The pharmacokinetics and pharmacodynamics of thiopental as used in lethal injection

Thiopental (sometimes called, although inaccurately, Sodium Pentothal) was the most commonly used intravenous anesthetic agent for about fifty years, beginning in the mid-1940s. (1) As states began to discuss and develop protocols for lethal injection in the 1970s, thiopental was the logical choice as the medication to render the inmate unconscious prior to the administration of subsequent medications, most commonly pancuronium (a medication that paralyzes skeletal muscle and results in cessation of breathing) followed by potassium chloride (a salt that is a necessary component of the diet but when given intravenously in large doses results in the cessation of electrical activity in the heart). It is virtually unanimously accepted by physicians, particularly anesthesiologists, that the administration of lethal doses of pancuronium and/or potassium chloride to a conscious person would result in extreme suffering. For this reason, all of the protocols for lethal injection that we have reviewed precede the administration of pancuronium and potassium chloride with a dose of thiopental intended to render the inmate unconscious for a period of time far in excess of that necessary to complete the execution. (2) When implemented as written, meaning the correct doses of the correct medications are administered in the correct order into a properly functioning intravenous delivery system and with sufficient time for thiopental to produce its effect, all of the protocols we have reviewed are intended to result in the rapid death of the inmate without undue pain or suffering. This paper will concentrate on the pharmacokinetics and pharmacodynamics of thiopental. As applied here, pharmacokinetics is the study of the concentration of thiopental as a function of time in tissues (particularly brain), while pharmacodynamics is the study of the effects of thiopental (particularly the production of unconsciousness and impairment of the heart's ability to circulate blood). (3) By using generally accepted computer modeling techniques, and considering the wealth of published studies on the pharmacology of thiopental, we can prepare predictions of such relevant parameters as the onset (how long it takes for the inmate to become unconscious) and duration (how long the inmate would remain unconscious) of the pharmacological effects of thiopental. (4) Thiopental is usually described as an "ultra-short acting" sedative/hypnotic agent in pharmacology and anesthesiology texts. (5) This description is semantically correct, but only when thiopental is compared to other barbiturates. Indeed, when thiopental was used to induce (i.e., begin) a general anesthetic, the typical adult dose was about 300 mg and the typical patient would remain unconscious for 5 to 10 minutes. (6) The usual anesthetic regimen would involve the subsequent administration of anesthetic gases that would keep the patient unconscious for the duration of the surgical procedure. The protocols for lethal injection mandate doses of thiopental ranging from 2000 to 5000 mg, i.e., about seven to sixteen times higher than those used to begin a typical anesthetic. (7) However, the relationship between the dose of thiopental and its duration of action is not linear. For example, as the dose of thiopental is increased sevenfold to 2000 mg, the duration of unconsciousness is not also increased sevenfold but actually much more, as described later. The pharmacological term "sedative/hypnotic" means that at low doses (e.g. 25-100 mg), thiopental causes sedation (i.e., sleepiness), while at higher doses it produces hypnosis (i.e., unconsciousness). (8) At sedative doses, it produces no analgesia (pain relief) and in fact probably increases the perception of painful stimuli. When a person is rendered unconscious by thiopental, the conscious perception of pain is abolished. The body may, however, react in a reflex manner to pain and exhibit such phenomena as movement, a fast heart rate, sweating, or tearing. …