Chemistry - An inhalant general anesthetic agent, halothane occurs as a colorless, nonflammable, heavy liquid. It has a characteristic odor resembling chloroform and sweet, burning taste. Halothane is slightly soluble in water and miscible with alcohol. At 20°C, halothane’s specific gravity is 1.872-1.877 and vapor pressure is 243 mm Hg.
Storage/Stability/Compatibility - Store halothane below 40°C in a tight, light-resistant container. Halothane stability is maintained by the addition of thymol and ammonia. The thymol does not vaporize so it may accumulate in the vaporizer causing a yellow discoloration. Do not use discolored solutions. Discolored vaporizer and wick may be cleaned with diethyl ether (all ether must be removed before reuse).
In the presence of moisture, halothane vapor can react with aluminum, brass and lead (not copper). Rubber and some plastics are soluble in halothane leading to their rapid deterioration.
Pharmacology - While the precise mechanism that inhalent anesthetics exert their general anesthetic effect is not precisely known, they may interfere with functioning of nerve cells in the brain by acting at the lipid matrix of the membrane. Some key pharmacologic effects noted with halothane include: CNS depression, depression of body temperature regulating centers, increased cerebral blood flow, respiratory depression (pronounced in ruminants), hypotension, vasodilatation, and myocardial depression.
Minimal Alveolar Concentration (MAC; %) in oxygen reported for halothane in various species: Dog = 0.76; Cat = 0.82; Horse = 0.88; Human = 0.76. Several factors may alter MAC (acid/base status, temperature, other CNS depressants on board, age, ongoing acute disease, etc.).
Uses/Indications - Halothane remains a useful general anesthetic in veterinary medicine due to its relative safety, potency, controllability, non-flammability, and comparative low cost.
Pharmacokinetics - Halothane is rapidly absorbed through the lungs. About 12% of absorbed drug is metabolized by the liver to trifluoroacetic acid (only small amounts), chlorine and bromine radicals which are excreted in the urine. The bulk of the absorbed drug is re-excreted by the lungs and eliminated with expired air. Halothane is distributed into milk.
Contraindications/Precautions/Reproductive Safety - Halothane is contraindicated in patients with a history or predilection towards malignant hyperthermia or significant hepatotoxicity after previous halothane exposure (see Adverse Reactions below). It should be used with caution (benefits vs. risks) in patients with hepatic function impairment, cardiac arrhythmias, increased CSF or head injury, myasthenia gravis, or pheochromocytoma (cardiac arrhythmias due to catecholamines).
Some animal studies have shown that halothane may be teratogenic; use only when benefits outweigh potential risks.
Adverse Effects/Warnings - Hypotension may occur and is considered to be dosage related. A malignant hyperthermia-stress syndrome has been reported in pigs, horses, dogs and cats. Halothane may cause cardiac depression and dysrhythmias. Halothane-induced hypotension may be treated by volume expansion and dobutamine. Lidocaine has been used to treat or prevent halothane-induced cardiac dysrhythmias.
In humans, jaundice and a postanesthetic fatal liver necrosis has been reported rarely. The incidence of this effect in veterinary species is not known. However, halothane should be considered contraindicated for future use if unexplained fever, jaundice or other symptoms associated with hepatotoxicity occur.
Drug Interactions - Acetaminophen is not recommended to be used for postoperative analgesia in animals who have received halothane anesthesia. Because halothane sensitizes the myocardium to the effects of sympathomimetics, especially catecholamines, severe ventricular arrhythmias may result. Drugs included are: dopamine, epinephrine, norepinephrine, ephedrine, metaraminol, etc. If these drugs are needed, they should be used with caution and in significantly reduced dosages with intensive monitoring. Non-depolarizing neuromuscular blocking agents, systemic aminoglycosides, systemic lincomycins should be used with caution with halogenated anesthetic agents as additive neuromuscular blockade may occur. Reportedly, d-tubocurarine may cause significant hypotension if used with halothane. Concomitant administration of succinylcholine with inhalation anesthetics (halothane, cyclopropane, nitrous oxide, diethyl ether) may induce increased incidences of cardiac effects (bradycardia, arrhythmias, sinus arrest and apnea) and in susceptible patients, malignant hyperthermia.
Laboratory Considerations - Halothane may transiently increase values of liver function tests.
a) For draft horses: Following induction, the largest ET tube that will comfortably fit (20 - 40 mm) should be placed and cuff inflated. In an oxygen-enriched semi-closed large animal circle system 4-5% of halothane is administered initially and is reduced as indicated by physical monitoring of neural reflexes and cardiopulmonary parameters. The goal should be the lowest concentration inhalant anesthetic that provides adequate surgical anesthesia and restraint. Most draft horses can be maintained on 2.5 - 3% halothane. (See reference for more information on monitoring and use.) (Geiser 1992)
CAUTION! Sedative and anesthetic drug dosages for African elephants often vary from those for Asian elephants. Do not assume that the recommendations for one species can be applied to the other. Significant variation may also occur between individual elephants. Higher doses may be needed in wild or excited animals. Unless otherwise specified, doses refer to captive elephants. The information provided here should be used as a guideline only. Consultation with experienced colleagues is advised.
Special Note Concerning the Use of Halothane: several authors recommend that halothane be discontinued for a period of time (10-40 minutes) prior to the administration of narcotic antagonists in elephants immobilized with etorphine or carfentanil. The administration of oxygen (with a high flow rate and frequent emptying of the re-breathing bag) facilitates removal of halothane and can prevent ataxia once the narcotic antagonist is given.
a) Halothane at 1-2% was used to maintain anesthesia in two five-year-old Africanelephants with estimated weights of 1200 and 1000 kg subsequent to the administration of azaperone and etorphine. See abstract below for further details (Stegmann, 1999).
b) Halothane at 1-2% was used to maintain anesthesia in 6 elephants ( 650-1500 kg) immobilized with etorphine or carfentanil. Flow rates varied from 5ml/kg/min to 10 ml/kg/min (Welsch et.al, 1989).
c) Halothane was used to maintain anesthesia in 16 juvenile (3-5 yr) African elephants immobilized 1 or more times (27 procedures). Xylazine (0.1 ± 0.04 mg/kg) and ketamine (0.6 ± 0.13 mg/kg) were given IM for a 45-minute transport. Anesthesia was induced with etorphine (1.9 ±0.56 µg/kg). Endotracheal tubes of 18, 22, and 26 mm (I.D.) were used in elephants weighing 150-304 kg, 204-350 kg, and 280-636 kg respectively. Halothane %
varied from 0.5 ± 0.78% during the first 30 minutes to 1.0 ± 0.42% which was attributed to the additive effect of the etorphine and/or the xylazine/ketamine combination given for transport (Heard et.al. 1988).
d) Seven young African elephants (1-2 yrs) were maintained on 0.5 % halothane following induction with etorphine and intubated with 22-26 mm (I.D.) endotracheal tubes (Jacobson et.al. 1986).
e) A 25-year-old African elephant (estimated weight 3000 kg) was induced with 6 mg etorphine IM. Trunk passages were intubated with 13 mm (I.D.) endotracheal tubes and cuffs partially inflated. Halothane was initially given at 2.5% at a flow rate of 14L/min. A 30-L rebreathing bag was used. At 30 minutes the halothane was decreased to 0.5%. At 45 minutes the elephant showed signs of arousal. Etorphine (1 mg) was given and halothane increased to 2.5%. Total anesthesia time was 150 minutes. Halothane was discontinued and oxygen administered for 10 minutes prior to narcotic reversal (Tamas et.al. 1983).
f) Halothane was used to maintain etorphine-acepromazine induced anesthesia in two Asian elephants. Procedure 1: Elephant “Joti” estimated weight 1000 kg. Premedicated with 1.3 etorphine plus acetylpromazine (Immobilon®). Induced with 5% halothane at a flow rate of 1.5L/min for 10 minutes (HR = 64). Maintained for 25 minutes with 2 % halothane at 5 L/min. Anesthesia discontinued due to shallow respiration but resumed after 20 minutes with 3% halothane at 5 L/min. A total of 38 ml of halothane was administered in 68 min (0.55 ml/min). Procedure 2: same elephant: 80-minute procedure with total consumption of halothane 26 ml (0.43 ml/min). Procedure 3: Elephant : Raima” weight 890 kg premedicated with 1.2 mg Immobilon®). Anesthesia induced with 2% halothane at 2 L/min. Total duration of anesthesia 52 minutes and total halothane consumption 17 ml (0.33 ml/min) (Jarofke, 1961).
a) Stegmann,G.F. 1999. Etorphine-halothane anaesthesia in two five-year-old African elephants (Loxodonta africana). Journal of the South African Veterinary Medical Association 70:(4):164-166 Abstract: Anaesthesia of 2 five-year-old female African elephants (Loxodonta africana) was required for dental surgery. The animals were each premedicated with 120 mg of azaperone 60 min before transportation to the hospital. Before offloading, 1 mg etorphine was administered intramuscularly (i.m.) to each elephant to facilitate walking them to the equine induction/recovery room. For induction, 2 mg etorphine was administered i.m. to each animal. Induction was complete within 6 min. Surgical anaesthesia was induced with halothane-in-oxygen after intubation of the trunk. During surgery the mean heart rate was 61 and 45 beats/min respectively. Systolic blood pressures increased to 27.5 and 25.6 kPa respectively, and were treated with intravenous azaperone. Blood pressure decreased thereafter to a mean systolic pressure of 18.1 and 19.8 kPa, respectively. Rectal temperature was 35.6 and 33.9 degrees C at the onset of surgery, and decreased to 35.3 and 33.5 degrees C, respectively, at the end of anaesthesia. Etorphine anaesthesia was reversed with 5 mg diprenorphine at the completion of 90 min of surgery. Additional information: Case 1 (1200 kg): A narrow oropharynx precluded tracheal intubation. Latex tubing (15mm) was inserted 30 cm into one trunk passage and a 16 mm silicone endotracheal tube was placed in the other trunk passage to administer anesthesia at a flow rate of 15 l/min. Additional etorphine was given 1.5 hours after induction when anesthetic depth suddenly decreased. Azaperone (40 mg) IV reduced blood pressure from systolic/diastolic 27.5/20.5 kPa to 14.4/7.1 kPa within 15 minutes. Total duration of the procedure was 1 hour 45 minutes. Case 2 (1000kg): Trunk passages were intubated with 12 mm cuffed silicon endotracheal tubes and connected to the circle anesthetic machine with a 2nd Y-piece. The flow rate was 15l/min. Azaperone (20 mg IV) reduced blood pressure from systolic/diastolic 29.2/23.2 kPa after instrumentation to 19.3/8 kPa within 5 minutes. Etorphine (0.5 mg) was given IV at 60 and 75 minutes to maintain anesthesia. Duration of procedure was 2 hr.
b) Welsch,B., Jacobson,E.R., Kollias,G.V., Kramer,L., Gardner,H., and Page,C.D. 1989. Tusk extraction in the African elephant (Loxodonta africana). Journal of Zoo and Wildlife Medicine 20:(4):446-453 Abstract: Unilateral dentoalveolar abscesses and/or tusk fractures were identified and tusk extractions performed in seven 3.5-21-yr-old African elephants (Loxodonta africana) of both sexes weighing 650-3,000 kg. Following immobilization with etorphine hydrochloride or carfentanil citrate, six of seven elephants were intubated and maintained on a 1-1.5% halothane in oxygen mixture; one elephant was maintained in lateral recumbency by multiple i.v. injections of etorphine. All elephants were positioned with the affected tusk up. For one elephant, two surgical procedures were required to remove the tusk. In six of seven elephants, the tusks were sectioned transversely and the tusk wall thinned by enlarging the pulp cavity with carbide burs. In those tusks with remaining pulp, the pulp was removed with stainless steel rods and hooks. Next, the tusk was sectioned longitudinally into three or four segments using a wood saw within the pulp chamber. bone gouges, osteotomes, and a mallet were used to free the outer epithelial and alveolar attachments from the tusk. Starting with the smallest segment, the sections were removed using long screwdriver-shaped stainless steel rods. The alveolar chamber was then periodically flushed postsurgically with a dilute organic iodine solution. For six of seven elephants, complete granulation of the alveolar chamber was evident by 4 mo postsurgery; the seventh elephant showed partial healing with granulation tissue at 2 mo following surgery.
c) Heard,D.J., Kollias,G.V., Webb,A.I., Jacobson,E.R., and Brock,K.A. 1988. Use of halothane to maintain anesthesia induced with etorphine in juvenile African elephants. Journal of the American Veterinary Medical Association 193:254-256 Excerpts: Sixteen 3- to 5-year-old African elephants were anesthetized one or more times for a total of 27 diagnostic and surgical procedures. Xylazine (0.1 ± 0.04 mg/kg of body weight, mean ± SD) and ketamine (0.6 ± 0.13 mg/kg) administered IM induced good chemical restraint in standing juvenile elephants during a 45-minute transport period before administration of general anesthesia. After IM or IV administration of etorphine (1.9 ± 0.56 micrograms/kg), the mean time to lateral recumbency was 20 ± 6.6 and 3 ± 0.0 minutes, respectively. The mean heart rate, systolic blood pressure, and respiration rate during all procedures was 50 ± 12 beats/min, 106 ± 19 mm of Hg, and 10 ± 3 breaths/min, respectively.
Cardiac arrhythmias were detected during 2 procedures. In one elephant paroxysmal ventricular tachycardia was detected and the procedure terminated when the arrhythmia failed to stabilize after multiple doses of lidocaine (1 mg/kg, IV). In another elephant, second degree atrioventricular block returned to normal sinus rhythm after IV administration of atropine (0.04 mg/kg).
In one elephant, low mean blood pressure (54 mm of Hg) responded to reduction in halothane (vaporizer setting 1 to 0.75%) and slow infusion of dobutamine HCl ((250 mg/1,000 ml) given to effect. The systolic blood pressure increased to 90 mm of Hg and remained high with a continuous infusion of dobutamine (5 µg/kg/min).
Immediately after induction in another elephant, profound respiratory depression (< 1breath/minute) and palpably weak arterial pulse were identified. Intravenous administration of diprenorphine at half the recommended reversal dose resulted in improvement of respiration and palpable arterial pulse, without the elephant developing signs of complete anesthetic reversal.
Alterations in systolic blood pressure, ear flapping, and trunk muscle tone were useful for monitoring depth of anesthesia. Results indicated that halothane in oxygen was effective for maintenance of surgical anesthesia in juvenile African elephants after induction with etorphine. Note: A correction appeared in a later volume 193(6): p.721.
d) Jacobson,E.R., Chen,C.-L., Gronwall,R., and Tiller,A. 1986. Serum concentrations of etorphine in juvenile African elephants. Journal of the American Veterinary Medical Association 189:(9):1079-1081 Abstract: Eleven juvenile African elephants were given etorphine hydrochloride (2.19 + 0.11 micrograms/kg body weight, mean +SD) as a single IM injection; 3 elephants were given additional etorphine (0.42+0.09) IV. After immobilization, each elephant was maintained in lateral recumbency by administration of a 0.5% halothane/oxygen mixture or by administration of multiple IV injections of etorphine. At postinjection hours 0.25 and 0.5 and at 30-minute intervals thereafter, blood samples were collected via an auricular artery, and serum concentrations of etorphine were determined by use of radioimmunoassay. The highest mean serum concentration of etorphine in 6 elephants given a single IM injection and subsequently maintained on halothane and oxygen was 1.62+0.97 ng/ml at postinjection hours 0.5; thereafter, the mean serum concentration decreased steadily. In 4 elephants maintained in lateral recumbency with multiple IV administrations of etorphine, a correlation was not found between the time to develop initial signs of arousal and serum concentrations of etorphine before arousal. After administration of the initial immobilizing dose of etorphine, the interval between successive IV administrations of etorphine decreased.
e) Tamas,P.M. and Geiser,D.R. 1983. Etorphine analgesia supplemented by halothane anesthesia in an adult African elephant. Journal of the American Veterinary Medical Association 183:(11):1312-1314
f) Jarofke,D. 1981. Use of halothane oxygen anesthesia in elephants (Elephas maximus). Journal of Zoo Animal Medicine 12:(3):93-95
Jacobson,E.R. 1988. Chemical restraint and anesthesia of elephants. Proc.Ann.Elephant Workshop 9. Pages: 112-119
Lateur,N. and Stolk,P. 1986. Repeated general anesthesia in a male Indian elephant. Proc.Am.Assoc.Zoo Vet. Pages: 128-131 (a 4500 kg Asian elephant was immobilized with etorphine, acepromazine and xylazine and maintained on halothane at 30L/min)
Monitoring Parameters - 1) Respiratory and ventilatory status; 2) Cardiac rate/rhythm; blood pressure (particularly with “at risk” patients); 3) Level of anesthesia
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Halothane, USP (with thymol 0.01% and ammonia 0.00025%) in 250 ml bottles; (Fort Dodge); (Rx)
Halothane in 125 & 250 ml bottles; Halothane® (Abbott) (Rx), Fluothane® (Wyeth-Ayerst) (Rx)
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