Usage
Sevoflurane is a halogenated inhalational anesthetic indicated for the induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery. It belongs to the pharmacological class of general anesthetics. Sevoflurane’s mechanism of action involves enhancing the effects of inhibitory neurotransmitters like GABA and glycine in the central nervous system, ultimately leading to a decrease in neuronal activity and a state of general anesthesia.
Alternate Names
While “sevoflurane” is the generic name, a popular brand name is Ultane. There are no widely recognized alternate or regional variations of the generic name itself.
How It Works
Pharmacodynamics: Sevoflurane primarily acts on the central nervous system (CNS) to produce general anesthesia. It affects multiple ion channels in neurons, potentiating the action of inhibitory neurotransmitters like GABA and glycine while inhibiting excitatory neurotransmitters such as NMDA. This leads to decreased neuronal activity and loss of consciousness. Sevoflurane also impacts cardiovascular function, typically causing a decrease in blood pressure and systemic vascular resistance. Respiratory effects include decreased tidal volume and respiratory rate, as well as bronchodilation.
Pharmacokinetics: Sevoflurane is administered via inhalation and is rapidly absorbed through the lungs. It is minimally metabolized in the liver (approximately 3-5%) primarily by CYP2E1, with inorganic fluoride being the major metabolite. The majority of sevoflurane is eliminated unchanged through the lungs. It has a short elimination half-life, allowing for rapid recovery from anesthesia.
Mode of Action: At the cellular and molecular level, sevoflurane binds to specific sites on GABA receptors, increasing their sensitivity to GABA, leading to enhanced chloride influx and neuronal hyperpolarization. It also binds to glycine receptors, potentiating their inhibitory effect. Sevoflurane inhibits NMDA receptors, reducing the excitatory effects of glutamate.
Elimination: Primarily eliminated unchanged through the lungs. A small fraction is metabolized by hepatic CYP2E1 enzymes.
Dosage
Standard Dosage
Adults:
Induction: Up to 8% v/v for unpremedicated patients; up to 5% v/v for premedicated patients, titrated to effect.
Maintenance: 0.5-3% v/v, with or without nitrous oxide.
Children:
Induction: Up to 7% v/v for premedicated patients, titrated to effect.
Maintenance: 0.5-3% v/v, with or without nitrous oxide.
Note: MAC values are age-dependent and generally higher in younger children. Premature infants have not been studied.
Special Cases:
- Elderly Patients: Dose reduction may be necessary due to decreased MAC.
- Patients with Renal Impairment: Caution advised; monitor renal function postoperatively.
- Patients with Hepatic Dysfunction: Contraindicated in patients with a history of halogenated anesthetic-induced hepatitis or unexplained hepatic dysfunction.
- Patients with Comorbid Conditions: Exercise caution in patients with heart failure, coronary artery disease, seizure disorder, mitochondrial disorders, hypovolemia, hypotension, or those at risk of QT prolongation or increased intracranial pressure.
Clinical Use Cases:
- Intubation: Sevoflurane can be used for rapid sequence intubation due to its non-pungent odor.
- Surgical Procedures: For induction and maintenance of anesthesia across a wide range of surgical procedures.
- Mechanical Ventilation: Sevoflurane can be used to facilitate mechanical ventilation.
- Intensive Care Unit (ICU) Use: May be used for sedation in the ICU.
- Emergency Situations: Not typically the agent of choice for emergency situations.
Dosage Adjustments:
Adjustments should be based on patient age, comorbidities, and response to anesthesia. Consider renal/hepatic function, concomitant medications, and genetic polymorphisms affecting drug metabolism. Lower concentrations are typically needed in elderly patients.
Side Effects
Common Side Effects:
Drowsiness, dizziness, nausea, vomiting, shivering, cough, agitation, delirium.
Rare but Serious Side Effects:
Malignant hyperthermia, respiratory depression, hypotension, laryngospasm, apnea, seizures, hepatotoxicity, nephrotoxicity, cardiac arrhythmias, hypersensitivity reactions, postoperative hepatic dysfunction.
Long-Term Effects:
Potential for cognitive dysfunction with prolonged or repeated exposure, particularly in young children and pregnant women.
Adverse Drug Reactions (ADR):
Malignant hyperthermia, anaphylaxis, severe hypotension, cardiac arrest, acute renal failure, hepatitis, seizures.
Contraindications
- Known hypersensitivity to sevoflurane or other halogenated anesthetics.
- Susceptibility to malignant hyperthermia.
- History of halogenated anesthetic-induced hepatitis or unexplained hepatic dysfunction.
- Situations where general anesthesia is contraindicated.
Drug Interactions
- CYP2E1 Inducers: Isoniazid, alcohol – increased sevoflurane metabolism, higher fluoride levels.
- Barbiturates, Benzodiazepines, Opioids: May decrease MAC of sevoflurane.
- Calcium Channel Blockers: Increased risk of hypotension.
- Succinylcholine: Increased risk of hyperkalemia and cardiac arrhythmias in children.
- Beta-Sympathomimetics (e.g., isoprenaline, adrenaline, noradrenaline): Increased risk of ventricular arrhythmia.
- Non-selective MAO Inhibitors: Risk of intraoperative crisis.
Pregnancy and Breastfeeding
Pregnancy Category: There are no adequate and well-controlled studies in pregnant women. Animal studies show reduced fetal weights with prolonged exposure. Use only if clearly needed. It has been used in cesarean sections without apparent adverse effects. Safety in labor and vaginal delivery has not been established.
Breastfeeding: Limited data. Advise women to interrupt breastfeeding for 48 hours after sevoflurane administration and discard milk produced during this period.
Drug Profile Summary
- Mechanism of Action: Enhances GABA and glycine activity, inhibits NMDA receptors, leading to CNS depression and general anesthesia.
- Side Effects: Drowsiness, dizziness, nausea, vomiting, shivering; rarely: malignant hyperthermia, respiratory depression, seizures, hepatic dysfunction.
- Contraindications: Hypersensitivity, malignant hyperthermia susceptibility, prior halogenated anesthetic-induced hepatitis, conditions precluding general anesthesia.
- Drug Interactions: CYP2E1 inducers, barbiturates, benzodiazepines, opioids, calcium channel blockers, succinylcholine.
- Pregnancy & Breastfeeding: Use with caution in pregnancy if benefits outweigh risks. Interrupt breastfeeding for 48 hours post-administration.
- Dosage: See detailed section above.
- Monitoring Parameters: ECG, blood pressure, pulse oximetry, end-tidal CO2, temperature, urine output.
Popular Combinations
Often combined with nitrous oxide to reduce the required concentration of sevoflurane and potentially improve cardiovascular stability. Premedication with benzodiazepines or opioids is common to reduce anxiety and postoperative pain. Neuromuscular blocking agents may be used to facilitate intubation and surgery.
Precautions
General precautions include pre-operative assessment of patient medical history, allergies, and organ function. Specific populations: pregnant women (fetal risk), breastfeeding mothers, children, and the elderly require careful consideration and dosage adjustments. Ensure appropriate facilities for airway management, ventilation, and resuscitation are readily available. Avoid desiccated carbon dioxide absorbents.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sevoflurane?
A: See the detailed “Dosage” section above for age-specific and clinical scenario-based dosage recommendations.
A: Primarily eliminated unchanged through the lungs. Minimally metabolized (3-5%) by hepatic CYP2E1 to inorganic fluoride.
Q3: What are the contraindications to using Sevoflurane?
A: Hypersensitivity to sevoflurane or other halogenated anesthetics, susceptibility to malignant hyperthermia, history of halogenated anesthetic-induced hepatitis, and any condition where general anesthesia is contraindicated.
Q4: What are the common side effects of Sevoflurane?
A: Drowsiness, dizziness, nausea, vomiting, shivering, cough, agitation, and delirium.
Q5: Can Sevoflurane be used in pregnant women?
A: Use only if clearly needed. Weigh the benefits against potential risks to the fetus. There are no adequate and well-controlled studies in pregnant women.
Q6: What are the potential drug interactions with Sevoflurane?
A: Sevoflurane interacts with several medications, including CYP2E1 inducers (isoniazid, alcohol), barbiturates, benzodiazepines, opioids, calcium channel blockers, succinylcholine, beta-agonists, and non-selective MAO inhibitors.
Q7: How should Sevoflurane be administered?
A: Administered via inhalation using a calibrated vaporizer. The concentration should be carefully titrated to achieve the desired depth of anesthesia.
Q8: What is the recovery time like after Sevoflurane anesthesia?
A: Sevoflurane has a short elimination half-life, resulting in generally rapid emergence from anesthesia.
Q9: What monitoring parameters are essential during Sevoflurane anesthesia?
