Saturday, 13 January 2007

The Lancet September 24, 2005; v. 366, n. 9491, p. 1074

The Lancet September 24, 2005; v. 366, n. 9491, p. 1074
Leonidas Koniaris and colleagues Research Letter1 raises several important ethical and pharmacokinetic issues. The finding that 43 of 49 executed inmates had post-mortem thiopental concentrations in blood below that considered adequate for surgical anaesthesia raises the issue of awareness and suffering before death.
Post-mortem drug concentrations are extremely difficult to interpret and there is substantial variability in results depending on timing, anatomical origin of the specimen, and physical and chemical properties of the drug.2 Despite these limitations, the consistent finding of low thiopental concentrations in executed prisoners from four different locations requires further assessment.
The distribution of thiopental in a dying prisoner is likely to be very different from its distribution in a ventilated and oxygenated patient. The development of cellular hypoxia and metabolic acidosis will increase the proportion of drug in the non-ionised form and the rate and extent of rapid distribution into muscle and fat. In an experimental dog model, Brodie and colleagues3 showed that inhalation of carbon dioxide such that arterial pH decreased to 7·09–6·80 produced a 40·15% decrease in thiopental plasma concentrations. When the animals' blood was allowed to recover to a normal pH, the thiopental concentrations increased.
The pharmacokinetics of thiopental are extremely complex.4 The end of anaesthetic effect of thiopental is believed to be due to the rapid distribution of drug into muscle and fat. If acidaemia causes a more rapid distribution of thiopental away from its receptor sites, the current thiopental protocol might not provide adequate thiopental anaesthesia during the execution of prisoners.
We declare that we have no conflict of interest.


1. Koniaris LG, Zimmers TA, Lubarsky DA, Sheldon JP. Inadequate anaesthesia in lethal injection for execution. Lancet 2005; 365: 1412-1414. Abstract | Full Text | Full-Text PDF (66 KB) | CrossRef
2. Pounder DJ. The nightmare of postmortem drug changes In: , Wecht CH, ed. Legal medicine. Salem: Butterworth, 1993: 163-191.
3. Brodie BB, Mark LC, Papper EM, et al. The fate of thiopental in man and a method for its estimation in biological material. J Pharmacol Exp Therap 1950; 98: 85-96. MEDLINE
4. Russo H, Bressolle F. Pharmacodynamics and pharmacokinetics of thiopental. Clin Pharmacokinet 1998; 35: 95-134. MEDLINE | CrossRef

a. University of Miami, School of Medicine, 1601 NW 12th Avenue, Miami, FL 33136, USA
Dr. Richard Weisman – mail:
b. Florida Poison Information Center—Miami, Miami, FL, USA

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