Isoflurane

Name: Isoflurane

Warnings

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

Pharmacology

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)

Clinical pharmacology

FORANE (isoflurane, USP) is an inhalation anesthetic. The MAC (minimum alveolar concentration) in man is as follows:

Age 100% Oxygen 70% N20
26±4 1.28 0.56
44±7 1.15 0.50
64±5 1.05 0.37

Induction of and recovery from isoflurane anesthesia are rapid. Isoflurane has a mild pungency, which limits the rate of induction, although excessive salivation or tracheobronchial secretions do not appear to be stimulated. Pharyngeal and laryngeal reflexes are readily obtunded. The level of anesthesia may be changed rapidly with isoflurane. Isoflurane is a profound respiratory depressant. RESPIRATION MUST BE MONITORED CLOSELY AND SUPPORTED WHEN NECESSARY. As anesthetic dose is increased, tidal volume decreases and respiratory rate is unchanged. This depression is partially reversed by surgical stimulation, even at deeper levels of anesthesia. Isoflurane evokes a sigh response reminiscent of that seen with diethyl ether and enflurane, although the frequency is less than with enflurane.

Blood pressure decreases with induction of anesthesia but returns toward normal with surgical stimulation. Progressive increases in depth of anesthesia produce corresponding decreases in blood pressure. Nitrous oxide diminishes the inspiratory concentration of isoflurane required to reach a desired level of anesthesia and may reduce the arterial hypotension seen with isoflurane alone. Heart rhythm is remarkably stable. With controlled ventilation and normal PaCO2, cardiac output is maintained despite increasing depth of anesthesia, primarily through an increase in heart rate, which compensates for a reduction in stroke volume. The hypercapnia, which attends spontaneous ventilation during isoflurane anesthesia further increases heart rate and raises cardiac output above awake levels. Isoflurane does not sensitize the myocardium to exogenously administered epinephrine in the dog. Limited data indicate that subcutaneous injection of 0.25 mg of epinephrine (50 mL of 1:200,000 solution) does not produce an increase in ventricular arrhythmias in patients anesthetized with isoflurane.

Muscle relaxation is often adequate for intra-abdominal operations at normal levels of anesthesia. Complete muscle paralysis can be attained with small doses of muscle relaxants. ALL COMMONLY USED MUSCLE RELAXANTS ARE MARKEDLY POTENTIATED WITH ISOFLURANE, THE EFFECT BEING MOST PROFOUND WITH THE NONDEPOLARIZING TYPE. Neostigmine reverses the effect of nondepolarizing muscle relaxants in the presence of isoflurane. All commonly used muscle relaxants are compatible with isoflurane.

Isoflurane can produce coronary vasodilation at the arteriolar level in selected animal models1,2; the drug is probably also a coronary dilator in humans. Isoflurane, like some other coronary arteriolar dilators, has been shown to divert blood from collateral dependent myocardium to normally perfused areas in an animal model (“coronary steal”)3. Clinical studies to date evaluating myocardial ischemia, infarction and death as outcome parameters have not established that the coronary arteriolar dilation property of isoflurane is associated with coronary steal or myocardial ischemia in patients with coronary artery disease 4,5,6,7.

Pharmacokinetics

Isoflurane undergoes minimal biotransformation in man. In the postanesthesia period, only 0.17% of the isoflurane taken up can be recovered as urinary metabolites.

REFERENCES

1. J.C. Sill, et al, Anesthesiology 66:273-279, 1987

2. RF. Hickey, et al, Anesthesiology 68:21-30, 1988

3. C.W. Buffington, et al, Anesthesiology 66:280-292, 1987

4. S. Reiz, et al, Anesthesiology 59:91-97, 1983

5. S. Slogoff and A.S. Keats, Anesthesiology 70:179-188, 1989

6. K.J. Tuman, et al, Anesthesiology 70:189-198, 1989

7. D.T. Mangano, Editorial Views, Anesthesiology 70:175-178, 1989

Uses of Isoflurane

Isoflurane is used in the treatment of:

  • Depressive Disorder
  • Status Asthmaticus

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Isoflurane Drug Class

Isoflurane is part of the drug class:

  • Halogenated hydrocarbons

Forms of Medication

Isoflurane is available in the following forms:

  • Inhalant Solution

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take isoflurane or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to isoflurane. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Storage

Store at 20° to 25°C (68 to 77°F; excursions permitted to 15° to 30°C (59° to 86°F) [See Controlled Room Temperature]. Preserve in tight containers. Isoflurane contains no additives and has been demonstrated to be stable at room temperature for periods in excess of five years.

For the Consumer

Applies to isoflurane: inhalation solution

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