Intravenous Anesthesia – TCI/TIVA

Intravenous Anaesthesia

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


Intravenous anesthesia (TIVA/TCI) involves a complete anesthetic method conducted only with intravenous drugs without inhalation anesthetics. The anesthetic form is usually completely controlled by infusion pumps, but the dosage may be supplemented with manually administrated doses of intravenous medication if necessary. The technique is described in detail below. The drugs used provide sleep, hypnosis and analgesia which together provide adequate anesthesia. In intravenous anesthesia, drug delivery is usually divided into two phases, induction dose and maintenance dose. The drugs are given intravenously with high accuracy in infusion pumps set for TIVA technology or TCI according to preprogrammed protocols. Most often, a combination of propofol and remifentanil is used, but several different variants are available.

Intravenous anesthesia provides a controllable and well-balanced form of anesthesia that allows the patient of rapid awakening with a short postoperative period and rapid recovery. The method can also be combined with inhalation anesthesia but then with significantly lower doses of inhalation anesthetics than normal. Respiratory efforts and muscle tonus of the respiratory tract recover faster with intravenous anesthesia than after inhalation anesthesia, and the patient is sooner awake and mentally clear afterwards. In addition, the method is environmentally friendly, since no leak of anesthetic gases occurs in the operating room or at the post-operative department. The anesthetic form is adapted and controlled after the surgery/procedure with regard to the patient’s medical condition and general condition. The anesthetic form requires good knowledge of the pharmacology and pharmacodynamics of the drugs used and good familiarity with the medical equipment. The method assumes safe venous access throughout the procedure and good monitoring of the patient’s vigilance, respiration, hemodynamic status, infusions and venous access (PVC/CVC).

The drugs usually used should ideally have as short a half-life as possible, as well as a favorable “Context Sensitive Halftime” as possible. Context Sensitive Halftime expresses the time it takes for a drug to equilibrate between blood compartments and compartments in the CNS. This applies to both premedication drugs as well as anesthetics and agents for postoperative pain relief. The aim is, among other things, to reduce the risk of POCD (Postoperative Cognitive Dysfunction) and the risk of postoperative nausea (PONV).

Intravenous drugs for induction, hypnosis (sleep), analgesia and neuromuscular blockade

Usually, a balanced combination of remifentanil and propofol is used for induction and maintenance, but several different combinations are possible. See different anesthetic protocols below. Several different drugs are available for intravenous anesthesia, for example:

Induction agents: Propofol, Remifentanil, Thiopental, Ketamine

Hypnotic agents: Propofol, Remifentanil

Analgesic agents: Remifentanil, Alfentanil, Ketamine (+ Optionally regional block)

Neuromuscular block: Suxamethonium, Rocuronium, Atracurium (in hepatic or renal failure patients)

When dosing the drugs, age, weight, disease, ASA class, general condition of the patient, and the concurrent regional blockade with local anesthetic agents must be taken into account. At rising age, high ASA class and concomitantly muscular relaxation, the doses for the anesthetic drugs should be lowered. The infusion pumps (syringe pumps) used should be of such quality that they can function safely at the various infusion techniques used in TIVA or TCI mode.

Anesthesia technique

The various infusion techniques for intravenous anesthesia commonly used are Target Controlled Infusion (TCI) or TIVA technique (Total Intravenous Anesthesia) with weight-based dosage – TIVA mode). The infusion pump provides the induction dose and maintenance dose by body weight, as well as third method and nowadays rarely used method with determined volume per unit of time (x number of ml/h by volume pump).

Anticholinergic drugs

It is common to give an anticholinergic drug prior to anesthesia where alfentanil and remifentanil are included to counteract airway secretion and bradycardia/hypotension. The most used agents are glycopyrronium (Robinul) and atropin, preferably Robinul. This because the preparation does not give tachycardia that we want to avoid, partly to shorten the diastolic phase, and partly because the bradycardia most commonly occurring with the use of remifentanil is an indirect sign of the anesthetic depth.

Anesthesia induced hypotension

Hypotension can be seen due to intravenous anesthesia as well as other anesthesia methods, especially after the induction dose. In the first place, hypotension should be avoided by keeping the patient normovolemic and in a cardiac optimal condition.

The methods commonly used in hypotension associated with anesthesia induction are fluid administration in the form of crystalloids and/or colloids and or fast-acting inotropic drugs such as ephedrine and phenylephrine in small incremental doses. The crystalloid usually used is Ringer-Acetate and colloids often used are albumin, hydroxyethyl starch (Venofundin or similar solutions) or dextrane containing solutions. If the patient has a creatinine elevation or a risk of renal failure after the operation, hydroxyethyl starch should not be used.

Furthermore, pharmacological treatment may be used in hypotension. Common medicines are ephedrine and phenylephrine for short-term hypotensive episodes. If the heart rate is over 80 beats/min phenylephrine is preferable. In case the patient has arrhythmias (atrial fibrillation), one should not use ephedrine but rather phenylephrine. In case of severe hypotension, a continuous phenylephrine infusion (at 0.1 mg/ml or 0.2 mg/ml) may be used alternatively noradrenaline (0.04 mg/ml or 0.1 mg/ml) or dopamine in infusion. Ephedrine and phenylephrine should be assigned to the operating room, and phenylephrine infusion equipment should be available. In intestinal surgery and larger vascular surgery, one should be restrictive with fluid and more widely use phenylephrine or ephedrine to regulate blood pressure. If the patient is treated with beta blockers, ephedrine is preferable.

Airway

The airway is secured by intravenous anesthesia in the usual way with laryngeal mask or endotracheal intubation. During intubation or insertion of a laryngeal mask, it is not always necessary to provide muscle relaxing agents especially if remifentanil is used. Muscle relaxant agents are not given in thyroid or parathyroid surgery where a detector of neuronal transmission (“Neurosign”) is used. If muscle relaxants are avoided it is common to give higher doses of remifentanil before intubation.

Routinely, patients are mechanically ventilated with positive-pressure ventilation during anesthesia. This, regardless of whether they have laryngeal mask or are intubated. It is done to avoid hypoventilation, hypoxia and to counteract atelectasis. An auto-PEEP is usually set on the ventilator, but if the patient is overweight or in laparoscopic surgery, the PEEP level should be increased. To those patients who have laryngeal mask or endotracheal tube and remifentanil are used, the patient should be ventilated and not put on spontaneous respiration. This because of that remifentanil can rapidly induce apnea.

If you use alfentanil in infusion, the patient can breathe on his own in the ventilator with pressure-assisted ventilation. This method is less suitable for remifentanil where controlled ventilation is preferred. In the case of intubation with alfentanil in continuous infusion, bolus should be given prior to intubation and the dosage is significantly higher than during laryngeal mask anesthesia.

To be considered

If you use intravenous anesthesia technique with regional blockade, eg. epidural, and decreases the doses relatively much, the anesthetic depth becomes quite light, then one cannot introduce a nasogastric tube, or insert catheters into the radial artery, or peripheral venous catheters without anesthetizing the patient a little deeper. The patient may then wake up with such a stimulus. This also applies to neuromuscular function stimulation that might be painful such as TOF, (“Train of Four”), on the upper limb. Neuromuscular function measurement is not routinely used (TOF) in intravenous anesthesia, but only on a given indication. If a repeat dose of muscle blocking agent is given with the above anesthetic technique, one must ensure that the patient has adequate anesthetic depth. This is to avoid “awareness” (superficial anesthesia/unplanned alertness). Patients should normally wear hearing protection during surgery, with or without music.

Anesthesia to the elderly (80 years and up)

Peroperative complications of given anesthetics, especially hemodynamic instability (blood pressure drop), are usually due to overdose of given drugs. Therefore, it is essential to know the changes that aging causes. Infusion protocol according to Minto with remifentanil takes into account age. The Marsh propofol infusion protocol does not take into account age, but this must be taken into account in dosing by the anesthesia personnel.

Changes in body constitution

The body constitution of the elderly changes so that lean body mass and total body water decrease, while a relative increase of the fat tissue occurs.

Pharmacokinetic changes

In the elderly, the effect of intravenous drugs is increased. This means that the volume of distribution of fat-soluble drugs increases, e.g. propofol. This results in a relatively lower plasma concentration and delayed elimination. Furthermore, the distribution volume for drugs that are less fat-soluble, e.g. remifentanil, which results in faster plasma concentrations and faster elimination. This is due, among other things, to decreased plasma volume and increased sensitivity to given drugs. In elderly, there is also a slower distribution from plasma to effector organs.

The doses for the elderly must be reduced. As for propofol given by TCI technique after Marsh algorithm, which does not take into account age, the anesthetist must do this dose reduction himself. Remifentanil given according to Minto’s algorithm, takes account of age. Despite this, one should also do a dose reduction to the elderly.

Anesthesia to obese and overweight patients

The biggest change in body composition is, of course, increased amount of adipose tissue in obese subjects. This means that high fat solubility drugs have increased volume of distribution, especially propofol, while low fat solubility drugs do not have a correspondingly changed (increased) distribution volume. The drug doses are calculated based on the ideal body weight plus about 10%. (Ideal body weight can be calculated to correspond to body length in cm minus 105 for women and minus 100 for men.)

It is of great value to use short-term drugs for this patient group, so that they receive postoperative spontaneous breathing as soon as possible.

For propofol and obese patients, one can control the dosage in two ways:

1.      An ideal dose of induction dose is given. When the distribution volume is high, the maintenance dose will increase almost the absolute weight. You can not underestimate the maintenance dose. This results in a relatively large amount of propofol accumulating in the fatty tissue, which can lead to prolonged awakening time.

2.      An induction dose corresponding to the ideal weight is given and the maintenance dose is dosed accordingly. This may lead to an underdosage of propofol, but this is compensated by an increase in the dose of remifentanil, which compensates for a possible underdosage of propofol. This means that the wake-up time is not prolonged.

For remifentanil, the TCI setting can be calculated after ideal weight plus 10%, which has been shown to work well in clinical practice. In order not to risk awareness in the case of anesthesia to heavily obese, where muscle relaxant drugs are used, routine use should be made of anesthetic depth monitoring systems such as BIS/Entropy. Use of opioids for postoperative pain relief at the end of anesthesia, e.g. morphine, is balanced to ideal body weight, as morphine does not have high fat solubility.

Anesthesia to patients with ischemic heart disease and intravenous anesthesia

These patients should be kept as hemodynamically stable as possible. It is important to avoid hypotension, hypoxia or tachycardia. Therefore, it is often indicated to use a continuous infusion of a vasopressor agent, e.g. phenylephrine in infusion (0.2 mg/ml alt. 0.1 mg/ml) or noradrenaline in infusion (0.04 mg/ml alt. 0.1 mg/ml). Sevoflurane is likely to have a cardioprotective effect in patients with ischemic heart disease. In anesthesia to this group of patients sevoflurane can be added to propofol for anesthesia to intubated patients. Following intubation and control of position of the tube, sevoflurane (recommended MAC value of 0.2 – 0.3 – 0.6) is added. The propofol infusion is lowered in combination with inhalation anesthesia. If the patient has peanut allergy, propofol is not recommended for induction (but seems to be safe!).


Drugs for Intravenous Anesthesia

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


Propofol (Diprivan®, Propolipid®, Recofol®, Propofol)

Propofol is a hypnotic drug used as an anesthesia inducing agent and aid for intravenous anesthesia. As described above, there are various techniques for administering propofol, such as Target Controlled Infusion (TCI), Total Intravenous Anesthesia (TIVA) and single volume controlled infusion (ml/hr). In intravenous anesthesia, propofol is usually used in the strength of 10 mg/ml (5 mg/ml to children). The anesthetist (or nurse) normally pulls the drug into the syringes before each anesthetic procedure. One disadvantage of propofol is that the drug affects circulation substantially, mainly through hemodynamic instability with a risk of blood pressure drop. Hypotension is most pronounced in older, stressed or hypovolemic patients. This may be due to the fact that the sensitivity to endogenous noradrenaline decreases.

Remifentanil (Ultiva®)

Remifentanil is an ultra-short acting opioid with a half-life of 3-10 minutes. It is a so-called esterase metabolized opioid which is metabolized by “non-specific” blood and tissue esterase’s. Degradation occurs independently of failure of organs such as liver and kidney and remifentanil is broken down into two decomposition products, among other things a carboxylic acid metabolite. Both have negligible activity with a half-life of approximately 2 hours. Ninety five percent (95%) have been excreted through the kidneys within 7-10 hours. Degradation is independent of liver function.

Remifentanil and age

Clearance is lower for elderly patients and the pharmacodynamic activity increases with increasing age. Therefore, doses should be reduced to elderly patients, even though the software in the pump takes into account the age of the patient.

1 μg/kg to a young, tall thin woman gives a plasma concentration peak of approximately 13 ng/ml and it takes about 4 minutes until the concentration reaches 2 ng/mL in the CNS and spontaneous breathing starts.

The same dose for an elderly, short-lived woman gives a plasma concentration peak of approximately 28 ng/ml and it takes about 10 minutes until the concentration reaches 2 ng/ml in the CNS. Since there is a higher susceptibility to the elderly for the drug, spontaneous breathing does not start until the concentration is 1 ng/ml and it takes about 4 min.

Advantages of remifentanil

  • A unique pharmacokinetic profile with rapid insertion and decreasing effect without accumulation
  • Very good intraoperative analgesia
  • Easy to titrate the appropriate dose
  • Doses need not be adjusted with regard to renal or hepatic failure
  • Adjustment of doses of co-administered hypnotics relative to the remifentanil dose is adjusted
  • Rapid and predictable recovery after discontinuation of analgesia

Disadvantages

  • A pronounced muscle rigidity may occur
  • Tendency to give bradycardia
  • Pronounced apnea tendency

As a rule, routinely, remifentanil is not currently used in patients < 12 years old, but the preparation is registered for use down to one year of age. Remifentanil is delivered in 1, 2 or 5 mg dry vials which are subsequently diluted before anesthesia. It is common to mix remifentanil to a strength of 50 μg/ml with Sodium Chloride. Remifentanil should always be given as a continuous infusion in a syringe pump. Remifentanil is for intravenous administration only and must not be given as epidural or intrathecal injection. Remifentanil is miscible with 5% glucose solution or sodium chloride 0.9 %. If you use remifentanil as the only peroperative analgesic drug, postoperative pain relief must be carefully planned and started on time. Preoperatively given paracetamol, possibly some NSAIDs or COX-2 inhibitors, and oxycodone (Oxycontin) 5 or 10 mg depending on the age of the patient. Thirty minutes before surgery ends morphine is given i.v. or both i.v. and s.c. The appropriate dose is 0.2-0.3 mg/kg. Even parecoxib (Dynastat) can be given at this time if there are no contraindications and the surgeon should be informed before the drug is given.

If it is an operation lasting less than 30 minutes, morphine is given in conjunction with the anesthesia induction. For some short-time procedures, for example endoscopy, which does not give significant postoperative pain, morphine can be ruled out. Also consider local infiltration of a local anesthetic drug in the end of the operation or a regional block (activate epidural anaesthesia). For surgery in a joint, ropivacaine (Naropin) 7.5 mg/ml may be advantageously installed locally in the joint by the orthopedic surgeon.

Remifentanil and hyperalgesia

Hyperalgesia is defined as an increased pain intensity in a constant pain stimulus. This hyperalgesia may be due to two mechanisms. In part, opioid induced hyperalgesia and induction of acute opioid tolerance. Studies show an increased morphine consumption postoperatively after anesthesia in which large doses of remifentanil are given and no regional blocks are used. This compared to corresponding operations where other anesthesia technique were used. This hyperalgesia can be counteracted in some ways by the use of gabapentin in premedication, or if ketamine is additionally administered in low dose peroperatively. One disadvantage of gabapentin is that patients can get to sedated.

The patient groups most current to administer ketamin are those who have received high doses of remifentanil, patients with ulcerative colitis/morbus Chron, and those who have a pre-operative pain problem with high consumption of opiates.

Alfentanil (Rapifen®)

Alfentanil is a relatively short acting opioid with a triphasic elimination. Alfentanil can be used in intermittent administration (bolus doses) or in continuous infusion. The following dosage provides guidance both when using a laryngeal mask or if the patient is intubated.

Short intervention (less than 30 minutes)

Alfentanil in intermittent administration (bolus doses). The initial dose varies between 5-15 μg/kg. Patient factors like age, ASA class, gender, weight, fitness must be considered. The dose is given before the propofol infusion is started. Half or full dose may be repeated if necessary after approximately 15-20 minutes.

Long-term surgery (over 30 minutes)

Alfentanil is then given as an initial dose with subsequent infusion. The initial dose varies between 5-15 μg / kg. Factors like age, ASA class, etc. must be considered. The dose is given before the propofol infusion is started. Once the initial dose is given, the infusion is started. The size of this is as mentioned earlier, age class, ASA class, type of surgery, etc. A target value is 30 μg/kg/h. During longer-term infusions, take into account that alfentanil’s context sensitive half-life is approximately one hour.

Maintenance dose must be adjusted downwards if it is a long operation. It decreases with 5 μg/kg/h after approximately 2 hours and another 5-10 μg/kg/h after 3 hours. Infusion is usually stopped when 15 minutes remain. Depends, of course, on the duration of the infusion and the type of procedure.


Anesthesia with TCI, Target Controlled Infusion

Posted by Carl Öhman, Senior Physician in Anesthesia & Intensive Care, Southern Älvsborg Hospital, Borås.
Updated 2019-06-12


The various infusion techniques commonly used in intravenous anesthesia are TCI (Target Controlled Infusion) or TIVA technique (Total Intravenous Anesthesia with weight-based dosage) i.e. the pump provides induction dose and maintenance dose by body weight, as well as a third and nowadays rarely used method, Volume Controlled Infusion (ml/h – by a volume set infusion pump). Infusion pumps provide induction dose and maintenance dose after preprogrammed protocols with a display showing either TCI or TIVA technology. Some infusion pumps, but not all, can show both TCI and dose by body weight (TIVA) at the same time. All infusion pumps cannot provide TCI but only pumps with this feature built-in. In children, mainly the TIVA technology is used, not TCI. We do not recommend TCI to children under the age of 16.

TCI technique, Target Controlled Infusion

Practical Aspects

TCI mode should be the first choice for intravenous anesthesia. The method can be used for induction and maintenance of anesthesia to adults. The technique is based on setting of a desired target concentration of selected drugs (propofol/remifentanil/alfentanil) in plasma (Cpt = Concentration plasma target) and thus indirectly in the effector organ CNS (Ce). Cp (Concentration in plasma) and Ce (Concentration in Effect Organ) are calculated values ​​that can be compared to MAC-values during inhalation anesthesia. Furthermore, in the pump, age and body weight are entered for the propofol infusion and age, body weight, body length and gender are entered for the remifentanil infusion. In highly overweight patients, one chooses to set an estimated ideal weight. The conventional administration technique, VCI (volume pump – determined amount of drug/time unit), results in a slower change in plasma concentration and hence the concentration in the target organ, CNS – Ce.

In the use of anesthesia with TCI technique, the following procedure is usually performed:

A drug with anticholinergic activity is initially given i.v. (Atropine/Glycopyrronium). The pumps are set so the so-called text display is showed. There the CE value is clearly visible. One usually start the procedure with preoxygenation. Then, the propofol infusion is started first. Throughout the induction phase, one speaks calmly with the patient with the oxygen mask applied over mouth and nose.

Usually the patient is quite quiet initially. As propofol becomes effective, some patients begin to speak as they relax. The Ce values ​​are noted for the changes in alertness that the patient display.

When the Ce value for propofol reaches 0.2-0.4 μg/ml, the remifentanil infusion is initiated if remifentanil is used. If alfentanil is used instead of remifentanil, a bolus dose is given by hand if the TIVA technique is used for alfentanil and then an infusion is started before starting the propofol infusion (in TIVA or TCI-mode). When the patient feels an effect of alfentanil, usually mild dizziness and sedation, the propofol infusion is started with this technique. Dosage for alfentanil, see below. As infusions continue, the patient’s speech is slacker to eventually cease and breathing is getting slower and shallower. Note the drug’s CE values. Also note when the patient’s spontaneous breathing expires, and the Ce-value remifentanil then reached.

Wait 30-60 seconds and take a good grip of the jaw and try to ventilate manually with care by mask. If the patient reacts with arm-hand movements, wrinkles the face, wait for another 30-60 seconds and resume the maneuver. Doses may be raised or unchanged. Keep calm all the time!

When the patient is not responding to stimuli, wait about 30 seconds. Note if the lower jaw is relaxed. Ventilate manually by face mask and if the patient accept positive pressure ventilation, try to insert the laryngoscope gently into the mouth for laryngoscopy or put down the laryngeal mask. Note the Ce values. Should the patient react, usually by touching the arm/hand, foot or wrinkle face as above, wait another minute, about one minute. New attempt is then made. When the patient does not respond to stimuli, it is known that at these Ce values, there is no risk for this particular patient. You do not need to assume a certain value, but you know what values applies to this particular patient. The Ce values ​​have very large individual variations. The Ce value noted when the patient does not respond to airway manipulation should preferably be noted on the anesthetic chart. Then you administer muscle relaxing drugs if you have decided to do so. If you want to intubate without muscle relaxing agents, wait another minute before doing so. The remifentanil dose should be increased if you do not give any muscle relaxants (Ce > 8). Thus, there is no standard dosage for all patients, but the dosage is extremely individual and the dose applicable to the patient is shown by the Ce value when the patient does not respond to any pain stimuli.

During induction of anesthesia, the pulse rate is observed when remifentanil is used. When remifentanil starts to give effect, the pulse rate usually decreases and approximately at the same time apnea occurs and one may notice the corresponding Ce value on chart. Pulse rate decline is a sign that the patient is sleeping. This is another reason to use glycopyrronium, which does not give the same tachycardia as atropine may give. Atropine may mask this sign of effect of remifentanil but normally it does not. This technique avoids any overdose of the drugs and avoids the risk of awareness.

When the patient is intubated or is having a laryngeal mask inserted, the rate of infusion of propofol and remifentanil is adjusted. An eventual infusion of local anesthetics in an epidural catheter for regional blockade can be started.

Preoperative sedation via pump

One effective procedure is that both propofol and remifentanil are started in TCI at low dose 0.7-1.0 once the patient is connected to the infusion pumps. Respiration is carefully monitored. The patient soon becomes lightly sedated and the total dose of the induction decreases, thus resulting in more stable hemodynamics. During the awakening phase, propofol is usually stopped first (when the last stitch is set) and the administration of remifentanil is stopped at the dressing. For a quiet awakening, a small dose of morphine, e.g. 5 mg, may be given about 30 min. before the end of anesthesia. The syringe pumps should not be switched off, but the infusion must be stopped with active pumps showing targeted concentrations. One may then follow the Ce values during the awakening phase. If the patient fell asleep at a determined Ce value, they usually wake up at about the same value (but sometimes lower). This depends on the so-called “hysteresis”, which means a combined effect of the drugs used in anesthesia, e.g. an opioid given just prior to the awakening. One cannot expect the patient to wake up at a higher Ce value than he or she fell asleep. The same applies to the Ce value of remifentanil. If the apnea occurred at a certain Ce value, you cannot expect spontaneous breathing to return before the Ce value dropped to this value.

As mentioned above, patients who are given remifentanil in normal doses are ventilated artificially. During the wake up phase, the patient is ventilated until they open both eyes and breathe against the ventilator. The opening of the eyes and the return of spontaneous breathing usually comes relatively quickly and simultaneously. Should the pump be turned off or the TCI function is interrupted otherwise during anesthesia, TCI should not be restarted. This because the pump may give a high dose after a break to maintain high Ce values (backlash), it should rather be reset in the TIVA setting.

Propofol and TCI

The most commonly used TCI pumps work at TCI according to Marsh algorithm. The pump then calculates based on set data, (body weight), an induction dose and maintenance dose. During the course of the anesthesia, the pump calculates and adjusts the current maintenance dose based on Context Sensitive Halftime, the time of ongoing anesthesia, etc. Note, this algorithm does not take into account age, which must be done by the anesthetic staff.

The pump has a preset target concentration (default setting), typically 4 μg/ml in Cpt (Target plasma). Of course, you can change this target concentration according to your current needs. The pump does not take into account simultaneous administration of opiates or concomitant regional blockade, but it takes into account the patient’s weight, the duration of the infusion, and, if necessary, a stop in the infusion for syringe replacement, etc.

At the start of anesthesia, the person who sets the pump should take into account the age of the patient, ASA classification, type of surgery, simultaneous delivery of opiates, blockades, etc. when setting the desired target concentration. Higher age, hypovolemia, ascending ASA class, more serious disease states, etc. requires lower dosage.

Appropriate settings for propofol at TCI

In patients under 60 years of age and ASA class 1-2, a setting of 3-6 μg/ml is recommended. The above considerations are taken into account.

For example, if a relatively high dose of remifentanil is given, you can start at a lower dose with propofol, and vice versa. One can also start on a relatively low target concentration and increase gradually with 0.5 μg/ml, after which the pump after each change upwards gives a small bolus dose and then a slightly higher infusion rate. This increase in target concentration can be done during anesthesia if necessary. Of course, the change can also be done elsewhere. The pump then stops and then stays at a lower infusion rate. For all adjustements, the Ce values ​​are noted for the patient’s condition. Use of remifentanil as an analgesic typically starts with propofol TCI and when the Ce value for propofol reaches 0.2-0.4 μg/ml, you can start the remifentanil infusion. This is mainly due to two reasons:

  • The time for the effect of propofol is slightly slower than for remifentanil. If you start propofol slightly earlier, the effect of the two drugs will occur approximately simultaneously.
  • When remifentanil is given quickly and in a high dose, it is likely that the patient develops a muscle rigidity, which in the worst case can threaten the ventilation.

It is a good procedure to start remifentanil before the propofol infusion, but in a low dose. Approximately at 1-2 nanograms/ml, with TCI technique, when the patient has entered the operating theatre and the monitoring is connected. Respiration is closely monitored.

When initiating the induction, the propofol infusion is started and immediately after the target concentration of remifentanil is increased. When laryngeal mask is inserted, alternatively, the patient is intubated, the doses of propofol and opioid are adjusted. If you use a simultaneous regional blockade (that has previously been evaluated), you will go to low doses on both formulations. At TCI and propofol, you can go to the level that the Ce value showed when the patient did not respond to airway manipulation or pain stimulus. For remifentanil, you can go to the Ce-value shown at the intubation or slightly higher.

One can lower the propofol level below the Ce value where the patient did not respond to the aforementioned stimuli, but then you should raise the level of remifentanil. This may be many times more beneficial since remifentanil does not affect the circulation as much as propofol. Anesthesia is controlled advantageously by changes in dose adjustments of remifentanil.

The propofol infusion is stopped finally when it remains about 5-15 minutes of the procedure. The length of time before depends entirely on the anesthetic technique chosen, the duration of the anesthesia, the age of the patient, the blockade, the type of procedure, etc.

In patients over 60 years and/or ASA class > 2, an initial setting of 2-5 μg/ml is recommended. For this patient category, it may be more appropriate to use the above-mentioned step-by-step method. All the time, Ce values ​​are noted for the patient’s condition.

Remifentanil and TCI

During dosage in TCI with remifentanil, target concentration in nanogram/ml of blood is determined in the CNS effector organ. Since there is a pronounced synergy between propofol and remifentanil, the dose of the drug used for hypnosis must be reduced compared to the use of alfentanil. How much depends on the type of surgery that is performed and the age and condition of the patient. When Lean Body Mass is calculated according to Minto, this is a little too low for women with a BMI > 35 kg/m2 and for male patients with a BMI > 40 kg/m2. The target concentration for these patients should be set slightly higher to avoid to low dosage. Regularly, ideal weight is used when dosing remifentanil. The target concentration of remifentanil starting an operation with (used in conjunction with a hypnotic drug, gas or propofol) is usually set at 4-8 nanogram/ml. The level is adjusted according to the patient’s age and type of surgery. Usually at 6 nanogram/ml.

Then, an appropriate maintenance dose, monitored by the Ce value, is titrated by following the usual parameters of an adequate anesthesia depth. For very painful intervention, target concentrations up to 15 nanogram/ml may be required.

At the end of anesthesia and TCI for remifentanil, the patient recovers spontaneous breathing at an approximate target concentration of 2 nanogram/ml, sometimes slightly lower. Consideration must, of course, be taken to the current concentration of the current hypnotic agent (i.e. mostly propofol).

Remifentanil administered with TCI technique and in adequate doses and associated with narcosis, not sedation (see below), is not normally used in patients with spontaneous breathing or for postoperative analgesia or in children under 16 years of age.

Intravenous anesthesia with propofol in combination with alfentanil (Rapifen)

Connection according to the above guidelines. Anesthesia is started with an anticholinergic agent being given and the patient preoxygenated. An initial dose of alfentanil may be given by hand and it may vary between 5-15 μg/kg. Patient factors like age, ASA class, etc. must be considered. Once the initial dose is given, the infusion is started, normally in TIVA mode either per minute or per hour. The size of this is due to the age, ASA class, type of surgery, etc. A common target value is 30 μg/kg/h (0.3-0.5 μg/kg/min) or 50-60 ng/ml in TCI mode. In the case of anesthesia with laryngeal mask, a target value of 50-60 ng/ml in TCI usually is sufficient while anesthesia with intubation need to be significantly higher 90-120 ng/ml for alfentanil.

The maintenance dose is adjusted downwards if there is a long operation in TIVA mode (> 2 hours). One must decrease the dose with 5 μg/kg/h after about 2 hours and another 5 μg/kg/h after 3 hours. A larger decrease depending on the age of the patient. Infusion is usually stopped when 15 minutes remain but it depends, of course, on the duration of the infusion and the type of procedure.

When the patient feels the effect of the given initial dose of alfentanil, propofol in TCI modus is started, Usually with the setting of Cpt at 4.0 μg/ml, but adjusted according to age, type of surgery, simultaneous blocks etc. The Ce values ​​are followed during the induction and are noted for the different stages in which the patient is. Speak calmly with the patient during induction. When the patient is not responding, this Ce value is noted and it is considered as a guideline for the continued anesthesia. At this stage, any muscle relaxant may be given.

At the end of the operation, the infusion of alfentanil will be completed at approximately 15-30 minutes before the end of the operation and the propofol infusion will end approximately 5 minutes before the end of the operation.


TCI Protocol for Day Care Surgery

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


Work description and key moments with TCI in day care surgery

  • Fixed placements of syringes carrying the infusions: Remifentanil at the top and propofol at the bottom.
  • Back valve for the remifentanil infusion
  • Remifentanil infusion pump is set to TCI according to the Minto protocol (model plasma)
  • Age, weight, length and sex of the patient are entered in the pump
  • Induction dose is usually set with active “Flash” mode (small, fast induction dose)
  • Propofol infusion pump is set to TCI with propofol according to Marsh (model plasma), which adjusts by weight but not age (as stated)
  • Avoid blood pressure cuffs on the same arm as the drug infusion

Remifentanil and propofol are set relative to Cpt, i.e. the desired plasma concentration, and the infusion pumps calculate the plasma concentration (Cp) and the concentration in the brain (Ce) according to protocol.

Cpt: Plasma concentration with target concentration – Desired plasma concentration (target concentration)

Cp: ​​Plasma concentration – Estimated plasma concentration at any time

Ce: “Concentration site” – calculated concentration at the effector site, i.e. in the brain

The concentration in the effector organ (Ce) is passively adjusted by the pump after Cp with a few minutes delay.

Selection of target concentration depends on several factors: use of tub/laryngeal mask, concomitant use of fentanyl, type of surgery, use of local anesthesia, sex, age and weight. The pharmacokinetic model of remifentanil (Mintos) takes into account weight, length, gender and age, while the propofol model (Marsh) only takes into account weight.

Solution procedure: Remifentanil is mixed to a concentration of 50 micrograms/ml: 2 mg of remifentanil are dissolved in 40 ml of 0.9% NaCl. Propofol is given in a concentration of 10 mg/ml to adults and 5 mg/ml to children.

Important moments with TCI

  • Do not use in anesthesia for children under 16 years of age.
  • If a syringe pump has to be restarted during anesthesia, you should not continue with TCI, but you should switch to TIVA without TCI.
  • The values ​​of drug concentrations on the syringe pumps are calculated from a pharmacokinetic model. Individual patient conditions may cause actual plasma concentrations and effector concentrations to differ from those indicated on the pumps.
  • Press the “Menu button” (Fresenius Agilia pump) and then the battery capacity to see the dose in ml/h.
  • Press “Menu” (Fresenius Agilia pump) and then the arrow buttons (up/down) until you get “ml?” at the left of the display to see the volume/amount of drug actually given.

Patients with ASA 1 and 2, under 60 years with BMI <35

Induction

Prior to initiation of the medication, patients may receive sedative doses of propofol and remifentanil in the induction. This calms the patient and at the same time you get a picture of how well the patient can withstand the medicine.

Sedation dosage

  • The target concentration (Cpt) for propofol is set at 0.5 – 1 microgram/ml.
  • The target concentration (Cpt) for remifentanil is adjusted to 0.5 – 1.0 ng/ml.
  • In some cases, fentanyl 50-100 micrograms may be given initially, especially if the patient is to be intubated.
  • Preoxygenation should be given with 80% oxygen.

Anesthesia Induction

  • The target concentration (Cpt) for propofol is set at 4 – 6 micrograms/ml.
  • The target concentration (Cpt) of remifentanil is adjusted to 5 – 6 ng/ml using laryngeal mask and 10 – 12 ng/ml for intubation without muscle relaxation (> 8 ng/ml if muscle relaxation is used).

The patient is manually ventilated with respiratory mask and respiratory bag until the patient is ready for insertion of laryngeal mask or intubation (evaluated clinically after Ce for remifentanil has reached the target concentration).

Intubation

  • Minimize the use of muscle relaxants.
  • Give remifentanil until Ce > 8 ng/ml before intubation.
  • Note do not intubate when the vocal cords are closed! This may damage the vocal cords.

Maintenance

The target concentration (Cpt) for propofol is set to 1.8 – 2.5 micrograms/ml.

The target concentration (Cpt) of remifentanil is adjusted to:

  • 5 – 6 ng/ml until the operation begins
  • 7 – 8 ng/ml at the start of medium-sized surgery
  • 9 – 10 ng/ml at the beginning of major surgery
  • 12 – 16 ng/ml for particularly large surgery (e.g. skeletal surgery, back surgery)
  • 9 – 10 ng/ml for operations where it is very important that the patient is laying still (e.g. myringoplasty, ENT, plastic surgery)

The doses are adjusted in relation to the clinical setting. Optional doses of fentanyl 50 – 100 micrograms in v can be given in addition.

Closure

Approximately 5 minutes prior to surgery ends, the infusions are terminated with propofol and remifentanil (the infusion of remifentanil may continue until the operation is complete). Keep in mind the pain problem when remifentanil is discontinued and optionally give fentanyl 50 – 100 micrograms IV or other opioid. The ventilator continues to go until the patient wakes up and you can remove the laryngeal mask or extubate.

Patients over 60 years and/or ASA 3

Begin with low target concentrations for both propofol and remifentanil, which is 25% to 50% lower than for healthy patients under 60 years. Induce slowly and increase target concentrations by 0.5 – 1 microgram/ml for propofol and 0.5 – 1.0 ng/ml at a time until satisfactory clinical effect is obtained.

Maintenance with propofol should not be less than 1.8 micrograms/ml due to the risk of excessive anesthesia. Maintenance doses with remifentanil can be maintained 25% – 50% lower than for healthy patients under 60 years, but must be adjusted to the clinical picture.


RSI with TCI

Posted by Carl Öhman, Senior Physician in Anesthesia & Intensive Care, Southern Älvsborg Hospital, Borås.
Updated 2019-06-12


Rapid Sequence Induction, RSI and TCI

You can choose TCI technology also for Rapid Seqence Induction, RSI. At RSI, you aim for rapid induction and dose the induction dose after mg/kg body weight. If you choose propofol as an inducer then doses may vary. Everything from an old severely ill patient, about 1 mg/kg, to a young healthy patient who gets about 3 mg/kg.

The induction at RSI can be done in two ways.

Alt. 1: TCI plus extra bolus by hand

If the propofol pump is set in TCI setting at the target value 4 μg/ml, it gives about 1 mg/kg in induction dose. This no matter what body weight is set. If you have a patient weighing 80 kg and want to give an induction dose of 2.5 mg/kg, you can do the following in the induction. Pull a 20 ml syringe with propofol. In induction, the TCI pump provides 4 μg/ml, approximately 1 mg/kg = 80 mg, and the remaining amount should be given to 2.5 mg/kg by hand. That is, in this example, 120 mg extra by hand up to the total dose of 200 mg. Extradosen is given with the 20 ml syringe containing propofol. When looking at the Ce value, it should be borne in mind that these 120 mg are not present in the calculated Ce value at the beginning of anesthesia. Start the remifentanil infusion with TCI technology, while initiating the induction. Dosage 5-8 ng/ml depending on which patient is appropriate. Muscle-releasing drugs are given when the reflexes are gone. Giving precursorization with 2-3 mg rocuronium in conjunction with induction reduces the asymmetric muscle contractions that succinylcholine causes.

Alt. 2: Induction with pure TCI

Another method of TCI technology and rapid sequence induction, RSI, is that the propofol pump is initially set to a high Cpt value. Suggestion for setting is a Cpt value of 15 μg/ml. When the pump is started, it provides a fast dose at a high rate. Follow the value of the given dose in mg/kg. These are visible with small numbers just to the right of the Ce value of the infusion pump. When the desired induction dose is reached, 1-3 mg/kg, the Cpt value changes to the desired level around 2-5 μg/ml. It is important that during this procedure, continuous attention is paid to the pump until it provides the desired induction dose and then stop the pump and adjust the rate of infusion.

When starting the pump at the reduced rate of infusion, the pump does not start at once, depending on the calculated Cp value, exceeds the currently set Cpt value. Note that the Ce value is not so high when this induction dose is given. There is some lag in the software calculation.

Start the remifentanil infusion with TCI technology, while initiating the induction. The usual dosage is around 5-8 ng/ml depending on the patient in question. Muscle relaxants are given in this type of induction when the desired dose of propofol is given and the flashing reaction is gone. Here too, one can precurise with 2-3 mg rocuronium in conjunction with induction, to reduce the asymmetric muscle contractions that succinylcholine causes.

If you choose to inject the entire induction dose of propofol manually with syringe and then use propofol as a hypnotic, TCI technology should not be used, because then the patient will receive an induction dose to choose TIVA instead. Option 1 may be preferred from a safety point of view because there is some risk that you forget to stop the pump and reduce the rate of infusion when the desired induction dose is given. If the patient is allergic to propofol or any of its components or if you do not want to use propofol as hypnotics for other reasons, thiopentone is used as an inducer and Sevorane as a hypnotic drug.


Anesthesia with TIVA-technique (TIVA-mode)

Posted by Carl Öhman, Senior Physician in Anesthesia & Intensive Care, Southern Älvsborg Hospital, Borås.
Updated 2019-06-12


This anesthetic technique is usually a second choice for TCI technology. TIVA technology provides a total intravenous anesthesia with weight-based dosage ie. The pump provides induction dose and maintenance dose after body weight with a supply determined for each unit of time (for example, alfentanil can be dosed per hour or per minute, different for different pumps).

When using this anesthetic form, the same considerations apply to the TCI technique with lower doses at higher age, high ASA grade, concomitant opioid delivery, simultaneous blockades, etc. In case of longer anesthesia procedures there is a risk of accumulation of drugs, predominantly propofol and alfentanil, when technology does not take into account context sensitive half-time.

The TIVA pumps are preset to give an induction dose of propofol of 1.5 mg/kg for 90 seconds and then start an infusion rate of 10 mg/kg/h. You set the age and body weight. In highly overweight patients, pump settings are selected according to the estimated ideal weight. These settings can be changed depending on the factors that affect the dosage. You will decide on the appropriate induction dose, time of induction dose and maintenance dose when making pump settings. If you use propofol and remifentanil in combination, you can use a technique that does not give a bolus dose of propofol. The two infusions are then started in parallel. The maintenance dose of propofol should be decreased gradually every 10 minutes from the usual dose of 10 mg/kg/h to 8 mg/kg/h, after about 20 min being about 6 mg/kg/hr. Consideration is given to the amount and type of opioid given at the same time. Lower infusion rate at high age and ASA class. The propofol infusion is stopped when it remains about 5-15 minutes of the procedure. The length of time before depends entirely on the anesthetic technique chosen, the duration of the anesthesia, the age of the patient, the simultaneous blockade, the type of procedure, etc.

TIVA technology with propofol and remifentanil

With TIVA technology, it is possible to start the propofol infusion with an induction dose at 3-6 mg/kg/h and then thereafter infusion of remifentanil with 0.15-0.5 μg/kg/min. With this technique, it takes a little longer before the patient is sleeping, but there is less pronounced circulatory effects. When you intubate or insert the laryngeal mask, you can adjust the rate of infusion on both drugs. How much depends on the anesthetic depth, if you have a simultaneous regional block or not and of course depending on age, ASA class, etc.

The propofol infusion usually ends 5-10 minutes before end of surgery and the remifentanil infusion is usually terminated when attaching. In some types of surgery, the infusions of both propofol and remifentanil can be switched off at the same time during surgery, different endoscopies and laparoscopies if there is painful stimulus left until the final end of the operation. The awakening usually occurs relatively quickly and the patient usually opens his eyes while taking the first breath. Even then you can remove the laryngeal mask or the endotracheal tube.

TIVA technology with propofol and alfentanil

An anticholinergic drug is usually initially given and the patient is preoxygenated. Thereafter, alfentanil is given with the suggested dose suggestions below.

Short interventions < 30 min

Alfentanil is given as an intermittent injection. The initial dose varies between 5-15 μg/kg. Factors like age, ASA class, etc. must be considered. The dose is given before the propofolin fusion is started. Half or full dose may be repeated if necessary after approximately 15-20 minutes.

Long interventions > 30 min

Alfentanil is then given as an initial dose with subsequent infusion. The initial dose varies between 5-15 μg/kg. Factors like age, ASA class, etc. must be considered. The dose is given before the propofol infusion is started.

Once the initial dose is given, the infusion of alfentanil is started. The dosage of this is due to earlier, age, ASA class, type of surgery, etc. A target value is 30 μg/kg/h (can also be dosed in μg/kg/min). Considering long-term infusions is that the half-life is relatively long, about one hour. Maintenance dose must be adjusted downwards if there is a long operation. It decreases with 5 μg/kg/h after approximately 2 hours and another 5-10 μg/kg/h after 3 hours. Thereafter, an induction dose of propofol, usually 1-2.5 mg/kg, is given. Everything depends on age ASA class, etc. Then an infusion is also started with propofol. The maintenance dose of propofol should be reduced gradually every 10 minutes from the usual dose of 10 mg/kg/h to 8 mg/kg/h, after approximately 20 minutes being around 6 mg/kg/h. Consideration is given to the amount and type of opioid given at the same time. Lower infusion rate at high age and ASA class. The maintenance dose is adjusted downwards if it is a long operation. One then decreases with 5 μg/kg/h after about 2 hours and another 5 μg/kg/h after 3 hours. Infusion is usually stopped when 15 minutes remain. Depends, of course, on the duration of the infusion and the type of procedure. The propofol infusion closes approximately 5-10 minutes before the end of the operation.

Combination of remifentanil with alfentanil

A combination of remifentanil and alfentanil may be indicated in some situations. Use an anesthetic with propofol (alt. Sevorane) and alfentanil and you are forced to increase the dose of alfentanil due to that one gets a reaction in the patient who is suffering from pain, e.g. After about an hour of blood-staining field, the combination of remifentanil and alfentanil may be a good option. If you have had an infusion of 30-40 micrograms/kg/h with alfentanil, you can go down to 10-15 micrograms/kg/h and start an addition of remifentanil with 5-7 ng/ml in TCI technology. Then anesthesia is administered with remifentanil and has a background infusion of alfentanil and partly as a part of analgesin peroperatively, but also as a starting point for postoperative pain relief.

Muscle relaxing agents

The most commonly used muscle relaxant drug is rocuronium (Esmeron). For so-called Rapid Sequencing Induction (RSI) is usually used succinylcholine (suxamethonium). In case of liver and/or kidney failure, atracurium may be used to advantage. It is also useful to intubate without muscle relaxants if the combination of propofol-remifentanil is used. This is especially true for surgical procedures in parathyroid or thyroid. If non-depolarising muscle relaxants have been given only during induction and it has elapsed for more than 60 minutes, we rarely reverse the neuromuscular block. If you have iterated the doses and received a full TOF response, no reversal is needed either.


TIVA protocol for Day Care Surgery

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


Procedures for TIVA

Practical management

  • The propofol syringe pump should be set to mg/kg/hour.
  • The syringe pump with remifentanil should be set to micrograms/kg/minute.
  • Fixed placement of drugs in syringe pumps: Remifentanil at the top and propofol below
  • Back valve for the infusion of remifentanil.
  • Avoid blood pressure cuff on the same arm.

Remifentanil is mixed in the strength of 50 micrograms/ml: 2 mg of remifentanil are dissolved in 40 ml of 0.9% Sodium Chloride.

Patients with ASA 1 and 2, under 60 years with BMI <35

Induction

Remifentanil: 0.3 microgram/kg/min until the patient gets clearly sedated.

Then 1 to 2 mg/kg of propofol until the patient is asleep and achieves adequate anesthesia for ventilation/laryngeal mask. Adolescents receive higher doses of propofol (1.5 -2 mg/kg), lower doses are given to the elderly (1 mg/kg).

In some cases, fentanyl 50-100 micrograms may be given initially, especially if the patient is to be intubated.

Preoxygenation with 80% oxygen by mask. The patient is ventilated with mask and respiratory bladder until the patient is ready for insertion of laryngeal mask/intubation.

Intubation

  • Minimize the use of muscle relaxants.
  • Remifentanil 4 micrograms/kg usually provides good intubation conditions in combination with propofol.
  • Note do not intubate when the vocal cords are closed! This may damage the vocal cords.

Maintenance 

  • Remifentanil 0.3 microgram/kg/min
  • Propofol 3 mg/kg/h

The doses are adjusted in relation to clinical conditions (procedure and patient condition). In some interventions it is very important that the patient is laying completely still (e.g. myringoplasty). Then, higher doses of remifentanil should be given, e.g. 0.4 to 0.5 micrograms/kg/min.

Termination 

For prolonged anesthesia: last 15 minutes the dose of remifentanil is reduced to 0.15 micrograms/kg/min.

For major surgery where it has not been possible to provide good local/regional anesthesia, fentanyl (50-100 micrograms) may be given after discontinuation of postoperative pain relief.

Approximately 5 minutes before the end of the operation, the infusions are terminated with propofol and remifentanil (the remifentanil infusion may continue until the operation is complete.) The ventilator should continue to go until the patient wakes up and can be extubated or the laryngeal mask is removed.

Patients over 60 years and/or ASA 3 

Evaluate reduced starting doses:

  • Remifentanil 0.2 microgram/kg/min.
  • Propofol 1 mg/kg

Take good time with slow induction to the elderly, increase the doses until satisfactory clinical effect is obtained. Maintenance doses for remifentanil should be 25% to 50% lower than healthy patients under 60, but must be adapted to the clinic. Otherwise, the procedure for “patients with ASA 1 and 2, under 60 years and with BMI <35” is followed.

Obese patients 

Consider dose reduction by specifying the patient’s weight on the syringe pumps lower than the actual weight. The specified patient weight is max 100 kg, even if the actual weight is higher.

Local anesthesia

Good local anesthetic with ev. regional blocks should be sought in all patients if possible.

 


TIVA for Pediatric Anesthesia

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


Practical management

  • Fixed placements of syringe pumps with drugs: Remifentanil at the top and propofol at the bottom.
  • The syringe pump with remifentanil should be set to micrograms/kg/minute.
  • The propofol syringe pump should be set to mg/kg/hour.
  • Back valve for the infusion with remifentanil.
  • Avoid blood pressure cuff on the same arm.

Induction anesthesia 

Preoxygenation is given with 80% oxygen by mask. The patient is ventilated with facial mask and respiratory bag until the patient is ready for insertion of laryngeal mask or intubation.

  • Bolus Propofol 5 mg/ml (“pediatric propofol”) 3 – 6 mg/kg iv.
  • Bolus fentanyl 1 – 3 micrograms/kg iv in induction.
  • Begin infusion with remifentanil 0.5 microgram/kg/min when the child has fallen asleep.
  • Atropine 0.01 mg/kg iv is given only on indication.

If anesthesia begins with sevoflurane inhalation (for example, when a venous access is missing), it may be converted to TIVA after the child has fallen asleep. Half the bolus dose with propofol is then given and other medications according to previous protocols.

Intubation

  • Minimize the use of muscle relaxants.
  • Remifentanil 4 micrograms/kg usually provides good intubation conditions in combination with
  • Propofol 3.5 mg/kg
  • Note: Do not intubate when the vocal cords are closed! This may damage the vocal cords.

Maintenance 

  • Remifentanil 0.5 – 1.0 microgram/kg/min
  • Propofol 8 – 12 mg/kg/h which can be gradually reduced to 6 mg/kg/h.

The doses are adjusted in relation to the clinical situation.

Termination

  • Infusions with propofol and remifentantil are switched off when approaching the end of surgery.
  • Remember to give bolus fentanyl 1 – 2 micrograms/kg IV for postoperative pain relief.

The ventilator continues to go until the patient wakes up and can be extubated or the laryngeal mask is removed.

Local anesthesia 

Good local anesthesia/regional anesthesia should be given to as many patients as possible. In case of skin wound closure, local wound infiltration may be given with bupivacaine 2.5 mg/kg 0.5 ml/kg.

Drug mixture

  • Remifentanil 50 micrograms/ml: 2 mg of remifentanil is dissolved in 40 ml of 0.9% Sodium Chloride.
  • Propofol is given at the concentration of 5 mg/ml

References

  1. Solheim A, Raeder J. Remifentanil versus fentanyl for propofol-based anesthesia in ambulatory surgery in children. Ambulatory surgery. 2011 March; 17 – 20.
  2. Klemola UM, Hiller A. Tracheal intubation after induction of anesthesia in children with propofol – remifentanil or propofol rocuronium. Can J Anaesth. 2000 September, 47 (9): 854 – 9.
  3. Procedures by Ahus: “Anesthesia for children – TIVA in patients under the age of 16”, version 1.4, date 24.01.2014.

Alfentanil (Rapifen®) with Desflurane (Suprane®)

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


Induction by hand with Propofol and Fentanyl. Maintenance anesthesia with alfentanil in the syringe pump and Desflurane by inhalation.





Propofol and Remifentanil (Ultiva®)

Below are a number of suggestions on doses of anesthetic agents in chronologically-based graphical anesthetics. For each schedule, you can see the dose in TIVA dosing or TCI dosing. Click the arrows to switch from TIVA dosing to TCI dosing.

Induction by hand with Propofol and Fentanyl. Maintenance anesthetics with Remifentanil and Propofol by syringe pumps.









Standard Anesthesia Procedure

Induction by hand with Propofol and Fentanyl. Maintenance anesthesia with Fentanyl i v and Sevoflurane in inhalation. Muscle relaxants as requested.


Dosage Guides for Propofol, Remifentanil and Alfentanil in TIVA/TCI

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


Below you will see dynamic dosage guides that will give you the right dose for the correct level of anesthesia. The dosage is read either in TIVA dosing or in TCI dosing depending on the setting and programming of the infusion pump. Click on the arrows to switch preparations between propofol, remifentanil and alfentanil.


Propofol (Diprivan®, Propolipid®, Recofol®, Propofol)

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


Propofol is a substituted phenol which, when administered intravenously, causes general anesthesia. Here you will find basic pharmacological information about this medicine.

Propofol is a short acting intravenous anesthetic agent for induction and maintenance of general anesthesia in adults and children over 1 month. Propofol is also used for sedation in diagnostic and surgical procedures, in adults and children over 1 month. Propofol is used for sedation of ventilated patients over the age of 16 in the intensive care unit.

Propofol (2,6-diisopropylphenol) is a substituted phenol which, when administered intravenously, causes anesthesia. The mechanism of action of propofol is not fully known, but probably the effect is exerted through a non-specific membrane binding of the substance in the vascular regulating neurons in the brain, primarily in the thalamus. Intravenous administration of propofol causes rapid anesthesia, within about 30 seconds, and the effect lasts about 5-10 minutes. The awakening is relatively fast.

Concentration

5 mg/ml, 10 mg/ml or 20 mg/ml.

Dosage

Normal dose in the induction of anesthesia is 1.5-2.5 mg/kg intravenously at a rate of 40 mg/10 sec until anesthesia occurs. In patients with complicated diseases (ASA 3 and 4) anesthesia should be induced slower, 20 mg/10 sec. Patients over 55 years of age may require a lower induction dose. The total dose may be reduced if the induction dose is given at a lower rate (20-50 mg/min). Depending on the rate of injection, the time for induction of anesthesia is between 30 and 40 seconds. After a bolus injection, the effect is short-lived due to the rapid metabolism and elimination (4-6 min).

TIVA dose

Intubation dose: 10-14 mg/kg/h. Maintenance dose for light surgery: 6-12 mg/kg/h. Maintenance dose for surgical anaesthesia: 14-16 mg/kg/h. Induction 1-2-3 mg/kg over 45 sec.

TCI dose  

Intubation dose: 4-6 μg/ml. Maintenance dose for light surgery: 2-4 μg/ml. Maintenance dose for surgical anaesthesia: 4-6 μg/ml.

Propofol distribueras i stor omfattning och elimineras snabbt från kroppen (total kroppsclearance: 1,5–2 liter/minut). Eliminationen sker genom metaboliska processer, huvudsakligen i levern där den är blodflödesberoende, varvid det bildas inaktiva konjugat av propofol och motsvarande kinol, vilka utsöndras i urinen.

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 blood-dependent depending on the formation of inactive conjugates of propofol and the corresponding quinol excreted in the urine. Propofol 20 mg/ml is not recommended for general anesthesia in children under 3 years of age as it is difficult to set the correct dose of strength 20 mg/ml as treatment of young children requires extremely small volumes. For children between 1 month and 3 years, when a dose less than 100 mg/hour is required, Propofol 10 mg/ml is recommended instead. Administration of Propofol with Target Controlled Infusion (TCI) systems is not recommended for use in children.

Warning

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


Remifentanil (Ultiva®)

Intravenous short acting anesthetic agent. 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 esterases.

Solution at 50 μg/ml. Recommended dilution for general anesthesia is 50 μg/ml for adults and 20 μg/ml for children ≥ 1 year.

Indication

Used as analgesic in induction and/or maintenance of general anesthesia under assisted breathing in surgical procedures including anesthesia in cardiac surgery. For pain relief and sedation in intensive care of mechanically ventilated patients 18 years of age and older.

Dosage

Intubation dose TIVA 0.25-0.5 μg/kg/min, TCI 6-8-(12) ng/ml. Maintenance dose during light surgery TIVA 0.15-0.25 μg/kg/min, TCI 4-6 ng/ml. Maintenance for major surgery TIVA 0.2-0.5 μg/kg/min, TCI 5-10 ng/ml. 0.5 μg/kg/min can be given as induction dose in TIVA up to 100-150 μg.

Following administration of recommended doses of remifentanil, the effective half-life is 3-10 minutes. The mean clearance of remifentanil in young healthy adults 40 ml/min/kg, central volume of distribution 100 ml/kg and steady state volume of distribution 350 ml/kg.

Remifentanil reduces the need for hypnosis necessary to maintain anesthesia, so 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.


Alfentanil (Rapifen®)

Intravenous anesthetic agent and analgesic. Alfentanil is intended for use in pain relief in short and medium surgical procedures. Alfentanil is a selective μ-opioid agonist with rapid onset and very short duration of action. Maximum effect is reached within 90 seconds with an effect duration of 5-10 minutes. Alfentanil is chemically related to fentanyl. In pharmacodynamic terms, alfentanil reminds of morphine but has more potent analgesic and respiratory depressant effect.

The distribution volume is 0.4-1.0 l/kg. Plasma protein binding is 92%. Alfentanil is not plasma cell bound and plasma protein binding is affected to a small extent by pH. Alfentanil is metabolised in the liver to inactive metabolites.

Dosage

In case of a short procedure: 0.25-0.5 mg i v – repeat when needed. Optimal intubation dose: 20-40 μg/kg iv (70 kg = 1.5-3 mg = 3-6 ml). Estimated operating time 10-30 minutes: 20-40 μg/kg, intravenous bolus dose in 3-6 ml/70 kg. Estimated operating time 30-60 minutes: 40-80 μg/kg, intravenous bolus dose in 6-12 ml/70 kg.

TIVA dose

Maintenance dose for surgical anesthesia: 0.20-0.70 μg/kg/min, Default dose: 0.35 μg/kg/min. Intubation dose: 0.70 μg/kg/min.

TCI dose

Maintenance dose for surgical anesthesia: 40-70 ng/ml, Default concentration 50 ng/ml (Cpt). Induction: 109 μg (0.218 ml) is given for 10 sec.

Concentration

Solution at 0.5 mg/ml.

Strength

Approximately 25 times the potency of morphine (1 ml Alfentanil ≈ 12.5 mg morphine).

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 hypotension. 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 non-vagolytic muscle relaxants. Secondary respiratory depression has been observed rarely.

Warning

Alfentanil reduces the need for hypnosis necessary to maintain anesthesia, so the dose of hypnotic should be reduced. Since 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 observed when administering Alfentanil to this patient population.


Sevoflurane (Sevorane®, Sevofluran®)

Sevoflurane is a halogenated methyl isopropyl ether. It is an inhalation anaesthetic agent used for induction and maintenance of general anesthesia. Sevoflurane is administered after vaporization, by laryngeal mask or endotracheal intubation.

Indication

Induction and maintenance of general anesthesia. Changes in the clinical effects of sevoflurane follow rapid changes in inhaled concentration. Like all inhaled anaesthetics, sevoflurane provide a controlled degree of unconsciousness and analgesia (anesthesia) and, in addition, reduces cardiovascular function in a dose-related manner. The low solubility of sevoflurane in blood causes the alveolar concentration to rapidly increase upon induction and rapidly decreases upon discontinuation of the inhalation anaesthetic agent. The blood/gas solubility coefficient is 0.68 for sevoflurane.

Dosage

Surgical anesthesia can be maintained at a concentration of 0.5 – 3% with or without simultaneous administration of nitrous oxide. Normally, a MAC value is sought between 0.8 and 1.6, usually 1.2-1.4. As with other halogenated volatile anaesthetics, the MAC for sevoflurane decreases when given in combination with nitrous oxide. The MAC value for sevoflurane decreases by 25-50% for adults and about 25% for children when 60-65% nitrous oxide is given at the same time. As with other inhalation anaesthetics, elderly patients usually require lower concentrations of sevoflurane to maintain surgical anesthesia. In humans, < 5% of absorbed sevoflurane is metabolized in the liver to hexafluoroisopropanol (HFIP) with the release of inorganic fluorine and carbon dioxide. HFIP is then conjugated rapidly with glucuronic acid and excreted in the urine. The fast and extensive lung elimination of sevoflurane minimizes the amount available for metabolism.

Recovery

Recovery is generally rapid after sevoflurane anesthesia with awakening within 5-30 minutes. Patients may therefore need postoperative pain relief early.

Caution

Sevoflurane may trigger malignant hyperthermia in predisposed patients. Caution in severe renal impairment or greatly increased intracranial pressure.


Desflurane (Suprane®)

Desflurane is a halogenated methyl ethyl ether (difluoromethyl-1,2,2,2-tetrafluoroethyl ether). It is an inhalation anaesthetic agent used for the maintenance of general anesthesia via the respiratory tract. It is supplied in the respiratory tract after gasification, via laryngeal mask or an endotracheal tube.

Indication

Induction and maintenance of general anesthesia. Changes in the clinical effects of desflurane follow rapid changes in inhaled concentration. Like all inhalation anaesthetics, desflurane delivers a controlled degree of unconsciousness and analgesia (anesthesia), and desflurane also decreases the cardiovascular function in a dose-related manner. Desflurane should not be used for anesthesia induction in children due to the high incidence of coughing, respiratory arrest, apnea, laryngospasm and increased secretion of the sebum. The blood/gas solubility coefficient is 0.42 for desflurane. The low solubility of desflurane in blood causes the alveolar concentration to rapidly increase upon induction and rapidly decreases upon discontinuation of the inhalation anaesthetic agent. Desflurane provide a dose-dependent reduction of blood pressure and breathing..

Dosage

Surgical anesthesia can be maintained at a concentration of 2.5-8% with or without simultaneous use of nitrous oxide. Usually 4-6% of desflurane is given in the inspiratory air. Normally, a MAC value is aimed at between 0.8 and 1.6, usually 1.2-1.4. In adults, surgical anaesthetic depth can be maintained with a reduced concentration of desflurane when nitrous oxide is used simultaneously. Higher concentrations of desflurane may be indicated. However, one should take into account the risk of hypoxia and adjust nitrous oxide/oxygen supply. The maintenance dose should be adjusted gradually in relation to the clinical effect. Desflurane is indicated for maintenance anesthesia to in neonates and children. Surgical anaesthetic depth can be maintained in children with end-tidal concentrations of 5.2 to 10% desflurane with or without simultaneous use of nitrous oxide. Studies have shown that only 0.02% of the absorbed desflurane is metabolized. Only marginal increases in inorganic fluoride can be seen in serum and urine. The rapid and extensive lung elimination of desflurane minimizes the amount available for metabolism. Generally, awakening is rapid after desflurane anesthesia for 5-30 minutes. Patients may therefore need postoperative pain relief early.

Recovery

Recovery is generally very rapid after desflurane anesthesia with awakening within 5-10 minutes. Patients may therefore need postoperative pain relief early.

Side effects

Desflurane may trigger cough and airway obstruction as well as increased airway mucous production. It should not be used for induction of anesthesia. It has dose dependent cardiac depression.

Warning

To rapid increase desflurane in the inspiratory air can cause respiratory irritation with bronchospasm and increased mucus secretion. Cough, laryngospasm, apnea and bronchospasm may occur. Desflurane is not recommended for induction by spontaneous breathing in children. May trigger malignant hyperthermia in predisposed patients. Caution in patients with elevated intracranial pressure.