Elephant specific information, if available, is in blue.

Chemistry – A thiobarbiturate, thiopental occurs as a bitter-tasting, white to off-white, crystalline powder or a yellow-white hygroscopic powder. It is soluble in water (1 gram in 1.5 ml) and alcohol. Thiopental has a pKa of 7.6 and is a weak organic acid.

 

Storage/Stability/Compatibility – When stored in the dry form, thiopental sodium is sta­ble indefinitely. Thiopental should be diluted with only sterile water for injection, sodium chloride injection, or D5W. Concentrations of less than 2% in sterile water should not be used as they may cause hemolysis. After reconstitution, solutions are stable for 3 days at room temperature and for 7 days if refrigerated. However, as no preservative is present, it is recommended it be used within 24 hours after reconstitution. After 48 hours, the solu­tion has been reported to attack the glass bottles it is stored in. Thiopental may also adsorb to plastic IV tubing and bags. Do not administer any solution that has a visible precipitate.

   

The following agents have been reported to be compatible when mixed with thiopental: aminophylline, chloramphenicol sodium succinate, hyaluronidase, hydrocortisone sodium succinate, neostigmine methylsulfate, oxytocin, pentobarbital sodium, phenobarbital sodium, potassium chloride, scopolamine HBr, sodium iodide, and tubocurarine chloride (recommendations conflict with regard to tubocurarine; some clinicians recommend not mixing with thiopental).

 

The following agents have been reported to be incompatible when mixed with thiopen­tal: Ringer’s injection, Ringer’s injection lactate, amikacin sulfate, atropine sulfate, ben­zquinamide, cephapirin sodium, chlorpromazine, codeine phosphate, dimenhydrinate, diphenhydramine, ephedrine sulfate, glycopyrrolate, hydromorphone, insulin (regular), levorphanol bitartrate, meperidine, metaraminol, morphine sulfate, norepinephrine bitar­trate, penicillin G potassium, prochlorperazine edisylate, promazine HCl, promethazine HCl, succinylcholine chloride, and tetracycline HCl. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for more specific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).

 

Pharmacology – Because of their high lipid solubility, thiobarbiturates rapidly enter the CNS and produce profound hypnosis and anesthesia. They are also known as ultrashort-acting barbiturates. See the monograph: Barbiturates, Pharmacology of, for additional in­formation.

 

Uses/Indications – Because of their rapid action and short duration, the thiobarbiturates are excellent induction agents for general anesthesia with other anesthetics or as the sole anesthetic agent for very short procedures.

 

Pharmacokinetics – Following IV injection of therapeutic doses, hypnosis and anesthesia occur within one minute. The drug rapidly enters the CNS and then redistributes to muscle and adipose tissue in the body. The short duration of action of these agents is due less to rapid metabolism than to this redistribution out of the CNS and into muscle and fat stores. Greyhounds and other sight hounds may exhibit longer recovery times than other breeds. This may be due to these breeds low body fat levels or differences in the metabolic han­dling of the thiobarbiturates.

 

Thiopental is metabolized by the hepatic microsomal system and several metabolites have been isolated. The elimination half-life in dogs has been reported as being approxi­mately 7 hours and in sheep, 3-4 hours. Very little of the drug is excreted unchanged in the urine (0.3% in humans), so dosage adjustments are not necessary in patients with chronic renal failure.

 

Contraindications/Precautions – The following are considered to be absolute contraindi­cations to the use of thiopental: absence of suitable veins for IV administration, history of hypersensitivity reactions to the barbiturates, and status asthmaticus. Relative contraindi­cations include: severe cardiovascular disease or preexisting ventricular arrhythmias, shock, increased intracranial pressure, myasthenia gravis, asthma, and conditions where hypnotic effects may be prolonged (e.g., severe hepatic disease, myxedema, severe ane­mia, excessive premedication, etc). These relative contraindications do not preclude the use of thiopental, but dosage adjustments must be considered and the drug must be given slowly and cautiously.

 

Because greyhounds (and other sight hounds) metabolize thiobarbiturates much more slowly than methohexital, many clinicians recommend using methohexital instead.

 

Thiopental readily crosses the placental barrier and should be used with caution during pregnancy.

 

In horses, thiopental should not be used if the patient has preexisting leukopenia. Some clinicians feel that thiopental should not be used alone in the horse as it may cause exces­sive ataxia and excitement.

 

Concentrations of less than 2% in sterile water should not be used as they may cause hemolysis. Extravasation and intra-arterial injections should be avoided because of the high alkalinity of the solution. Severe CNS toxicity and tissue damage has resulted in horses receiving intra-carotid injections of thiobarbiturates.

 

Adverse Effects/Warnings – In dogs, thiopental has an approximate arrhythmogenic inci­dence of 40%. Ventricular bigeminy is the most common arrhythmia seen and is usually transient and generally responds to additional oxygen. Administration of catecholamines may augment the arrhythmogenic effects of the thiobarbiturates, while lidocaine may in­hibit it. Cardiac output may also be reduced, but is probably only clinically significant in patients experiencing heart failure.

 

Cats are susceptible to developing apnea after injection and may also develop a mild arte­rial hypotension.

 

Horses can exhibit symptoms of excitement and severe ataxia during the recovery period if the drug is used alone. Horses also can develop transient leukopenias and hyperglycemia after administration. A period of apnea and moderate tachycardia and a mild respiratory acidosis may also develop after dosing.

 

Too rapid IV administration can cause significant vascular dilatation and hypoglycemia. Repeated administration of thiopental is not advised as recovery times can become signifi­cantly prolonged. Parasympathetic side effects (e.g.,salivation, bradycardia) may be man­aged with the use of anticholinergic agents (atropine, glycopyrrolate).

 

Overdosage – Treatment of thiobarbiturate overdosage consists of supporting respirations (O2, mechanical ventilation) and giving cardiovascular support (do not use cate­cholamines, e.g., epinephrine, etc).

 

Drug Interactions – A fatal interaction has been reported in a dog receiving the propri­etary product, Diathal® (procaine penicillin G, dihydrostreptomycin sulfate, diphemanil methylsulfate, and chlorpheniramine maleate) and the related compound thiamylal. Avoid using thiopental with this product. The ventricular fibrillatory effects of epinephrine and norepinephrine are potentiated when used with thiobarbiturates and halothane. CNS and respiratory depressant effects of CNS depressants (narcotics, phenothiazines, antihistamines, etc.) may be enhanced by thiobarbiturate administration. Thiopental with furosemide may cause or increase postural hypotension. Sulfisoxasole IV has been shown to compete with thiopental at plasma protein binding sites. This may also occur with other sulfonamides.

 

Doses – Note: Atropine sulfate or glycopyrrolate are often administered prior to thiobarbi­turate anesthesia to prevent parasympathetic side effects. Some clinicians question, how­ever, whether routine administration of the anticholinergic agents are necessary.

 

Thiobarbiturates are administered strictly to effect; doses are guidelines only.

 

 

Horses:

a)   With preanesthetic tranquilization: 6 – 12 mg/kg IV (an average of 8.25 mg/kg is recommended); Without preanesthetic tranquilization: 8.8-15.4 mg/kg IV (an average horse: 9.9 – 11 mg/kg IV) (Pentothal® package insert; Ceva Laboratories)

b)   One gram of thiopental per 90 kg body weight as a 10% solution given evenly over 20 seconds 15 minutes after premedication with either 0.22 mg/kg IV xy­lazine or 0.05 mg/kg IV acepromazine. (Booth 1988a)

c)   5.5 mg/kg IV after sedation and administration with guaifenesin; or 8.8 – 11 mg/kg IV after tranquilization. (Mandsager 1988)

Elephants:
a) One tusker (approx.3000kg) was immobilized with 100 g chloral hydrate orally and 4 grams thiopentone sodium IV.  Another tusker (approx 3000 kg) was immobilized with 1600 mg Flaxedil (gallamine triethiodide) IM and 4 grams thiopentone sodium IV. In both cases, induction occurred within 5 minutes of thiopentone administration.  Both elephants became recumbent and surgical anesthesia was achieved adequate to permit scarification and suturing.  Duration of anesthesia was 60 minutes when chloral hydrate was used and 40 minutes when Flaxedil was used (Nayar et.al. 1992).

Elephant  References:
a) Nayar,K.N.M., Radhakrishnan,K., Chandrasekharan,K., Cheeran,J.V., Ravindran,S., and George,P.O., 1992. Anaesthesia for surgical manipulations in the elephant. In: Silas,E.G., Nair,M.K., and Nirmalan,G. (Editors), The Asian Elephant: Ecology, Biology, Diseases, Conservation and Management (Proceedings of the National Symposium on the Asian Elephant held at the Kerala Agricultural University, Trichur, India, January 1989). Kerala Agricultural University, Trichur, India pp. 156-158  Abstract: Anaesthesia using chloral hydrate, thiopentone sodium, xylazine and ketamine was induced in ten elephants. The effects, duration of induction and anaesthesia were recorded. Post anaesthesia complications were not encountered in any of the animals. Surgical manipulations could be carried out under anaesthesia induced with these drugs.

Monitoring Parameters –

1)   Level of hypnosis/anesthesia

2)   Respiratory status;  cardiac status (rate/rhythm/blood pressure)

 

Client Information – This drug should only be used by professionals familiar with its ef­fects in a setting where adequate respiratory support can be performed.

 

Dosage Forms/Preparations –

 

Veterinary-Approved Products: None

 

Human-Approved Products:

Thiopental Sodium  Powder for Injection: 2% (20 mg/ml) in 1, 2.5 & 5 g kits, 400 mg syringes; 2.5% (25 mg/ml) in 250 & 500 mg vials and 500 mg, 1, 2.5, 5 and 10 g kits, 250 & 500 mg syringes; Pentothal®  (Abbott/Ceva); Generic; (Rx) (C-III)

 

Preparation of Solution for Administration: The veterinary labeled product comes in a 5 gram kit for dilution to 2.5% or 5%. If using other products without diluent, use only sterile water for injection, normal saline, or D5W to dilute. A 5 gram vial diluted with 100 mls will yield a 5% solution and diluted with 200 ml will yield a 2.5% solu­tion. Discard reconstituted solutions after 24 hours.

Also known as thiopentone sodium , thiopental is a Class-III controlled substance and is 
    a legend (Rx) drug.