Thiopental

Overview

Thiopental (Pentothal®) is an ultra-short-acting thiobarbiturate used in dogs and cats for induction of general anesthesia or as the sole anesthetic for very short procedures. It is no longer available in many markets, including the United States and Canada.

Following IV administration, anesthesia occurs rapidly, usually within 15–30 seconds (and within 1 minute), with a short duration of action of approximately 10–30 minutes due to rapid redistribution from the CNS into muscle and adipose tissue rather than rapid metabolism. Recovery may require several hours, and repeated doses can significantly prolong recovery. Greyhounds and other sighthounds may have longer recovery times because they metabolize thiobarbiturates more slowly than other breeds.

Mechanism of Action (MOA): Thiopental rapidly enters the CNS because of its high lipid solubility and produces profound hypnosis and anesthesia. It acts directly on CNS neurons as an agonist at the GABA-A receptor, enhancing the inhibitory neurotransmission that GABA itself mediates.

Indications

Thiopental is used in dogs and cats as an intravenous anesthetic for rapid induction of general anesthesia or as the sole anesthetic for very short procedures. In debilitated patients, it may be administered slowly to effect with appropriate dose adjustment.

• Induction of general anesthesia: Administered as a rapid IV bolus before maintenance with other anesthetic agents.
• Anesthesia for very short procedures: Used as the sole anesthetic when only a brief duration of anesthesia is required – published guidance describes procedures of about 10 to 15 minutes.
• Anesthesia in debilitated patients: May be administered slowly IV to effect with cautious dose adjustment.

Dosage (Reference)

Dog

Thiopental is given intravenously and titrated strictly to effect: part of the calculated dose is given as a rapid bolus and the remainder more slowly. The listed doses are guidelines only.

Cat

Thiopental is given intravenously and titrated strictly to effect: part of the calculated dose is given as a rapid bolus and the remainder more slowly. The listed doses are guidelines only.

Warnings & Precautions

Thiopental should be administered only by IV injection with careful patient selection and close monitoring. Dose adjustment and cautious administration are required in patients with conditions that increase sensitivity to its cardiovascular or CNS effects.

• IV administration only: Contraindicated when suitable veins are unavailable. Avoid extravasation and intra-arterial injection because the highly alkaline solution can cause severe tissue irritation and necrosis.
• Hypersensitivity: Contraindicated in patients with a history of hypersensitivity to barbiturates.
• Status asthmaticus: Contraindicated in patients with status asthmaticus.
• Cardiovascular disease: Use cautiously in patients with severe cardiovascular disease, pre-existing ventricular arrhythmias, shock, hypotension, or hypovolemia; in patients with ventricular tachycardia, guidance is to avoid thiopental altogether as a proarrhythmic drug. Dose adjustment and careful patient management are required.
• Increased intracranial pressure: Use cautiously. Respiratory depression and hypoventilation may increase ICP if ventilation is inadequate; with properly controlled ventilation thiopental instead lowers ICP and cerebral metabolic oxygen consumption, which is neuroprotective.
• Myasthenia gravis and asthma: Use cautiously in affected patients.
• Conditions prolonging hypnotic effects: Use cautiously in severe hepatic disease, myxedema, severe anemia, or after excessive premedication, as recovery may be prolonged.
• Renal dysfunction, acidemia, or hypoproteinemia: Patients may exhibit increased sensitivity to thiopental.
• Sighthounds: Greyhounds and other sighthounds metabolize thiobarbiturates more slowly than other breeds and may experience prolonged recovery, which may also reflect their low body fat; methohexital is recommended by many clinicians instead.
• Solution concentration: Concentrations below 2% in sterile water should not be used because they may cause hemolysis.
• Pregnancy and lactation: Thiopental crosses the placenta and should be used during pregnancy only when maternal benefits outweigh potential fetal risks. Small amounts may appear in milk after large doses but are unlikely to be clinically significant in nursing animals.
• Airway control: Use cautiously in patients with respiratory disease, and do not use the drug unless the airway can be secured and ventilation supported – apnea can occur during induction.
• Narrow margin of safety: The therapeutic index is low, so the dose is given as intermittent injections and titrated to effect while the patient’s response is observed.
• Controlled substance: Thiopental is a Schedule III (C-III) controlled substance in the United States.

Drug Interactions

Clinically relevant interactions with thiopental primarily involve additive CNS depression, altered anesthetic requirements, cardiovascular effects, or potentiation of arrhythmias. Dose adjustment and appropriate monitoring are recommended when these drugs are used concurrently; sedatives and other anesthetics lower the dose of thiopental required.

• Clonidine: IV administration before induction may reduce thiopental dose requirements by up to 37%.
• Other CNS depressants (e.g., methocarbamol): May enhance CNS and respiratory depression.
• Diazoxide: May increase the risk of hypotension.
• Epinephrine and norepinephrine: May potentiate ventricular fibrillatory effects when used with thiobarbiturates and halothane.
• Ketoprofen: May prolong anesthesia recovery time.
• Metoclopramide: Administration before induction may reduce thiopental dose requirements.
• Midazolam: May potentiate hypnotic effects.
• Opioids (e.g., buprenorphine, fentanyl, morphine, tramadol): Administration before induction may reduce thiopental dose requirements.
• Phenothiazines (e.g., acepromazine): May potentiate thiopental effects and increase the risk of hypotension.
• Xylazine, halothane and methoxyflurane: May exacerbate the arrhythmogenic effects of thiobarbiturates; lidocaine may inhibit them.
• Incompatible drugs and fluids: Do not mix thiopental in the same syringe or line with lactated Ringer’s solution, atropine, glycopyrrolate, morphine, hydromorphone, meperidine, insulin or succinylcholine, which have been reported to be physically incompatible with it. Compatibility also depends on pH, concentration, temperature and the diluent used. Propofol is compatible and has been used as a 1:1 mixture for induction.

Side Effects & Overdose

Side Effects

Adverse effects of thiopental are primarily dose-related and involve the cardiovascular and respiratory systems. Repeated administration may prolong recovery because of drug accumulation.

• Cardiac arrhythmias (dogs): Ventricular bigeminy is the most common arrhythmia and the reported arrhythmogenic incidence in dogs is 40%; it is usually transient and generally responds to additional oxygen.
• Reduced cardiac output: Thiopental causes dose- and administration-rate-dependent cardiorespiratory depression, including reduced stroke volume, hypotension, and apnea. Cardiac output may be relatively preserved in healthy patients but can decrease substantially with cardiovascular compromise or hypovolemia. Appropriate premedication reduces dose requirements but may add depressant effects. Supplemental oxygen reduces hypoxemia risk but does not prevent direct cardiovascular depression.
• Apnea: Dose-related apnea is the most common adverse effect and may occur particularly after IV administration; cats are especially susceptible.
• Hypotension: Dose-related hypotension may occur; cats may develop mild arterial hypotension.
• Rapid IV administration: May cause significant vascular dilatation and hypoglycemia.
• Repeated dosing: Drug accumulation can markedly prolong recovery, with residual effects lasting several hours; after multiple doses the drug requires metabolism rather than redistribution, and hangover effects of 24 hours or more have been described.
• Parasympathetic effects: Salivation and bradycardia may occur.
• Perivascular administration: The highly alkaline solution (pH 10 to 11) can cause significant tissue irritation and necrosis, so administration through an IV catheter is advised.

Overdose

Thiopental overdose primarily causes severe respiratory and cardiovascular depression. Treatment is supportive.

• Respiratory depression: Provide oxygen supplementation and mechanical ventilation as needed.
• Cardiovascular depression: Provide appropriate cardiovascular support.
• Epinephrine and other catecholamines: Should not be used during management of thiopental overdose.
• Maximum dose: Overdose is caused by injecting too rapidly or by repeating doses; a maximum total dose of 30 mg/kg has been described for a fit dog.
• Where to get advice: For a suspected overdose, consultation with a 24-hour poison control center providing veterinary-specific information is recommended.

Key Notes

Practical clinical points to optimize the use of thiopental in dogs and cats:

• Rapid induction: Loss of consciousness typically occurs within 15–30 seconds (usually within 1 minute) after IV administration, making thiopental suitable for rapid anesthetic induction.
• Short anesthetic duration: The anesthetic effect usually lasts only 10–30 minutes because the drug is rapidly redistributed from the CNS to muscle and fat rather than rapidly metabolized.
• Professional use only: Thiopental should be administered only by personnel familiar with its anesthetic effects and in facilities capable of providing adequate respiratory support; federal law restricts it to use by or on the order of a licensed veterinarian.
• Continuous monitoring: Monitor the depth of anesthesia along with respiratory function and cardiovascular status, including heart rate, cardiac rhythm, and blood pressure.
• Analgesia: Thiopental produces anesthesia by CNS depression and provides no analgesia, so appropriate analgesic medication is required for painful procedures.
• Half-life: Thiopental is metabolized by the hepatic microsomal system and is about 75% protein-bound; the reported elimination half-life in dogs is 7 hours, far longer than the 10 to 30 minutes of anesthesia, which is why repeated doses accumulate.
• Renal failure: Very little of the drug is excreted unchanged in the urine – about 0.3% in people – so no dose reduction is needed for chronic renal failure itself, although renal dysfunction, acidemia and hypoproteinemia each increase sensitivity to a given dose.
• Storage and reconstitution: The dry powder is stable indefinitely. Reconstitute only with sterile water for injection, 0.9% sodium chloride or 5% dextrose; concentrations of less than 2% in sterile water should not be used, as they may cause hemolysis.
• Shelf life after reconstitution: Once reconstituted the solution contains no preservative. It is reported stable for 3 days at room temperature and 7 days refrigerated, and using it within 24 hours is advised. A longer refrigerated shelf life of up to 4 weeks is also published.
• Preparing the solution: A 5 g vial diluted with 100 mL gives a 5% solution and with 200 mL a 2.5% solution; 2.5% is generally used for small animals and 2.5% or 5% for larger ones. Discard reconstituted solution after 24 hours.
• Tubing and containers: The made-up solution can adsorb to plastic IV tubing and bags, and after 48 hours has been reported to attack the glass container it is stored in. Do not administer any solution that has a visible precipitate.
• Other names: Also known as thiopentone sodium, and sold outside the United States under trade names including Pentothal, Intraval, Trapanal, Nesdonal and Farmotal.