Isoflurane

Indications

Isoflurane may be used for induction and maintenance of general anesthesia. Adequate data have not been developed to establish its application in obstetrical anesthesia.

Pharmacology

Isoflurane may be used for induction and maintenance of general anesthesia. Adequate data have not been developed to establish its application in obstetrical anesthesia.

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 models; 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”). 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

Dosage & Administration

Premedication: Premedication should be selected according to the need of the individual patient, taking into account that secretions are weakly stimulated by Isoflurane, and the heart rate tends to be increased. The use of anticholinergic drugs is a matter of choice.

Inspired Concentration: The concentration of Isoflurane being delivered from a vaporizer during anesthesia should be known. This may be accomplished by using:

Vaporizers calibrated specifically for Isoflurane;
Vaporizers from which delivered flows can be calculated, such as vaporizers delivering a saturated vapor, which is then diluted. The delivered concentration from such a vaporizer may be calculated using the formula: % Isoflurane = 100 PvFv/FT (PA - PV)

Where:

• PA= Pressure of atmosphere
• PV= Vapor pressure of Isoflurane
• FV= Flow of gas through vaporizer (mL/min)
• FT= Total gas flow (mL/min)

Isoflurane contains no stabilizer. Nothing in the agent alters calibration or operation of these vaporizers.

Induction: Induction with Isoflurane in oxygen or in combination with oxygen-nitrous oxide mixtures may produce coughing, breath holding, or laryngospasm. These difficulties may be avoided by the use of a hypnotic dose of an ultra-short-acting barbiturate. Inspired concentrations of 1.5 to 3.0% Isoflurane usually produce surgical anesthesia in 7 to 10 minutes.

Maintenance: Surgical levels of anesthesia may be sustained with a 1.0 to 2.5% concentration when nitrous oxide is used concomitantly. An additional 0.5 to 1.0% may be required when Isoflurane is given using oxygen alone. If added relaxation is required, supplemental doses of muscle relaxants may be used.

The level of blood pressure during maintenance is an inverse function of Isoflurane concentration in the absence of other complicating problems. Excessive decreases may be due to depth of anesthesia and in such instances may be corrected by lightening anesthesia.

Interaction

Enhances effects of neuromuscular blockers. May sensitise the myocardium to adrenaline and other sympathomimetics. Enhances hypotensive effects of ACE inhibitors, TCAs, MAOIs, antihypertensives, antipsychotics or beta-blockers. May have synergistic effects with CNS depressants.

Contraindications

Known or suspected susceptibility to malignant hyperthermia. Porphyria.

Side Effects

Nausea, Vomiting, Shivering, 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),Respiratory depression may occur

Pregnancy & Lactation

Pregnancy Category C. Isoflurane has been shown to have a possible anesthetic-related fetotoxic effect in mice when given in doses 6 times the human dose. There are no adequate and well-controlled studies in pregnant women. Isoflurane should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Isoflurane is administered to a nursing woman.

Precautions & Warnings

Perioperative hyperkalaemia; raised intracranial pressure. May impair ability to drive or operate machinery. Pregnancy and lactation. Do not allow carbon dioxide absorbents in anaesthetic apparatus to dry out when delivering isoflurane to minimise the risk of developing elevated carboxyhaemoglobin levels.

Therapeutic Class

General (Inhalation) anesthetics

Storage Conditions

Store at room temperature 15°-30°C. Isoflurane contains no additives and has been demonstrated to be stable at room temperature for periods in excess of five years.