THIOPENTAL SODIUM
Chemistry - A thiobarbiturate, thiopental occurs as a bitter-tasting, white to off-white, crystallinepowder 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.
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, potassiumchloride, scopolamine HBr, sodium iodide, and tubocurarine chloride (recommendations conflictwith 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, andtetracycline HCl. Compatibility is dependent upon factors such as pH, concentration, temperatureand diluents used. It is suggested to consult specialized references for more specific information(e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
See the monograph: Barbiturates, Pharmacology of, for additional information.
Thiopental is metabolized by the hepatic microsomal system and several metabolites have beenisolated. The elimination half-life in dogs has been reported as being approximately 7 hours and insheep, 3-4 hours. Very little of the drug is excreted unchanged in the urine (0.3% in humans), sodosage adjustments are not necessary in patients with chronic renal failure.
Contraindications/Precautions - The following are considered to be absolute contraindicationsto the use of thiopental: absence of suitable veins for IV administration, history of hypersensitivityreactions to the barbiturates, and status asthmaticus. Relative contraindications include: severecardiovascular disease or preexisting ventricular arrhythmias, shock, increased intracranial pressure, myasthenia gravis, asthma, and conditions where hypnotic effects may be prolonged (e.g., severehepatic disease, myxedema, severe anemia, excessive premedication, etc). These relativecontraindications do not preclude the use of thiopental, but dosage adjustments must be consideredand the drug must be given slowly and cautiously.
Because greyhounds (and other sight hounds) metabolize thiobarbiturates much more slowly thanmethohexital, 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 cliniciansfeel that thiopental should not be used alone in the horse as it may cause excessive ataxia andexcitement.
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 thesolution. Severe CNS toxicity and tissue damage has resulted in horses receiving intra-carotidinjections of thiobarbiturates.
Cats are susceptible to developing apnea after injection and may also develop a mild arterialhypotension.
Horses can exhibit symptoms of excitement and severe ataxia during the recovery period if thedrug 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 alsodevelop after dosing.
Too rapid IV administration can cause significant vascular dilatation and hypoglycemia. Repeatedadministration 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 ofanticholinergic 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).
The ventricular fibrillatory effects of epinephrine and norepinephrine are potentiated whenused 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 hasbeen shown to compete with thiopental at plasma protein binding sites. This may also occur withother sulfonamides.
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 maycause hemolysis. After reconstitution, solutions are stable for 3 days at room temperature and for 7days if refrigerated. However, as no preservative is present, it is recommended it be used within 24hours after reconstitution. After 48 hours, the solution has been reported to attack the glass bottles itis stored in. Thiopental may also adsorb to plastic IV tubing and bags. Do not administer anysolution 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, potassiumchloride, scopolamine HBr, sodium iodide, and tubocurarine chloride (recommendations conflictwith 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, andtetracycline HCl. Compatibility is dependent upon factors such as pH, concentration, temperatureand diluents used. It is suggested to consult specialized references for more specific information(e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology - THIOPENTAL SODIUM
Because of their high lipid solubility, thiobarbiturates rapidly enter the CNS andproduce 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 agentfor very short procedures.Pharmacokinetics - THIOPENTAL SODIUM
Following IV injection of therapeutic doses, hypnosis and anesthesia occurwithin one minute. The drug rapidly enters the CNS and then redistributes to muscle and adiposetissue in the body. The short duration of action of these agents is due less to rapid metabolism thanto this redistribution out of the CNS and into muscle and fat stores. Greyhounds and other sighthounds may exhibit longer recovery times than other breeds. This may be due to these breeds lowbody fat levels or differences in the metabolic handling of the thiobarbiturates.Thiopental is metabolized by the hepatic microsomal system and several metabolites have beenisolated. The elimination half-life in dogs has been reported as being approximately 7 hours and insheep, 3-4 hours. Very little of the drug is excreted unchanged in the urine (0.3% in humans), sodosage adjustments are not necessary in patients with chronic renal failure.
Contraindications/Precautions - The following are considered to be absolute contraindicationsto the use of thiopental: absence of suitable veins for IV administration, history of hypersensitivityreactions to the barbiturates, and status asthmaticus. Relative contraindications include: severecardiovascular disease or preexisting ventricular arrhythmias, shock, increased intracranial pressure, myasthenia gravis, asthma, and conditions where hypnotic effects may be prolonged (e.g., severehepatic disease, myxedema, severe anemia, excessive premedication, etc). These relativecontraindications do not preclude the use of thiopental, but dosage adjustments must be consideredand the drug must be given slowly and cautiously.
Because greyhounds (and other sight hounds) metabolize thiobarbiturates much more slowly thanmethohexital, 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 cliniciansfeel that thiopental should not be used alone in the horse as it may cause excessive ataxia andexcitement.
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 thesolution. Severe CNS toxicity and tissue damage has resulted in horses receiving intra-carotidinjections of thiobarbiturates.
Adverse Effects, Warnings
In dogs, thiopental has an approximate arrhythmogenic incidence of40%. Ventricular bigeminy is the most common arrhythmia seen and is usually transient andgenerally responds to additional oxygen. Administration of catecholamines may augment the arrhythmogenic effects of the thiobarbiturates, while lidocaine may inhibit it. Cardiac output may alsobe 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 arterialhypotension.
Horses can exhibit symptoms of excitement and severe ataxia during the recovery period if thedrug 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 alsodevelop after dosing.
Too rapid IV administration can cause significant vascular dilatation and hypoglycemia. Repeatedadministration 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 ofanticholinergic 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 proprietaryproduct, Diathal® (procaine penicillin G, dihydrostreptomycin sulfate, diphemanil methylsulfate, and chlorpheniramine maleate) and the related compound thiamylal. Avoid using thiopental withthis product.The ventricular fibrillatory effects of epinephrine and norepinephrine are potentiated whenused 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 hasbeen shown to compete with thiopental at plasma protein binding sites. This may also occur withother sulfonamides.