Dosing and uses of Ethrane, Compound 347 (enflurane)
Adult dosage forms and strengths
volatile liquid for inhalation
- 250mL per bottle (99.9%)
Anesthesia
Surgical anesthesia
- Induction: 2-4.5% inspired concentrations produce surgical anesthesia within 7-10 min; administer with oxygen or combination of oxygen/nitrous oxide mixture
- Maintenance: 0.5-3% inspired concentrations maintain surgical anesthesia; if added relaxation is required, supplemental with muscle relaxants; ventilate to maintain carbon dioxide tension in arterial blood between 35-45 mmHg
Cesarean Section
- 0.5-1% as supplement to other general anesthetics
Analgesia
Vaginal delivery: 0.25-1% provides analgesia equivalent to that produced by 30-60% nitrous oxide
Pediatric dosage forms and strengths
Safety and efficacy not established
Ethrane, Compound 347 (enflurane) adverse (side) effects
Frequency not defined
Malignant hyperthermia
Motor activity/seizures (with deep anesthesia or light anesthesia accompanied by hypocapnia)
Hypotension
Respiratory depression
Hypoxia
Arrhythmias
Shivering
Nausea
Vomiting
Increased WBCs
Liver impairment, including hepatic failure (rare)
Warnings
Contraindications
Hypersensitivity
Seizure disorders
Known or suspected genetic susceptibility to malignant hyperthermia
Cautions
Avoid hyperventilation to minimize possible CNS excitation
Continuous blood pressure monitoring required; lighten administration if excessive BP decrease occurs (unless hypovolemic)
Renal dysfunction is associated with serum fluoride levels >50 micromol/L
Postoperative hepatitis reported
Increased intracranial pressure may occur
May trigger skeletal muscle hypermetabolic state leading to high oxygen demand and malignant hyperthermia
Caution in patients considered more susceptible to cortical stimulation
Decrease dose of neuromuscular blocker if coadministered (longer recovery when coadministered with enflurane compared with halothane or nitrous oxide)
May decrease hepatic, renal, hepatic, and splenic blood flow
Should not be used as a sole agent of induction in patients with ventricular dysfunction
Perioperative Hyperkalemia
- Inhaled anesthetics associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients postoperatively
- Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable
- Concomitant use of succinylcholine has been associated with most, but not all, of these cases
- Elevated serum creatinine kinase levels and, in some cases, changes in urine consistent with myoglobinuria observed
- Despite similar presentation to malignant hyperthermia, none of affected patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state
- Early and aggressive intervention to treat hyperkalemia and resistant arrhythmias recommended
- Evaluation for latent neuromuscular disease recomended
Pregnancy and lactation
Pregnancy category: B
Lactation: Unknown whether distributed in breast milk, caution advised
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ethrane, Compound 347 (enflurane)
Mechanism of action
Inhalation anesthetic
Pharmacokinetics
Onset of action: 7-10 minutes
Peak Plasma Concentration: Biotransformation results in low serum fluoride levels (average 15 micromol/L); can exceed 50 micromol/L if anesthesia >2 MAC hr
Metabolism: Liver
Excretion: Respiratory exhaled gases
Pharmacogenomics
Increased incidence of malignant hyperthermia with use of volatile anesthetics or depolarizing neuromuscular blockers in patients with gene mutations in ryanodine receptor (RYR1) or calcium channel alpha (1S)- subunit gene (CACNA1S)
