HALOTHANE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HALOTHANE (HALOTHANE).
Halothane is a volatile halogenated hydrocarbon anesthetic that acts as a positive allosteric modulator of GABA-A receptors and glycine receptors, and inhibits NMDA and nicotinic acetylcholine receptors, leading to neuronal hyperpolarization and general anesthesia.
| Metabolism | Halothane is metabolized in the liver primarily by cytochrome P450 2E1 (CYP2E1) to trifluoroacetic acid and bromide ion; reductive metabolism also produces chloride ions and free radicals. |
| Excretion | Primarily eliminated via pulmonary excretion (60-80% unchanged); approximately 20% metabolized in liver via CYP2E1, with metabolites excreted renally (trifluoroacetic acid, chloride, bromide). Only about 0.5% excreted unchanged in urine. Fecal excretion negligible. |
| Half-life | Terminal elimination half-life approximately 5-10 hours post-anesthesia, with a slower terminal phase (up to 3 days) due to redistribution from fat stores. Clinically, washout is rapid initially but prolonged exposure in obese patients may lead to detectable levels for days. |
| Protein binding | Approximately 20-30% bound to plasma proteins, primarily albumin and lipoproteins. |
| Volume of Distribution | Volume of distribution at steady state (Vdss) approximately 2-5 L/kg; large Vd indicates extensive tissue distribution, especially to adipose tissue, brain, and muscle. |
| Bioavailability | 100% bioavailable via inhalation (only route of administration). Oral bioavailability not applicable. |
| Onset of Action | Inhalation: Induction of anesthesia occurs within 30-60 seconds with adequate alveolar concentration; peak effect in 2-5 minutes. |
| Duration of Action | Anesthetic duration depends on concentration and duration of administration; after discontinuation, emergence occurs within 5-15 minutes. Residual sedation and psychomotor impairment may persist for hours. Clinical context: prolonged emergence with higher doses or prolonged surgery. |
Induction: 0.5-3% in oxygen or oxygen-nitrous oxide mixture, titrated to effect; Maintenance: 0.5-2% in oxygen or oxygen-nitrous oxide mixture.
| Dosage form | LIQUID |
| Renal impairment | No specific dose adjustment required for renal impairment; use with caution due to potential nephrotoxicity from fluoride ions. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B and C: avoid use; contraindicated in patients with hepatic impairment or history of halothane-induced hepatotoxicity. |
| Pediatric use | Induction: 0.5-2% in oxygen or oxygen-nitrous oxide mixture, gradually increased; Maintenance: 0.3-1.5% as needed. Use lowest effective dose. |
| Geriatric use | Reduce dose by 25-50% due to increased sensitivity and reduced clearance; monitor hemodynamics closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HALOTHANE (HALOTHANE).
| Breastfeeding | Halothane is excreted into breast milk in small amounts. The milk-to-plasma (M/P) ratio is approximately 0.4. Due to low oral bioavailability, risks to the nursing infant are minimal. However, caution is advised as effects on the infant have not been fully studied. Consider pumping and discarding milk for 24-48 hours after anesthesia to minimize exposure. |
| Teratogenic Risk | Halothane is classified as FDA Pregnancy Category C. Animal studies have shown teratogenic effects, but adequate human studies are lacking. First trimester exposure is associated with a potential increased risk of congenital malformations based on limited epidemiological data. Second and third trimester use may cause fetal depression and uterine atony; prolonged exposure can lead to neonatal respiratory depression. Avoid use during pregnancy unless clearly needed. |
■ FDA Black Box Warning
Halothane can cause hepatic necrosis, which may be fatal. Fatalities have occurred in patients with previous halothane exposure. Avoid repeat exposure within 3-6 months.
| Serious Effects |
Hypersensitivity to halothane, known or suspected susceptibility to malignant hyperthermia, history of unexplained jaundice or fever after halothane, hepatic dysfunction following previous halothane exposure, pregnancy (relative, especially first trimester).
| Precautions | Hepatotoxicity (halothane hepatitis), malignant hyperthermia, cardiac arrhythmias (sensitizes myocardium to catecholamines), respiratory depression, hypotension, increased intracranial pressure. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, oxygen saturation, and end-tidal CO2. Fetal heart rate monitoring (cardiotocography) is recommended during prolonged surgery. Assess uterine tone to detect postpartum hemorrhage. Monitor for signs of malignant hyperthermia (muscle rigidity, hyperthermia, tachycardia) in both mother and fetus. |
| Fertility Effects | Halothane has been associated with reduced fertility in animal studies, including alterations in spermatogenesis and ovulation. Occupational exposure to halogenated anesthetics in healthcare workers may increase the risk of spontaneous abortion and infertility. Use in patients attempting conception should be avoided if alternatives exist. |