SEVOFLURANE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEVOFLURANE (SEVOFLURANE).
Sevoflurane is a volatile general anesthetic that potentiates GABA-A receptors and glycine receptors, inhibits NMDA receptors and nicotinic acetylcholine receptors, leading to reversible loss of consciousness and analgesia.
| Metabolism | Primarily metabolized by cytochrome P450 2E1 (CYP2E1) to hexafluoroisopropanol and inorganic fluoride; minor metabolism via CYP2A6. |
| Excretion | Sevoflurane is eliminated primarily via exhalation. Over 95% of absorbed dose is eliminated unchanged by the lungs. Less than 5% is metabolized by hepatic CYP2E1 to hexafluoroisopropanol and inorganic fluoride, which are renally excreted. Biliary/fecal excretion is negligible. |
| Half-life | The terminal elimination half-life of sevoflurane is approximately 15-23 hours. This reflects slow equilibration from poorly perfused fat stores. Clinically, the context-sensitive half-life after prolonged anesthesia is longer than desflurane but shorter than isoflurane. |
| Protein binding | Minimal protein binding: approximately 5-10% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution at steady state is approximately 0.4-0.8 L/kg, reflecting extensive distribution into vessel-rich tissues and muscle. The large apparent Vd (up to 5-10 L/kg) reflects accumulation in fat. |
| Bioavailability | Inhalation: Essentially 100% bioavailability via inhalation. No oral or parenteral formulations. |
| Onset of Action | Inhalation: Loss of consciousness occurs within 60-90 seconds at 1-2 MAC with fresh gas flow of 4-6 L/min. Onset is rapid due to low blood/gas partition coefficient (0.65-0.69). |
| Duration of Action | Duration of anesthesia is determined by inspired concentration and duration of administration. After discontinuation, emergence occurs within 5-15 minutes depending on depth and duration. Full recovery from cognitive effects may take 30-60 minutes. |
Induction: 0.5–5% inhaled, titrated to effect; Maintenance: 0.5–3% inhaled with 50–70% N2O/O2 or 1.5–6% with O2 alone.
| Dosage form | LIQUID |
| Renal impairment | No dose adjustment required for any degree of renal impairment. Sevoflurane does not depend on renal function for elimination. |
| Liver impairment | No specific dose adjustment required for Child-Pugh A or B. Use with caution in severe hepatic impairment (Child-Pugh C) due to potential for hepatotoxicity; consider alternative agents. |
| Pediatric use | Induction: 3–8% inhaled (sevoflurane in 50–70% N2O/O2 or O2 alone) titrated to effect; Maintenance: 0.5–3% inhaled with 50–70% N2O/O2 or 1.5–6% with O2 alone. |
| Geriatric use | Lower doses recommended due to decreased minimum alveolar concentration (MAC). Induction: 0.25–4% inhaled, titrated slowly; Maintenance: 0.25–2% inhaled with 50–70% N2O/O2 or 0.5–4% with O2 alone. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SEVOFLURANE (SEVOFLURANE).
| Breastfeeding | Sevoflurane is rapidly eliminated from the body after anesthesia. The M/P ratio is not established. Limited data suggest minimal excretion into breast milk. The American Academy of Pediatrics considers sevoflurane compatible with breastfeeding. However, due to rapid clearance, mothers can resume breastfeeding once fully awake and alert, typically after 24 hours to avoid any theoretical risk of infant sedation. |
| Teratogenic Risk | Sevoflurane is a pregnancy category B drug. Animal studies have not demonstrated teratogenic effects, but there are no adequate and well-controlled studies in pregnant women. First trimester: No definitive evidence of teratogenicity, but elective use is avoided due to potential risk. Second and third trimesters: Used for general anesthesia when indicated; may cause transient fetal depression if maternal hypotension occurs. Near term: Crosses placenta, can cause neonatal respiratory depression if used during labor and delivery. |
■ FDA Black Box Warning
Risk of malignant hyperthermia; sevoflurane can cause a rapid increase in body temperature and muscle rigidity. Avoid in patients with known susceptibility.
| Serious Effects |
["Known or suspected genetic susceptibility to malignant hyperthermia","History of severe hepatic injury after sevoflurane or other halogenated anesthetics","Known hypersensitivity to sevoflurane or other halogenated agents"]
| Precautions | ["May cause malignant hyperthermia","Can lower seizure threshold, especially in children","May cause hepatic injury, particularly with repeated use","Risk of QT prolongation and cardiac arrhythmias","Can cause renal injury due to fluoride levels with prolonged use"] |
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| Fetal Monitoring | Continuous maternal vital signs: heart rate, blood pressure, oxygen saturation, end-tidal CO2. Fetal heart rate monitoring (if viable) during non-obstetric surgery. Monitor for maternal hypotension and hypoxia, which can reduce uterine blood flow and cause fetal distress. Postoperative monitoring for neonatal respiratory depression if used near delivery. |
| Fertility Effects | No direct evidence of impaired fertility in humans. Animal studies show no adverse effects on reproductive performance. Reversible effects on spermatogenesis have been reported in male rats at high concentrations, but clinical significance is unknown. Infertility from occupational exposure is not established. |