ENFLURANE
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 184.49 |
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 | Use only if clearly needed; risks of anesthesia complications and potential teratogenicity (limited data, avoid elective procedures). |
| 2nd trimester | Use only if clearly needed; possible fetal hypoxia from maternal hypotension. |
| 3rd trimester | Use only if clearly needed; risk of neonatal respiratory depression and uterine relaxation leading to bleeding. |
Clinical note
Comprehensive clinical and safety monograph for ENFLURANE (ENFLURANE).
| Placental transfer | Rapidly crosses placenta; fetal concentrations reach 50-70% of maternal levels. |
| Breastfeeding | Minimal excretion into breast milk; use caution as infant may be exposed to small amounts; monitor infant for drowsiness. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Known hypersensitivity to halogenated anestheticsHistory of malignant hyperthermiaUse of sevoflurane or enflurane with known hepatitis
| 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 |
| Food/Dietary | No specific food interactions known for enflurane. Avoid alcohol for at least 24 hours post-anesthesia as it may increase sedation and hepatotoxicity risk. |
| Clinical Pearls | Enflurane is a potent inhalation anesthetic that can cause dose-dependent myocardial depression and hypotension. It sensitizes the myocardium to catecholamines, increasing arrhythmia risk. Enflurane may provoke seizure activity at high concentrations or with hypocapnia. Malignant hyperthermia trigger. Use caution in patients with hepatic or renal impairment due to fluoride ion release. |
| Patient Advice | You will be unconscious and feel no pain during surgery. · You may experience nausea or shivering after waking up. · Inform your anesthesiologist if you have a personal or family history of malignant hyperthermia. · Avoid operating machinery or driving for at least 24 hours after anesthesia. · Report any unusual muscle stiffness, fever, or dark urine after surgery. |
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