isoflurane (Rx)

1-10%

Nausea

Vomiting

Shivering

<1%

Dose-dependent hypotension

Arrhythmias

Malignant hyperthermia (rare)

Elevations in white blood count

May decrease creatinine and increase BUN

Ileus, severe (fatal)

Hepatic dysfunction (postoperative period) (rare)

Respiratory depression may occur (rare)

Contraindications

Hypersensitivity to isoflurane & halogenated agents

Genetic susceptibility to malignant hyperthermia

Cautions

Caution in coronary heart disease

May decrease renal and hepatic blood flow

Postoperative hepatic dysfunction and hepatitis reported

Rare risk of perioperative hyperkalemia & malignant hyperthermia

Adequate data have not been developed to establish its application in obstetrical anesthesia

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

General anesthetics and sedation drugs in young children and pregnant women

• Brain development

  • Prolonged or repeated exposure may result in negative effects on fetal or young children’s brain development
  • Caution with use during surgeries or procedures in children younger than 3 yr or in pregnant women during their third trimester
  • Assess the risk:benefit ratio in these populations, especially for prolonged procedures (ie, >3 hr) or multiple procedures

Pregnancy

There are no adequate and well-controlled studies in pregnant women; in animal reproduction studies, embryofetal toxicity was noted in pregnant mice exposed to 0.075% (increased post implantation losses) and 0.3% isoflurane (increased post implantation losses and decreased live- birth index) during organogenesis

Lactation

Use caution

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.

Mechanism of Action

Volatile liquid inhalation anesthetic

Pharmacokinetics

Onset: Rapid (7-10 min)

Duration: Short (depends on blood concentration)

Minimum Alveolar Conc: 1.3%

Metabolism: Liver (0.2%)

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)