Source: FDA, National Drug Code (US) Revision Year: 2022
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. 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 PaCO 2, 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.
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.
Isoflurane undergoes minimal biotransformation in man. In the postanesthesia period, only 0.17% of the isoflurane taken up can be recovered as urinary metabolites.
Swiss ICR mice were given isoflurane to determine whether such exposure might induce neoplasia. Isoflurane was given at 1/2, 1/8 and 1/32 MAC for four in-utero exposures and for 24 exposures to the pups during the first nine weeks of life. The mice were killed at 15 months of age. The incidence of tumors in these mice was the same as in untreated control mice, which were given the same background gases, but not the anesthetic.
Isoflurane was negative in the in vivo mouse micronucleus and in vitro human lymphocyte chromosomal aberration assay. In published studies, isoflurane was negative in the in vitro bacterial reverse mutation assay (Ames test) in all strains tested (Salmonella typhimurium strains TA98, TA100, and TA1535) in the presence or absence of metabolic activation.
Male and female Sprague-Dawley rats were exposed to isoflurane at concentrations of 0%, 0.15%, and 0.60% (0, 1/8, and ½ MAC) 2 hours per day for 14 consecutive days prior to mating. Isoflurane had no effects on either male or female fertility.
Published studies in animals demonstrate that the use of anesthetic agents during the period of rapid brain growth or synaptogenesis results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. Based on comparisons across species, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester through the first several months of life, but may extend out to approximately 3 years of age in humans.
In primates, exposure to 3 hours of an anesthetic regimen that produced a light surgical plane of anesthesia did not increase neuronal cell loss, however, treatment regimens of 5 hours or longer increased neuronal cell loss. Data in rodents and in primates suggest that the neuronal and oligodendrocyte cell losses are associated with subtle but prolonged cognitive deficits in learning and memory. The clinical significance of these nonclinical findings is not known, and healthcare providers should balance the benefits of appropriate anesthesia in neonates and young children who require procedures against the potential risks suggested by the nonclinical data. (See WARNINGS/Pediatric Neurotoxicity and PRECAUTIONS/Pregnancy, Pediatric Use).
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