Active ingredient: Sevoflurane - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Anesthetics, Inhalation
• Platelet Aggregation Inhibitors

Dosage Forms

• Liquid (in a canister, to be vaporized for inhalation)

Brands / Synonyms

Sevofluran; Sevoflurane; Sevoflurano [INN-Spanish]; Sevofluranum [INN-Latin]; Sevorane; Sojourn; Ultane

Indications

Used for induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery.

Pharmacology

Sevoflurane (also called fluoromethyl) is a halogenated ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology. It is often administered in nitrous oxide and pure oxygen. After desflurane it is the volatile anesthetic with the fastest onset and offset. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.

Mechanism of Action

Sevoflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Sevoflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase and also binds to the GABA receptor, the large conductance Ca²⁺ activated potassium channel, the glutamate receptor, and the glycine receptor.

Absorption

Rapidly absorbed into circulation via the lungs, however solubility in the blood is low.

Toxicity

LC50=49881 ppm/hr (rat), LD₅₀=10.8 g/kg (rat)

Biotrnasformation / Drug Metabolism

Relatively little biotransformation, only 5% is metabolized by cytochrome P450 CYP2E1 to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. No other metabolic pathways have been identified for sevoflurane.

Contraindications

Sevoflurane can cause malignant hyperthermia. It should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents nor in patients with known or suspected susceptibility to malignant hyperthermia.

Drug Interactions

In clinical trials, no significant adverse reactions occurred with other drugs commonly used in the perioperative period, including: central nervous system depressants, autonomic drugs, skeletal muscle relaxants, anti-infective agents, hormones and synthetic substitutes, blood derivatives, and cardiovascular drugs.

Intravenous Anesthetics: Sevoflurane administration is compatible with barbiturates, propofol, and other commonly used intravenous anesthetics.

Benzodiazepines and Opioids: Benzodiazepines and opioids would be expected to decrease the MAC of sevoflurane in the same manner as with other inhalational anesthetics. Sevoflurane administration is compatible with benzodiazepines and opioids as commonly used in surgical practice.

Nitrous Oxide: As with other halogenated volatile anesthetics, the anesthetic requirement for sevoflurane is decreased when administered in combination with nitrous oxide. Using 50% N₂O, the MAC equivalent dose requirement is reduced approximately 50% in adults, and approximately 25% in pediatric patients.

Neuromuscular Blocking Agents: As is the case with other volatile anesthetics, sevoflurane increases both the intensity and duration of neuromuscular blockade induced by nondepolarizing muscle relaxants. When used to supplement alfentanil-N₂O anesthesia, sevoflurane and isoflurane equally potentiate neuromuscular block induced with pancuronium, vecuronium or atracurium. Therefore, during sevoflurane anesthesia, the dosage adjustments for these muscle relaxants are similar to those required with isoflurane.

Potentiation of neuromuscular blocking agents requires equilibration of muscle with delivered partial pressure of sevoflurane. Reduced doses of neuromuscular blocking agents during induction of anesthesia may result in delayed onset of conditions suitable for endotracheal intubation or inadequate muscle relaxation.

Among available nondepolarizing agents, only vecuronium, pancuronium and atracurium interactions have been studied during sevoflurane anesthesia. In the absence of specific guidelines:

1. For endotracheal intubation, do not reduce the dose of nondepolarizing muscle relaxants.

2. During maintenance of anesthesia, the required dose of nondepolarizing muscle relaxants is likely to be reduced compared to that during N₂O/opioid anesthesia. Administration of supplemental doses of muscle relaxants should be guided by the response to nerve stimulation.

The effect of sevoflurane on the duration of depolarizing neuromuscular blockade induced by succinylcholine has not been studied.

Hepatic Function

Results of evaluations of laboratory parameters (e.g., ALT, AST, alkaline phosphatase, and total bilirubin, etc.), as well as investigator-reported incidence of adverse events relating to liver function, demonstrate that sevoflurane can be administered to patients with normal or mild-to-moderately impaired hepatic function. However, patients with severe hepatic dysfunction were not investigated.

Occasional cases of transient changes in postoperative hepatic function tests were reported with both sevoflurane and reference agents. Sevoflurane was found to be comparable to isoflurane with regard to these changes in hepatic function.

Very rare cases of mild, moderate and severe post-operative hepatic dysfunction or hepatitis with or without jaundice have been reported from postmarketing experiences. Clinical judgement should be exercised when sevoflurane is used in patients with underlying hepatic conditions or under treatment with drugs known to cause hepatic dysfunction.