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Post Mortem: What Happens to Drugs after Death?

morgue

Many factors result in drug concentrations rising, falling or even disappearing after death.

By Michael Kennedy

Drug levels can rise, fall or even disappear entirely after death, potentially leading to incorrect conclusions about murder, suicide and drug overdoses.

In 1865 the bodies of Mary Pritchard and her mother were exhumed and found positive for antimony. Up to that point in time, poisonings were detected not by laboratory testing for drugs but entirely by symptoms exhibited before death and examination of organs at autopsy. Pritchard’s husband, Dr Edward William Pritchard, was presumably unaware of these new laboratory techniques. He was charged with murder and later became the last person to undergo public execution in Scotland.

Post mortem detection of drugs has moved on since Pritchard’s day. Laboratories now routinely measure nanogram quantities of drugs from samples of blood, urine, vitreous humour in the eye, bile, gastric contents and often liver. They can also undertake analysis of hair, bone, brain and other body parts.

Prior to death, the concentration of a drug in any part of the body will be a function of drug absorption, its distribution throughout the body, metabolism and elimination. The big question for each death is what to make of the various drug concentrations found.

Many factors result in drug concentrations rising, falling or even disappearing after death (Table 1), when there is disruption of cellular membranes, alteration in the acidity of blood, chemical breakdown of some molecules and rapid bacterial invasion from the gastrointestinal tract. Bodies that have been altered by fire, immersion in water, animal consumption, burial or a long period of time since death each provide unique difficulties.

The forensics database is heterogeneous due to variations in cases and circumstances of death. Specimen collection, transport, storage and analytical issues arising from the sample of tissue used can provide challenges that are not present in routine sample collection from patients. Changes in the concentrations of drugs are due to the sum of many interacting processes that differ from drug to drug and case to case.

Drug Redistribution within the Body

In large overdoses, drugs may remain in the gastrointestinal tract and subsequently diffuse into blood vessels in the chest, upper abdomen and liver. During life some drugs are concentrated in organs such as the lung, liver and cardiac muscle, but after death they diffuse rapidly into surrounding blood vessels such as the pulmonary vessels, cardiac chambers and veins as well as the vena cavae.

The ratio of central blood concentration (usually cardiac) to peripheral blood concentration (usually the femoral vein) is referred to as the C/P ratio (Table 2), and this is used as a guide to alterations in drug concentrations after death. There are considerable ranges for the ratio. The central blood from the heart or central veins has the highest concentrations, while peripheral vein concentrations may be closest to the drug concentration immediately prior to death. Unfortunately even their interpretation may not be straightforward, as peripheral blood collected from leg or arm veins can be subject to diffusion of drug from surrounding tissues and may also have received central blood as a result of post mortem blood circulation caused by body movement.

Generally drugs that are widely distributed through the body are more likely to undergo redistribution because they are bound to tissues throughout the body and diffuse out when cell membranes break down after death. Post mortem increases in concentration can be fivefold for some antidepressants, such as amitriptyline and the analgesic propoxyphene. At times, lack of awareness of this process has led to patients being wrongly considered to have suicided or even to have been murdered when high concentrations of antidepressants were found at post mortem.

Bacterial and Other Processes

Within hours of death, bacteria such as Escherichia coli have moved from the intestinal tract and invaded most of the body. Many drugs, such as some of the benzodiazepines, are metabolised by these bacteria, and this lowers their concentration and can even make them disappear entirely.

Bacteria can also have the reverse effect and metabolise glucose to alcohol, with alcohol levels at times being above the driving limit of 0.05 g/100 mL. This is a very important factor when considering the sobriety or otherwise of airline pilots or train drivers who have died in accidents.

Cocaine, in contrast, is broken down by residual esterase activity in blood, with concentrations falling after death.

On the other hand gamma hydroxyl butyrate (GHB) – also known as fantasy, grievous bodily harm and by many other street names – is a normal neurotransmitter whose synthesis continues after death, so it will be detected in post mortem blood at concentrations that can resemble drug overdoses. GHB concentrations were an important factor in court proceedings associated with the death of Dianne Brimble on a cruise ship in 2002.

How to Interpret the Results

Judicial decisions rely heavily on the interpretation of post mortem drug concentrations by forensic clinical pharmacologists. Every death will have unique features. While the blood concentration is important, it is only one of many factors that need to be considered.

Large published tables stating therapeutic, toxic and lethal concentrations of many drugs are of limited use in interpreting post mortem findings for two reasons.

First, therapeutic ranges are derived from living subjects and are almost always obtained from plasma. Post mortem samples are, obviously, obtained from the dead and are almost always derived from blood. As red blood (and other) cells make up about 50% of blood, the ratio of red blood cells to plasma can be important in some cases. In the case of chloroquine, for example, the blood/plasma partition ratio is 3.7:1, so blood concentrations will be higher than plasma. In the case of the principal psychoactive component of cannabis, ∆9 THC, it is 0.6 so blood concentrations will be lower than in plasma. Even allowing for redistribution and other factors, post mortem concentrations cannot be directly compared with ones that have been obtained in patients or in normal subjects participating in scientific investigations of the drug.

Second, in clinical use there is considerable overlap between toxic and therapeutic concentrations for many drugs, particularly opioids such as morphine, methadone and oxycodone. For example, a person on the autopsy table as a result of a methadone overdose may have the same blood concentration of methadone as a patient in a methadone maintenance program. For some drugs, intercurrent factors such as low potassium levels in the case of the cardiac drug digoxin, or renal disease in the case of the anti-epileptic phenytoin, will cause drug-induced toxicity at low drug concentrations.

As a result, events leading up to death and the medical history of the deceased are very important. For instance, the absence of an antiepileptic drug in an epileptic who has drowned may indicate that the death was due to a convulsion because the deceased did not take the medication. Likewise the detection of morphine in nine exhumed bodies was one of the principal factors in Dr Harold Shipman’s conviction for murder. Heroin is metabolised to morphine, so the presence of morphine indicated that heroin had been administered to Shipman’s dead patients. While it is in routine therapeutic use for pain relief in the United Kingdom, none of Shipman’s patients had any medical indication for heroin or any sign of any other heroin use.

Laboratory findings may also provide critical clues to antemortem activity and drug supply. Finding acetylcodeine in a case of heroin overdose indicates that the heroin was synthesised in an illicit, and not a pharmaceutical, laboratory. The presence of cocaethylene, a cardiotoxic derivative of cocaine, indicates that alcohol was consumed at the same time as cocaine.

Where deaths have occurred with illicit drugs such as amphetamines or derivatives such as ecstasy, it is not possible to directly correlate a post mortem concentration with a specific event. However, we can use the published clinical and toxicological data to make projections about the series of events that resulted in death. For example, if methamphetamine is detected in the blood of an individual who has a cardiac arrest and there is no clinical or autopsy evidence of cardiac disease, then the drug is the cause of death irrespective of the concentration detected.

Analogue drugs provide a new challenge. These drugs are usually minor chemical modifications of well-known drugs such as amphetamine, cannabis or anabolic steroids. They are promoted as being undetectable, less toxic and of course giving better feelings than previous drugs. While the pharmacology of the analogue has almost invariably not been studied, laboratories are keeping up with the illegal laboratories and the database for these drugs is growing.

Conclusion

Post mortem pharmacology is a relatively new and challenging area. The level of diagnostic ease portrayed on television does not reflect the real world.

It is essential that any post mortem result is interpreted in relation to the individual circumstances involved. It is never correct to rely on published lists of drug concentrations alone.

As technology advances and the evidence base expands, interpretation of results will become more precise. If interest and funding is sustained it will be soon very difficult for any drug-related death, toxicity or poisoning to go undetected.

Michael Kennedy is Conjoint Associate Professor at the University of New South Wales, and the Department of Clinical Pharmacology at St Vincent’s Hospital in Sydney.