Anesthetics – Anesthesia Agents

Hemodynamic effects of Anesthetics

Sevoflurane (Sevorane®)

Sevoflurane is a halogenated methyl isopropyl ether. It is an inhalation anesthetic used for the induction and maintenance of general anesthesia. Sevoflurane is administered via vaporization through a mask, laryngeal mask, or endotracheal tube.

Indication

Induction and maintenance of general anesthesia. Changes in the clinical effects of sevoflurane quickly follow changes in inhaled concentration. Like all inhalation anesthetics, sevoflurane provides a controlled degree of unconsciousness and pain relief (anesthesia) and additionally lowers cardiovascular function in a dose-related manner. The low solubility of sevoflurane in blood allows the alveolar concentration to quickly rise during induction and quickly decrease upon discontinuation of the inhalation anesthetic. The blood/gas partition coefficient is 0.68 for sevoflurane.

Dosage

Surgical anesthesia can be maintained with a concentration of 0.5 – 3% with or without simultaneous administration of nitrous oxide. Typically, a MAC value between 0.8 and 1.6 is targeted, usually 1.2-1.4. As with other halogenated volatile anesthetics, the MAC for sevoflurane decreases when given in combination with nitrous oxide. The MAC value for Sevorane decreases by 25-50% for adults and about 25% for children when 60-65% nitrous oxide is administered simultaneously. As with other inhalation anesthetics, lower concentrations of sevoflurane are generally required to maintain surgical anesthesia in older patients. In humans, less than 5% of absorbed sevoflurane is metabolized in the liver to hexafluoroisopropanol (HFIP) with the release of inorganic fluoride and carbon dioxide. HFIP is then rapidly conjugated with glucuronic acid and excreted in the urine. The rapid and extensive pulmonary elimination of sevoflurane minimizes the amount available for metabolism.

Recovery

Recovery generally occurs quickly after Sevorane anesthesia within 5-30 minutes. Patients may therefore require postoperative pain relief early.

Warning

May trigger malignant hyperthermia in predisposed patients. Caution is advised in patients with severely impaired renal function or significantly elevated intracranial pressure.

Desflurane (Suprane®)

Desflurane is a halogenated methyl ethyl ether (difluoromethyl-1,2,2,2-tetrafluoroethyl ether). It is an inhalation anesthetic used for the maintenance of general anesthesia via the airways. It is administered in the airways after vaporization through a mask, laryngeal mask, or endotracheal tube.

Blood/gas solubility coefficient 0.42

• N₂O reduces the requirement by about 25%
• Airway irritant, unsuitable for induction
• Uterine relaxation
• Dosage-dependent cardio-depression

Physiological Effects of Desflurane

• CO±0
• HR ↑↑
• SVR↓
• BP↓
• RR↑↑
• TV↓↓
• pCO2↑↑

MAC Values for Desflurane

• 25 years 7%
• 60 years 6.0%
• 80 years 5%

Indication

Induction and maintenance of general anesthesia. Changes in the clinical effects of desflurane quickly follow changes in inhaled concentration. Like all inhalation anesthetics, desflurane provides a controlled degree of unconsciousness and pain relief (anesthesia) and additionally lowers cardiovascular function in a dose-related manner. Desflurane should not be used for induction of anesthesia in children due to the high incidence of cough, breath-holding, apnea, laryngospasm, and increased mucus secretion. The blood/gas solubility coefficient is 0.42 for desflurane. The low solubility of desflurane in blood allows the alveolar concentration to quickly rise during induction and quickly decrease upon discontinuation of the inhalation anesthetic. Desflurane produces a dose-dependent reduction in blood pressure and respiration.

Dosage

Surgical anesthesia can be maintained with a concentration of 2.5-8% with or without simultaneous administration of nitrous oxide. Typically, 4-6% desflurane is given in the inhaled air. A MAC value between 0.8 and 1.6 is generally targeted, usually 1.2-1.4. In adults, the depth of surgical anesthesia can be maintained with a reduced concentration of desflurane when nitrous oxide is used simultaneously. Higher concentrations of desflurane may be indicated. However, the risk of hypoxia should be considered, and nitrous oxide/oxygen administration adjusted accordingly. The maintenance dose should be adjusted gradually based on clinical effect. Desflurane is indicated for maintenance anesthesia in infants and children. Surgical depth of anesthesia can be maintained in children with end-tidal concentrations of 5.2 to 10% desflurane with or without the simultaneous use of nitrous oxide. Studies have shown that only 0.02% of absorbed desflurane is metabolized. Only marginal increases in inorganic fluoride can be seen in serum and urine. The rapid and extensive pulmonary elimination of desflurane minimizes the amount available for metabolism. Recovery: Recovery generally occurs quickly after desflurane anesthesia, within 5-30 minutes. Patients may therefore require postoperative pain relief early.

Side Effects

May trigger cough and airway obstruction as well as increased mucus production in the airways. Should not be used for induction of anesthesia. Dosage-dependent cardio-depression.

Warning

Too rapid an increase in desflurane in the inhaled air may cause airway irritation with bronchospasm and increased mucus secretion. Cough, laryngospasm, apnea, and bronchospasm may occur. Desflurane is not recommended for induction via inhalation in children. May trigger malignant hyperthermia in predisposed patients. Caution is advised in patients with elevated intracranial pressure.

Isoflurane (Isoflurane®, Forene®)

Isoflurane is a halogenated ethyl methyl ether. It is an inhalation anesthetic used for the induction and maintenance of general anesthesia via the airways in a closed breathing system. It is typically administered after vaporization through a mask, laryngeal mask, or endotracheal tube.

Indication

Induction and maintenance of general anesthesia. Changes in the clinical effects of isoflurane quickly follow changes in inhaled concentration. Like all inhalation anesthetics, isoflurane provides a controlled degree of unconsciousness and pain relief (anesthesia) and additionally lowers cardiovascular function in a dose-related manner. The low solubility of isoflurane in blood allows the alveolar concentration to quickly rise during induction and quickly decrease upon discontinuation of the inhalation anesthetic. The blood/gas partition coefficient is 1.4 for isoflurane.

Dosage

Surgical anesthesia can be maintained with 1-2.5% isoflurane in oxygen/nitrous oxide. A higher concentration, 1.5-3.5% isoflurane, is necessary if administered with pure oxygen. For cesarean section, 0.5-0.75% isoflurane in oxygen/nitrous oxide is suitable. Like other halogenated volatile anesthetics, the MAC for isoflurane decreases when given in combination with nitrous oxide. MAC is reduced with increasing age. The MAC value for isoflurane decreases by about 50% for adults and about 25% for children when 60-65% nitrous oxide is administered simultaneously. As with other inhalation anesthetics, lower concentrations of isoflurane are generally required to maintain surgical anesthesia in older patients. The biotransformation of isoflurane is minimal in humans. On average, about 95% of administered isoflurane is found in exhaled air. The rapid and extensive pulmonary elimination of isoflurane minimizes the amount available for metabolism. Recovery: Recovery generally occurs quickly after isoflurane anesthesia. Patients may therefore require postoperative pain relief early.

Side Effects

Should not be used for induction of anesthesia. Dosage-dependent cardio-depression.

Warning

May trigger malignant hyperthermia in predisposed patients. Caution is advised in patients with significantly elevated intracranial pressure. Rare cases of hypersensitivity (including contact dermatitis, rash, dyspnea, wheezing, chest discomfort, facial swelling, or anaphylactic reaction) have been reported, mainly in connection with prolonged occupational exposure to inhalation anesthetics, including isoflurane.

Nitrous Oxide

Nitrous oxide is a medical gas with good analgesic effects and moderate anesthetic effects. Nitrous oxide was discovered in the 1700s and came into medical use in the mid-1800s due to its analgesic and sedative properties. By the late 1800s, nitrous oxide began to be used for analgesia during childbirth as well as for tooth extractions and other minor surgical procedures. Nitrous oxide was a standard agent in anesthesia throughout most of the 20th century. During the 21st century, the use of nitrous oxide has declined but can still be beneficial when used appropriately.

Effects of Nitrous Oxide N₂O

• Blood/gas solubility coefficient 0.42
• Little effect on circulation and respiration.
• BP± 0
• TV↓
• RR↑
• MAC: 105%. During induction 30-70 volume % with O2 + possibly another anesthetic gas.

Cave: Pneumothorax, pneumopericardium, gas embolism, head injury, ileus, B12 deficiency

Indication

Maintenance of general anesthesia. Analgesic for childbirth and minor surgical procedures such as tooth extractions. Prehospital analgesic. Nitrous oxide provides an additive effect when combined with most other anesthetics, both intravenous drugs and inhalation anesthetics. The MAC value is stated to be 105%. Nitrous oxide potentiates the effect of other inhalation anesthetics, allowing the concentration of these to be significantly reduced to maintain the same depth of anesthesia (MAC value). Thus, anesthesia with nitrous oxide and other inhalation agents produces less hemodynamic impact than without nitrous oxide. Nitrous oxide has dose-dependent effects on sensory perception and cognitive functions starting at 15 volume percent. Concentrations above 60-70 volume percent result in unconsciousness. Nitrous oxide has dose-dependent analgesic properties that are clinically noticeable at end-tidal concentrations around 20 volume percent. The blood/gas solubility coefficient is 0.46 for nitrous oxide. The low solubility of nitrous oxide in blood allows the alveolar concentration to quickly rise during induction and quickly decrease upon discontinuation of the inhalation anesthetic. Nitrous oxide provides rapid saturation of the blood and reaches equilibrium faster than other inhalation anesthetics.

Dosage

During general anesthesia, nitrous oxide is typically used in concentrations between 35-70 volume percent in combination with oxygen and, when necessary, other anesthetics. Typically, oxygen/nitrous oxide is administered in a 1:2 or 1:1 ratio. Nitrous oxide as a sole anesthetic is usually not potent enough to create surgical anesthesia and should therefore be combined with other anesthetics when used for general anesthesia. Nitrous oxide is rapidly eliminated from the body after short-term inhalation, and the impact on psychometric functions typically subsides about 20 minutes after discontinuation.

Recovery

Recovery generally occurs quickly after nitrous oxide anesthesia. Patients may therefore require postoperative pain relief early.

Warning

Gas-filled cavities may expand due to the diffusion capacity of nitrous oxide. As a result, nitrous oxide is contraindicated in patients with symptoms of pneumothorax, pneumopericardium, gas embolism, severe head injury, ileus, or distended intestines. In case of suspected or actual vitamin B12 deficiency or symptoms consistent with methionine synthase inhibition, B-vitamin supplementation should be administered to minimize the risk of side effects/symptoms related to methionine synthase inhibition, such as leukopenia, megaloblastic anemia, myelopathy, and polyneuropathy.

Fentanyl (Fentanyl, Leptanal®)

Fentanyl is a potent opioid and a short-acting intravenous anesthetic and analgesic. Fentanyl is intended for use during anesthesia for surgical procedures and for sedation during painful or stressful medical procedures. Fentanyl is a selective and potent μ-opioid agonist with rapid onset and short duration of action. Despite its rapid onset, the maximum analgesic and respiratory depressant effects are reached only after a few minutes. Normally, the analgesic effect of an intravenous injection of 100 micrograms of fentanyl lasts about 30 minutes. In pharmacodynamic terms, fentanyl is similar to morphine but has more potent analgesic and respiratory depressant effects. Even in large bolus doses, fentanyl has often been used for induction of anesthesia in patients with heart disease due to its cardiovascular stability and its ability to suppress hemodynamic responses to intubation.

Plasma protein binding is 80-85%. Fentanyl is not plasma cell-bound, and plasma protein binding is minimally affected by pH. Fentanyl is metabolized in the liver to inactive metabolites.

The plasma concentration of fentanyl decreases rapidly after an intravenous injection. The elimination of fentanyl is triphasic with half-lives of about 1 minute, 15 minutes, and 6 hours. The distribution volume in the central compartment is about 15 liters, and the total distribution volume is about 400 liters. Secondary peaks in plasma levels may occur. About 75% of the dose is eliminated within 72 hours.

Dosage

In anesthesia procedures, the usual initial dose of fentanyl for adults is 50-100-200 μg, 1-2-4 ml, slowly injected intravenously. The dose can be repeated 20-30-45 minutes after the initial dose. Secondary respiratory depression has been observed in cases where large doses have accumulated. During continuous infusion, there is a risk of accumulation.

Fentanyl should be used with caution in uncompensated hypothyroidism, lung disease, particularly with reduced lung capacity, alcohol abuse, liver, or kidney insufficiency. Tolerance and abuse may be induced. Fentanyl reduces the need for hypnotics necessary to maintain anesthesia, so the dose of hypnotics or volatile anesthetics should be reduced.

• Intubation dose for general anesthesia: 1–8 μg/kg i.v. (70 kg = 70-600 μg = 2-12 ml).
• For children 2 – 12 years, 1-3 μg/kg in combination with inhalation anesthesia.

TIVA Dosage

Fentanyl can be given as an infusion.

• Maintenance dose for surgical anesthesia: 0.1-0.70 μg/kg/min.
• Standard dose: 0.15 μg/kg/min.
• Intubation dose: 1-2 μg/kg.

In ventilated patients, a loading dose of fentanyl can be given as a rapid infusion of about 1 μg/kg/minute during the first 10 minutes, followed by an infusion of about 0.1 μg/kg/minute. Alternatively, the loading dose of fentanyl can be given as a bolus dose. The infusion rate should be titrated based on individual patient response; lower infusion rates may be sufficient.

TCI Dosage (insufficient data)

Fentanyl is typically not given in TCI mode but rather in TIVA mode or in intermittent boluses. Maintenance target concentration (TCI) for surgical anesthesia is unknown: (1-4 ng/ml?). Standard concentration is unknown (2 ng/ml?) (Cpt).

Induction: 100 μg (2 ml) given over 10 seconds.

Concentration

Solution 50 μg/ml.

Strength

About 100 times the strength of morphine. (1 ml fentanyl ~ 10 mg morphine).

Side Effects

May cause respiratory failure and respiratory depression. Can cause muscle rigidity, especially at high doses and difficulties in manually ventilating the patient. It can cause drowsiness and increased fatigue. May cause bradycardia and hypotension. Muscle rigidity has been observed more frequently at high doses and with rapid administration of fentanyl. Bradycardia and possibly asystole may occur if the patient receives an insufficient dose of anticholinergic or if fentanyl is combined with non-vagolytic muscle relaxants. Secondary respiratory depression has been observed.

Warning

Fentanyl reduces the need for hypnotics (inhalation anesthetics) necessary to maintain anesthesia, so the dose of other anesthetics should be reduced. Since adverse hemodynamic effects of fentanyl are more pronounced and frequent in patients with ASA IV than with long-acting opiates, great caution should be exercised when administering fentanyl to this patient population.

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

Propofol is a substituted phenol that provides general anesthesia when administered intravenously. This section provides basic pharmacological information about this drug.

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

Propofol (2,6-diisopropylphenol) is a substituted phenol that provides anesthesia when administered intravenously. The mechanism of action of propofol is not fully understood but is likely mediated via non-specific membrane binding of the substance in wakefulness-regulating neurons in the brain, primarily in the thalamus. Intravenous administration of propofol provides rapid anesthesia, within about 30 seconds, and the effect lasts about 5-10 minutes. Awakening is relatively quick.

Concentration: 5 mg/ml, 10 mg/ml, or 20 mg/ml. For children, 5 mg/ml is recommended for induction by hand.

Dosage: The normal dose for 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 complex diseases (ASA 3 and 4), anesthesia should be induced more slowly, 20 mg/10 sec. Patients over 55 years may require a lower induction dose. The total dose may be reduced if the induction dose is administered at a slower rate (20-50 mg/min). Depending on the injection rate, the time to induction of anesthesia is between 30 and 40 seconds. After a bolus injection, the effect is short due to rapid metabolism and excretion (4-6 minutes).

TIVA Dosage

Intubation dose: 10-14 mg/kg/h.

Maintenance dose for superficial surgery: 6-12 mg/kg/h. Maintenance dose for deep surgery: 14-16 mg/kg/h.

Induction 1-2-3 mg/kg over 45 sec.

TCI Dosage

Intubation dose: 4-6 μg/ml.

Maintenance dose for superficial surgery: 2-4 μg/ml. Maintenance dose for deep surgery: 4-6 μg/ml.

Propofol is extensively distributed and rapidly eliminated from the body (total body clearance: 1.5–2 liters/minute). Elimination occurs through metabolic processes, primarily in the liver, where it is blood flow-dependent, resulting in inactive conjugates of propofol and corresponding quinol, which are 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 adjust the correct dose of the 20 mg/ml strength since treatment of small children requires extremely small volumes. For children between 1 month and 3 years, when a lower dose than 100 mg/hour is needed, Propofol 10 mg/ml is recommended instead.

Administration of Propofol with TCI systems (Target Controlled Infusion) is not recommended for use in children.

Warning: A few reports have been received of adult patients who developed metabolic acidosis, rhabdomyolysis, hyperkalemia, and/or rapidly progressive heart failure (in some cases with a fatal outcome ) after being sedated for more than 58 hours with doses exceeding 5 mg/kg/hour.

Remifentanil (Ultiva®)

Intravenous short-acting anesthetic. Solution 50 μg/ml. Recommended dilution for general anesthesia is 50 μg/ml for adults and 20 μg/ml for children ≥ 1 year.

Remifentanil is a selective μ-opioid agonist with rapid onset and very short duration of action. Remifentanil is an esterase-metabolized opioid, metabolized by non-specific blood and tissue esterases.

Indication: Used as an analgesic during induction and/or maintenance of general anesthesia during assisted ventilation for surgical procedures, including anesthesia for cardiac surgery. For pain relief and sedation in the intensive care of mechanically ventilated patients who are 18 years and older.

Dosage

Intubation dose TIVA 0.25-0.5 μg/kg/min, TCI 6-8 ng/ml. 0.5 μg/kg/min can be given as an induction dose in TIVA up to 100-150 μg.

Maintenance superficial surgery TIVA 0.15-0.25 μg/kg/min, TCI 4-6 ng/ml.

Maintenance deep surgery TIVA 0.2-0.5 μg/kg/min, TCI 5-10 ng/ml.

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

Remifentanil reduces the need for hypnotics necessary to maintain anesthesia, so the dose of hypnotics 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 exercised when administering Ultiva to this patient group.

Remifentanil and Hyperalgesia

Hyperalgesia is defined as increased pain intensity with a constant pain stimulus. This hyperalgesia can be due to two mechanisms. Both opioid-induced hyperalgesia and induction of acute opioid tolerance. Studies show that increased morphine consumption postoperatively is observed after anesthetics where high doses of remifentanil were given and no blocks were placed. This compared to similar operations where other anesthesia techniques were used. This hyperalgesia can be partially counteracted by using gabapentin in the premedication or by administering ketamine as an intraoperative adjunct in low doses. A disadvantage of gabapentin is that patients may become very tired.

The patient groups most relevant to adding Ketalar are those who received high doses of Ultiva, patients with ulcerative colitis/Crohn’s disease, and those who preoperatively have known pain issues with high consumption of opiates.

Alfentanil (Rapifen®)

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

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

Concentration: Solution 0.5 mg/ml

Side Effects: May cause respiratory failure and respiratory depression. Can cause muscle rigidity, especially at high doses and difficulties in manually ventilating the patient. It can cause somnolence and increased fatigue. May cause bradycardia and blood pressure drop at high doses. Muscle rigidity has been observed more frequently at high doses and with rapid administration of alfentanil. Bradycardia and possibly asystole may occur if the patient receives an insufficient dose of anticholinergic or if alfentanil is combined with non-vagolytic muscle relaxants. Secondary respiratory depression has been observed in rare cases.

Warning: Alfentanil reduces the need for hypnotics necessary to maintain sedation in intensive care patients, so the dose of hypnotics 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 exercised when administering alfentanil to this patient group.

Rocuronium (Esmeron®)

Non-depolarizing muscle relaxant. Adjunct to general anesthesia to facilitate endotracheal intubation and to achieve skeletal muscle relaxation during surgical procedures of medium to long duration. Patients are usually muscle-relaxed during abdominal surgery (open or laparoscopic), orthopedic surgery, and other surgeries where the patient must remain absolutely still. To facilitate manual or mechanical ventilation of anesthetized patients.

Concentration: 10 mg/ml

Intubation Dose

• 0.6 mg/kg i.v. (90 sec -> intub)
• 1.0 mg/kg (60 sec -> intub) 1.0 mg/kg for RSI
• 40-50 mg to a normal-weight adult = 4-5 ml

Standard dose: 50 mg. Maintenance 0.15 mg/kg, 10-20 mg per dose. Given every 20 to every 60 minutes during general anesthesia.

Cave: Previous reaction to muscle relaxants, myasthenia gravis, or similar neuromuscular disease.

Reversal:

• Robinul-Neostigmine 1-2 ml intravenously (neostigmine 2.5-5 mg + glycopyrronium 0.5-1 mg) or.
• Atropine 1 mg + Neostigmine 2.5 mg i.v.
• Emergency reversal: Bridion 16 mg/kg (70 kg = 1120 mg = 11.2 ml). Given i.v. as a bolus over 10 sec

Thiopental (Pentocur®/Pentothal®)

Ultra-short-acting intravenous anesthetic that is a barbituric acid derivative. Thiopental induces sleep when given intravenously. It induces hypnosis and anesthesia, but not analgesia. Primarily used for induction of anesthesia for surgery but also for short medical procedures where short-term sleep is desired. Typically administered manually with a syringe (25 mg/ml) where speed and dose are adjusted according to the patient’s condition and the nature of the procedure. Thiopental can be given as a continuous infusion in the treatment of status epilepticus and elevated intracranial pressure in cerebral edema. Thiopental was the standard agent for anesthesia induction for several decades but has recently been replaced by propofol and other anesthetics. It produces a dose-dependent depression of respiration and circulation. Thiopental is only a hypnotic and not a true analgesic, but pain relief is somewhat associated with the depth of anesthesia. For surgical anesthesia, thiopental is typically supplemented with potent opioids such as fentanyl in a balanced anesthesia. Compared to propofol, thiopental does not produce the same relaxation in the upper airways, which can cause some rigidity and difficulties in manual ventilation. A small dose of thiopental can be given to prevent or treat laryngospasm.

Concentration: 25 mg/ml.

Pentothal is supplied and stored as a dry powder and is usually diluted to a fresh daily concentration of 25 mg/ml. Diluted solution has a shelf life of only 24 hours and should be stored in the refrigerator.

Dosage

Induction anesthesia: 4-6 mg/kg. The normal dose for a 70 kg patient is about 14 ml (± 4 ml) = 350 mg. A normal induction dose for adults is 4-6 mg/kg body weight, but the individual response is so variable that no fixed dosage can be specified. Typically, between 200 and 400 mg is given as an induction dose (8 – 16 ml à 25 mg/ml), default 14 ml. In patients with poor general condition, the dose is usually reduced and carefully titrated. After intravenous administration, unconsciousness occurs within 30 seconds and lasts for 20-30 minutes after a single dose. Rapid uptake occurs in most vascular areas of the brain, followed by redistribution to other tissues. It is rarely justified to administer more than 500 mg intravenously. Thiopental has a distribution half-life of 2-4 hours after an intravenous single dose, and the elimination half-life is 9-11 hours. Plasma protein binding is 80-90% at therapeutic concentration.

Cave

Porphyria, upper airway obstruction, asthma attack, extravasal, and intra-arterial injection. Pentothal releases histamine, and a transient skin redness (usually over the chest and neck) can be seen after intravenous injection.

Caution

Caution in severe obesity, hypovolemia, hypotension, or severe shock.

Preparation Names

Pentocur, Thiopental (deregistered).

Ketamine (Ketalar®)

Anesthetic for intravenous or intramuscular administration for anesthesia induction and maintenance. Provides analgesia and dissociative anesthesia. Can also be given orally for sedation. Induction and maintenance of anesthesia for diagnostic and surgical procedures, as the sole anesthetic or in combination with other anesthetics. Ketamine can be given before or as a complement to regional anesthesia, even in acute fracture surgery. Ketamine or ketanest can be given as a continuous infusion in the treatment of severe pain alone or in addition to other pain treatment. Ketamine has been described as providing a rapid-acting antidepressant effect and is now being tested in depressions and severe pain conditions. (For this purpose, ketamine can be administered in a nasal spray).

• Ketalar = Ketamine in racemic form (50% Ketamine-R + 50% Ketamine-S)
• Ketanest = Ketamine-S = Esketamine. Ketanest is about twice as potent as Ketalar and causes less cognitive impairment.

Ketamine is an NMDA receptor blocker and produces a so-called dissociative anesthesia with effective pain relief through selective interruption of association pathways in the brain. The patient easily falls asleep after induction and enters a hypnotic state where pain or perception (other sensory impressions) is no longer experienced normally. The state is dreamlike, and vivid dreams of a hallucinatory nature are often described. The dreams can be both pleasant and unpleasant. The patient has increased sensitivity to sound, so the environment should be calm, quiet, and peaceful. The depth of anesthesia can be difficult to assess as the patient no longer reacts to sound, light, touch, or speech without appearing to be asleep. At sub-anesthetic doses, ketamine has an analgesic effect that is likely due to interaction with biogenic amine and endogenous opiate systems. Ketamine usually does not affect the reflexes in the pharynx and larynx, and muscle tone remains normal or slightly increased. Cardiovascular and respiratory stimulating effects allow ketamine to be given to high-risk patients in hypovolemic shock. The analgesic effect can be used as a complement to regional anesthesia or in mass casualty situations/disaster settings.

Concentration

10 mg/ml for intravenous use, 50 mg/ml for intramuscular use.

Induction Anesthesia

1-2 mg/kg iv, alternatively (5)-10 mg/kg im (+ midazolam 1-3 mg). An intravenous dose of 2.0 mg/kg body weight provides surgical anesthesia within one minute after injection, and the anesthetic effect lasts for 5-15 minutes. Intramuscular dosing 10.0 mg/kg body weight provides surgical anesthesia within 3-5 minutes after injection with a duration of 12-25 minutes. To achieve prolonged anesthesia or analgesia, ketamine can be administered in infusion (0.5-4 mg/kg/h) or syringe pump for even administration, e.g., during anesthesia of a patient in bleeding shock. The onset of anesthesia is accompanied by transient tachycardia, elevation of blood pressure, and cardiac output, which return to baseline within 15 minutes after injection. (Preferably quiet in the room or headphones on the patient). Orally, ketamine provides good sedation after 10-15 minutes and lasts about 30-45 minutes. It can be administered diluted in juice in a dose of about 4-5 mg/kg.

Maintenance Dose Anesthesia

• 0.5-4 mg/kg/h iv in decreasing dosage
• Postoperative pain relief: 5-15 mg bolus
• Maintenance infusion for postoperative pain relief: 0.05-0.5 mg/kg/h

Cave

Hypertension (relative contraindication). In liver failure, the dose should be reduced. There is a risk of abuse in non-medical use.

Suxamethonium (succinylcholine) (Celocurine®)

Depolarizing muscle relaxant. Ultra-short-acting agent with very rapid onset. Used to quickly achieve muscle relaxation and airway control. For intravenous use only. Adjunct to general anesthesia to facilitate endotracheal intubation and to achieve skeletal muscle relaxation during surgical procedures of short duration. To facilitate manual ventilation of anesthetized patients. Onset within 60-90 seconds. Used to create optimal intubation conditions quickly.

Intubation dose: 1-1.5 mg/kg iv = 25-100 mg i.v. (pre-treatment with atropine if needed), 50 mg/ml solution.

Standard dose: 75 mg i.v., 50-100 mg, 1-2 ml i.v.

Cave: Hyperkalemia, fresh burn, malignant hyperthermia, muscle diseases, large tissue injuries, bradycardia.

Neostigmine (Neostigmine®)

Neostigmine is a cholinesterase inhibitor that increases acetylcholine concentration, reversing the effect of muscle relaxants and restoring muscle activity and strength after muscle relaxation during anesthesia. Used to reverse the effects of non-depolarizing muscle relaxant anesthetics at the end of anesthesia. Neostigmine can also be used to increase bowel peristalsis in paralytic ileus and to enhance muscle activity in myasthenia gravis. Administration of neostigmine is preceded by intravenous administration of an anticholinergic (atropine sulfate or glycopyrronium). Neostigmine is then given in a dose of 0.5-2.5 mg (0.2-1 ml) intravenously. In exceptional cases, doses up to 5 mg (2 ml) may be needed. The injection should be given slowly and with respect to the effect.

Concentration: 2.5 mg/ml i.v.

Dosage

30-70 ug/kg. Standard dose for reversal 2.5 mg = 1 ml. If the effect is insufficient, half the standard dose can be repeated (after 10-15 min) = 0.5 ml.

Routinely combined with anticholinergics in the form of atropine or glycopyrronium to avoid bradycardia and bronchospasm.

• Neostigmine 2.5 mg + 0.5 mg glycopyrronium (Robinul) (1 ml)
• Neostigmine 2.5 mg (1 ml) + 0.5 mg atropine (1 ml)

Dosage for constipation: 1-2.5 mg i.v.

Caution

Concomitant treatment with beta-blockers may cause bradycardia and hypotension.

Sugammadex (Bridion®)

Antidote to non-depolarizing muscle relaxants for intravenous use. Sugammadex is a derivative of gamma-cyclodextrin. Sugammadex forms a complex with the neuromuscular blocking agents rocuronium and vecuronium in plasma, thereby reducing the amount of muscle relaxant available to bind to the nicotinic receptor in the neuromuscular junction.

Dosage: For normal reversal 4 mg/kg, which gives 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.

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

Concentration: Solution 100 mg/ml (2 or 5 ml ampoules).

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

Warning: Risk of rapid recovery of muscle tone during surgery, which may complicate the surgical work. Anaphylactic reactions may occur.

Oxygen (O₂)

Oxygen is essential for human cellular respiration and is necessary for normal aerobic cellular metabolism. Normally, the concentration is about 21% in air, but it varies with partial pressure. Oxygen is always administered in all closed ventilator systems, at least 21 percent. Oxygen counteracts nausea secondary to hypoxia. Normal saturation in arterial blood is 95-98%. Less than 90% saturation poses a risk of organ damage. Less than 70% is only tolerated briefly. Less than 50% is immediately life-threatening. Supranormal values cause vasoconstriction. Can cause alveolar hypoventilation.

Dosage

Administered via nasal cannula, prongs, breathing mask, or through a closed breathing system.

Standard Dose

Normally given in 30-40% in the inhaled air. 2-17 l/min during spontaneous breathing. With the Optiflow system, oxygen can be delivered at even higher flow rates up to 60 l/min. In the treatment of COPD with respiratory insufficiency, oxygen is usually given in low doses, 0.2-1 l/min, requiring a specially calibrated flow regulator.

Cave

Caution in respiratory insufficiency and hypoventilation. Caution after treatment with cytostatics of the type bleomycin.