HALOTHANE
DESCRIPTION:
Fluothane (halothane, USP) is supplied as a liquid and is vaporized for use as
an inhalation anesthetic. It is 2-bromo-2-chloro-1, 1, 1-trifluoro-ethane.
C2HBrClF3
The molecular weight is 197.38. The drug substance halothane molecule has an
asymmetric carbon atom; the commercial product is a racemic mixture. Resolution
of the mixture has not been reported.*
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Halothane is miscible with alcohol, chloroform, ether, and other fat solvents.
The specific gravity is 1.872-1.877 at 20 deg C, and the boiling point (range)
is 49 deg C-51 deg C at 760 mm Hg. The vapor pressure is 243 mm Hg at 20 deg C.
The blood/gas coefficient is 2.5 at 37 deg C, and the olive oil/water
coefficient is 220 at 37 deg C. Vapor concentrations within anesthetic range are
nonirritating and have a pleasant odor.
Fluothane is nonflammable, and its vapors mixed with oxygen in proportions from
0.5 to 50% (v/v) are not explosive.
Fluothane does not decompose in contact with warm soda lime. When moisture is
present, the vapor attacks aluminum, brass, and lead, but not copper. Rubber,
some plastics, and similar materials are soluble in Fluothane; such materials
will deteriorate rapidly in contact with Fluothane vapor or liquid. Stability of
Fluothane is maintained by the addition of 0.01% thymol (w/w), up to 0.00025%
ammonia (w/w).
ACTIONS/CLINICAL PHARMACOLOGY:
Fluothane is an inhalation anesthetic. Induction and recovery are rapid, and
depth of anesthesia can be rapidly altered. Fluothane progressively depresses
respiration. There may be tachypnea with reduced tidal volume and alveolar
ventilation. Fluothane is not an irritant to the respiratory tract, and no
increase in salivary or bronchial secretions ordinarily occurs. Pharyngeal and
laryngeal reflexes are rapidly obtunded. It causes bronchodilation. Hypoxia,
acidosis, or apnea may develop during deep anesthesia.
Fluothane reduces the blood pressure and frequently decreases the pulse rate.
The greater the concentration of the drug, the more evident these changes
become. Atropine may reverse the bradycardia. Fluothane does not cause the
release of catecholamines from adrenergic stores. Fluothane also causes dilation
of the vessels of the skin and skeletal muscles.
Cardiac arrhythmias may occur during Fluothane anesthesia. These include nodal
rhythm, AV dissociation, ventricular extrasystoles, and asystole. Fluothane
sensitizes the myocardial conduction system to the action of epinephrine and
norepinephrine, and the combination may cause serious cardiac arrhythmias.
Fluothane increases cerebrospinal-fluid pressure. Fluothane produces moderate
muscular relaxation. Muscle relaxants are used as adjuncts in order to maintain
lighter levels of anesthesia. Fluothane augments the action of nondepolarizing
relaxants and ganglionic-blocking agents. Fluothane is a potent uterine
relaxant.
The mechanism(s) whereby Fluothane and other substances induce general
anesthesia is unknown. Fluothane is a very potent anesthetic in humans, with a
minimum alveolar concentration (MAC) determined to be 0.64%. The MAC has been
found to decrease with age (see MAC table in "Dosage and Administration").
INDICATIONS AND USAGE:
Fluothane (halothane, USP) is indicated for the induction and maintenance of
general anesthesia.
CONTRAINDICATIONS:
Fluothane is not recommended for obstetrical anesthesia except when uterine
relaxation is required.
WARNINGS:
When previous exposure to Fluothane was followed by unexplained hepatic
dysfunction and/or jaundice, consideration should be given to the use of other
agents.
PRECAUTIONS:
GENERAL
Fluothane 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 increases cerebrospinal-fluid pressure. Therefore, in patients with
markedly raised intracranial pressure, if Fluothane 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 CO2 absorption system (hot canister).
PaO2 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, condition of the patient, and
consideration given to other drugs administered after anesthesia).
DRUG INTERACTIONS
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.
PREGNANCY
Teratogenic Effects: Pregnancy Category C. Some studies have shown Fluothane 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 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, unless carefully controlled, may
fail to respond to ergot derivatives and oxytocic posterior pituitary extract.
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 Fluothane is
administered to a nursing woman.
PEDIATRIC USE
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."
DRUG INTERACTIONS:
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.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
The following adverse reactions have been reported: mild, moderate, and severe
hepatic dysfunction (including hepatic necrosis); cardiac arrest; hypotension;
respiratory arrest; cardiac arrhythmias; hyperpyrexia; shivering; nausea; and
emesis.
OVERDOSAGE:
In the event of overdosage, or what may appear to be overdosage, drug
administration should be stopped, and assisted or controlled ventilation with
pure oxygen initiated.
DOSAGE AND ADMINISTRATION:
Fluothane may be administered by the nonrebreathing technique, partial
rebreathing, or closed technique. The induction dose varies from patient to
patient but is usually within the range of 0.5% to 3%. The maintenance dose
varies from 0.5% to 1.5%.
Fluothane may be administered with either oxygen or a mixture of oxygen and
nitrous oxide.
Fluothane should not be kept indefinitely in vaporizer bottles not specifically
designed for its use. Thymol does not volatilize along with Fluothane and,
therefore, accumulates in the vaporizer and may, in time, impart a yellow color
to the remaining liquid or to wicks in vaporizers. The development of such
discoloration may be used as an indicator that the vaporizer should be drained
and cleaned, and the discolored Fluothane (halothane, USP) discarded.
Accumulation of thymol may be removed by washing with diethyl ether. After
cleaning a wick or vaporizer, make certain all the diethyl ether has been
removed before reusing the equipment to avoid introducing ether into the system.
Because of the more rapid uptake of Fluothane and the increased blood
concentration required for anesthesia in younger patients, the minimum alveolar
concentration (MAC) (REF. 1) values will decrease with age as follows:
AGE MAC %
Infants 1.08
3 yrs. 0.91
10 yrs. 0.87
15 yrs. 0.92
24 yrs. 0.84
42 yrs. 0.76
81 yrs. 0.64
REFERENCES:
PHYSICIAN REFERENCE
1. Gregory, GA et al: Anesthesiology 1969; 30(5):488-491.
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