Since prepared solutions of thiopental are relatively unstable, the drug is supplied as a yellow powder to be dissolved in sterile water for injection, forming a highly alkaline solution (pH >12). It is commonly formulated to a concentration of either 2.5% or 5% for small animal use. The more dilute solution is preferable, as the drug is extremely irritant to tissues due to its high pH, and can lead to venous thrombosis when injected intravenously, and tissue sloughing if accidentally administered perivascularly. In cats and dogs <5 kg, further dilution to 1% or 1.25% is recommended when using thiopental, to increase the volume of solution to be injected, thereby reducing the risk of overdose. Concentrations of 10% are commonly used in large animals: these are highly irritant, and an intravenous catheter is mandatory.
• Central nervous system: Thiopental has a rapid onset (within one arm-brain circulation time), allowing dose titration to the desired effect. Around 85% of the administered drug is carried bound to plasma albumin, and it is only the remaining 15% which exists ‘free’ in plasma and is available to cross biological cell membranes and exert an effect. Similarly, thiopental exists in both charged and uncharged forms in plasma, the ratio between the two being dictated by plasma pH. As only the uncharged form can travel across cell membranes, alterations in plasma pH can markedly influence the biological activity of thiopental: a decrease in pH increases active drug fraction and vice versa. Thus, patients with acid-base abnormalities may exhibit altered sensitivity to the drug. Similarly, there will be increased active drug concentration in patients with hypoalbuminaemia, due to decreased protein binding.
• Cardiovascular effects: The underlying mechanisms of thiopental’s cardiovascular effects are controversial. The drug can cause hypotension (related to dose and speed of injection), probably through a reduction in myocardial contractility with a lesser contribution from peripheral vasodilation. This is partially compensated for by a baroreceptor-mediated increase in heart rate. These effects are more marked in hypovolaemic animals. In addition, thiopental sensitises the myocardium to circulating catecholamines and commonly causes cardiac arrhythmias at induction, which are usually relatively benign in healthy patients but may take on more significance in those with cardiovascular disease. Thiopental can cause splenic enlargement, which may be marked in some cases. While this is generally of little consequence in most patients, the drug is best avoided in animals undergoing splenectomy, or in cases of diaphragmatic rupture, where the spleen may be within the thorax.
• Respiratory effects: Thiopental causes dose-dependent respiratory depression, and post-induction apnoea is common. The ability to secure and protect the airway by endotracheal intubation is a prerequisite for its use.
Recovery of consciousness from thiopental depends on redistribution from the brain to the muscles, and subsequently to adipose (fatty) tissue. As a consequence, recovery is prolonged in thin animals, with sighthounds (greyhounds, lurchers, borzois, etc.) being particularly susceptible. The drug then slowly redistributes from the fat back into the circulation over many hours, and is eventually metabolised and inactivated by the liver. Thus, the patient regains consciousness because the drug redistributes away from the brain, but there is then a prolonged hangover due to subanesthetic doses of the drug circulating in the bloodstream, while awaiting the slow hepatic metabolism.
It has recently been suggested that sighthound breeds may also be deficient in the hepatic microsomal enzymes necessary for breakdown of thiopental, and this may explain why these animals have much slower recoveries than other breeds which are just as deficient in body fat.
Thiopental is licensed for induction of anesthesia in both dogs and cats. The recommended dose is approximately 10mg/kg intravenous, but this is markedly influenced by both the premedication the animal has received and its health status. Recently, supplies of thiopental have become increasingly difficult to obtain in the UK, and its use as an anesthetic induction agent has consequently declined dramatically.
Thiopental – Summary
Induction of general anesthesia
Irritant to tissue
Relatively long hangover
Inability to secure airway