Post-mortem toxicology in the elderly

Abstract

Thearticle by Professor Byard on the ‘‘post-mortem toxicology in the elderly’’ provides timely advice on the substantial difficulties encountered in the interpretation of toxicology results in this population [1]. Aging in humans results in gradual deterioration of organ function; and particularly important when dealing with the pharmacokinetics of drugs are the heart, liver and kidney. These changes mainly affect protein binding, drug clearance and distribution; all of which may increase the sensitivity to drugs in the elderly, and in some require the use of smaller doses. However, these changes do not occur suddenly at age 65, but occur gradually, and importantly, vary significantly from one person to another. For example, in a study by Shi and Klotz one-third of elderly persons showed no decrease in renal function while in about twothirds of elderly subjects the age-related decline of renal function was associated with coexisting cardiovascular diseases and other risk factors [2]. Co-morbidity is a significant factor, if not for the effect of the diseases on drug clearance and associated clinical effects, but for the presence of a number of drugs that increase the risk of adverse effects [3]. As Prof Byard rightly points out, underlying disease will be higher in this age group, but it will be very difficult, if not impossible in most cases, to differentially separate out disease as a cause of death from drugs which have the potential (at least) to contribute to sudden death. One of the more common examples is the presence of morphine (or other opioids) in a person with terminal disease (e.g., cancer) when one or more critical organ is affected. Any concentration can be toxic depending on the established tolerance and the circumstances. While pharmacokinetic (and other) changes with age may have occurred the development of tolerance will be a far bigger factor. Unfortunately this cannot be assessed from a blood (or tissue) concentration. As with all deceased persons, young or old, the availability of relevant medical information such as dose information and vital signs such as blood pressure, pulse, breathing rate, oxygen tension are required to establish if any impending opioid toxicity was developing. This information may be available in a hospital death, but would rarely all be available in other settings. In the elderly a large inter-individual variability in drug disposition is particularly prominent [2] however this is not unique to the older population since most drugs show only a poor correlation with blood concentration and pharmacological effect. Hence it will always be difficult to ascertain what a particular concentration means, particularly if it has also changed in concentration after death [4]. These post-mortem changes are dynamic, with concentrations increasing and then decreasing as the post-mortem intervals increase, as typified by the antipsychotics [5]. While the elderly provide more difficulties in the interpretation of post-mortem toxicology results, the interpretation of drug concentrations in deceased persons provide great difficulties at all ages and as usual require a thorough appraisal of available information.