Drugs in the ICU

Acetylcystein (N-Acetylcystein®)

Posted by Kai Knudsen, Senior Physician in Anesthesia & Intensive Care. Sahlgrenska University Hospital.
Updated 2019-06-12


Antidote for paracetamol poisoning.

Indication: Paracetamol poisoning. Acute liver failure. Poisoning with white (“Destroying Angel” – Amanita Virosa) or lame fly fungus (“Death Cap” – Amanita Phalloides) (amatoxin containing).

In paracetamol poisoning, n-acetylcysteine (NAC) ​​is effective because its metabolite cysteine ​​converts into glutathione which breaks down the reactive metabolite NAPQI of paracetamol. Acetylcysteine ​​should be given if S-paracetamol is above 1000 μmol/l at 4 hours after overdose, > 700 μmol/l at 6 hours and > 350 μmol/l at 10 hours after overdose. In alcoholism, starvation, dehydration, hepatic failure or treatment with enzyme inducing drugs, lower limits should be applied: >650, >450 and >230 μmol/l respectively. If treatment with acetylcysteine ​​begins within 8-10 hours after ingestion, the treatment gives close to 100% protection against liver damage. Then 20 hours of treatment with acetylcsytein will suffice. In case of severe hepatic failure, at least 3 PK-INR at 6 hour intervals should show decreasing values ​​before discontinuation of treatment

Dosage: Starting dose: 150 mg/kg in 250 ml of sodium chloride is given for 15 minutes iv (1000 ml/h), followed by 50 mg/kg in 500 ml glucose 5% for 4 hours iv (125 ml/h), followed by 100 mg/kg in 1000 ml glucose 5% for 16 hours iv (62 ml/h, 6.25 mg/kg/hour, practical is 75 mg/kg dissolved in 500 ml and given per 12-hour pass).

DosageDoseInfusion time
Dose I (Startdos)150 mg/kg in 250 ml NaCl Administer during 15 min i v (1000 ml/h)
Dose II50 mg/kg in 500 ml glucose 5% Administer during 4 hours i v (125 ml/h)
Dose III100 mg/kg in 1000 ml glucose 5% Administer during 16 hours i v (62 ml/h, 6,25 mg/kg/hour)
Conveniently, 75 mg/kg is dissolved in 500 ml and given per 12-hour pass
The latter NAC dose (Dos III) should be continued if the s-paracetamol level is still high or acute hepatic toxicity is apparent
Modified Acetylcysteine ​​schedule when poisoning with Paracetamol 665 mg/tablet in modified release form
Dose I (Starting dose)150 mg/kg in 250 ml NaCl Given for 15 minutes i v (1000 ml/h)
Dose II12,5 mg/kg/h in 500 ml glucose 5% Given for at least 20 hours i v (125 ml/h)
Dose II may be repeated until PK-INR drops or liver enzymes have been normalized
In case of severe hepatic impairment, at least 3 PK-INR with 6-hour intervals should show decreasing values ​​before treatment is terminated

Stock strength: Ampoules of 2000 mg/ampoule are diluted according to the given schedule (200 mg/ml, volume 10 ml). 

Side effects: Histamine release, bronchospasm, bradycardia, nausea, flushing, itching, urticaria, angioedema, hypotension.

Warning: Inhalation fluid of NAC is given intravenously! In the event of symptoms of histamine release, first try to pause the infusion when treating paracetamol poisoning and treat with antihistamine (clemastine 2 mg i.v.). Acetylcysteine ​​should be used with caution to persons with asthma or persons who have previously had bronchospasm.


Alfentanil (Rapifen®)

Intravenous sedative and potent analgesic. Alfentanil is a selective μ-opioid agonist with rapid onset and very short duration of action. Intravenous injection gives maximal effect within 90 seconds with a duration of 5-10 minutes. Alfentanil can be used for the sedation of intensive care patients in continuous infusion. Alfentanil is chemically related to fentanyl. In pharmacodynamic terms, alfentanil resembles of morphine but has more potent analgesic and respiratory depressant effect. Used for pain relief and sedation in intensive care of mechanically ventilated patients 18 years and older.

Dosage: 0.5-3 mg/hour (1-6 ml/hour), at a concentration of 0.5 mg/ml.

Stock strength: Solution 0.5 mg/ml 

Side effects: May cause respiratory failure and respiratory depression. May give muscle rigidity especially at high doses and difficulty in ventilating the patient manually. It can cause somnolence and increased fatigue. May cause bradycardia and high blood pressure fall. Muscle rigidity has been observed in increased frequency at high doses and on rapid administration of alfentanil. Bradycardia and possibly asystole may occur if the patient is given an insufficient dose of anticholinergics or if alfentanil is combined with nonvagolytic muscle relaxants. Secondary respiratory depression has been observed rarely.

Warning: Alfentanil reduces the need for hypnosis necessary to maintain sedation on intensive care patients, so the dose of hypnotic should be reduced. Because adverse hemodynamic effects of alfentanil are more pronounced and frequent in patients with ASA III-IV than with longer-acting opiates, great caution should be exercised when administering alfentanil to this patient population.


Alteplas (Actilyse®)

Anticoagulant. Alteplas is a recombinant human tissue plasminogen activator, a glycoprotein that activates plasminogen to plasmin. Following intravenous administration, alteplas remains relatively inactive in systemic circulation. After binding to fibrin, an activation occurs which leads to the conversion of plasminogen to plasmin, which in turn leads to the dissolution of the fibrin thrombus.

Indication: Acute myocardial infarction. Pulmonary embolism. Ischemic stroke.

Dosage: In the treatment of acute myocardial infarction with symptom debut within 6 hours, 100 mg is given to persons over 65 kg. 15 mg is given as a bolus, then 50 mg for 30 minutes and then 35 mg for 60 minutes. For persons under 65 kg, 15 mg is given as bolus, then 0.75 mg/kg i.v. for 30 minutes and then 0.5 mg/kg for 60 minutes. In the treatment of acute myocardial infarction with symptom debut 6-12 hours, 100 mg is given to persons over 65 kg. Ten (10) mg is given as a bolus, then 50 mg for 60 minutes and then 40 mg for 120 minutes. For people under 65 kg, 1.5 mg/kg is given. In the treatment of acute pulmonary embolism, 100 mg is given in 2 hours (120 min). Weighing less than 65 kg gives maximum 1,5 mg/kg. At weight over 65 kg, 100 mg is given. 10 mg (10 ml) is given as bolus, then 90 mg for 2 hours.

Stock strength: 1 mg/ml. Infusion substance 10 mg, 20 mg and 50 mg (I + II). 

Side effects: Hypotension, bradycardia, respiratory distress. 

Warning: Actilyse is contraindicated when there is a high risk of bleeding.


Amiodarone (Cordarone®)

Antiarrhythmic drug by prolongation of cardiac action potential phase-3 by inhibition of potassium channels. Reduced sinusoidal automation leading to frequency reduction. Non-competitive alpha- and beta- blocking effect.

Indication: Serious symptomatic ventricular and supraventricular arrhythmias, including atrial fibrillation/flutter. 

Dosage: 5 mg/kg body weight given via intravenous infusion over a period of 20 minutes to 2 hours as slowly as possible depending on the clinical picture. This amount is given as a dilute solution in 250 ml of glucose 50 mg/ml. Usually 300 mg is given for 30 minutes, then 900-1200 mg further for 24 hours, the infusion rate is controlled on the basis of clinical response. In resuscitation, amiodarone can be given as a bolus dose, 300 mg in 20 ml of glucose.

Stock strength: Injection solution at 50 mg/ml. Normal strength is 50 mg/ml.

Side effects: Bradycardia, hypotension, micro deposits in cornea, hypothyroidism.

Warning: Very rare cases of interstitial pneumonitis have been reported with intravenous amiodarone.


Argatroban (Novastan®)

Argatroban is a direct thrombin inhibitor to prevent thromboembolic disease at heparin-induced thrombocytopenia (HIT). Argatroban, a synthetic L-arginine derivative, is a direct thrombin inhibitor that reversibly binds to thrombin. Argatroban exerts its anticoagulant effect independent of antithrombin III and inhibits fibrin formation, activation of coagulation factors V, VIII and XIII, activation of protein C, and platelet aggregation.

Indication: Thrombosis prophylaxis in HIT. 

Dosage: 0.5-2 micrograms/kg/min as continuous infusion. Normal starting dose is 2 micrograms/kg/min, but several studies have shown that in intensive care patients a low dose (0.5 microgram/kg/min) has been sufficient. The target value of APTT is extended to 1.5-3 times the patient’s initial APTT value, but always at least 100 seconds.

Stock strength: Concentrate of 100 mg/ml is dissolved to 1 mg/ml, (250 mg – 2.5 ml) is dissolved in 250 ml sodium chloride 9 mg/ml or 250 ml Glucose 5%.

Warning: Contraindicated in case of ongoing bleeding. Caution in hepatic failure.


Clonidine (Catapresan®)

Sympathetic tone inhibitor. Central alpha2 agonist. It may reduce heart rate, lower blood pressure and reduce anxiety and stress.

Indication: Hypertension, sympathetic state, stress condition. Withdrawal from drugs or alcohol abuse. Stress or anxiety following head injury or subarachnoidal bleeding (SAH) with elevated blood pressure or elevated intracranial pressure. 

Dosage: In continuous infusion 15 μg/ml 2-5 ml/hour, 0.25-1 μg/kg/h. Normal dose 0.33 μg/kg/h. Maximum dose in continuous infusion is 2 μg/kg/h.  

Stock strength: Solution at 150 μg/ml. For continuous infusion 15 μg/ml. 

Side effects: Hypotension, bradycardia, respiratory distress. 

Clonidine solution for injection 50-150 μg can be injected directly intravenously, intramuscularly or subcutaneously three to four times a day. In intravenous infusion, the contents of 1 ampoule (150 μg) should be mixed with 10 ml of sterile saline (15 μg/ml) and distributed slowly (over a period of about 10 minutes) to avoid transient blood pressure increase. For continuous infusion dilution to 15 μg/ml is recommended.

 Warning: In abrupt administration of high doses, symptoms such as palpitations, anxiety, nervousness, motor anxiety, and occasional cases of blood pressure that exceeded untreated pressure have been observed. Hypersensitivity to clonidine or to any excipient, severe bradyarrhythmias caused by sick sinus syndrome or AV block grade II-III, hypotension.


Desmopressin (Octostim®)

Hemostatic (for blood clotting). Structural analogue to the natural posterior lobe hormone arginine vasopressin (ADH).

Indication: Abnormal bleeding. Abbreviation or normalization of prolonged bleeding time in uremia, liver cirrhosis, congenital or drug induced platelet dysfunction as well as in patients with prolonged bleeding time without detectable etiology. If positive effect is obtained, the initial dose of Octostim may be repeated 1-2 times at 6 to 12 hours intervals.

Dosage

0.3 μg/kg diluted in physiological saline to 10 ml as intravenous injection for 10 minutes or 0.3 μg/kg as subcutaneous injection.

Dosage of Desmopressin after Body Weight

Weight (kg)Dose (ml)
651.3
701.4
751.5
801.6
851.7
901.8
951.9
1002

Stock strength: Solution at 15 μg/ml

Side effects: Risk of decreased urinary output, water retention and hyponatraemia with associated symptoms, headache, nausea, vomiting, weight gain, decreased serum sodium and severe seizures.

Warning: Small children and elderly patients, in conditions requiring treatment with diuretics, in the event of a disrupted fluid and/or electrolyte balance, and at risk of increased intracranial pressure.

Contraindications: Unstable angina pectoris, uncompensated heart failure, von Willebrand disease type 2 B.


Dexmedetomidin (Dexdor®)

Sympathetic inhibitor. Central alpha2 agonist. Provides sedation, reduced heart rate, lowered blood pressure and less stress and anxiety. Dexmedetomidine is the S-enantiomer of medetomidine. 

Indication: For sedation of adult intensive care patients who require a level of sedation that is not deeper than that they may be woken by verbal stimulus (equivalent to Richmond Agitation-Sedation Scale (RASS) 0 to -3). Symptomatic states of hypertension, stress condition, and withdrawal. 

Dosage: Infusion rate is adjusted stepwise within the dose range of 0.2 – 1.4 micrograms/kg/hour. Charging doses of dexmedetomidine are not recommended and are associated with increased adverse events. Propofol or midazolam may be given as needed until the clinical effect of dexmedetomidine is achieved. Patients who are already intubated and sedated can switch to dexmedetomidine at an initial infusion rate of 0.7 microgram/kg/hour. Infusion rate can then be adjusted gradually within the dose range of 0.2 – 1.4 micrograms/kg/hour. 

Stock strength: One ml of concentrate contains dexmedetomidine hydrochloride equivalent to 100 micrograms dexmedetomidine. The concentration of the infusion after dilution should be either 4 micrograms/ml or 8 micrograms/ml. 

Side effects: Hypotension, bradycardia, respiratory distress.

Warning: In abrupt discontinuation of high doses, symptoms such as palpitations, anxiety, nervousness, motor anxiety, and occasional cases of blood pressure that exceeded untreated pressure have been observed. 

Contraindications: Hypersensitivity to dexmedetomidine or to any excipient, severe bradyarrhythmia caused by sick sinus syndrome or AV block grade II-III, hypotension.


Epoprostenol (Flolan®)

Prostacyclin, a metabolite to arachidonic acid. The main pharmacological effects of prostacyclin (PGI-2) consists of marked vasodilation of the pulmonary vascular bed and systemic circulation, inhibition of platelet aggregation and antiproliferative effects. Plasma half-life is 2-3 minutes. The vasodilatory effect ceases within 30 minutes after discontinuation of the infusion. 

Indication: Pulmonary hypertension, right ventricular failure. 

Dosage: 500 μg of dry powder is diluted with 10 ml of the supplied diluent. Add the dissolved epoprostenol in the remaining dissolving liquid, i.e. a total of 50 ml. The strength is now 10 μg/ml. 4 ml of the solution of 10 μg/ml is added through the supplied particle filter in a 50 ml syringe with 36 ml sodium chloride 9 mg/ml. The strength is 1 μg/ml. Starting dose is 0.24 μg/kg/hour = 0.24 ml/kg/hour. The effect is at 0.6 – 1 μg/kg/hour = 0.6 – 1 ml/kg/hour. 

Stock strength: 1 μg/ml. Given intravenous infusion by a central venous catheter (CVC).

Side effects: Hypotension, prolonged bleeding time, jaw pain, headache, leg pain and diarrhea. All symptoms are dose dependent. 

Warning: Adverse reactions in the form of thoracic wall rigidity, difficulty in breathing, irregular heart rhythm, skin bleeding, hematuria.


Eptacog alfa (Novoseven®)

Hemostatic drug (promotes blood clotting). Activated recombinant coagulation factor VII.

Indication: Major uncontrolled bleeding. Novoseven is indicated for the treatment of major bleeding and for prevention of bleeding in surgical or invasive surgery in particular risk groups. Among these risk groups are congenital or acquired hemophilia, isolated factor VII deficiency, and Glanzmann’s thrombastenia.

Dosage: An initial dose of 90 μg/kg is recommended. The dose should be repeated after 2 hours and then 2-3 hours apart during the first 24-48 hours depending on the coagulation status and the patient’s general condition.

Stock strength: Solution at 1 mg/ml. Prepare the solution and administer it as an intravenous injection over 2-5 minutes.

Side effects: Arterial thromboembolic events (cerebral artery occlusion, cerebrovascular event), venous thromboembolic events (pulmonary embolism, hepatic artery and deep vein thrombosis), angina pectoris, nausea, fever, erythematous skin rash. Lack of effect.

Warning: In case of disease where tissue factor may be expected to be higher than normal, there may be a risk of thrombotic disease or induction of disseminated intravascular coagulation (DIC).

Contraindications: Hypersensitivity to the active substance or to mice, hamster or bovine proteins.


Fibrinogen (Riastap®)

Human fibrinogen concentrate. 

Indication: Large bleeding, traumatic bleeding. Treatment of bleeding in patients with congenital hypo- or afibrinogenemia with bleeding tendency. The normal plasma fibrinogen level is 1.5-4.5 g/l. The critical fibrinogen level in plasma during which bleeding can occur is 0.5-1.0 g/l. In case of a major surgical procedure, it is essential to perform accurate monitoring of the replacement treatment through coagulation assays. 

Dosage: In order to calculate the individual dose, the functional fibrinogen level should be determined. If the patient’s fibrinogen level is unknown, an intravenous dose of 70 mg per kg body weight is recommended. Target level (> 2 g/l) for major bleeding (e.g. head injury or hemorrhage) should be maintained for seven days. The dose fibrinogen (mg/kg body weight) to be given = [target level (g/l) – measured level (g/l)]/0.017 (g/l per mg/kg body weight). Usually 1-2-4 g intravenously per occasion are given, repeated as needed after control of bleeding parameters. One gram of fibrinogen raises the plasma value by about 0.5 g/l.

Stock strength: Powder for solution 1 g. 

Side effects: Thromboembolic events including myocardial infarction and pulmonary embolism. Lack of effect. 

Warning: An increased thrombotic risk is present in patients with congenital deficiency when treated with human fibrinogen concentrate, especially at high dose or repeated dosing. Patients receiving human fibrinogen concentrate should be carefully monitored for signs and symptoms of thrombosis.

Contraindications: Hypersensitivity to the active substance or to any of the excipients.


Glyceryl Nitrate (Nitroglycerin®)

Reduces ischemic chest pain. Relaxes smooth muscle in the blood vessels and appears to be vasodilating by formation of NO and cGMP. Reduces venous return to the heart and reduces cardiac oxygen demand. Improves working conditions of the heart with less oxygen requirements and counteracts myocardial ischemia.

Indication: Angina pectoris, myocardial disease, heart failure, especially left ventricular pulmonary edema.

Dosage: In continuous infusion 1-5 ml/h, 20-80 μg/min, 0.1-1.6 μg/kg/min. Initial dose 0.5 μg/kg/min.

Stock strength: Solution at 1 mg/ml.

Side effects: Hypotension, tachycardia, flush, headache, dizziness, even bradycardia occur.

Warning: Caution in the case of hypovolemia or tachycardia. May trigger hypotension in mitral stenosis or aortic stenosis. Serious hypotension may occur when co-administered with sildenafil, which may trigger hypotension and myocardial infarction. Concomitant treatment with beta blockers, vasodilators, calcium antagonists, ACE inhibitors and antidepressants may potentiate the blood pressure lowering effect of nitroglycerin.

Contraindications: Hypersensitivity to nitrates and related organic nitrate compounds. Systolic blood pressure below 90 mm Hg. Serious hypotension and hypovolemia.


HCl (Hydrochloric Acid)

Indication: Severe metabolic alkalosis. 

Dosage: H + ion deficit (mEq) = 0.3 x weight (kg) x (measured HCO3 – desired HCO3 [mEq/L]). The rate of hydrochloric acid infusion should be 0.1 – 0.2 mEq/kg/hour. For example, 0.1 N solution i.v. at 100 ml/h gives about 10 mEq/h.

Stock strength: Concentrated solution HCl 5 mmol/ml, 10 ml of solution (= 50 mmol) is diluted in 240 ml Glucose 5% or Sodium chloride 9 mg/ml = 0.2 mmol/ml.

Side effects: Vascular irritation. Metabolic acidosis.

Warning May only be given slowly in a central venous catheter. May cause vascular injury and tissue necrosis. Should be given from a glass bottle. HCl must not go along with other solutions but must be infused as a single drug in a separate channel in a central venous catheter.


Heparin (Heparin®)

Heparin, which is usually found in the body complexed to protein, is a highly acidic, sulphated glucosaminoglucane (mucopolysaccharide) with anticoagulant effect. In combination with the co-factor, antithrombin III, heparin affects several steps in the coagulation mechanism, which promotes an anticoagulant effect. Heparin is given in the treatment of thromboembolic events such as pulmonary embolism or deep vein thrombosis.

 Dosage:

  • In the treatment of deep vein thrombosis, a bolus dose of 5000 E (1 ml) i.v. weighing less than 85 kg.
  • At a weight of more than 85 kg, a 7500 E (1.5 ml) bolus is given i.v. In the treatment of pulmonary embolism, a bolus of 7500 E (1.5 ml) i.v.
  • At massive DVT/PE: larger bolus (100-150 E/kg).
  • At increased bleeding risk, a bolus of 2500 E i.v. is given, except for massive pulmonary embolism/DVT.
  • In case of suspected pulmonary embolism, bolus and infusion are given pending the diagnosis. Subsequently, a continuous infusion of heparin, heparin body is given. 15000 E (3 ml) are added in 500 ml 0.9% Sodium chloride or 7500 E (1.5 ml) in 250 ml 0.9% Sodium chloride. The droplet is started at the same time as the bolus dose.
  • At weight > 60 kg and age < 65 years, 42 ml/h is given. Other adults are given 36 ml/h. The treatment effect is monitored by plasma activated partial thromboplastin time (APTT) controls. First APTT check after 6 hours. APTT should be 1.5-3 times the reference value, that is, 60-120 sec (at increased bleeding risk 50-80 sec). 

Heparin Dosing Schedule

aPTT value without increased bleeding risk (target value 60-120 sec)aPTT value at increased bleeding risk (target value 50-80 sec)Primary actionAdjust the drop rateNew sample checked
> 200 sec >160 secCheck the infusion mixture. Take a new test APTT sample, turn off the drop for 1 hour (not the first APTT after drip start)Reduce at 9 ml/hNew test after 4 hours
181-200 sec141-160 secReduce at 9 ml/hNew test after 6 hours
141-180 sec111-140 secReduce at 6 ml/hNew test after 6 hours
121-140 sec81-110 secReduce at 3 ml/hNew test after 6 hours
60-120 sec 50-80 secUnchanged infusion rateIf the first value after drip start, take a new test after 6 hours, or after 12 hours.
50-59 sec 40-49 secIncrease at 2 drops/min (= 6 ml/h)New test after 6 hours
< 50 sec < 40 secGive 2500 E of Heparin i.v. andIncrease infusion rate at 9 ml/hNew test after 6 hours

Indication: Anticoagulation. Deep vein thrombosis (DVT), pulmonary embolism, intravascular coagulation, and peritendinitis crepitans. Extracorporeal circulation associated with cardiovascular surgery and hemodialysis.

Side effects: Bleeding, thrombocytopenia, transient liver affection.

Stock strength: 5000 IU/ml, 25,000 IU/ml.

 Warning: Heparin is contraindicated when there is a high risk of bleeding. Caution is advised in the event of thrombocytopenia and platelet function defects (including drug-induced) and severe liver and renal failure. 

Standard schedule for adjustment of a heparin drip:  

  • If APTT > 200 sec or > 160 at increased bleeding risk. Check the infusion mixture. Take a new APTT test, turn off the dropped for 1 hour (not the first APTT after drip start). Reduce at 9 ml/h. New test after 4 hours.
  • If APTT 181-200 or 141-160 with increased bleeding risk decrease with 9 ml/hr. New test after 6 hours.
  • If APTT 141-180 or 111-140 at increased bleeding risk decrease at 6 ml/h, take a new test after 6 hours.
  • If APTT 121-140 or 81-110 at increased bleeding risk decrease at 3 ml/h. Take a new test after 6 hours.
  • If APTT 60-120 or 50-80 at increased bleeding risk unchanged infusion rate. If the first value after drip start, take a new test after 6 hours, or after 12 hours.
  • If APTT 50-59 or 40-49 at increased bleeding risk increases by 2 rpm (= 6 ml/h) take a new test after 6 hours.
  • If APTT <50 or <40 at increased bleeding risk give 2500 E heparin i.v. and increase infusion rate at 9 ml/h. Take a new test after 6 hours.

Human Immunoglobulin (Gammagard® – IVIG)

Gammagard S/D mainly contains immunoglobulin G (IgG) with a wide range of antibodies to infectious agents. Gammagard S/D has immediate and complete bioavailability in the recipient’s circulation after intravenous administration. It is distributed relatively quickly between plasma and extravascular fluid, after approximately 3-5 days, intra- and extravascular equilibrium is achieved.

Indication: Guillain-Barre syndrome (GBS), primary immunodeficiency syndrome, e.g. congenital agammaglobulinemia and hypogammaglobulinemia, common variable immunodeficiency, pronounced immunodeficiency, Wiskott-Aldrich syndrome, myeloma or chronic lymphocytic leukemia (CLL) with pronounced secondary hypogammaglobulinemia and recurrent infections. Idiopathic thrombocytopenic purpura (ITP) in children or adults with high risk of bleeding or before surgery to correct the number of platelets. Kawasaki’s disease.

Dosage: For treatment of an acute episode, 0.8-1.0 g/kg is given on the first day, which can be repeated once within 3 days or 0.4 g/kg daily for 2 to 5 days. The dosage varies with the indication.

Stock strength: Powder for 2.5-5-10 g vial.

Side effects: Genuine hypersensitivity reactions are rare. They may occur in very rare cases of IgA deficiency with anti-IgA antibodies. In rare cases, human normal immunoglobulin may induce hypotension with anaphylactic reaction, even in patients who previously tolerated treatment with human normal immunoglobulin.

Caution: In patients at risk of acute renal failure or thromboembolic adverse events, IVIG products should be administered at the lowest possible rate of infusion and dose. In all patients, IVIG administration requires adequate fluid delivery before the IVIG infusion begins with monitoring of urine volume, monitoring of serum creatinine levels, and loop diuretics are not used at the same time. Hypersensitivity to homologous immunoglobulins, especially in the very rare cases of IgA deficiency when the patient has antibodies to IgA.


Levosimendan (Simdax®)

Calcium sensitizers.

Physiological effects: Increased cardiac contractility, CO↑, HR↑, vasodilation, increased ejection fraction, hypotension, decreased SVR. Levosimendan provides increased contraction force and a reduction of both preload and afterload without the diastolic function being adversely affected. Levosimendan activates so-called stunned myocardium.

Indication: Short-term treatment of acute impaired severe chronic cardiac failure (ADHF) in situations where conventional treatment is insufficient and when inoculated support is considered appropriate. 

Dosage: 6-12 μg/kg/min for 10 minutes followed by a continuous infusion of 0.1 μg/kg/min for 24 hours. Normal starting dose at 6 μg/kg/min, adjusted for blood pressure. Avoid bolus dose at risk of hypotension .

Stock strength: Solution 2.5 mg/ml, normal strength 0.025 mg/ml alt. 0.05 mg/ml.

Side effects: Tachycardia, hypotension, headache, atrial fibrillation, ventricular arrhythmias, hypokalaemia.

Dosage activity: 0.05-2 μg/kg/min – usually moderate effect on blood pressure, Hypotension

Contraindications: Hypothyroidism and tachycardia, mechanical obstruction of the left ventricle, Torsade de Pointes, severe renal impairment. Correct hypokalaemia, hypovolemia.


Magnesium Sulphate (Magnesium)

Magnesium is an essential mineral. In physiological conditions it acts as the body’s own calcium antagonist and a moderate vasodilator. It reduces sinus automaticity in the heart leading to frequency reduction following intravenous administration. Provides moderate blood pressure reduction and pulse reduction. Relaxing smooth muscles. Provides increased seizure threshold and appears to be anticonvulsant.

Indication: Serious symptomatic ventricular and supraventricular arrhythmias, including atrial fibrillation/flutter, especially in sympathetic states with heart failure. Eclampsia with convulsions. Hypertension.

Dosage: 20 mmol is given via intravenous infusion over a period of 20-30 minutes. An infusion of another 20 mmol of magnesium is then given for 20 hours. Rule of thumb: 20 mmol in 20 min + 20 mmol in 20 h.

Stock strength: 1 mmol/ml (plastic bottles of 10 ml containing 10 mmol) are diluted in 100 ml of sodium chloride to a concentration of 0.2 mmol/ml. 20 ml of stock solution 1 mmol/ml (20 mmol) are diluted in 100 ml of sodium chloride.

Side effects: Blood pressure fall, bradycardia, respiratory distress. The infusion may give flush and warmth. May cause pain in the injection site.

Warning: Caution in renal failure and respiratory failure.


Metoprolol (Metoprolol®, Seloken®)

Selective beta receptor blocker. Some physiological effects are: HR↓, BP↓, CO↓, decreased ejection fraction (EF↓), decreased cardiac contractility, hypotension, unchanged SVR.

Indication: Tachycardia, hypertension, supraventricular and ventricular tachyarrhythmia, angina, myocardial disease. 

Dosage: In continuous intravenous infusion 1-4 mg/h, adjusted to pulse and blood pressure, 1-4 ml/h. Can be given in bolus doses of 1-2 mg at a rate of 1-2 mg/minute.

Stock strength: Solution 1.0 mg/ml.

Concentration for infusion: Normal strength 1 mg/ml (alt. 0.05 mg/ml).

Side effects: Bradycardia, blood pressure fall, asystole, bronchospasm, sleep disorders.

Contraindications: Bronchospasm, pronounced hypotension, pronounced cardiac failure, Takatsubo’s cardiomyopathy, hypovolemia, left ventricular mechanical obstruction, hypercalcemia, and hypoglycemia. Caution when co-administered with other antiarrhythmic drugs, digitalis or amiodarone.


Metylnaltrexon (Relistor®)

Opioid antagonist for parenteral use (subcutaneous injections) against opioid induced obstipation. Methylnaltrexone is a quaternary amine that cannot penetrate the blood-brain barrier, thereby selectively affecting intestinal receptors and produces no systemic effect but only local effect in the intestines. Relistor is primarily indicated in cancer patients but may also be used in intensive care patients with opioid induced obstipation. Few studies are available on intensive care patients, but it is likely to have the same clinical effect as oral naloxone. Opioids have an inhibitory effect on the intestinal peristalsis by releasing acetylcholine into the parasympathetic nervous system, which results in increased tone, reduced fluid secretion and reduced intestinal peristalsis. Methylnaltrexone results in increased intestinal passage and reduced ororectal transit time. Can be used concurrently with other treatment for obstipation like Movicol and laxantia droplets.

Indication: Opioid induced obstipation. 

Dosage: 8-12 mg x 1 sc.

Stock strength: Injection solution 12 mg/0.6 ml.


Midazolam (Dormicum®)

Fast acting sedative benzodiazepine. Midazolam is a potent sedative intravenous drug that requires careful titration and slow administration. Consideration must be given to the patient’s physical status, age, respiratory effort and other medication. The effect is prominent about 2 minutes after the injection. Maximum effect is reached after 5 – 10 minutes. Volume of distribution at steady state is 0.7-1.2 l/kg. Midazolam is 96 to 98% bound to plasma proteins, mainly albumin. In healthy volunteers, the elimination half-life of midazolam is between 1.5 and 2.5 hours. The half-life and effect are significantly prolonged in severe liver disease.

Indication: Sedation of patients in intensive care or for diagnostic or therapeutic examinations. For premedication.

Dosage: For sedation intravenous infusion 1-2-5 ml/h, 1-10 mg/h. In adults over 60 years of age, weak or chronically ill patients, a dose of 0.5 – 1 mg is initially given. Additional doses of 0.5 – 1 mg may be given if necessary.  Intravenous maintenance dose: doses may vary between 0.03 and 0.2 mg/kg/h. In patients with hypovolemia, vasoconstriction or hypothermia, maintenance dose should be reduced. The level of sedation should be evaluated on a regular basis. After prolonged sedation, tolerance may develop and an increase in dose may be necessary. 

Stock strength: Solution at 1 mg/ml or 5 mg/ml. Given usually intravenously but can also be given orally (1 mg/ml), rectally or intramuscularly.

Side effect: Respiratory distress, somnolence, increased fatigue.

Warning: Caution in renal failure, high age, muscle weakness, liver failure and respiratory failure. The effect is potentiated by other centrally acting sedatives. Prolonged half-life is observed in liver failure.


Milrinone (Corotrop®)

Phosphodiesterase III inhibitor. Some physiological effects are: SVR↓, CO↑, HR↑, and BP +/-. Provides increased contraction force and increased stroke volume. Vasodilator.

Indication: Reported heart failure, cardiogenic shock. 

Dosage: Initially a slow (10 minute) intravenous injection of 50 μg/kg. Thereafter a continuous infusion of 0.37 μg/kg/min to 0.75 μg/kg/min. The usual starting dose is 0.5 μg/kg/min, the dose is adjusted for blood pressure. In the overwhelming number of patients, hemodynamic improvement is noted within 5-15 minutes. Doses in the range of 0.375-0.50 μg/kg/min tend to maximize the initial improvement in cardiac output, while doses in the range of 0.50-0.75 μg/kg/min tend to maximize the improvement in the pre- and afterload parameters such as PCW pressure, median arterial pressure and systemic vascular resistance. 

Dose activity: <0.375 μg/kg/min – usually moderate effect on the circulation, 0.5-0.75 μg/kg/min predominantly β1 effect, blood pressure increase, increased CO and EF. 

Stock strength: Solution 1 mg/ml. Normal strength 0.2 mg/ml alt 100 μg/ml alt. 150 μg/ml.

Side effects: Hypotension, increased cardiac oxygen consumption, tachycardia, ventricular extrasystoles, and ventricular tachycardia.

Contraindications: Hypovolemia, obstructive aortic or pulmonary valve disease. In case of acute myocardial infarction observe caution.


Naloxone hydrochloride (orally)

Naloxone hydrochloride antagonizes the inhibitory effect of opioids on the intestinal peristalsis by blocking my-receptor receptors in the intestinal tract. Opiates have an inhibitory effect on the intestinal peristalsis by releasing acetylcholine into the parasympathetic nervous system, which results in increased tonus, reduced fluid secretion and reduced intestinal peristalsis. Naloxone is resorbed from the gastrointestinal tract, but is metabolized in the liver and gives no systemic effect but only local effect in the intestines. Laxatives may reduce the risk of nosocomial pneumonia during intensive care due to lower risk of regurgitation. Naloxone can be used concurrently with other treatment for obstipation like macrogol (Movicol) and purgative droplets.

Indication: Opioid induced obstipation.

Dosage: 5-8 ml x 3 orally.

Stock strength: 1 mg/ml (ex tempore preparation).

Warning: Naloxone should not be given in severe liver failure as it may cause systemic effects with central opioid antagonism due to impaired liver metabolism.


Octreotide (Sandostatin®)

Octreotide is a synthetic octapeptide analogue to naturally occurring somatostatin with similar pharmacological effects but with a significantly longer duration of action.

Indication: Carcinoma syndrome and VIP-producing tumors. Bleeding esophageal varices. 

Dosage: Initially, 50 μg 1-2 times daily is given as subcutaneous injection. If necessary, the dose may be gradually increased to 200 μg 3 times daily. May be given intravenously in infusion when treating bleeding esophagus varices, 25 μg per hour.

Side effects: Bradycardia. Reduced levels of vitamin B12. Gallstone. Cholecystitis. 

Stock strength: 50 μg/ml, 100 μg/ml, 200 μg/ml, 500 μg/ml.

Warning: Patients with insulin-dependent diabetes may have reduced insulin requirements.


Phytomenadion (Vitamin K – Konakion®)

Vitamin K is needed to synthesize the K-vitamin-dependent coagulation factors II, VII, IX, X and proteins C and S to effective coagulation factors.

Dosage: In case of acute bleeding, 10-20 mg Konakion IV is given. The effect begins after 4-6 hours. The injection is given slowly for at least 30 seconds.

Indication: Increased PK (INR) with bleeding risk or ongoing bleeding. Accelerate reduction of PK (INR) prior to surgery when co-administered with coumarin preparation (Waran). Malnutrition with liver or bowel disease.

Stock strength: Injection liquid 10 mg/ml.

Adverse reactions: Thromboembolic complications. Caution in patients with increased risk of thromboembolic or mechanical heart valve.

Warning: Injection of Konakion may cause a fall in blood pressure, therefore caution must be observed when treating patients in shock.


Physostigmine (Anticholium®)

Reversible cholinesterase inhibitor. Physostigmine passes the blood brain barrier as opposed to neostigmine and can reverse central anticholinergic effects of drugs and drug effects such as confusion and anxiety. Other anticholinergic symptoms include tachycardia, high blood pressure, large pupils, red hot and dry skin, and urinary retention. Physostigmine has a half-life of 30-60 minutes and may need to be repeatedly given. 

Indication: Overdose or poisoning with anticholinergic drugs. Anticholinergic Syndrome. Unspecified treatment for some of the side effects of baclofen treatment.

Stock strength: 5 ml ampoules of 2 mg Physostigmine (0.4 mg/ml). 

Dosage: Adults 1-2 mg intravenously, slow administration approximately 0.2 mg/min. Children: 0.02 mg/kg intravenously. Take special care due to the risk of developing epileptic seizures and bradycardia.


Propofol (Propofol®, Diprivan®, Propolipid®)

Intravenous anesthetic agents and sedatives. Propofol is used for sedation of ventilated patients over the age of 16 in the intensive care unit. Propofol can also be used with caution to non-ventilated patients for sedation. Propofol (2,6-diisopropylphenol) is a substituted phenol which, when administered intravenously, causes anesthesia. The mechanism of action of propofol is not known but probably the effect is exerted through a non-specific membrane binding of the substance.

Dosage: 1-3 mg/kg/hour (2-15 ml/h, 20 mg/ml). TIVA mode.

Sedation of Intensive Care Patient: For sedation in connection with intensive care, it is recommended that propofol is given as continuous infusion. Infusion rate should be adjusted according to the sedation depth sought. For most patients, adequate sedation is obtained at a dose of 0.3-4 mg/kg/h. Propofol should not be given for intensive care in patients under 16 years of age. Propofol is extensively distributed and eliminated quickly from the body (total body clearance: 1.5-2 liter/minute). Elimination occurs through metabolic processes, mainly in the liver where it is bloodflow dependent with formation of inactive conjugates of propofol and the corresponding quinol is excreted in the urine. Administration of Propofol with Target Controlled Infusion (TCI) systems is not recommended for use in children.

Stock strength: 20 mg/ml, 10 mg/ml.

Warning: A few reports have been reported on adult patients suffering from metabolic acidosis, rhabdomyolysis, hyperkalaemia and/or fast-developing cardiac failure (sometimes fatal) after having been sedated for more than 58 hours at doses above 5 mg/kg/hour.


Protamine Sulfate (Protamin®)

Protamine sulfate contains basic peptide sulfates that binds heparin to a complex. When protamine is given after low-weight molecular heparin (LMWH), anti-IIa activity is completely neutralized and anti-Xa activity is neutralized in part. The degree of neutralization varies between different LMWHs. The counter acting effect of protamine comes almost immediately.

Indication: Overdose and severe bleeding with heparin or LMWH. To reduce the heparin effect prior to emergency surgery. To neutralize heparin effect in conjunction with cardio pulmonary by-pass surgery. 

Dosage: A bolus dose of 5 ml (50 mg) is given i.v. for 10 minutes which neutralizes about 7,000 IU of heparin. One ml of protamine neutralizes 1400 IU of heparin. If possible, plasma activated partial thromboplastin time (APTT) or ACT (activation clotting time) is checked immediately before and 15 minutes after administration of protamine.

Stock strength: Injection Fluid 1400 IU/ml.

Side effects: Excess dosage may cause bleeding and APTT prolongation. 

Warning: Hypersensitivity to protamine or fish allergy. Thrombocytopenia after cardiopulmonary by-pass can be exacerbated.


Prothrombin Complex Concentrate (Ocplex®)

Prothrombin Complex Concentrate (Ocplex®). Hemostatic (blood clotting). The coagulation factors II, VII, IX and X, which are synthesized in the liver using vitamin K.

Indication: Large bleeding, hepatic failure bleeding. Treatment of bleeding and perioperative bleeding prophylaxis in acquired deficiency of prothrombin complex coagulation factors, such as deficiency caused by treatment with vitamin K antagonists (Waran) or in case of overdose of Waran when rapid correction of the deficiency is required. Correction of elevated PK/INR. 

Dosage:

The dose is determined by INR before treatment and the target value of INR. Usually 2-3000 IU Ocplex is given. The single dose should not exceed 3,000 IU (120 ml Ocplex 25 IU/mL).

Initial INR-valueDose (ml/kg)
(25 E/ml)
2 - 2,5 0,9 - 1,3
2,5 - 3 1,3 - 1,6
3 - 3,5 1,6 - 1,9
> 3,5 > 1,9

Stock strength: Dry powder for Solution 500 IU.

Side effects: Thromboembolic events including myocardial infarction and pulmonary embolism. Lack of effect.

Warning: Patients who receive a vitamin K antagonist may have an underlying condition of hypercoagulability and infusion of prothrombin complex concentrates may exacerbate this. Substitution therapy may rarely (> 0.01% and <0.1%) lead to the formation of circulating antibodies that inhibit one or more of the human prothrombin complex factors.

Contraindications: Known heparin-related allergy to heparin-induced thrombocytopenia.


Racemic Adrenalin (Racepinephrine®)

Synthetic catecholamine with sympathomimetic and mucosal anti-swelling effect. For inhalation therapy in case of subglottic edema. Adrenaline stimulates alpha-1, alpha-2, beta-1 and beta-2 receptors, predominantly beta-2 receptors. Adrenaline provides a relaxation of smooth muscles and counteracts bronchospasm and swelling of mucous membranes. Racemic epinephrine can be used in subglottic edema, above all in children up to 20 kg but can also be tested on adults, for example, after prolonged intubation with stridorous respiration. Treatment with racemic epinephrine in inhalation must not delay other procedures to control threats to open airways such as intubation or acute tracheostomy. The treatment has effect within a few minutes with a duration of about 30 minutes.

Dosage: Racemic epinephrine 22.5 mg/ml is diluted in a nebulizer with Sodium chloride 9 mg/ml to a volume of at least 2 ml. Half the amount is inhaled first. Then wait 10 minutes under the control of the child’s pulse and respiratory rate. Pulse rate must not be too high, usually it is accepted up to 120 bpm, depending on age. Then start the second half of the dose. In case of impaired oxygenation consider acute intubation.

Dosage for Inhalation Therapy

Body WeightRacepinephrine 22,5 mg/ml
< 5 kg0,25 ml
5-10 kg0,3 ml
10-15 kg0,5 ml
15-20 kg0,7 ml

Alternatively to Racepinephrine, adrenaline solution 1 mg/ml may be inhaled, up to 5 mg (= 5 ml). Can possibly be repeated, but no earlier than 2 hours after first treatment. 

Indication: Acute subglottic laryngitis, pseudo croup, croup, bronchospasm, stridorous respiration. 

Stock strength: Inhalation fluid 22.5 mg/ml (2.25%). 

Warning: May cause tachycardia, high blood pressure, cardiac arrhythmia, anxiety, tremor, palpitations. Caution for pulse rate over 120.


Remifentanil (Ultiva®)

Intravenous short-acting opioid for sedation of intensive care patients or total intravenous anesthesia. Solution 50 μg/ml. The recommended concentration for adult sedation in continuous infusion is 0.05 mg/ml (50 μg/ml). Remifentanil is a selective μ-opioid agonist with rapid onset and very short duration of action. Remifentanil is a so-called esterase metabolized opioid, which is metabolized by non-specific blood and tissue esterase’s. Following administration of recommended doses of remifentanil, the effective half-life is 3-10 minutes. The mean clearance of remifentanil in young healthy adults is 40 ml/min/kg, central volume of distribution 100 ml/kg and steady state volume of distribution 350 ml/kg.

Indication: For pain relief and sedation in intensive care of mechanically ventilated patients 18 years and older. 

Dosage: 0.01-0.10 μg/kg/min (1-6 ml/h) at a concentration of 0.05 mg/ml.

Side effects: Hypotension . May cause breathing failure and respiratory depression. May cause muscle rigidity especially at high doses or rapid infusion and difficulty in ventilating the patient manually. It can cause somnolence and increased fatigue. May cause bradycardia and high blood pressure fall. Muscular rigidity has been observed in increased frequency at high doses and on rapid administration of remifentanil. Bradycardia and possibly asystole may occur if the patient is given an insufficient dose of anticholinergics or if remifentanil is combined with non-vagolytic muscle relaxants.

Warning: Remifentanil reduces the need for hypnosis necessary to maintain sedation, and therefore the dose of hypnotic should be reduced. Since adverse hemodynamic effects of remifentanil are more pronounced and frequent in patients with ASA III-IV than with longer-acting opiates, great caution should be observed when administering remifentanil to this patient population.


Rituximab (Mabthera®)

Mediates B-cell lysis. Rituximab specifically binds to the transmembrane antigen, CD-20, a non-glycosylated phosphoprotein, located on pre-B and mature B lymphocytes. By binding to the CD20 antigen on B lymphocytes, rituximab has also been shown to induce cell death via apoptosis.

Indication: Prophylaxis of rejection and treatment of rejection after organ transplantation. Non-Hodgkin’s lymphoma, chronic lymphocytic leukemia (KLL), rheumatoid arthritis. 

Dosage: 375 mg/m2 body surface area as single dose. The recommended initial infusion rate is 50 mg/hour. After the first 30 minutes, the rate can be gradually increased at 50 mg/h every 30 minutes to a maximum of 400 mg/h 

Stock strength: Concentrate of 100 mg or 500 mg.

Side effects: Hypotension, bronchospasm, severe infections including sepsis and pneumonia, hepatitis B reactivation. 

Warning: Acute severe infections, severe immunosuppression. Risk of progressive multifocal leukoencephalopathy (PML) development. There is a risk of allergic reactions with infusion of any protein products. Fifteen minutes before injection of Mabthera is given: Solu-Medrol 250 mg i.v. and Tavegyl 2 mg i.v. In Mabthera treatment, all patients should receive steroid protection. In the case of rejection and prior treatment with mouse products (OKT3, Simulect), the risk of cytokine release syndrome increases, so you should carefully monitor the patient.


Sodium Dantrolene (Dantrium®)

Dantrolene is a muscle relaxant with postsynaptic effect. Dantrolene is an antidote on the occurrence of malignant hyperthermia. Through muscle relaxation, hyperthermia is counteracted by muscle activity. The dantrolene inhibits calcium release from the sarcoplasmic reticle by antagonizing ryanodine receptors, which weakens excitation and contraction in peripheral skeletal muscle. The dantrolene probably has no or very weak effect on hyperthermia secondary to drug induced serotonergic syndrome.

Indication: Malignant hyperthermia. Certain cases of malignant neuroleptic syndrome with high temperature, rigidity and marked hypermetabolism. 

Dosage: Starting dose at 2 mg/kg i.v. (preferably in a CVC or a coarse PVC), repeat with 1 mg/kg until symptoms wear off. If necessary, continue with an infusion of 0.25-0.5 mg/kg per hour. The maximum dose of 10 mg/kg may need to be exceeded in some cases.  

Stock strength: License preparations. Dried 20 mg powder vials are diluted with 60 ml of sterile water. As much as 35-60 ampoules may be needed for an adult patient! (Call in 5-10 people who can prepare the mixture when the preparation is difficult to solve!). Sodium chloride or glucose solutions should not be used when they are not compatible with dantrolene. 

Warning: Drowsiness, worsening or blurred speech, impaired vision. Observe muscle weakness and therefore risk of respiratory failure. Other side effects may include local thrombophlebitis, confusion and dizziness. In extravascular injection there is a risk of tissue necrosis.


Sodium Nitroprusside (Nitropress/Nipride)

Fast acting vasodilator

Relaxes smooth muscle in blood vessels and acts as vasodilator by the formation of NO and cGMP. Reduces the venous reflux to the heart and reduces the heart’s oxygen demand. Improves heart work conditions with less oxygen requirements and counteracts myocardial ischemia. Nitroprusside has effects on both the arterial and venous side but with major effects on veins (though less pronounced than nitroglycerin). The result is “venpooling” and thus reduced filling pressure and afterload reduction due to the reduced system vascular resistance. The effect sets in after 1-2 minutes and ceases after about the same time during exposure.

Dosage: In continuous infusion 1-5 ml/h, 20-80 μg/min, 0.1-1.6 μg/kg/min. Initial dose 0.5 μg/kg/min increase by 0.5-1.0 μg/kg/min every 4-5 minutes until the desired effect is reached or systolic blood pressure dropped to as low as 90-95 mmHg systolic, check that urine production is not adversely affected.

Indication: Severe hypertension, aortic dissection, myocardial ischemia, severe heart failure, especially left ventricular failure with pulmonary edema, critical peripheral ischemia.

Concentration: Solution 25 mg/ml is mixed to 0.5 mg/ml.

Side effects: Blood pressure drop, tachycardia, flush, headache, dizziness, even bradycardia occur.

Caution: Caution in hypovolaemia or tachycardia. May trigger blood pressure drop in mitral stenosis or aortic stenosis. Severe blood pressure drop may occur during concomitant treatment with sildenafil which may trigger hypotension and myocardial infarction. Concomitant treatment with beta-blockers, vasodilators, calcium antagonists, ACE inhibitors and antidepressants may potentiate the antihypertensive effect of nitroprusside. Hepatic insufficiency, renal insufficiency. Light-sensitive drug.

Risk (very small) of cyanide poisoning occurs with prolonged or very high infusion rates, and especially with hepatic insufficiency.

Contraindications: Hypersensitivity to nitrates and related organic nitrate compounds. Systolic blood pressure below 90 mm Hg. Severe hypotension and hypovolaemia. aortic stenosis


Sugammadex (Bridion®)

Antidote to non-depolarizing muscle relaxants, for intravenous use. Sugammadex is a derivative of gamma cyclodextrine. Sugammadex forms complexes with the neuromuscular blocking agents rocuronium and vecuronium in plasma, thereby reducing the amount of muscle relaxants that can bind to the nicotinic receptor in the neuromuscular synapse.

Indication: Reversal of the rocuronium (Esmeron) and vecuronium (Norcuron) muscle relaxants. Effect usually occurs within 2 minutes with almost complete recovery of muscle strength. 

Dosage: For normal reversal 4 mg/kg, giving 280 mg (2.8 ml) to a 70 kg patient. For children and adolescents, only 2 mg/kg, which gives 80 mg (0.8 ml) to a 40 kg child.

Stock strength: Solution at 100 mg/ml (2 or 5 ml vials). 

Side effects: Hypersensitivity, anesthetic complications such as rapid recovery of muscle tone during surgery.

Warning: Risk of rapidly restoring muscle tone during surgery may complicate surgical work. Anaphylactic reactions may occur.


Tacrolimus (Prograf®)

Tacrolimus is a highly potent immunosuppressant and has been shown to be effective both in vitro and in vivo. Tacrolimus specifically inhibits the formation of the cytotoxic lymphocytes, which mainly causes transplant rejection. Tacrolimus suppresses the activation of T lymphocytes and T helper cell-dependent proliferation of B cells as well as the formation of cytokines such as interleukin-2, 3 and gamma-interferon, as well as the expression of the interleukin-2 receptor.

Indication: Treatment of transplant rejection resistant to treatment with other immunosuppressive drugs. Prophylaxis of transplant rejection in liver, kidney and cardiac transplant patients.

Dosage: Oral treatment with Prograf should be started at 0.10-0.20 mg/kg/day given as two daily doses. Administration should begin approximately 12 hours after surgery is completed. If the dose cannot be given orally due to the patient’s condition, treatment should be initiated by intravenous administration of 0.01-0.05 mg/kg/day as continuous intravenous infusion. A majority of patients can be treated satisfactorily if levels of tacrolimus are kept below 20 ng/ml. In clinical use, the whole blood values ​​have been within the 5-20 ng/ml range in liver transplant patients and 10-20 ng/ml in renal and cardiac transplant patients during the post-transplant period.

Stock strength: Injection 5 mg/ml. Capsules 0.5, 1, 2 mg.

Side effects: Left ventricular hypertrophy and/or septum hypertrophy, reported as cardiomyopathy, have been reported rarely. Development of EBV-associated lymphoproliferative diseases and posterior reversible encephalopathy syndrome (PRES).

Stock strength: Injection 5 mg/ml. Given intravenous infusion at a central infarction.

Warning: Hypersensitivity to tacrolimus or other macrolides.


Terlipressin (Glypressin®)

Vasoconstrictor, the synthetic, long-acting analogue of vasopressin. Terlipressin initially has its own effect, but passes by enzymatic cleavage to lysine vasopressin. Dosages of 1 and 2 mg are effective to reduce the portal pressure and lead to clear vasoconstriction. The desired concentration of lysine vasopressin in plasma is initially achieved after approximately 30 minutes and reaches a peak after 60 to 120 minutes. Adjuvant to failing noradrenaline treatment in sepsis with vasoplegia.

Indication: Bleeding esophageal varicose veins. Sepsis with vasoplegia and profound hypotension.

Dosage: Initially, an intravenous injection of 2 mg terlipressin solution for injection is given every four hours. Treatment should continue until bleeding has been under control for 24 hours, but not more than 48 hours. After the initial dose, the dose may be adjusted to 1 mg intravenously every four hours in patients with a body weight < 50 kg or if the patient experiences side effects.

Stock strength: Solution 1 mg/ml.

Side effects: Bleeding, increased blood pressure, abdominal pain, nausea, diarrhea and headache.

Contraindications: Pregnancy  

Warning: Blood pressure, heart rate and fluid balance should be checked during treatment. The injection must be given intravenously to prevent local necrosis at the injection site.


Thiopental (Pentocur®), Sodium thiopental (Thiopentone®)

Intravenous fast-acting anesthetic drug, which is a barbituric acid derivative. Hypnosis occurs within 30-40 seconds after injection. Anticonvulsant. Some physiological effects are: BP↓, CO↓, decreased ejection fraction (EF↓), decreased contractility, hypotension, unchanged or decreased SVR.

Indication: For induction of general anesthesia, especially in acute caesarean section or neuroanesthesia. For the treatment of general seizures, status epilepticus or elevated intracranial pressure. 

Dosage: In case of manual induction 4-6 mg/kg body weight slowly intravenously, a test dose is usually given only at 25-50 mg. Lower doses for elderly patients and patients with hypotension, hepatic failure or compromised hemodynamics. In continuous intravenous infusion 2-4 mg/kg/h (2-10 ml/h) for the treatment of elevated intracranial pressure, adjusted to pulse and blood pressure, 1-4 ml/h. Can be given in bolus doses of 4-8 mg/kg (40-300 mg) at a rate of 50 mg/minute depending on the circulation status.

Stock strength: Dry substance is usually diluted to solution 25 mg/ml (2.5%).

Concentration for infusion: Normal strength 25 mg/ml (total 12.5 mg/ml). In case of continuous infusion, the drug should be administered to a central venous catheter (CVC).

Side effects: Hypotension, somnolence, prolonged awakening, respiratory depression, asystole, bronchospasm, laryngospasm, sleep disorders. Tiopental can cause addiction. Tiopental passes the placenta.

Contraindications: Bronchospasm, pronounced hypotension, pronounced heart failure, Takatsubo’s cardiomyopathy, hypovolemia, left ventricular mechanical obstruction, porphyria, and asthma. Caution in renal failure or hepatic failure. Caution when co-administered with other antiarrhythmics, digitalis or amiodarone.


Tranexamic acid (Cyklokapron®)

Indication: Fibrinolysis, severe traumatic bleeding, SAH. Tranexamic acid inhibits fibrinolysis by preventing plasminogen activation to the plasmin. Tranexamic acid does not cause thrombosis, but the dissolution of existing thrombus is inhibited.

 Dosage: Initially, a slow (10 minutes) intravenous injection of 1-2 g i.v. can be repeated after 4-6 hours. Infusion can be given at the dose of 70-700 mg/hour. Tranexamic acid can be given in local treatment on the mucous membranes, the oral cavity and the nose.

Indication: In surgery and bleeding in patients with increased bleeding tendency. For surgery with increased fibrinolysis such as mucosal, mammary, thoracic and liver surgery and prostate surgery. In the operation of patients with increased risk of bleeding such as known platelet deficiencies, von Willebrand’s disease and hemophilia. Can be tested for major bleeding in case of severe trauma or subarachnoid hemorrhage. 

Stock strength: Solution for injection 100 mg/ml. 

Side effects: In DIC and micro thrombotic syndrome, tranexamic acid may reduce fibrin dissolution in the microcirculation, thereby increasing the risk of organ failure. 

Contraindications: Tranexamic acid should be avoided during the first six months after acute thrombosis. In case of severe bleeding, single doses of tranexamic acid may be given but several days of treatment should be avoided. Urinary tract bleeding is a contraindication due to the risk of obstructive clot formation.


Vasopressin (Vasopressin)

Provides increased peripheral vasoconstriction. An antidiuretic hormone that regulates the resorption of water into the renal distal tubules. Regulates water balance, resulting in increased urinary maturity. Receptor activity: α1 +++, β1-0, β2 +. DA-1 0

Physiological effects: SVR↑↑, CO, HR↓, BP↑↑.

Indication: Sepsis, supplementary therapy for vasopressor treatment with norepinephrine in septic shock. 

Dosage: 0.01-0.06 IU/min = 2-4 ml/h for 70 kg. Normal starting dose 0.04 IU/min, adjusted for blood pressure. Higher doses of hemorrhagic shock than in sepsis treatment. Dosage activity: <0.02 IU/min small blood pressure increase,> 0.04 IU/min – α1 effect, high blood pressure increase, vasoconstriction.

Stock strength: Normal Strength 0.4 IU/ml.

Side effects: Bradycardia, vasoconstriction, pulmonary edema, arrhythmias, renal and intestinal hypoperfusion, peripheral ischemia, intestinal ischemia.

Contraindications: Hypertension , hypovolemia, hyperthyroidism, peripheral hypoxia, peripheral vasoconstriction, hyperadrenergic conditions.