, eg carbon monoxide.

Laryngospasm itself can cause severe hypoxia, fainting and unconsciousness. When the laryngospasm releases, a reflective pulmonary edema may appear. When exposed to sparingly soluble gases or nitrous gases, a toxic pulmonary edema can occur late in the process and the patient therefore needs to be monitored for at least 24 hours.

TREATMENT

General treatment

Patients who inhale toxic gas or smoke are usually treated with both corticosteroids and bronchodilator inhalation treatment (beta-stimulants).

Budesonide and terbutaline or salbutamol are given in repeated inhalations. Combination pharmaceuticals may contain both ipratropium and salbutamol. Corticosteroids may need to be given in repeated doses in inhalation, usually not given systemically. Give treatment with beta stimulators before treatment with corticosteroids to improve the ability of the steroids to reach more pulmonary segments.

In cases with highly inclusive patients, it is better to secure the airway acutely through intubation with controlled breathing and respiratory care. Respiratory arrest can come suddenly in an exhausted patient. Bronchoscopy should be performed for the diagnosis and cleansing of mucus and soot. Soot in the airways can plug the bronchial tree again and should be obtained via bronchoscopy with lavage. Note the risk of early or late pulmonary edema. In case of burn over jugulum caution with tracheotomy.

Awake patient

  • Peace and quiet
  • After inhalation of irritating gases, toxic gases or smoke, the patient should preferably rest in sitting, so-called heart position, preferably with oxygen on tight-fitting mask.
  • In the event of heavy exposure with swelling of the airways or the presence of soot, the airways should be inspected with fibrosis.

Unconscious patient

  • The patient is placed in the left side position, or in the forward side position.
  • Initially, 100% oxygen is given to the mask and acute intubation with controlled ventilation should be performed quickly in unconsciousness. If cardiac arrest occurs after flue gas poisoning, there is a great risk of global anoxic brain injury.
  • In case of heavy exposure with swelling of the airways or the presence of soot, the airways should be inspected with fiber bronchoscopy, liberal indication for intubation.

Oxygen

Initially, 100% oxygen is given on tight-fitting mask with reservoir blow until it is determined CO-Hb and excluded serious carbon monoxide poisoning. If CO-Hb is less than 10%, oxygen can in the future be given via the semi-open respirator, Optiflow system or halter. Via nasal gripping is given 4-6 liters/min to reach SaO2 ≥ 90%. Difficulties can arise with mask ventilation when the patient has a great need for coughing. The cough can be suppressed with morphine and theophylamine.

Inhalation therapy

Inhalation therapy is given early with beta stimulators and steroids. Repeated treatment is often necessary.

Beta-2 stimulator therapy

  • Terbutaline 0.5 mg/dose 2-3 inhalations as soon as possible alternatively
  • Salbutamol 5 mg/ml, 1-2 ml inhalation solution in nebuliser. The above inhalation can be combined with 2 ml of ipratropium bromide inhalation solution 0.25 mg/ml at apparent mucus secretion.
  • If the patient cannot inhale, beta 2 stimulants may be administered parenterally. Injection solution terbutaline 0.5 mg/ml, 0.5-1.0 ml subcutaneously. In severe seizures, 1 ml of the solution for injection is diluted with 10 ml of NaCl and given slowly (over 5 minutes) intravenously.

Steroids

  • Indication for cortisone treatment exists if the patient has had pronounced legal symptoms with intensive troublesome cough or respiratory effects, obstructive effects or been exposed to phosgene or nitrous gases.
  • Steroids are primarily given as inhalation via nebuliser. Budesonide (Pulmicort) suspension for nebuliser 2 mg x 2 (4 ml x 2).
  • In case of severe symptoms, initially 10 inhalations and, if necessary, 4-5 inhalations x 1-2 within the first hour. After each inhalation, keep your breath for about 10 seconds. The next inhalation is done after a couple of normal breaths. With recurrent symptoms, another 2-3 treatments are given the first day. For children, the doses are halved.
  • Steroid therapy parenterally (intravenously) is not normally recommended. If steroids cannot be given in inhalation, systemic administration may be considered (intravenous / intramuscular).

CPAP treatment

Resistance breathing with CPAP can be tested with 100% oxygen (BiPAP). The resistance is varied between 5 and 10 cm H 2 O. Never start on 10 cm H2O but normally on 5 cm H2O. Note, however, that this involves extra breathing work and can mean a tremendous strain on the patient. Sedation is often required. In CPAP treatment, there must be immediate readiness for intubation. An exhausted patient should not be treated with CPAP. Intubation and controlled ventilation are considerably safer and better if the patient is included.

Optiflow system

An optiflow system can advantageously be used if the patient has a pronounced cough as it is difficult to cough in a tight-fitting mask. Optiflow provides increased resistance in the exhalation and contributes to the aeration of atelectases.

Anticholinergic therapy

In the case of excessive mucus secretion, an anticholinergic drug is given intravenously.

Atropine 0.5 mg/ml, 2 ml i.v. or glycopyrronium (Robinul) 0.2 mg/ml, 1-2 ml i.v. Note that in rare cases of poisoning with organophosphates, isocyanide and certain insecticides and pesticides, significantly higher doses of atropine may be required (SIC doses). Treatment is controlled by the clinical picture with mucus secretion in the airways or other cholinergic symptoms.

Theophylline

May be given in severe breathing difficulties or persistent coughing. Give 10 ml (23 mg/ml) of theophylamine slowly (10 minutes) i.v. Never to be given in a central venous line. Overdose can cause life-threatening arrhythmias. Then add 20 ml of theophylamine in 500 ml of 5% glucose over 12 hours. Check theophylamine concentration in serum.

Specific treatment

Cyanide poisoning – Inhalation of hydrogen cyanide

Antidote treatment for cyanide poisoning can be initiated at the injury site in connection with exposure to fire smoke, but usually it is sufficient to start treatment after arriving at a hospital with the guidance of an arterial blood gas measuring SvO2 and lactate. Cyanide is not usually measured. Antidote for cyanide poisoning is given if the injured has been or is unconscious and has been withdrawn from a burning house and has soot in the nasal openings or coughing soot. Lactate values ​​less than 10 mmol / l indicate that severe cyanide poisoning is not present and does not require antidote treatment. Severe cyanide poisoning is usually associated with fainting and unconsciousness. Thus, if the patient is awake, severe cyanide poisoning is less likely. Hydroxycobolamine (Cyanokit) is given intravenously in poisoning with hydrogen cyanide (fire) or other cyanide compounds.

Treatment with Hydroxocobolamine (Cyanokit):

  • Adults: 5 g are given i.v. as infusion for 15-30 minutes, repeat as needed
  • Children: 70 mg / kg body weight

Note after treatment with hydroxocobalamin, the skin, urine and other body fluids become strongly red colored. This should be communicated to the staff and the patient who might otherwise be surprised and worried. The color can affect chemical assays based on chromatography.

If hydroxocobolamine is not available, treatment may also be given with Sodium Thiosulfate.

  • Adults: sodium thiosulfate 150 mg / ml: 15 g (100 ml) given i.v. for 5-10 minutes. May be repeated
  • Children: 375 mg (= 2.5 ml) / kg body weight

Carbon Monoxide Poisoning

Carbon monoxide poisoning is common after exposure to smoke. Carbon monoxide provides alertness and respiratory failure. Consider pressure chamber treatment (HBO) and acute transport to pressure chamber if the patient is unconscious or has been unconscious. Consult the Poison Information Center in case of doubt. CO-Hb values ​​above 25% indicate severe carbon monoxide poisoning. The treatment primarily consists of oxygen on tight-fitting breathing mask (NBO, normobaric oxygen therapy). Lactate values ​​rarely exceed 10 mmol in pure carbon monoxide poisoning.

Cutaneous exposition to chemicals

If the patient has a chemical accident with cutaneous exposure (poisoning through the skin) of chemicals, sometimes in combination with a burn, the patient should be remedied. Remove all clothing (wear strong protective gloves when contacting chemical fluids). Shoes and jewelry should also be taken off. Flush or shower the patient with plenty of water. Use warm water and make sure the patient is not cooled down. In case of chemical exposure, the patient should first be remedied once outdoors and then once indoors. Be careful with your eyes. If the patient’s clothes are dry, you generally do not need to clean up. Wash exposed skin with soap and water. However, the procedure should not be exaggerated.

Some remediation rooms are located in semi-enclosed rooms, such as an ambulance entrance. There, as a rule, the temperature is low and it is important to quickly give the patient warm clothes and blankets to avoid cooling down. When exposed to highly alkaline chemicals, rinsing should be carried out for a long time. Gas and odor from toxic chemicals is blown away or sucked out with fan systems – make sure the air is warm!

If the staff are exposed to irritating gases, these may also require treatment with cortisone inhalations! Note if someone has given the patient a mouth-to-mouth resuscitation.

Eye irritants (eye exposure)

If burning, itching or redness occur in the eyes, rinse as fast as possible with running water for 5-15 minutes. Keep the eyelids wide apart so that flushing becomes effective. Examples of eye irritants are chlorine gas, lye or acids of various kinds. Exposure to these substances may require longer than 15 minutes of flushing. Eye irritation is common among bathers in connection with technical swimming pool accidents with chlorine release.

FOLLOW-UP

Follow-up of the patient who is exposed to fire smoke is important since the respiratory tract and respiratory distress may cause long-term problems and in some cases persistent. Referral to lung medical clinic is urgent. Notification of work injury must also be carried out in relevant cases.

ICD-10

  • Gases, fumes and vapors, unspecified T59.9
  • Bronchitis and pneumonitis caused by chemicals, gases, smoke and steam J68.0
  • Upper respiratory tract inflammation caused by chemicals, gases, fumes and vapors not classified elsewhere J68.2

References

  1. Toxic smoke inhalation: Cyanide poisoning in fire victims. Jones J, McMullen J, Dougherty J. Am J of Emerg Med. Volume 5, Issue 4, July 1987, Pages 317-321, Länk.
  2. Toxic smoke inhalation and cyanide poisoning. Merril A, Cohen MD, Lawrence J, Guzzardi MD. The American Journal of Emergency Medicine Volume 6, Issue 2, March 1988, Pages 203-204, Länk.
  3. Chlorine Gas Exposure and the Lung: A Review Rupali Das, Paul D. Blanc. Toxicology and Industrial Health Vol 9, Issue 3, 1993, Länk.
  4. The Role of Bronchoscopy in Pulmonary Complications due to Mustard Gas Inhalation. Freitag L, Firusian N, Stamatis G, Greschuchna D. Chest Volume 100, Issue 5, November 1991, Pages 1436–1441, Länk.
  5. Behandlingsanvisningar vid händelse med kemiska ämnen. Fastställt av RKMK 206-05-10. Reviderade 2011.
  6. Wang J, Winskog C, Edston E, Walther SM. Inhaled and intravenous corticosteroids both attenuate chlorine gas-induced lung injury in pigs. Acta Anaesthesiol Scand 2005;49:183–190.
  7. Wang J, Zhang L, Walther SM. Inhaled budesonide in experimental chlorine gas lung injury: influence of time interval between injury and treatment. Intensive Care Med 2002;28:352–357.

 

Published with permission from Internetmedicin AB


Bites and Sting

By Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2019-02-18


Symptoms from bites and sting occur mainly in summer when people out in nature come in contact with gnats, mosquitoes, bees, wasps, ticks, jellyfish, etc.

Most bites and stitches in the Nordic countries are of benign nature and cause only mild to moderate symptoms. Some stitches can give rise to more serious symptoms and the number of healthcare-related cases can be counted in thousands every summer. Deaths are very rare, but occasional cases occur every year, mainly in the form of allergic reactions after bipolar disorder with anaphylactic shock resulting in 2-3 deaths per year. Deaths after snake bites occur only sporadically, around one case per decade in Sweden.

A number of diseases transmitted from insects to humans (zoonoses) can cause very serious symptoms. Below is a brief summary of the bites and stitches of different genes.

SYMPTOMS after Insect Bite

  • Pain
  • Swelling
  • Redness
  • Itching
  • Discoloration
  • Moderate general symptoms

TREATMENT

  • Clean the bite site with soap and water
  • Apply cooling and decongestant treatment, eg ice packing. Alternatively, you can apply cooling gel or special insect gel (eg mosquito gel – contains menthol and eucalyptus oil).
  • Avoid scratching the bite site.
  • If possible, remove the remaining tag or mouthpieces with a pair of tweezers. Avoid squeezing the bite of the bite.
  • Local anesthetics in ointment relieve itching, eg Xylocain ointment 5%.
  • Antihistamines per os, e.g. with body weight below 30 kg, Loratidyn (Clarityn) syrup 1 mg/ml is recommended rather than tablets.
  • Hydrocortisone cream locally, eg Hydrocortisone CCS or Mildison when swollen.
  • Antiseptic cream locally, eg LHP 1% containing hydrogen peroxide.

DIFFERENT TYPES OF BITE AND STING

Mosquito bite

Mosquito bites are commonly found every summer in connection with moisture and heat, especially evening and night time in woodland or in the vicinity of watercourses. There are more than 30,000 different kinds of mosquitoes, of which about 2000 are in Sweden. In essence, there are two types of gland, forest ridges (Aedes communis) and floods (Aedes sticticus). It is only the female mosquito that sucks blood.

Forest Mosquitoes

Forest mosquitoes are mainly active at dawn and in the evening. They take time before they stand, and can fly no more than two kilometers from the hatching site. It is only the females who stand to suck blood. The mosquitoes can live for up to two months. Most bites occur peripherally on the extremities, ie around the ankles and wrists. The mosquitoes are active from June, most are around midsummer and become fewer in July.

Flooding Mosquitoes

Flood mosquitoes are active throughout the bright part of the day, they can bite even in the middle of the day in sunshine.The flood mosquitoes are more aggressive and sting directly when in contact with people. They can fly up to two miles from the hatching site and are active until September.

General aspects of mosquito bite

  • Different people attract mosquitoes to varying degrees, but are attracted mainly by warm and sweaty skin. The alcohol effect that increases blood flow increases the risk of biting. People’s scents and sweating tendency play some role while the blood group plays less role. According to a Japanese study on tiger mosquitoes, these mosquitoes prefer people with blood group 0.
  • Mosquito bites swell and blush, but are rarely infected if you do not tear yourself and scratch the skin and thus get bacteria from the skin flora into the wound.
  • When the mosquito bites are in progress, let the mosquitoes suck clear so that they can finally aspirate their saliva, which possibly leaves less itching.
  • Mosquito bites can be prevented to some extent by wearing light and cool clothes or by applying cream or ointment from a mosquito pin that keeps mosquitoes away (“repellents” – spray or gel). Repellents contain, among others, DEET (N, N-diethyl-meta-toluamide).
  • The symptoms of mosquito bites can be alleviated by cold, such as an ice pack or cold conditioner. A variety of different house cures of varying quality are described, for example, to apply film milk or paste to the skin. For medical treatment, see above.
  • Mosquito bites in Sweden rarely give rise to dangerous diseases. Cases of mosquito-borne tularemia (Rabbit fever) occur. Rabbit fever is caused by the bacterium Francisella tularensis. Brake, ticks and knots can also spread this bacterium. Harpest can cause high fever, nausea and headaches. A sore wound occurs after the mosquito bite, the lymph nodes become sore and enlarged. The infection is treated with antibiotics, eg doxycycline or streptomycin.
  • “Ockelbo disease”, previously known as Berry pick disease or Pogostasis, is due to a virus called Sindbis virus which is transmitted by mosquitoes. The symptoms are rash, joint pain, fatigue and fever. The symptoms are usually moderate and transient, but joint pain has in some cases become protracted. The disease is most common during late summer and early autumn. The rash is speckled and pain has been described from eg hands and feet.
  • Ellioviricetes have mainly occurred in Finland. The disease is due to a virus called Bunay virus spread by mosquitoes. The infection is usually subclinical but can lead to a meningitis picture.
  • In 2015 and 2016, global alarms were issued about the dangerous Zika virus that can be transmitted by mosquitoes. The disease occurs in South and Central America, Southeast Asia and Africa. The severity is due to suspicion of serious neurological abnormalities on the fetus if the infection is transmitted during early pregnancy. Several children have been born with microcephaly. The course of the disease itself has been relatively benign, with mild flu-like symptoms, sometimes completely asymptomatic. The disease can be accompanied by a maculopapular exanthema, itching, joint pain, conjunctival injection and lymphadenopathy. There are also suspicions of links to fetal death, placental insufficiency, growth retardation and Guillain-Barré.
  • Several other diseases can be spread with mosquitoes in exotic countries, including malaria, West Nile virus and visceral leishmaniasis. Malaria mosquitoes also occur in Sweden but they are not carriers of the malaria parasite.

Gnats – Black fly

  • Black flys (Simuliidae) are a type of small mosquitoes (2-5 mm) with rounded height back and wide fly-like wings. There are about 35 different species in Sweden. Black fly bits, hence the common name “scorching”. Bites of black flys occur as well as mosquito bites mainly in the summer, especially in the northern parts of Sweden and at higher altitudes, such as in the mountain world.
  • Black flys attacks often give rise to a large number of bites simultaneously.
  • Like mosquitoes, black flys are drawn to warm and moist skin. Black fly bites causes the same symptoms as regular mosquito bites, even the bite itself can pain.
  • Avoid hiking with bare skin parts, avoid short sleeves and shorts. The treatment is the same as for mosquito bites.

Horse fly

  • Horse-flies is a type of two-winged fly that can bite people and suck blood. Note that horse flyes do not sting, they bite. Horse flies are similar to flies, but are usually slightly larger and louder. Horse flies fly silently and surprise with sudden blows on only skin parts. They particularly irritate horses and cows that go out in pasture pastures, but also bite people.
  • There are no chemicals that protect against horse flies. The bite often gives rise to a larger affected skin area compared to mosquito bites. Redness with episodes of hemorrhage (echymoses) causes a bruise to form, which can be large as a palm. The bleeding is due to the fly injecting coagulation inhibiting enzymes into the skin when it bites.
  • The treatment is essentially symptomatic with itchy creams as well as cooling and disinfecting solution, eg alsol solution.

Deer fly (Moose fly)

  • The deer fly is a 5-7 mm long lice fly (Lipoptena cervi) that can bite people. Normally it bites and sucks blood from moose and other fur-bearing deers. The fly has claw-like feet which it sticks to after impact and which makes it difficult to remove. When it gets stuck, it loses its wings, bites and sucks blood. The deer fly occurs most during the late summer and early autumn in forest-close terrain.
  • Perfumes and other scents that characterize people can keep the elk fly away. When knocking on humans, there may be bites of about twenty flies simultaneously.
  • The bite gives rise to itching and swelling. Normally, it does not cause any disease but can be a carrier of bacteria, eg Bartonella schoenbuchensis.
  • The treatment is essentially symptomatic with itchy creams as well as cooling and disinfecting solution, eg alsol solution.

Spider bites

  • There are about 42,000 known species of spiders, of which about 600 are in Scandinavia. Most people are completely harmless to people, but spiders still cause a lot of discomfort and fear. Common spiders in Sweden are domestic House Spider, Wolf Spider, Cross Spider, Amaurobiidae spider, Zebra spider, Silver sided sector spider, Rabbit huch spider. The spiders vary in size and color, but are recognized by the eight legs that are in four pairs of legs.
  • All spiders are predators and can therefore bite, but bites on humans are rare. The bite of the Cross spider can cause local redness and swelling, but the bite is harmless and the discomfort is usually transient. A weakly poisonous spider species that occurs in southern Sweden is the Hobo spider (Tegenaria agrestis). A spider that can cause more discomfort to the bite is the Prickly sack spider (Cheiracanthium punctorium); its bite causes trouble roughly on par with a wasp stick. Prickly sack spindle occurs mainly on Öland.

Foreign spiders

  • In other parts of the world, mainly in Africa, South America and Australia, there are several toxic species, some of which may even be fatal to humans.
  • The most famous poisonous spider is the Black Widow (Latrodectus mactans), where the female has a characteristic red hourglass-shaped spot over her back. Black widow carries a potent poison, latrotoxin. However, so little of the poison is injected that the effects on humans are rarely severe, deaths occur but are very rare. The bite is painful and the pain increases in intensity after a few days and then turns off. The black widow occurs mainly in the southern and central United States, but relatives of the black widow occur throughout much of the world.
  • In Australia, there are a number of toxic spiders that can cause serious human reactions. Among the most dangerous are the Red-Backed Spider (Red back spider, Latrodectus hasselti), which is a type of widow spider that moves relatively slowly. The most dangerous spider is the Sydney Funnel Web Spider (Atrax robustus), which is a type of hopper spider. The spider is relatively large (about 3 cm long) and becomes slightly aggressive. It is usually hidden in shoes! The spider is equipped with two powerful jaws and can inject relatively much poison which can be dangerous to humans. Serum for treating bite of the red-backed spider and Sydney funnel web spider is available in Australia and is given to patients who develop general symptoms after biting. Deaths occur sporadically among humans, but are very rare. Since serum was developed in 1981, no death has been recorded in Australia.

Bee and wasp-stings

  • There are more than 100,000 different species under the order hymenoptera.
  • Bee stings usually gives rise to local pain and swelling that normally ceases and disappears within a few days. A bee sting is considerably more painful than a mosquito bite. Bees and wasps usually only sting in self-defense when they feel threatened.
  • Allergy to bee stings can develop at all ages. Usually, allergy comes only after several harmless stings.
  • Children are usually stung more than adults, but systemic reactions only occur in about 1% of children. A few people react more strongly to these stings and can develop general symptoms with general malaise, anxiety, anxiety and shortness of breath.
  • Bees usually inject more poison than the wasp do, so its bite irritates more. The bee’s pike has barbs while the wasp’s lacks barbs. The bees sting therefore sticks to the skin more easily. Try to remove the remaining sting. Scrape away the thread without squeezing it together.
  • Bee stings can cause anaphylactic shock which can be life-threatening. Even stings in sensitive places, such as tongue and throat, can become life-threatening due to swelling and should therefore be treated with cortisone i.v. or i.m. to avoid breathing difficulties.
  • An uncomplicated bee sting can be treated locally with cooling ice pack or cooling compress and then with anti itching agents or local anesthetics, eg a hydrocortisone cream or lidoocaine ointment 5% 10 gram.
  • Peripheral venous catheters (PVC) are added and fluid is given in the form of crystalloid solution at general symptoms, e.g., Ringer-Acetate 1000 ml.
  • General reactions should be treated with antihistamines and corticosteroids.
  • Antihistamine, eg desloratidine 10 mg of mouth-soluble p.o. or loratidine 10 mg p.o.
  • Serious anaphylactic reaction must be treated with adrenaline, epinephrine (eg Epipene) 500/300/150 µg i.m. in the outside of the thigh. For adults over 60 kg, 500 µg i.m. For adults and children between 20 and 60 kg, 300 µg i.m. For children weighing 10-20 kg, 150 µg i.m. Beta-stimulants (eg salbutamol) are given in inhalation during broncho-obstruction.
  • Anaphylaxis is treated and monitored in hospitals.

One should avoid attracting bees and wasps by placing foodstuffs and sweets (especially juices) open in the vicinity of their nests or communities. In the presence of bees or wasps one should avoid waving or attacking the insects as this attracts to seizures. When attacked by an entire swarm, escape is preferred. Tobacco smoke and other fumes containing carbon monoxide significantly reduce bee activity.

Tick bites

  • Tick ​​bites are commonly found after barefoot walking in woodland or meadows, especially in high grass. The ticks found in Sweden (Ixodes ricinus) bite unnoticed firmly in the skin and then grow by sucking blood, from a few mm to about 10 mm in size.
  • Tick ​​bites do not usually give rise to particularly severe symptoms, but can transmit dangerous diseases such as Borrelia, Rickettsia, TBE (Tick-Borne Encephalitis) and Anaplasmos (Ehrlichia).
  • Ticks can carry on several different species of pathogenic microorganisms simultaneously.
  • If a tick is detected on the skin, it should be removed as soon as possible by grasping the tick around the head with a fine-toothed tweezers (or with a special tick tweezers) and pulling straight out. One should try to remove all insect parts. Applying fat around the tick’s head is no longer recommended. The bed site should be washed with soap and water or alsol sprite after the tick has been removed.
  • If a single redness (erythema migrans) greater than a five-crown occurs, it should be treated with antibiotics in the form of phenoxymethylpenicillin (PcV), (1 g x 3 for 10 days). Scattered blushes should be treated with antibiotics with better penetration to the CNS, eg doxycycline 200 mg x 1 for 10 days. Blushes below the size of a five-crown need not be treated with antibiotics unless there is a general symptom. If symptoms appear indicative of TBE, the patient should be treated by an infectious physician.

Borrelia (Lyme borreliosis)

  • Borrelia is caused by a group of bacteria (Borrelia burgdorferi) that spread with ticks. The ticks often get the bacteria from infected small rodents. The infection is more unusual north of the Dalälven river.
  • The incubation period varies from three days up to one month. Approximately 10 000 people are expected to have a drilling disorder every year in Sweden. There is the greatest risk in Sweden’s southern and middle parts, as well as along coasts and lakes.
  • Most of the borrelia sufferers only get local symptoms in the form of redness and lighter swelling around the site. The redness is usually rounded and ring-shaped, but can also be asymmetric. Usually, the glow spreads annularly outward from the bite site and fades centrally.
  • Borrelia should be treated with antibiotics in the form of PcV or tetracyclines (doxycycline) for 10-21 days. Doxycycline is selected if neurological symptoms are present. Vaccine is not yet available. Incorrect diagnosis of Lyme disease is common.
  • Borrelia can cause untreated encephalitis with severe symptoms of generalized feeling sick, fever, wakefulness and power reduction.
  • See separate treatment overview on Lyme disease.

TBE – Tick-Borne Encephalitis

  • TBE is caused by flaviviruses that spread with ticks. Every year 150-200 cases are reported in Sweden. TBE occurs mainly in the southern and middle parts of the country and is most common in the eastern parts around Mälaren, in Uppland and Södermanland.
  • TBE appears as an encephalitis with high fever, severe headache, occasionally with convulsions and development of peripheral neuropathy with numbness, paresthesia and dropout symptoms. Most of the sufferers are completely restored, but about 30 percent get long-lasting or permanent symptoms with chronic fatigue, weakness and memory disorders.
  • Specific treatment for flaviviruses is lacking and the treatment is essentially symptomatic.
  • TBE can be prevented by vaccination. Vaccination is recommended for specific risk groups, such as people who live permanently in high-risk areas and people who through their habits often become tick-borne.
  • See separate treatment overview on TBE.

Rickettsiosis

  • Rickettsiosis is caused by bacteria that are spread with ticks, lice, fleas and mites. Rickettsiae are small gram-negative bacteria that multiply intracellularly. Today there are about twenty known rickettsias, two of which occur in Sweden. Of these, Rickettsia helvetica (which is spread with ticks) is the more studied. Its importance as a disease maker is not fully understood.
  • The symptoms are high fever, headache, muscle aches, sweating, skin rash, hearing loss and, in severe cases, myocarditis. Fatal outcome cases secondary to myocarditis are described.
  • Treat with doxycycline (T Doxyferm) 100 mg 2 x 1 for 10 days.
  • See separate treatment overview on rickettsioses.

Anaplasmosis

  • Also known as tick fever. Formerly called Ehrlichia.
  • Gives symptoms such as fever, chills and night sweats. Headache, myalgia, fatigue, malaise, nausea, vomiting.
  • See separate treatment overview on Anaplasmosis.
  • Treat with doxycycline 100 mg 2 x 1 for 10 days.

Jellyfish sting

In Sweden, jellyfish sting is usually caused by the Lion Mane Jellyfish (Cyanea capillata), but also Compass Jellyfish (Chrysaora hysoscella) can cause stings, sometimes also redness and swelling. The lion mane jellyfish is common along the west coast from June onwards during the summer months. The symptoms of stings from the lion mane jellyfish are persistent itching and burning. Jellyfish are nettle animals and the damage is caused by millions of nematocysts in the jellyfish’s wires.

See separate treatment overview on eg jellyfish.

Treatment of jellyfish sting

  • First rinse off affected skin areas with plenty of sea water from a bucket.
  • Avoid contact with fresh water primarily, avoid showering.
  • Apply a cooling pack over the skin, eg ice cubes in a bag. Do not apply ice directly to the skin.
  • Avoid rubbing or rubbing the skin, eg with a towel.
  • Try removing residual jellyfish by scraping the skin with a credit card or shaving the skin with a razor and shaving cream.
  • If a pronounced reaction has occurred, you can try to lower the affected body part in hot water immersion (about 45 degrees) for about 20-30 minutes.
  • Apply a mild hydrocortisone cream or lidoocaine ointment 5% 10 gr.

Snake envenomation

Bites of snakes are usually caused by vipers in Sweden during the summer, mainly in coastal terrain. Bites of tropical snakes are more rare, but occur when snakes are handled abusively in private or public terrariums. Vipera berus (Scandinavian viper/European viper) venom is necrotizing and hemorrhagic.

Symptoms

  • Pain
  • Swelling
  • Discoloration (hemorrhage)
  • Numbness
  • Paralysis, paralysis
  • Paresthesia
  • Necrosis
  • Bleeding, eczema
  • Compartment syndrome

General Treatment

  • All snake bitten patients should be treated in hospitals
  • Insert at least one PVC. If necessary, an intravenous drip, eg Ringer’s Acetate.
  • Blood sampling of Hgb, wbc, platelets, INR, APTT and urine ticks.
  • Include all children and symptomatic patients to hospitals for at least 24 hours.
  • Unaffected patients should be observed for at least 6-8 hours.
  • Corticosteroids may be given (eg, Solu-Cortef 100-200 mg x 1-3 i.v. or i.m.). Scientific evidence is insufficient for treatment with steroids in snake bites, but constitutes a well-proven routine and is recommended primarily for allergic symptoms or after treatment with serum produced on horses. Is also likely to be of benefit in the case of a marked inflammatory reaction.
  • Antihistamine preparations (e.g., clemastine 1 mg i.v. x 1-2 or desloratidine).
  • Serum treatment should be considered in general symptoms. Serum is the most important part of treatment for severe snake bites. The best effect is achieved within four hours after the bite, but it can also be given later at general symptoms.
  • Immobilization of the bite body part, preferably in high position. At the bite in the hand hang up your arm high in a strap to a bed post or the like.
  • Morphine/oxicodon (5-10 mg i.v.) in pain.
  • Previously it was recommended that anyone who did not vaccinate in 5 years would receive an antitetanus booster dose. This recommendation has very weak scientific support but is based on the fact that the prey that the snake has just taken, type sorghum can carry on tetanus bacteria from underground passages (0.5 ml diTeBooster im x 1).
  • In allergic/anaphylactic reactions or bronchospasm, administer adrenaline (1 mg/ml, 0.3-0.5 ml i.m. in the outside of the thigh) and cortisone.
  • In circulatory shock, 0.1-0.5 mg adrenaline can be administered i.v. – The dose is titrated after the blood pressure.
  • Provide adequate fluid substitution, such as Ringeracetate, or Macrodex.
  • If dextran is not given, other thrombosis prophylaxis should be considered, eg, dalteparin (Fragmin) in low dose (2500-5000 units s.c.) alt Klexane 40 mg s.c. regardless of weight.
  • Inotropic support and other shock treatment are given in usual indications of circulatory failure, eg infusion of norepinephrine.
  • Oxygen by mask or via nasal catheter.
  • In severe cases, check Hgb, wbc, TPC, CRP, myoglobin, APTT, S-haptoglobin, creatinine, liver status, TNT and LD.

ICD-10

  • Non-toxic insect bite, unspecified T14.0D
  • Insect bites, toxic, UNS T63.4X
  • Toxic effect of poison from spindle T63.3
  • Punching stick, bump T63.4A
  • Toxic effect of contact with other marine animals T63.6
  • Toxic effect of snake venom T63.0

References

  1. Insect poisoning allergy – diagnostics can be difficult but good treatment exists. Theo Gülen,
  2. Janne Björkander, Swedish medical Journal  [Läkartidningen]. 2016; 113: D7CI
  3. P Brasil, et al. N Engl J Med. ZIKA virus. Epub 4 Mar 2016 doi: 0.1056 / NEJMoa1602412
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  7. Jaenson TG, Pålsson K, Borg-Karlson AK. Evaluation of extracts and oils or mosquito (Diptera: Culicidae) repellent plants from Sweden and Guinea-Bissau. J With Entomol. 2006 Jan; 43 (1): 113-9.
  8. Jensenius M, Fournier PE, Rauolt D. Rickettsiosis and international traveler. Clin Inf Disease 2004; 15: 39 (10) 1493-99.
  9. Karlsson et al. Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis. Neurology 1993; 43: 169-175
  10. Karlson-Stiber C, Persson H, Heath A, Smith D, Al-Abdulla IH, Sjöström L. First clinical experiences with specific sheep Fab fragments in snake bite. Report of a multicenter study of Vibera is based on an examination. J Intern Med 1997; 241: 53-8.
  11. Persson H, Karlson-Stiber C. Viper bite – clinic and treatment. Medical Journal 1995; 92: 2906-10.
  12. Reunala T, Brummer-Korven Kontio H, Karppinen A, Coulie P, Palosuo T. Treatment of mosquito bites with cetirizine. Clin Exp Allergy 1993; 23: 72-5.

 

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