When previous exposure to Fluothane (halothane) was followed by unexplained hepatic dysfunction and/or jaundice, consideration should be given to the use of other agents.
Fluothane (halothane) should be used in vaporizers that permit a reasonable approximation of output, and preferably of the calibrated type. The vaporizer should be placed out of circuit in closed-circuit rebreathing systems; otherwise, overdosage is difficult to avoid. The patient should be closely observed for signs of overdosage, i.e., depression of blood pressure, pulse rate, and ventilation, particularly during assisted or controlled ventilation.
Fluothane (halothane) increases cerebrospinal-fluid pressure. Therefore, in patients with markedly raised intracranial pressure, if Fluothane (halothane) is indicated, administration should be preceded by measures ordinarily used to reduce cerebrospinal-fluid pressure. Ventilation should be carefully assessed, and it may be necessary to assist or control ventilation to ensure adequate oxygenation and carbon dioxide removal.
In susceptible individuals, halothane anesthesia may trigger a skeletal-muscle hypermetabolic state leading to a 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 canister). PaO 2 and pH may decrease, and hyperkalemia and a base deficit may appear. Treatment includes discontinuance of triggering agents (e.g., halothane), administration of intravenous dantrolene, 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. Renal failure may appear later, and urine flow should be sustained if possible. It should be noted that the syndrome of malignant hyperthermia secondary to halothane appears to be rare.
INFORMATION FOR PATIENTS
When appropriate, as in some cases where discharge is anticipated soon after general anesthesia, patients should be cautioned not to drive automobiles, operate hazardous machinery, or engage in hazardous sports for 24 hours or more (depending on the total dose of Fluothane (halothane) , condition of the patient, and consideration given to other drugs administered after anesthesia).
Epinephrine or norepinephrine should be employed cautiously, if at all, during Fluothane (halothane, USP) anesthesia, since their simultaneous use may induce ventricular tachycardia or fibrillation.
Nondepolarizing relaxants and ganglionic-blocking agents should be administered cautiously, since their actions are augmented by Fluothane (halothane, USP).
Clinical experience and animal experiments suggest that pancuronium should be given with caution to patients receiving chronic tricyclic antidepressant therapy who are anesthetized with halothane, because severe ventricular arrhythmias may result from such usage.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
An 18-month inhalational carcinogenicity study of halothane at 0.05% in the mouse revealed no evidence of anesthetic-related carcinogenicity. This concentration is equivalent to 24 hours of 1% halothane.
Mutagenesis testing of halothane revealed both positive and negative results. In the rat, one-year exposure to trace concentrations of halothane (1 and 10 ppm) and nitrous oxide produced chromosomal damage to spermatogonia cells and bone marrow cells. Negative mutagenesis tests included: Ames bacterial assay, Chinese hamster lung fibroblast assay, sister chromatid exchange in Chinese hamster ovary cells, and human leukocyte culture assay.
Reproduction studies of halothane (10 ppm) and nitrous oxide in the rat caused decreased fertility. This trace concentration corresponds to 1/1000 the human maintenance dose.
Teratogenic Effects: Pregnancy Category C. Some studies have shown Fluothane (halothane) to be teratogenic, embryotoxic, and fetotoxic in the mouse, rat, hamster, and rabbit at subanesthetic and/or anesthetic concentrations. There are no adequate and well-controlled studies in pregnant women. Fluothane (halothane) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
LABOR AND DELIVERY
The uterine relaxation obtained with Fluothane (halothane) , unless carefully controlled, may fail to respond to ergot derivatives and oxytocic posterior pituitary extract.
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 Fluothane (halothane) is administered to a nursing woman.
Extensive clinical experience reveals that maintenance concentrations of halothane are generally higher in infants and children, and that maintenance requirements decrease with age. See MAC table, based upon age, in "Dosage and Administration."