Sevoflurane is a halogenated inhalational anesthetic that is FDA approved for the induction and maintenance of general anesthesia in adults and pediatric patients for inpatient and outpatient surgery. Sevoflurane is a volatile anesthetic that provides hypnosis, amnesia, analgesia, akinesia, and autonomic blockade during surgical and procedural interventions.

Clinical Uses

• Inhalational induction of general anesthesia in neonatal and pediatric patients secondary to inadequate pre-induction intravenous access
• Inhalational induction of general anesthesia in adult patients whose clinical condition necessitates spontaneous respirations during induction
• May be used for complete maintenance of general anesthesia or concurrently with intravenous anesthetics to maintain general anesthesia in adult and pediatric patients

Similar to other halogenated inhalational anesthetics, the precise mechanism of action of sevoflurane to induce and maintain general anesthesia is unknown. There have been multiple attempts to identify a unitary hypothesis. However, no single proposed mechanism of action has fully explained their clinical effects. A current working hypothesis is that inhaled anesthetics enhance inhibitory postsynaptic channel activity (gamma-aminobutyric acid (GABA) and glycine) and inhibit excitatory synaptic channel activity (N-methyl-D-aspartate (NMDA), nicotinic acetylcholine, serotonin, and glutamate) in the central nervous system.[1]

Route of Administration

Sevoflurane is an inhaled halogenated anesthetic that is delivered via a sevoflurane specific calibrated vaporizer attached to an anesthesia machine. Sevoflurane is delivered via the lungs as a volume percent of inspired gas. Pharmacodynamics/Kinetics

For sevoflurane to exert its effect, the agent must be passed from the inspired gas into the blood of the pulmonary capillaries, then circulated into the central nervous system. The onset of action of sevoflurane is determined by the inspired concentration of the agent, partition coefficients, the patient’s minute ventilation, and the patient’s pulmonary blood flow. These four factors are responsible for the speed of equilibration between the concentration gradient of sevoflurane between the alveoli, pulmonary blood flow, and the central nervous system, and therefore responsible for the speed of anesthetic induction.

Dosing

Adults MAC Values for Surgical Levels of Anesthesia

• Age 25 years: Sevoflurane in oxygen: 2.6%
• Age 40 years: Sevoflurane in oxygen: 2.1%
• Age 60 years: Sevoflurane in oxygen: 1.7%
• Age 80 years: Sevoflurane in oxygen: 1.4%

Pediatric MAC Values for Surgical Levels of Anesthesia

• Newborn to 1-month-old full-term neonates: Sevoflurane in oxygen: 3.3%
• One to  younger than six months: Sevoflurane in oxygen: 3%
• Six months to younger than one year: Sevoflurane in oxygen: 2.8%
• One to younger than three years: Sevoflurane in oxygen: 2.8%

Metabolism

Sevoflurane undergoes minimal hepatic metabolism or renal excretion.

Clearance

The clearance of sevoflurane and termination of its anesthetic effects depend on the same factors that influence the agent’s uptake.

Factors Affecting Inhalational Sevoflurane Uptake and Clearance

1. The concentration of inhaled anesthetic
2. Partition coefficients (blood:gas, brain:blood, tissue:blood, oil:gas)
3. Patient’s minute ventilation
4. Patient’s pulmonary blood flow

Cardiovascular

Sevoflurane induces a dose-dependent reduction in blood pressure and cardiac output primarily through the reduction of systemic vascular resistance.

Respiratory

Like all of the volatile anesthetic agents, sevoflurane is an airway irritant and may precipitate coughing, apnea, and laryngospasm. These reactions are less likely to be seen with sevoflurane as compared to desflurane and isoflurane due to the sweet smell and low pungency of sevoflurane. Respiratory side effects are more common in patients with pre-existing lung pathology such as asthma, chronic obstructive pulmonary disease, and or cystic fibrosis. Sevoflurane, and all other inhaled anesthetics, also result in bronchodilation, blunting of the hypoxia/hypercapnia ventilatory response, and reverse hypoxic pulmonary vasoconstriction.

Central Nervous System

Sevoflurane causes dose-dependent vasodilation of cerebral vasculature, thereby increasing cerebral blood flow and intracranial pressure. Sevoflurane reduces the cerebral metabolic rate. 

Pregnancy and Neurodevelopmental deficits: While several observational studies have found an increased risk of neurodevelopmental deficits in children exposed to anesthesia, at this time, there is no compelling evidence to attribute this effect to the anesthesia directly. At this time, no specific anesthetic agent should be avoided during pregnancy, nor should any necessary surgery be delayed due to concerns regarding neurotoxicity.

Adverse Reactions

Less than 10%

• Dose-dependent cardiovascular collapse: Hypotension (4% to 11%)
• Central nervous system: Emergence delirium and agitation (7% to 15%)
• Gastrointestinal: Nausea (25%); vomiting (18%)

One to 10%

• Cardiovascular: Tachycardia, bradycardia, hypertension
• Respiratory: Laryngospasm (2-8%), breath-holding, apnea 

Less than 1%

Anaphylaxis, anaphylactoid reaction, cardiac arrhythmias, QT prolongation, increased intracranial pressure, hepatotoxicity, electrolyte disturbances, malignant hyperthermia

Drug Interactions

Sevoflurane undergoes minimal hepatic metabolism. The small percentage, that is, acts as a substrate for multiple CYP enzymes (CYP2A6, CYP2B6, CYP3A4, CYP2E1). This metabolism creates the potential for many clinically relevant drug interactions secondary to the large percentage of drugs metabolized by these hepatic enzymes.

Sevoflurane is contraindicated in patients with known hypersensitivity to sevoflurane or any other halogenated anesthetics. The agent is also contraindicated in any patient with known or suspected susceptibility to malignant hyperthermia.