s, isoflurane anesthesia may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. the syndrome includes nonspecific features such as muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias and unstable blood pressure. (it should also be noted that many of these nonspecific signs may appear with light anesthesia, acute hypoxia, etc.) an increase in overall metabolism may be reflected in an elevated temperature (which may rise rapidly early or late in the case, but usually is not the first sign of augmented metabolism) and an increased usage of the co 2 absorption system (hot cannister). pao 2 and ph may decrease, and hyperkalemia and a base deficit may appear. treatment includes discontinuance of triggering agents (e.g., isoflurane), administration of intravenous dantrolene sodium, and application of supportive therapy. such therapy includes vigorous efforts to restore body temperature to normal, respiratory and circulatory support as indicated, and management of electrolyte- fluid-acid-base derangements. (consult prescribing information for dantrolene sodium intravenous for additional information on patient management). renal failure may appear later, and urine flow should be sustained if possible. since levels of anesthesia may be altered easily and rapidly, only vaporizers producing predictable concentrations should be used hypotension and respiratory depression increase as anesthesia is deepened. increased blood loss comparable to that seen with halothane has been observed in patients undergoing abortions. isoflurane markedly increases cerebral blood flow at deeper levels of anesthesia. there may be a transient rise in cerebral spinal fluid pressure which is fully reversible with hyperventilation. pediatric neurotoxicity published animal studies demonstrate that the administration of anesthetic and sedation drugs that block nmda receptors and/or potentiate gaba activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than 3 hours. the clinical significance of these findings is not clear. however, based on the available data, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately three years of age in humans (see precautions/ pregnancy , pediatric use , and animal toxicology and/or pharmacology ). some published studies in children suggest that similar deficits may occur after repeated or prolonged exposures to anesthetic agents early in life and may result in adverse cognitive or behavioral effects. these studies have substantial limitations, and it is not clear if the observed effects are due to the anesthetic/sedation drug administration or other factors such as the surgery or underlying illness. anesthetic and sedation drugs are a necessary part of the care of children and pregnant women needing surgery, other procedures, or tests that cannot be delayed, and no specific medications have been shown to be safer than any other. decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks.

anesthetic agents, isoflurane may cause sensitivity hepatitis in patients who have been sensitized by previous exposure to halogenated anesthetics (see contraindications ).

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.

se events cannot be established with certainty. cardiac disorders : cardiac arrest hepatobiliary disorders : hepatic necrosis, hepatic failure.

population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data pregnant rats were exposed to isoflurane at concentrations of 0%, 0.1%, or 0.4% for two hours per day during organogenesis (gestational days 6-15). isoflurane did not cause malformations or clear maternal toxicity under these conditions. pregnant mice exposed to isoflurane at concentrations of 0%, 0.075%, or 0.30% for 2 hours per day during organogenesis (gestational days 6-15). isoflurane increased fetal toxicity (higher post implantation losses at 0.075 and 0.3% groups and significantly lower live-birth index in the 0.3% isoflurane treatment group). isoflurane did not cause malformations or clear maternal toxicity under these conditions. pregnant rats were exposed to concentrations of isoflurane at 0%, 0.1%, or 0.4% for 2 hours per day during late gestation (gd 15-20). animals appeared slightly sedated during exposure. no adverse effects on the offspring or evidence of maternal toxicity were reported. this study did not evaluate neurobehavioral function including learning and memory in the first generation (f1) of pups. in a published study in primates, administration of an anesthetic dose of ketamine for 24 hours on gestation day 122 increased neuronal apoptosis in the developing brain of the fetus. in other published studies, administration of either isoflurane or propofol for 5 hours on gestation day 120 resulted in increased neuronal and oligodendrocyte apoptosis in the developing brain of the offspring. with respect to brain development, this time period corresponds to the third trimester of gestation in the human. the clinical significance of these findings is not clear; however, studies in juvenile animals suggest neuroapoptosis correlates with long-term cognitive deficits (see warnings/ pediatric neurotoxicity , precautions/ pediatric use , and animal toxicology and/or pharmacology ).

drocyte cell losses are associated with 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 pregnant women, neonates, and young children who require procedures with the potential risks suggested by the nonclinical data. (see warnings/ pediatric neurotoxicity , precautions/ pregnancy , and animal toxicology and/or pharmacology ).

lurane. 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. isoflurane does not sensitize the myocardium to exogenously administered epinephrine in the dog. limited data indicate that subcutaneous injection of 0.25mg 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. 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.

/8, and 1/2 mac) 2 hours per day for 14 consecutive days prior to mating. isoflurane had no effects on either male or female fertility.

not conclusive. since exposure to wags is one possible factor in the findings for these studies, operating room personnel, and pregnant women in particular, should minimize exposure. precautions include adequate general ventilation in the operating room, the use of a well-designed and well-maintained scavenging system, work practices to minimize leaks and spills while the anesthetic agent is in use, and routine equipment maintenance to minimize leaks. storage store at controlled room temperature 15° - 30°c (59° - 86°f) (see usp). isoflurane contains no additives and has been demonstrated to be stable at room temperature for a period in excess of five years.