The testing of stomach contents is only worthwhile if (1) the volume of the gastric contents is recorded, (2) a homogeneous specimen is analysed and (3) the total drug content within the stomach is computed. It does no good to know the drug concentration in gastric fluid if the total volume of the gastric contents is not also known. It may also be possible to identify small pill fragments by microscopic examination of the gastric fluid. Very little should be made of low-level drug con- centrations found in stomach, as ion trapping may cause small amounts of some charged drugs, such as cocaine and morphine, to appear in the gastric contents, even if the drug has been injected intravenously. However, the detection of high concentrations of some drugs in the stomach (such as morphine) does not necessarily prove oral ingestion; it may just be an artefact produced by enterohepatic circulation.
■ Interpretation
Post-mortem drug concentration measurements cannot be interpreted in isolation, if for no other reasons than that tolerance eventually emerges to most abused drugs. A living heroin addict may very well have a higher morphine concentration than an occasional heroin user lying in the morgue, but both might have much lower morphine concentrations than a hospice patient treated with a diamorphine syringe driver. Tolerance is not the only issue.
Drugs taken previously are likely to be stored in deep body compartments, only to be released as the body decomposes (a process that begins immediately after death). Drug measurements made under these circumstances might give the false impression that the drugs were, in fact, circulating in the blood at the time of death. This phenomenon was strikingly illus- trated in a recent study of post-mortem blood fen- tanyl concentrations. Fentanyl concentrations were measured in post-mortem specimens collected in 20 medical examiner cases from femoral blood, heart blood, heart tissue, liver tissue and skeletal muscle. In a subset of seven cases femoral blood was obtained shortly after death and then again at autopsy. The mean collection times of between the two post-mortem sam- ples were 4.0 hours and 21.6 hours, respectively. In four of the cases fentanyl concentrations rose from ‘none detectable’ in the samples taken shortly after death, to concentration as high as 52.5 μg/L. If only the toxi- cology results were considered in isolation, a pathol- ogist confronted with a case of unexpected sudden death might very well make the mistake of classifying fentanyl as the cause of death, even though none was present in the blood at the time of death.
Finally, there is the issue of genetic polymorphism.
Not only does post-mortem redistribution (Figure 18.1) ensure that concentration measured at autopsy will
Figure 18.1 Post-mortem redistribution. Blood values measured after death have little or no relationship between levels that existed in life. Aspiration of stomach contents into the lungs often occurs at the time of death, and drugs that were in the lungs diffuse into the heart. Blood from the illiofemoral vessels is generally considered preferable for testing.
F urther information sourc es
be higher than in life, there is always the possibility that high drug concentrations, even those measured in life, do not always reflect drug overdose: the individual simply may not have been able to metabolize the correct dose of drug they had been given. This possibility was only realized a few years ago when a newborn died of morphine poisoning that originated in the mother’s breast milk. As is often the case, she had been prescribed codeine for post-labour pain. When the infant died unexpectedly it was discovered that the mother was an ultra-rapid metabolizer of cytochrome P450 2D6, causing her to produce much more morphine when taking codeine than would normally be expected. Individuals with a normal genetic compliment convert roughly 10% of codeine into morphine, accounting for codeine’s modest pain- relieving effects, but because of the mother’s genetic make-up, much higher concentrations of morphine were found in the infant than would normally be predicted, even though the mother was not taking excessive doses of codeine.
■ Further information sources
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Arlington, VA:
American Psychiatric Association.
Drummer OH. Forensic toxicology. EXS 2010; 100: 579–603.
Ferner RE. Post-mortem clinical pharmacology. British Journal of Clinical Pharmacology, 2008; 66: 430–43.
Jung BF, Reidenberg MM. Interpretation of opioid levels:
comparison of levels during chronic pain therapy to levels from forensic autopsies. Clinical Pharmacology and Therapeutics 2005; 77: 324–34.
Karch SB, Stephens BG, Ho CH. Methamphetamine-related deaths in San Francisco: demographic, pathologic, and toxicologic profi les. Journal of Forensic Sciences 1999;
44: 359–68.
Karch S (ed.). Drug Abuse Handbook, 2nd edn. Boca Raton, FL: CRC Press, 2007.
Karch S. Karch’s Pathology of Drug Abuse, 4th edn. Boca Raton, FL: CRC Press, 2008.
Kintz P, Villain M, Cirimele V. Hair analysis for drug detection.
Therapeutic Drug Monitoring 2006; 28: 442–6.
Koren G, Cairns J, Chitayat D et al. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine- prescribed mother. Lancet 2006; 368: 704.
LeBeau M, Moyazani A. Drug-Facilitated Sexual Assault, A Forensic Handbook. London: Academic Press, 2001.
Levine B. Principles of Forensic Toxicology, 3rd edn, Washington, DC: American Association for Clinical Chemistry, 2010.
Moriya F, Hashimoto Y. Redistribution of basic drugs into cardiac blood from surrounding tissues during early-stages postmortem.Journal of Forensic Sciences 1999; 44: 10–16.
Olson KN, Luckenbill K, Thompson J et al. Postmortem redistribution of fentanyl in blood. American Journal of Clinical Pathology 2010; 133: 447–53.
Pélissier-Alicot AL, Gaulier JM, Champsaur P, Marquet P.
Mechanisms underlying postmortem redistribution of drugs: a review. Journal of Analytical Toxicology 2003;
27: 533–44.
Pounder DJ. The nightmare of postmortem drug changes.
Legal Medicine 1993: 163–91.
Chapter
■ Ethanol sources and concentrations
Alcohol (ethanol) may be ingested or it may be present by virtue of bacterial action occurring after death. Depending on local practice, blood alcohol concentrations can be expressed in many different units and notations, but they are all interchangeable in their meaning. The definition of what constitutes a standard drink of alcohol also varies from country to country. In the USA it is 14 g (17.74 mL) ethanol, but in the UK it is 7.9 g (10.00 mL) of ethanol. In most countries there are tables listing the alcohol content of common beverages by brand name, and there are standard formulae (such as the Widmark Formula, see Appendix 2, p. 243) for calculating the amount of alcohol ingested and the time of ingestion.
As an alternative to the complex equations used by toxicologists, many forensic practitioners find it easier to remember a simple formula first introduced by American toxicologist Charles Winnek (Box 19.1). It must always be remembered that Winnek’s formula is intended only to provide a rough working esti- mate. If a trial is to ensue, the Widmark formulae must be employed.
■ Ethanol absorption
Alcohol is absorbed from the stomach and small intestine by diffusion, with most of the absorption occurring in the small intestine. The rate of absorp- tion varies with the emptying time of the stomach but, as a rule, the higher the alcohol concentra- tion of the beverage, the faster the rate of absorp- tion. Gastric absorption accounts for 30 per cent and 10 per cent of ethanol administered with food and water, respectively, and only a small percentage of the ethanol undergoes first-pass metabolism in the
Box 19.1 Winnek’s formula
Winnek’s formula is based on the simple observation that, on average, a 150-pound (68 kg) man will have a blood alcohol concentration (BAC) of 0.025% after drinking 1 ounce (29.5 mL) of 100-proof (50%) alcohol. It follows that:
BAC = (150/body weight in pounds) (% ethanol/50) (ounces consumed) (0.025) Thus, if a 200-pound (90.7 kg) man drank fi ve 12-ounce (354.9 mL) cans of beer, and the beer contained 4% ethanol, then the BAC would be approximately:
BAC = (150/200) (4/50) (60) (0.025) = 0.090% (90 mg%)
■ Ethanol sources and concentrations
■ Ethanol absorption
■ Elimination of alcohol
■ Ethanol measurement
■ Clinical effects of alcohol
■ Post-mortem considerations
■ Further information sources