ISOFLURANE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ISOFLURANE (ISOFLURANE).

How it works

Isoflurane is a general inhalation anesthetic that acts as a positive allosteric modulator of GABA-A receptors and glycine receptors, and inhibits excitatory receptors such as NMDA and AMPA receptors. It potentiates inhibitory neurotransmission and depresses excitatory neurotransmission, leading to anesthesia, amnesia, and muscle relaxation.

What the body does with it

Metabolism	Isoflurane undergoes minimal metabolism (approximately 0.2%) primarily via hepatic cytochrome P450 enzymes (CYP2E1), leading to the production of inorganic fluoride and trifluoroacetic acid. The major route of elimination is via exhalation as unchanged drug.
Excretion	Primarily eliminated via exhalation through the lungs (>99%). Less than 1% undergoes hepatic metabolism to trifluoroacetic acid and fluoride ions, which are excreted renally.
Half-life	Terminal elimination half-life is approximately 2.5 to 5 hours. Context: The context-sensitive half-time varies with duration of anesthesia; for short procedures (<1 hour), half-life is about 2-4 minutes, but for prolonged anesthesia, it can be 30-60 minutes due to redistribution from fat stores.
Protein binding	Approximately 5-20% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution is about 2-5 L/kg, reflecting extensive tissue distribution, especially to lipid-rich tissues like brain and fat.
Bioavailability	Inhalation: Bioavailability is essentially 100% for inspired drug; systemic absorption is nearly complete due to rapid pulmonary exchange.
Onset of Action	Inhalation: Induction of anesthesia occurs within 5-10 minutes with 3-5% isoflurane in oxygen, though onset can be faster (2-3 minutes) with higher concentrations. Slower than sevoflurane or desflurane.
Duration of Action	Duration depends on depth and duration of administration. Recovery from anesthesia typically occurs within 10-30 minutes after discontinuation. Clinical context: Prolonged use leads to accumulation in fat, extending emergence.

Classification & Brands

Dosing & administration

Induction: 1-3% in oxygen or oxygen/nitrous oxide mixture via inhalation; Maintenance: 0.5-2% in oxygen or oxygen/nitrous oxide mixture via inhalation.

Dosage form	LIQUID
Renal impairment	No dose adjustment required in renal impairment; pharmacokinetics unaffected.
Liver impairment	No specific dose adjustment guidelines; use with caution in severe hepatic impairment due to potential for hepatotoxicity.
Pediatric use	Induction: 1.5-3% in oxygen or oxygen/nitrous oxide mixture; Maintenance: 0.5-2% in oxygen or oxygen/nitrous oxide mixture; titrate to effect.
Geriatric use	Reduce concentrations by 20-50% due to increased sensitivity and decreased MAC; monitor hemodynamics closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ISOFLURANE (ISOFLURANE).

Breastfeeding	Minimal transfer into breast milk; M/P ratio unknown. Considered compatible with breastfeeding after single exposure; observe infant for sedation.
Teratogenic Risk	Isoflurane is not associated with major congenital malformations but may cause fetal depression, especially during third trimester. Avoid elective use until after delivery.
Fetal Monitoring	Continuous fetal heart rate monitoring, uterine tone, maternal vital signs (BP, HR, O2 saturation), and depth of anesthesia. Assess fetal response to stress.

Warnings & precautions

■ FDA Black Box Warning

Because isoflurane is a potent halogenated anesthetic, it may cause malignant hyperthermia, a life-threatening condition characterized by hypermetabolism, muscle rigidity, tachycardia, and hyperthermia. Immediate treatment with dantrolene and discontinuation of triggering agents is essential.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known or suspected susceptibility to malignant hyperthermia","Prior history of unexplained jaundice or fever after isoflurane administration","Concurrent use of entacapone (increased risk of intraoperative myocardial depression)"]

Clinical Precautions

Precautions

["Risk of malignant hyperthermia","Respiratory depression","Hypotension and myocardial depression","Elevated intracranial pressure","Hepatic injury (rare)","Nephrotoxicity due to fluoride ion (rare)","QT interval prolongation","Use with caution in patients with coronary artery disease"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

ISOFLURANE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ISOFLURANE (ISOFLURANE).

How it works

What the body does with it

Metabolism	Isoflurane undergoes minimal metabolism (approximately 0.2%) primarily via hepatic cytochrome P450 enzymes (CYP2E1), leading to the production of inorganic fluoride and trifluoroacetic acid. The major route of elimination is via exhalation as unchanged drug.
Excretion	Primarily eliminated via exhalation through the lungs (>99%). Less than 1% undergoes hepatic metabolism to trifluoroacetic acid and fluoride ions, which are excreted renally.
Half-life	Terminal elimination half-life is approximately 2.5 to 5 hours. Context: The context-sensitive half-time varies with duration of anesthesia; for short procedures (<1 hour), half-life is about 2-4 minutes, but for prolonged anesthesia, it can be 30-60 minutes due to redistribution from fat stores.
Protein binding	Approximately 5-20% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution is about 2-5 L/kg, reflecting extensive tissue distribution, especially to lipid-rich tissues like brain and fat.
Bioavailability	Inhalation: Bioavailability is essentially 100% for inspired drug; systemic absorption is nearly complete due to rapid pulmonary exchange.
Onset of Action	Inhalation: Induction of anesthesia occurs within 5-10 minutes with 3-5% isoflurane in oxygen, though onset can be faster (2-3 minutes) with higher concentrations. Slower than sevoflurane or desflurane.
Duration of Action	Duration depends on depth and duration of administration. Recovery from anesthesia typically occurs within 10-30 minutes after discontinuation. Clinical context: Prolonged use leads to accumulation in fat, extending emergence.

Classification & Brands

Dosing & administration

Induction: 1-3% in oxygen or oxygen/nitrous oxide mixture via inhalation; Maintenance: 0.5-2% in oxygen or oxygen/nitrous oxide mixture via inhalation.

Dosage form	LIQUID
Renal impairment	No dose adjustment required in renal impairment; pharmacokinetics unaffected.
Liver impairment	No specific dose adjustment guidelines; use with caution in severe hepatic impairment due to potential for hepatotoxicity.
Pediatric use	Induction: 1.5-3% in oxygen or oxygen/nitrous oxide mixture; Maintenance: 0.5-2% in oxygen or oxygen/nitrous oxide mixture; titrate to effect.
Geriatric use	Reduce concentrations by 20-50% due to increased sensitivity and decreased MAC; monitor hemodynamics closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ISOFLURANE (ISOFLURANE).

Breastfeeding	Minimal transfer into breast milk; M/P ratio unknown. Considered compatible with breastfeeding after single exposure; observe infant for sedation.
Teratogenic Risk	Isoflurane is not associated with major congenital malformations but may cause fetal depression, especially during third trimester. Avoid elective use until after delivery.
Fetal Monitoring	Continuous fetal heart rate monitoring, uterine tone, maternal vital signs (BP, HR, O2 saturation), and depth of anesthesia. Assess fetal response to stress.