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Enflurane (Enflurane) - Warnings and Precautions



Perioperative Hyperkalemia
Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. 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. These patients also experienced significant elevations in serum creatinine kinase levels and, in some cases, changes in urine consistent with myoglobinuria.
Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.
Malignant Hyperthermia
In susceptible individuals, enflurane anesthesia may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinicalásyndrome 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 nonspecificsigns may appear with light anesthesia, acute hypoxia, etc. The syndrome of malignant hyperthermia secondary to enflurane appears to be rare; by March 1980, 35 cases had been reported in North America for an approximate incidence of 1:725,000 enflurane anesthetics.) 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 CO2 absorption system (hot cannister). PaO2 and pH may decrease, and hyperkalemia and a base deficit may appear. Treatment includes discontinuance of triggering agents (e.g., enflurane), 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 derangement. (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.

Increasing depth of anesthesia with Enflurane may produce a change in the electroencephalogram characterized by high voltage, fast frequency, progressing through spike-dome complexes alternating with periods of electrical silence to frank seizure activity. The latter may or may not be associated with motor movement. Motor activity, when encountered, generally consists of twitching or "jerks" of various muscle groups; it is self-limiting and can be terminated by lowering the anesthetic concentration. This electroencephalographic pattern associated with deep anesthesia is exacerbated by low arterial carbon dioxide tension. A reduction in ventilation and anesthetic concentrations usually suffices to eliminate seizure activity. Cerebral blood flow and metabolism studies in normal volunteers immediately following seizure activity show no evidence of cerebral hypoxia. Mental function testing does not reveal any impairment of performance following prolonged enflurane anesthesia associated with or not associated with seizure activity.

Since levels of anesthesia may be altered easily and rapidly, only vaporizers producing predictable concentrations should be used. Hypotension and respiratory exchange can serve as a guide to depth of anesthesia. Deep levels of anesthesia may produce marked hypotension and respiratory depression When previous exposure to a halogenated anesthetic is known to have been followed by evidence of unexplained hepatic dysfunction, consideration should be given to use of an agent other than enflurane.


Enflurane should be used with caution in patients who by virtue of medical or drug history could be considered more susceptible to cortical stimulation produced by the drug Enflurane, like some other inhalational anesthetics, can react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide, which may result in elevated levels of carboxyhemoglobin in some patients. Case reports suggest that barium hydroxide lime and soda lime become desiccated when fresh gases are passed through the CO2 absorber canister at high flow rates over many hours or days. When a clinician suspects that CO2 absorbent may be desiccated, it should be replaced before the administration of enflurane.

Information for Patients

Enflurane, as well as other general anesthetics, may cause a slight decrease in intellectual function for 2 or 3 days following anesthesia. As with other anesthetics, small changes in moods and symptoms may persist for several days following administration.

Laboratory Tests

Bromsulfalein (BSP) retention is mildly elevated postoperatively in some cases. This may relate to the effect of surgery since prolonged anesthesia (5 to 7 hours) in human volunteers does not result in BSP elevation. There is some elevation of glucose and white blood count intraoperatively. Glucose elevation should be considered in diabetic patients.

Drug Interactions

The action of nondepolarizing relaxants is augmented by enflurane. Less than the usual amounts of these drugs should be used. If the usual amounts of nondepolarizing relaxants are given, the time for recovery from neuromuscular blockade will be longer in the presence of enflurane than when halothane or nitrous oxide with a balanced technique are used


Occupational Caution
Ther is no specific work exposure limit established for Enflurane. However, the National Institute for Occupational Safety and Health Administration (NIOSH) recommends that no worker should be
exposed at ceiling concentrations greater than 2 ppm of any halogenated anesthetic agent over a sampling period not to exceed one hour.
The predicted effects of acute overexposure by inhalation of Enflurane include headache, dizziness or (in extreme cases)
unconsciousness, There are no documented adverse effects of chronic exposure to halogenated anesthetic vapors (Waste Anesthetic Gases or WAGs) in the workplace. Although results of some epidemiological studies suggest a link between exposure to halogenated anesthetics and increased health problems (particularly spontaneous abortion), the relationship is 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


Store at room controlled room temperature 15░ to 30░C (59░ to 86░F). Enflurane, USP contains no additives and has been demonstrated to be stable at room temperature for periods in excess of five years.

Carcinogenesis & Mutagenesis & Impairment Of Fertility

Swiss ICR mice were given enflurane to determine whether such exposure might induce neoplasia. Enflurane 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.
Exposure of mice to 20 hours of 1.2% enflurane causes a small (about 1/2 of 1.0%) but statistically significant increase in sperm abnormalities. In contrast to these results, in vitro approaches to the study of mutagenesis (Ames test, sister chromatid exchange test, and the 8-azaguanine system) have not shown a mutagenic effect of enflurane


Reproduction studies have been performed in rats and rabbits at doses up to four times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to enflurane. There are, however, no adequate and well-controlled studies inpregnant women. Because animalá reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed

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 enflurane is administered to a nursing woman

Page last updated: 2010-04-07

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