ISOFLURANE
Clinical safety rating
cautionComprehensive clinical and safety monograph for ISOFLURANE (ISOFLURANE).
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.
| 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. |
| Molecular Weight | 184.49 |
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. |
| 1st trimester | Avoid elective use; teratogenic risk uncertain; use only if clearly needed. |
| 2nd trimester | Use if benefits outweigh risks; monitor for maternal hypotension and fetal bradycardia. |
| 3rd trimester | Use with caution; may cause uterine relaxation and fetal depression; avoid prolonged use near term. |
Clinical note
Comprehensive clinical and safety monograph for ISOFLURANE (ISOFLURANE).
| Placental transfer | Rapidly crosses the placenta; fetal concentrations reach 50-70% of maternal levels within minutes. |
| Breastfeeding | Isoflurane is rapidly cleared from plasma; negligible amounts likely excreted into breast milk. Due to low oral bioavailability, risk to infant is minimal. Resume breastfeeding once fully awake. |
| Lactation Rating | L3 - Moderately Safe |
| 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. |
| Fertility Effects | No direct effect on fertility reported; occupational exposure may be associated with reduced fertility in female anesthesiologists, but evidence is limited. |
■ 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.
| Serious Effects |
Known hypersensitivity to isoflurane or other halogenated anestheticsKnown or suspected malignant hyperthermia susceptibilitySevere hepatic dysfunction (e.g., hepatitis) due to prior halogenated anesthetic exposure
| 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 |
| Food/Dietary | No specific food interactions with isoflurane. However, fasting before anesthesia is required to reduce the risk of pulmonary aspiration. |
| Clinical Pearls | Isoflurane is a halogenated ether anesthetic. It causes dose-dependent hypotension primarily through vasodilation. It is not recommended for induction in pediatrics due to pungency and airway irritability. Malignant hyperthermia trigger. Use with caution in patients with elevated intracranial pressure as it can increase cerebral blood flow. Monitor end-tidal CO2 and volatile agent concentration. |
| Patient Advice | You will receive isoflurane gas to keep you asleep and pain-free during surgery. · You may experience shivering or nausea after awakening; tell your nurse if severe. · Do not eat or drink for the time instructed before surgery to prevent aspiration. · If you have a personal or family history of malignant hyperthermia, inform your anesthesiologist immediately. · Arrange for a ride home after surgery as isoflurane can impair coordination and judgment for up to 24 hours. |
Loading safety data…