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Ethrane

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Ethrane

CLINICAL PHARMACOLOGY

ETHRANE (enflurane, USP) is an inhalation anesthetic. The MAC (minimum alveolar concentration) in man is 1.68% in pure oxygen, 0.57 in 70% nitrous oxide, 30% oxygen, and 1.17 in 30% nitrous oxide, 70% oxygen.

Induction of and recovery from anesthesia with enflurane are rapid. Enflurane has a mild, sweet odor. Enflurane may provide a mild stimulus to salivation or tracheobronchial secretions. Pharyngeal and laryngeal reflexes are readily obtunded. The level of anesthesia can be changed rapidly by changing the inspired enflurane concentration. Enflurane reduces ventilation as depth of anesthesia increases. High PaCO2 levels can be obtained at deeper levels of anesthesia if ventilation is not supported. Enflurane provokes a sigh response reminiscent of that seen with diethyl ether.

There is a decrease in blood pressure with induction of anesthesia, followed by a return to near normal with surgical stimulation. Progressive increases in depth of anesthesia produce corresponding increases in hypotension. Heart rate remains relatively constant without significant bradycardia. Electrocardiographic monitoring or recordings indicate that cardiac rhythm remains stable. Elevation of the carbon dioxide level in arterial blood does not alter cardiac rhythm.

Studies in man indicate a considerable margin of safety in the administration of epinephrine-containing solutions during enflurane anesthesia. Enflurane anesthesia has been used in excision of pheochromocytoma in man without ventricular arrhythmias. On the basis of studies in patients anesthetized with enflurane and injected with epinephrine-containing solutions to achieve hemostasis in a highly vascular area (transsphenoidal surgery), up to 2 micrograms per kilogram (2 µg/kg) of epinephrine may be injected subcutaneously over a 10 minute period in patients judged to have ordinary tolerance to epinephrine administration. This would represent up to 14 mL of 1:100,000 epinephrine-containing solution (10 µg/mL), or the equivalent quantity, in a 70 kilogram patient. This may be repeated up to 3 times per hour (total 42 mL per hour). The concomitant administration of lidocaine enhances the safety of the use of epinephrine during enflurane anesthesia. This effect of lidocaine is dose related. All customary precautions in the use of vasoconstrictor substances should be observed.

Muscle relaxation may be adequate for intra-abdominal operations at normal levels of anesthesia. Muscle relaxants may be used to achieve greater relaxation and all commonly used muscle relaxants are compatible with enflurane. THE NON-DEPOLARIZING MUSCLE RELAXANTS ARE POTENTIATED. In the normal 70 kg adult, 6 to 9 mg of d-tubocurarine or 1.0 to 1.5 mg of pancuronium will produce a 90% or greater depression of twitch height. Neostigmine does not reverse the direct effect of enflurane.

Enflurane 0.25 to 1.0% (average 0.5%) provides analgesia equal to that produced by 30 to 60% (average 40%) nitrous oxide for vaginal delivery. With either agent, patients remain awake, cooperative and oriented. Maternal blood losses are comparable. These clinical approaches produce normal Apgar scores. Serial neurobehavioral testing of the newborn during the first 24 hours of life reveals that neither enflurane nor nitrous oxide analgesia is associated with obvious neurobehavioral alterations. Neither enflurane nor nitrous oxide when used for obstetrical analgesia alters BUN, creatinine, uric acid or osmolality. The only difference in the use of these two agents for obstetrical analgesia appears to be higher inspired oxygen concentration that may be used with enflurane.

Analgetic doses of enflurane, up to approximately 1.0%, do not significantly depress the rate or force of uterine contraction during labor and delivery. A slowing of the rate of uterine contraction and a diminution of the force of uterine contraction is noted between the administration of 1.0 to 2.0% delivered enflurane; concentrations somewhere between 2.0 and 3.0% delivered enflurane may abolish uterine contractions. Enflurane displaces the myometrial response curve to oxytocin so that at lower concentrations of enflurane oxytocin will restore uterine contractions; however, as the dose of enflurane progresses (somewhere between 1.5 and 3.0% delivered enflurane) the response to oxytocin is diminished and then abolished. Uterine bleeding may be increased when enflurane is used in higher concentrations for vaginal delivery or to facilitate delivery by Cesarean section; however, this has not been demonstrated within the recommended dosage range (see DOSAGE AND ADMINISTRATION section). Mean estimated blood loss in patients anesthetized for therapeutic termination of pregnancy with 1.0% enflurane in 70% nitrous oxide with oxygen is approximately twice that noted following therapeutic termination of pregnancy performed with the use of a local anesthetic technique (40 mL versus 20 mL).

Pharmacokinetics

Biotransformation of enflurane in man results in low peak levels of serum fluoride averaging 15 µmol/L. These levels are well below the 50 µmol/L threshold level which can produce minimal renal damage in normal subjects. However, patients chronically ingesting isoniazid or other hydrazine-containing compounds may metabolize greater amounts of enflurane. Although no significant renal dysfunction has been found thus far in such patients, peak serum fluoride levels can exceed 50 µmol/L, particularly when anesthesia goes beyond 2 MAC hours. Depression of lymphocyte transformation does not follow prolonged enflurane anesthesia in man in the absence of surgery. Thus enflurane does not depress this aspect of the immune response.

Last reviewed on RxList: 2/10/2010
This monograph has been modified to include the generic and brand name in many instances.

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