Sevofluran: Volatile Inhalation Anesthetic in Modern General Anesthesia
Sevofluran is a fluorinated volatile inhalation anesthetic that has been widely used in modern anesthesia worldwide since the 1990s. Well-known brand names are Sevorane (AbbVie) and Sevoflurane generics. Sevofluran has largely replaced the older halothane and enflurane in many countries and is today, together with desflurane and isoflurane, the most commonly used inhalation anesthetic.
Sevofluran is characterized by a non-irritating odor, minimal airway irritation, and rapid uptake, making it particularly suitable for inhalation induction in children and for ambulatory anesthesia. It is used both for induction and for maintenance of general anesthesia.
Mechanism of Action
The exact molecular mechanism of action of volatile anesthetics is not fully understood. Sevofluran likely acts on multiple targets in the central nervous system, including enhancement of GABA A mediated inhibition, inhibition of NMDA receptor mediated excitation, activation of two pore potassium channels, and modulation of glutamatergic synapses. The sum of these effects leads to unconsciousness, analgesia, amnesia, and muscle relaxation.
Anesthetic potency is measured by the minimum alveolar concentration value (MAC). Sevofluran has a MAC of 2.0 volume percent for adults, which decreases with increasing age and is slightly higher in children. Uptake and elimination occur almost exclusively through the lungs, which allows very fine control.
Approximately 5 percent of absorbed sevofluran is metabolized in the liver by CYP2E1, producing inorganic fluoride and hexafluoroisopropanol. These metabolites can theoretically be nephrotoxic at very high or prolonged exposures, but this is not a clinically relevant problem in practice. When sevofluran comes into contact with dry CO2 absorbent, it can be converted to potentially toxic compound A, but with modern equipment and CO2 absorbents this rarely becomes clinically relevant.
Indications
- Induction of general anesthesia: via inhalation, especially in children and in patients with difficult venous access
- Maintenance of general anesthesia: in combination with oxygen, nitrous oxide, or other anesthetics
- Sedation in intensive care medicine: with special equipment (AnaConDa) for analgosedated ventilated patients
- Bronchodilation: in severe refractory status asthmaticus as last resort
Dosage and Administration
Inhalation induction: Concentrations of 4 to 8 volume percent in an oxygen nitrous oxide mixture. Loss of consciousness after 2 to 3 breaths at high concentration. Maintenance: 0.5 to 3 volume percent in oxygen or oxygen nitrous oxide mixture.
In children: often lower concentrations because MAC varies with age. In infants and young children, particularly careful monitoring due to bradycardia and respiratory depression.
Administration: exclusively via specially approved anesthesia equipment with vaporizer. Administration must be performed only by or under direct supervision of anesthesiologists.
Adverse Effects
Common: postoperative nausea and vomiting (PONV) in approximately 30 percent, especially in women and after longer procedures; hypotension dose dependent due to vasodilation and negative inotropy; bradycardia; emergence agitation and postoperative delirium particularly in elderly patients and children (Emergence Delirium).
Rare but important: malignant hyperthermia (genetically predisposed reaction with life threatening hyperthermia and muscle rigidity, therapy with dantrolene); QT prolongation and arrhythmias; hepatotoxicity (very rare); compound A formation with theoretical nephrotoxicity; postoperative cognitive dysfunction particularly in elderly patients.
Important: malignant hyperthermia is a rare but life threatening complication. If suspected (increase in end tidal CO2 concentration, tachycardia, muscle rigidity, hyperthermia), immediately stop sevofluran administration, hyperventilate with 100 percent oxygen, administer dantrolene, and provide symptomatic intensive care.
Drug Interactions
- Other CNS depressants (opioids, benzodiazepines, propofol): additive effect, lower sevofluran concentrations are sufficient
- Non depolarizing muscle relaxants (rocuronium, vecuronium): enhancement and prolongation of effect
- Sympathomimetics (epinephrine): increased arrhythmia risk
- Calcium channel blockers: additive hypotension
- St. John's Wort and CYP2E1 inducers: theoretically increased metabolite formation
Special Precautions
Pregnancy and breastfeeding: Sevofluran is used in obstetrics and cesarean section. In breastfeeding patients, breastfeeding can continue after short procedures, as sevofluran is rapidly eliminated through the lungs.
Malignant hyperthermia disposition: Patients with familial disposition or positive trigger test for malignant hyperthermia must not receive sevofluran. Alternative anesthesia procedures (total intravenous anesthesia with propofol, regional anesthesia) are indicated. A sevofluran contaminated anesthesia machine must be carefully decontaminated before use.
Postoperative phase: Patients should be monitored in the recovery room until they are awake, hemodynamically stable, and oriented. Nausea and vomiting can be treated prophylactically (dexamethasone, ondansetron).
Environmental aspects: Inhalation anesthetics are greenhouse gases with considerable CO2 equivalent. Modern concepts for reducing fresh gas flows (low flow anesthesia) and recycling equipment reduce environmental impact.
You may also be interested in
- Desfluran, another modern inhalation anesthetic
- Isofluran, older inhalation anesthetic
- Propofol, intravenous hypnotic
- Remifentanil, ultra short acting opioid
- Dantrolene, antidote for malignant hyperthermia
Frequently Asked Questions
Why is sevofluran used particularly in children?
Sevofluran has a non-irritating odor and causes less airway irritation than other inhalation anesthetics. In children, anesthesia is frequently induced via mask with sevofluran because venous puncture in awake children is often difficult and traumatic. After loss of consciousness, intravenous access can then be established.
What is malignant hyperthermia?
Malignant hyperthermia is a rare, genetically determined reaction to certain anesthetics, especially volatile inhalation anesthetics and depolarizing muscle relaxants (succinylcholine). It leads to uncontrolled skeletal muscle activation, severe hyperthermia, acidosis, rhabdomyolysis, and can be fatal without treatment. Therapy with dantrolene has significantly improved prognosis since the 1980s. Patients with familial disposition should announce this before any anesthesia.
Why am I nauseous after surgery?
Postoperative nausea and vomiting (PONV) is one of the most common adverse effects of inhalation anesthetics and occurs in approximately 30 percent of patients. Risk factors are female gender, nonsmoker status, history of motion sickness, and longer procedure duration. Prophylaxis with dexamethasone and ondansetron, or alternatively regional anesthesia or total intravenous anesthesia with propofol, significantly reduce the risk.
When will I wake up after sevofluran?
Sevofluran is eliminated very rapidly through the lungs. When administration is stopped, the concentration in the brain decreases within 5 to 10 minutes to the point where patients wake up. This rapid elimination makes sevofluran particularly suitable for ambulatory and short procedures.
Sources
- EMA Product Information Sevofluran
- DGAI Recommendations for General Anesthesia
- Gelbe Liste, Sevofluran Active Ingredient Profile
- BfArM, Federal Institute for Drugs and Medical Devices
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