ENFLURANE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ENFLURANE (ENFLURANE).
Enflurane is a volatile halogenated ether that potentiates GABA-A receptor activity, inhibits NMDA receptors, and enhances glycine receptor function, leading to generalized central nervous system depression and anesthesia.
| Metabolism | Primarily hepatic via cytochrome P450 (CYP2E1); approximately 2% undergoes oxidative metabolism to difluoromethoxy-difluoroacetic acid and fluoride ions; rest is excreted unchanged by lungs. |
| Excretion | Primarily eliminated by pulmonary excretion as unchanged drug (>90%); less than 5% is metabolized via CYP2E1 to fluoride ions and other metabolites, which are renally excreted. |
| Half-life | Terminal elimination half-life is approximately 4-8 hours in adults; context: prolonged with obesity due to high lipid solubility and storage in adipose tissue. |
| Protein binding | Approximately 55-75% bound to serum proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution at steady state (Vdss) is approximately 3.5-4.5 L/kg, indicating extensive tissue distribution and lipid solubility. |
| Bioavailability | Inhalation: Bioavailability is essentially 100% as administered via inhalation, with rapid absorption across the alveolar-capillary barrier. |
| Onset of Action | Inhalation: Induction occurs within 2-5 minutes at appropriate inspired concentrations (1-2% for induction). |
| Duration of Action | Clinical duration of anesthesia depends on depth and duration of administration; emergence typically occurs within 5-15 minutes after discontinuation. Prolonged use can lead to accumulation and slower recovery. |
Induction: 0.5-4.5% inspired concentration; Maintenance: 0.5-3% inspired concentration with oxygen/nitrous oxide; via inhalation.
| Dosage form | LIQUID |
| Renal impairment | No specific GFR-based dose adjustment required; however, monitor for nephrotoxicity in severe renal impairment (eGFR <30 mL/min) due to potential fluoride ion accumulation. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: use with caution, reduce concentration; Child-Pugh C: avoid due to risk of hepatotoxicity and altered metabolism. |
| Pediatric use | Induction: 1-4% inspired concentration; Maintenance: 0.5-2% inspired concentration; adjust based on age and response. |
| Geriatric use | Reduce inspired concentration by 25-50% due to decreased minimal alveolar concentration (MAC) and increased sensitivity; monitor hemodynamics closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ENFLURANE (ENFLURANE).
| Breastfeeding | Enflurane is excreted into breast milk in low concentrations. The M/P ratio is not well established but estimated around 0.5-1.0. Because of rapid clearance and minimal oral bioavailability, a single exposure is considered compatible with breastfeeding after waiting 24 hours. No adverse effects reported in infants. |
| Teratogenic Risk | Enflurane is not recommended during the first and second trimesters due to potential teratogenicity based on animal studies showing fetal malformations. During the third trimester, use is avoided for elective procedures as it may cause uterine relaxation and fetal depression. Risk is dose-dependent and duration-dependent. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to enflurane or other halogenated anesthetics","Known or suspected genetic susceptibility to malignant hyperthermia","Severe hypotension or hypovolemia (relative)","Prior history of hepatitis after halothane or other halogenated agents (relative)"]
| Precautions | ["May cause dose-dependent respiratory and cardiovascular depression","Risk of seizures (especially with deep anesthesia or hypocarbia)","Potential for hepatotoxicity (rare, but caution in patients with pre-existing liver disease)","Malignant hyperthermia risk","Should not be used in patients with known sensitivity to halogenated anesthetics"] |
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| Fetal Monitoring | Maternal: Continuous ECG, blood pressure, heart rate, oxygen saturation, end-tidal CO2, and anesthetic depth. Fetal: Fetal heart rate monitoring (external or internal) during obstetric anesthesia. Uterine tone monitoring if used during labor. |
| Fertility Effects | Enflurane has no well-documented effect on fertility in humans. Animal studies show no significant impairment. Occupational exposure may pose risks to fertility in operating room personnel, but data are inconclusive. |