Elephant specific information, if available, is in blue.

Note: Thiamylal is not available commercially at the time of this update but is still listed in the FDA’s “Green Book”. Most veterinary anestheisologists are recommending using thiopental as an alternative. The monograph remains in the VDH with the hope that the product may find its way back to the market in the near future.

 

Chemistry – A thiobarbiturate, thiamylal sodium occurs as a pale yellow, hygroscopic powder with an unpleasant odor. It is soluble in water and a 5% solution in water has a pH of 10.5-11.5.

 

Storage/Stability/Compatibility – Thiamylal is stable in the dry form when stored in air­tight vials. Thiamylal should be diluted with only sterile water for injection, sodium chlo­ride injection, or D5W (Note: A veterinary manufacturer (Bio-Ceutic) recommends using only sterile water or sodium chloride for injection). After reconstitution, solutions are sta­ble for 2 days when refrigerated (6 days according to some sources), but should generally be used within 24 hours. Do not administer any solution that has a visible precipitate. Little specific compatibility information is available other than not mixing with atropine, succinylcholine or tubocararine. Because of their chemical similarities, the compatibility listings in the thiopental monograph may be used as general guidelines with regard to thi­amylal.

 

Pharmacology – The thiobarbiturates, because of their high lipid solubility, rapidly enter the CNS and produce profound hypnosis and anesthesia. See the monograph: Barbiturates, Pharmacology of, for more information.

 

Uses/Indications – Because of their rapid action and short duration, the thiobarbiturates are excellent induction agents for general anesthesia when used 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, which may be due to these breed’s low body fat levels or differences in the metabolic handling of these agents.

 

Thiamylal is metabolized by the hepatic microsomal system. There was no information found regarding specific pharmacokinetic parameters in humans, dogs or horses. A paper on the pharmacokinetics of thiamylal in cats (Wertz et al. 1988) found a rapid first distri­bution phase (t1/2 = 1.91 minutes) followed by a second slower distributory phase (t1/2 = 26.5 minutes). The elimination half-life in cats was found to average 14.3 hours with a short period of anesthesia induced (dosage of 13.2 mg/kg IV) followed by a prolonged state of sedation. The authors concluded that based on the pharmacokinetic profile in cats, thiamylal should be used as an induction agent only followed by other anesthetic agents (e.g., halothane).

 

Contraindications/Precautions – The following are considered to be absolute con­traindications to the use of thiobarbiturates: abscence of suitable veins for IV administra­tion, history of hypersensitivity reactions to the barbiturates, and status asthmaticus. Relative contraindications include: metabolic acidosis, 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 thiamylal, 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. Siamese cats may develop more CNS depression than other feline breeds.

 

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

 

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. Do not administer intrapleurally or intraperi­toneally.

 

Adverse Effects/Warnings – The manufacturer (Bio-Ceutic) lists the following possible adverse reactions: circulatory depression, thrombophlebitis, pain at injection site, respira­tory depression including apnea, laryngospasm, bronchospasm, salivation, emergence delirium, injury to nerves adjacent to injection site, skin rashes, urticaria, nausea, and eme­sis.

 

In dogs, thiamylal has an approximate arrhythmogenic incidence of 60-85%. Ventricular bigeminy is the most common arrhythmia seen, is usually transient (over within 2 min­utes) and generally responds to additional oxygen. Incidence may be reduced to approxi­mately 25% by using a phenothiazine tranquilizer pre-operatively. Although the incidence of arrhythmias is higher with thiamylal than thiopental, thiamylal is considered to be less cardiotoxic.

 

Administration of catecholamines may augment the arrhythmogenic effects of the thiobarbiturates, while lidocaine may inhibit it. Systemic arterial pressure may be in­creased, but this is probably only clinically significant in patients with preexisting small vessel disease.

Repeated administration of thiamylal is not advised as recovery times can be become sig­nificantly prolonged. Should parasympathetic side effects (e.g., salivation, bradycardia) occur, they 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 thiamylal. Avoid using thiamylal with this combination.

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. Thiamylal 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 thiamylal and 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.

 

The manufacturer (Bio-Ceutic) recommends rapid injection 1/3 – 1/2 of the calculated dosage to carry the patient through the excitatory phase, then, if no apnea or severe respi­ratory depressant effects are seen, administer to the level of anesthesia desired.

 

Horses:

a)   For light anesthesia: One gram IV (jugular) for an animal weighing from 500 – 1100 lbs.;          Deeper anesthesia: 7.3 mg/kg IV (Package Insert; Bio-Tal® — Bio-Ceutic)

b)   4.4 – 6.6 mg/kg IV after sedation and guaifenesin; or 6.6 – 8.8 mg/kg IV after tranquilization. (Mandsager 1988)

 

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/FDA Approval Status/Withholding Times –

Note: Thiamylal is not currently available, it was (and perhaps again?) available as:

 

Thiamylal Sodium for Injection; available in 1 gram, 5 gram, & 10 gram vials for re­constitution and 5 gram ampules (Note: Veterinary products are available in 1 & 5 gram vials only)

Bio-Tal®  (Bio-Ceutic), Surital®  (Parke-Davis); (Rx)  Approved for use in dogs, cats, cattle, horses, and swine. No milk or meat withdrawal times are required.

 

Preparation of Solution for Administration-

The following table may be used to determine amount of diluent necessary to obtain de­sired concentrations:

 

 

 

 

Sterile water for injection is the preferred diluent. If preparing solutions for a maintenance continuous drip, use D5W or sterile isotonic saline to avoid hypotonic solutions. Some dextrose solutions may be acidic enough to cause precipitation. Do not use cloudy or pre­cipitated solutions.