34: Postmortem Toxicology

Postmortem toxicology is the study of the identification, distribution, and quantification of xenobiotics after death. This information is used to account for physiologic effects of a xenobiotic at the time of death through its quantification and possible redistribution in the body at the time of autopsy. ­Several variables may cause changes in xenobiotic concentrations during the interval between (1) the time of death and subsequent autopsy and (2) the storage interval between the time of sampling and the time of testing. Toxicologists and forensic pathologists are frequently asked to interpret postmortem xenobiotic concentrations and decide whether the reported values are meaningful and whether these xenobiotics were incidental or contributory to the cause of death.

The development of the field of forensic toxicology and the improvement of laboratory technology now permit more refined identification and quantification of xenobiotics. The interpretation of postmortem xenobiotic concentrations and their significance, however, continues to evolve.

This chapter reviews factors that affect xenobiotic concentrations identified at autopsy and discusses an approach for interpreting postmortem toxicologic reports as they relate to the cause and manner of death.^{38,41,43,49, 50, and 51,59,69,79,97}

The relationship between antemortem xenobiotic exposures and death has been a subject of investigation for centuries. In 12th-century England, an appointee of the royal court, eventually named the coroner, was designated to record and identify causes of death.⁷³ In suspicious circumstances, coroners investigated poisonings, but scientific methods were primitive, and conclusions regarding such deaths were conjecture at best.

By the mid-19th century, however, techniques for detecting certain xenobiotics in postmortem tissue were developed and focused generally on identifying heavy metals as a cause of death in homicides.^{44,73,77,94,99} At that time, coroners were still elected or appointed individuals with little or no medical training. However, with better laboratory techniques and autopsies being performed by trained pathologists, the specialty of forensic medicine continued to develop. In late 19th-century Massachusetts, trained pathologists, referred to as medical examiners, ultimately replaced the coroner system and were eventually empowered by the state to investigate certain types of unusual or suspicious deaths (medicolegal autopsies).⁷³ Currently in the United States, legal jurisdiction of death investigations is the responsibility of either a coroner or a medical examiner depending upon the state or county, with 19 states using medical examiner systems almost exclusively.⁴⁸

The medicolegal autopsy, ideally, is performed by a forensic pathologist who attempts to establish the cause and manner of death (Table 34–1). The cause of death is the etiology ultimately responsible for death to occur. For example, the presence of cyanide in the toxicologic evaluation may be sufficient to establish cardiorespiratory arrest from cyanide poisoning. The manner of death is an explanation of how the death occurred, or the circumstances surrounding the terminal events. It broadly distinguishes natural from nonnatural (or violent) deaths. Nonnatural deaths, depending on the jurisdiction, may be divided into several categories (Table 34–2). With the identification of cyanide, the manner of death cannot be considered natural because a poisoning is a “chemically traumatic” (violent) event. The medical examiner must make the best determination of the manner of death based on the available evidence.^99,106 An unintentional exposure may be classified as an accident (a legal term for some unintentional nonnatural deaths), and intentional self-injury may be classified as a suicide. If the circumstances indicate an exposure due to the acts of another person, the manner of death is classified as a homicide.

Determination of the manner of death has important consequences. Homicide necessitates involvement of law enforcement officials for further investigation. Cases deemed suicide not only impact survivors psychologically but also may nullify some life insurance payments. Conversely, a case deemed an “accident” may have a double-indemnity insurance clause. Assignment of financial responsibility for workplace deaths may be similarly affected when xenobiotics are identified in the postmortem specimens of involved workers.

Recognition of xenobiotic-related deaths also has significant public health consequences. The forensic pathologist may be the first to identify and report critical information regarding fatal drug reactions, medication errors, rapidly fatal epidemics associated with illicit xenobiotic use or malicious intent activities. In cases of occupational and environmental xenobiotic-related fatalities, interventions can be implemented to prevent subsequent morbidity and mortality. In addition, the pathologist describes gross and microscopic autopsy findings that may elucidate mechanisms of xenobiotic toxicity.

Postmortem toxicologic techniques may be used in other types of investigations as well. For example, when carboxyhemoglobin is identified in burned human remains from an airplane crash, a cabin fire before descent is more probable than deaths due to a fire on impact. This type of postmortem analysis is useful in the reconstruction of events leading to the crash.^8,55,64,98

Ordinarily, toxicologic samples are collected as part of a complete autopsy. In the hospital, when a death is assumed to be from natural causes, the hospital pathologist may perform an autopsy with the consent of the family. In a medicolegal investigation, however, the forensic pathologist determines the need for a complete or partial autopsy and has statutory authority to act on that determination independent of familial consent. Occasionally, only fluid samples may need to be obtained along with an external inspection of the body if a complete autopsy is either unnecessary or the family has legal or religious grounds for objection. The precise list of xenobiotics screened in postmortem samples varies greatly by jurisdiction. Investigations in large cities may routinely screen for hundreds of illicit, therapeutic, and environmental xenobiotics. Occasionally, the suspicions of the medical examiner or death scene investigator warrant special assays that are performed only upon request.

The sampling of fluid and tissue may be obtained minutes to years after death. The postmortem interval, defined by the time between death and autopsy, is important, but many other factors will define the extent of bodily decomposition. This is dependent on environmental conditionssuch as ambient temperature, humidity, aerobic versus anaerobic surroundings, and immersion in water.⁶⁵ Samples may be collected from a body during advanced stages of decomposition, after exhumation from graves, or even after embalming.^{8,37,38,45,62,78} Knowing the condition of the body at the time of sampling assists in interpreting the toxicologic findings. These postmortem changes are reviewed below.

The first stage of decomposition is autolysis, during which endogenous enzymes are released and normal mechanisms maintaining cellular integrity fail.⁵⁸ Chemicals move across compromised and leaky cellular membranes down relative concentration gradients. Glycolysis continues in the red blood cells until intracellular glucose is depleted, and then lactate is produced. Ultimately, intracellular ions and proteins are released into the blood, and tissue and blood acidemia develops leading to the biochemical changes described in Table 34–3.⁹⁹

The next stage of decomposition in most normal environments is putrefaction. This stage involves digestion of tissue by bacterial organisms, which typically colonize the bowel or respiratory system. Later, additional organisms may be introduced by insects or other external sources. As the putrefactive process advances, the colors of the skin and organs change; epithelial blebs may form and separate from the underlying dermis; and gases may accumulate, resulting in foul odors and bloating.⁹⁹

If death occurs in a very warm, dry climate, such as a desert or comparably arid environment, the body may desiccate so rapidly that putrefactive changes may not occur. This results in mummification and produces a lightweight cadaver with a tight, dry skin enveloping a prominent bony skeleton.⁹⁹

If the environment is very cold and devoid of oxygen, such as at great depths under water, putrefaction will be slowed. Anoxic decomposition of fatty tissues occurs, forming a white, cheesy material known as adipocere.

Another phase of decomposition, anthropophagia, occurs in unprotected environments where insects or other animals feed on the remains.⁹⁹

Because most postmortem changes are derived by chemical reactions and are temperature dependent, with increased temperatures accelerating the process and cooler temperatures retarding it. In general, morgue refrigerators achieve low enough temperatures (40°F {4°C}) to prevent further gross decomposition and many associated postmortem changes.

Another process that alters natural decomposition is embalming, a process of chemically preserving tissues that may be performed in a variety of ways.^46,47 Typically, blood is drained through large vessel pumps, and an embalming fluid is injected intravascularly to perfuse and preserve the face or other tissues. Intracavitary spaces may be injected with the preserving substances, and solid organs may or may not be removed.

Unless the medical examiner is suspicious about a death, only standard autopsy samples will be available in an otherwise intact body.^{24,38,53,60,82,97} These typically include samples of blood, gastric contents, bile, urine, and occasionally solid organs such as the liver or brain. Less commonly, vitreous humor is obtained for analysis (Table 34–4). If the decedent was hospitalized before death, antemortem specimens may also be available for evaluation and comparison. These specimen analyses are reviewed in greater detail below.

Blood

Postmortem cell lysis limits the concept of plasma concentrations, and “blood” concentrations are reported instead. Most commonly a single site such as femoral or subclavian blood is usually sampled unless an unusual xenobiotic with nonuniform distribution is suspected of causing the death. In patients with a prolonged postmortem interval and in cases where intravascular blood is coagulated, right heart blood may serve as an alternative sample site.

Other sources of blood may sometimes be available to the forensic pathologist. These frequently include antemortem samples and occasionally extravasated blood, which is unlikely to undergo extensive metabolism. Intracranial clots, in particular, serve as useful comparative samples in patients with a prolonged survival period after exposure to a xenobiotic.⁶⁶

In advanced states of decomposition, blood from the abdominal or thoracic cavities is less useful because it may be contaminated by bacteria or other substances that may affect xenobiotic recovery or analysis.

Vitreous Humor

Because of the relatively avascular and acellular nature of the fluid, the vitreous humor is well protected from the early decompositional changes that typically occur in blood.^{16,19, 20, and 21,25} When bodies are immediately refrigerated, creatinine, blood urea nitrogen, and sodium can be reliably approximated from vitreous humor samples for up to 3 or 4 days. Potassium concentrations are less reliable because cell lysis causes intracellular release. When vitreous glucose is elevated, hyperglycemia at the time of death can be assumed. A low vitreous glucose concentration, however, is a less reliable indicator of the antemortem serum glucose concentration, because a low vitreous glucose concentration may be attributable to either antemortem hypoglycemia or postmortem glycolysis even in the relatively avascular vitreous.

The aqueous content of the vitreous is normally higher than that of blood and may affect the partitioning of certain water-soluble xenobiotics, such as ethanol.

Urine

Urine may be available during the autopsy and may reveal renally eliminated substances or their metabolites. Because the bladder serves as a reservoir in which metabolism is unlikely to occur, the concentrations of xenobiotics obtained during the autopsy reflect antemortem urine concentrations. An isolated urine sample is of limited quantitative value but may be useful when compared with other sample sites.

Gastric Contents

The gross contents of the stomach are inspected for color, odor, and the presence or absence of pill fragments, food particles, activated charcoal, and other foreign materials.⁹⁷ Typically, gastric concentrations of xenobiotics are reported as milligrams of substance per gram of total gastric contents. Xenobiotic-induced pylorospasm, diminished intestinal motility, or decreased splanchnic blood flow may all decrease gastric emptying and affect the quantitative values obtained from sampling different parts of the gastrointestinal tract.

Solid Organs and Other Sources

Xenobiotic concentrations in solid organs, such as the liver and brain, are usually reported as milligrams of substance per kilogram of tissue. Other tissue samples, including hair and nails, are used for thiol-avid xenobiotics such as metals. Rarely, tracheal aspirates of gases may be analyzed to confirm inhalational exposures. Pleural fluid analysis of postmortem xenobiotics typically yields qualitative results in decomposed bodies because redistribution of xenobiotics from the stomach and intestines may occur.^32,89

In an embalmed body, either the organs or tissues that remain relatively unembalmed, such as deep leg muscle,⁶⁸ or the embalming fluid itself may be used for analysis. Some authorities regulate the contents of embalming fluid specifically to avoid confounding postmortem analysis. Most embalming fluid in the United States consists of formaldehyde, sodium borate, sodium nitrate, glycerin, and water. When a body is disinterred, soil samples are usually obtained from above and below the coffin to permit identification of xenobiotics that may have leeched into or out from the body.⁷⁸

On rare occasions, cremated remains, often referred to as cremains, are the only source of sampling available. Most metallic implants, such as pacemakers, are removed before cremation, and only dental remains, particulate matter, and occasionally calcified blood vessels are available for analysis.^3,105 In most cremations performed in the United States, the incineration process is followed by mechanical grinding to yield a fine particulate matter.¹⁰⁵ The ability to extract xenobiotics from cremains is markedly limited at best, and little published data are available on the subject. A new technique to identify heavy metals such as lead from cremains has been described, but is not routinely used at present.^3,105

A variety of other anthropophagic insect species may demonstrate the presence of xenobiotics.^1,42,62,63 This process of analysis is termed entomotoxicology. In putrefied bodies or bodies that have undergone anthropophagy, fluids and even insect parts can be analyzed. Forensic entomologists can collect samples of these insects from the remains. After taking into account the stage of insect life, environmental conditions, and the season, the approximate time of death can be extrapolated. The species Calliphoridae, or the bluebottle fly, is attracted to unprotected remains by a very fine scent that develops in the cadaver within hours of death. The adult fly lays eggs on mucosal surfaces or in open wounds. After the eggs hatch, the larvae feed on the decomposing tissue. Larval samples can then be examined for the presence of xenobiotics. To achieve accurate analysis, these samples must be preserved immediately after collection because living larvae can continue to metabolize certain xenobiotics. In another phase of their life cycle, the larvae undergo pupation, secreting a substance that encloses them into pupal casings until they hatch as adults. These pupal casings are often found in the soil beneath the body. Some xenobiotics have been identified in the casings long after the adult fly has emerged⁸⁴ (Table 34–5).

After fluid and tissue samples have been collected and analyzed for the presence of xenobiotics, the process of interpreting these results begins. This complex task attempts to account for the clinical effects of a xenobiotic at the time of death by integrating medical history, autopsy, death-scene findings, and toxicologic reports. Multiple confounding variables may affect the sample concentrations of xenobiotics from the time of death to the time of testing after the autopsy. Variables include the nature, metabolism, and distribution of the xenobiotic; the state of health of the decedent prior to death; physical and environmental variables during the postmortem interval; the techniques of analysis; and other findings of the autopsy (Tables 34–6 and 34–7).

Variables Relating to the Xenobiotic

Postmortem Redistribution.

The xenobiotic concentration in blood may be higher during the time of sampling at autopsy than at the actual time death occurred if significant postmortem redistribution occurs.^{54,81,104, 105, 106, 107, 108, 109, 110, and 111} Redistribution typically occurs with xenobiotics that have large volumes of distribution and when decomposition results in release of intracellular xenobiotic into the extracellular compartment.⁸⁶ For example, amitriptyline may be released from tissue stores into the blood as autolysis progresses, resulting in a significantly higher blood concentration during the autopsy than at the time of death. If postmortem redistribution is not considered, xenobiotic concentrations obtained during the autopsy may be misinterpreted as being supratherapeutic or even toxic, and the cause of death may be inappropriately attributed to this xenobiotic.

Postmortem Metabolism.

Less commonly, xenobiotic concentration may decrease secondary to postmortem metabolism. For example, cocaine continues to be degraded after death by endogenous enzymes such as cholinesterases in the blood, which continue to function in postmortem tissue and in vitro. Unless blood is collected immediately after death and placed in tubes containing enzyme inhibitors such as sodium fluoride, the concentration of cocaine will continue to decrease, and the analysis will not accurately reflect the concentration of the drug at the time of death.^59,71,98,102 All available information regarding postmortem redistribution or metabolism of a specific xenobiotic must be considered for the proper interpretation of the toxicologic results.

State of Absorption and Distribution.

Both in the living and deceased, the state of absorption, distribution, and other toxicokinetic principles affect the apparent concentration of a sampled xenobiotic. For a xenobiotic with minimal postmortem metabolism or redistribution, the phase of absorption is suggested by the relative quantity of the xenobiotic in different fluids and solid organs. For example, a high concentration of xenobiotic in the gastric contents, with progressively lower concentrations in the liver, blood, vitreous, and brain, suggests an early phase of absorption at the time of death. When a xenobiotic is orally administered and the tissue concentration is highest in the liver, the relationship suggests a postabsorption phase but a predistribution concentration. A concentration found to be highest in the urine suggests that the xenobiotic was in an elimination phase at the time of death. Although this approach has limitations, it may be important for correlating the state of absorption and the expected clinical course of the xenobiotic. Unfortunately, multiple samples may not always be available at the time of autopsy or the interpretation of reports, and opportunities for subsequent sampling are often limited.

Xenobiotic Stability.

Xenobiotic stability refers to the ability of a xenobiotic to maintain its molecular integrity despite postmortem changes such as decomposition of the body, adverse storage conditions, or the lack of preservatives.^{5,13,15,56,57,62,92,100,107,109,110} Postmortem xenobiotic stability was assessed in homogenized liver tissue infused with various concentrations of xenobiotics.¹⁰⁰ The samples were allowed to putrefy outdoors, and sequential sampling of xenobiotic concentrations was performed. The xenobiotics that decreased in concentration as putrefaction progressed were considered labile, and samples with a constant concentration were considered stable. The authors proposed that the chemical characteristics of a xenobiotic determine its stability. For example, labile xenobiotics share the molecular configuration of an oxygen–nitrogen bond, thiono groups, or aminophenols. Conversely, chemical structures that enhance stability include single-bonded sulfur groups, carbon–oxygen and carbon–nitrogen bonds, and sulfur–­oxygen and hydrogen–nitrogen bonds. Although not explicitly studied in otherwise intact but putrefying bodies, logically, a less stable xenobiotic may be recovered in a lower concentration than the actual concentration at the time of death. This must be considered when information regarding stability is available and the body of a decedent is in an advanced stage of decomposition.

Xenobiotic Chemical Interactions.

An artifact may result from a chemical interaction with a xenobiotic added during the postmortem interval, such as embalming fluid.³⁹ In a study of xenobiotic-spiked blood and formalin in test tubes, amitriptyline was formed by the methylation of nortriptyline.^27,110 Identification of amitriptyline, which was not present at the time of death, could confuse the interpretation of toxicologic analyses.

Expected Clinical Effects of the Xenobiotic.

For a fatality to be attributed to a xenobiotic, the expected clinical course from the exposure should be consistent with the autopsy findings. For example, what are the implications of a person found dead minutes after having been seen ingesting pills, if a large concentration of acetaminophen (APAP) is identified in both the gastric contents and blood but not in other tissues at autopsy?91 Although suicidal intent may be supported by this finding, the onset of death within minutes is inconsistent with a fatality due to an APAP overdose. Thus, another cause of death must be sought. Interpretation of postmortem toxicology must also incorporate clinically relevant consequences of xenobiotic interactions. For example, the combined ingestion of phenobarbital and ethanol can cause fatal respiratory depression. Although neither may be fatal alone, their additive effects must be acknowledged during toxicological interpretation.

Variables Related to the Decedent

Comorbid Conditions.

The clinical response to a xenobiotic may be affected by acquired and inherited physiologic conditions that are not always identified or identifiable on autopsy. A thorough medical history is important and may assist in interpreting the clinical effects of a xenobiotic exposure. Similarly, certain clinical conditions may produce substances that interfere with postmortem laboratory assays. For example, an individual with a critical illness may produce digoxinlike immunoreactive substances (DLIS), which may cross-react with the postmortem digoxin assay.⁶ Without knowledge of DLIS production, the results may confound toxicologic analysis (Chap. 65).

Tolerance.

Tolerance is an acquired condition in which increasingly higher xenobiotic concentrations are required to produce a given clinical effect. It is an important consideration for deaths in the presence of opioids, ethanol, and sedative–hypnotics. For example, respiratory depression and death from methadone may be easily diagnosed in an opioid-naive individual with a history of methadone exposure and methadone-positive postmortem samples. However, the same methadone concentrations in a patient on chronic methadone maintenance therapy will not produce the same outcome. Unfortunately, no autopsy markers are available to indicate tolerance, and no biochemical or histologic markers are available during autopsy that may be used to predict clinically dangerous xenobiotic concentrations in a tolerant individual.²⁸ Complex postmortem assays analyzing opioid receptors are not routinely used.³⁶ Postmortem assessment of tolerance ultimately depends on knowledge of the patient, pharmacokinetics of the xenobiotic, and the best judgment of the investigator.

Pharmacogenetics.

There is genetic variability in the expression of certain metabolic enzymes. For example, pharmacogenetic differences in metabolic enzymes, such as CYP2D6, predispose some individuals to fatal hypotension from an inability to metabolize debrisoquine.

Similarly, deaths in young children have been reported from the use of therapeutic codeine. Postmortem blood analysis may reveal an elevated concentration of morphine, the codeine metabolite, and raise suspicion for a malicious overdose. Postmortem genotyping may provide an alternate explanation. Individuals with duplicate alleles for CYP2D6 may be ultra­rapid metabolizers of codeine, rendering them susceptible to morphine toxicity despite generally acceptable dosing of codeine. Such distinctions are not routinely identifiable on autopsy.^17,29,30

Variables Relating to the Autopsy

State of Decomposition.

In decedents in advanced stages of decomposition, xenobiotics may diffuse from depot compartments such as the stomach or bladder into adjacent tissues and blood vessels and secondarily affect their sample concentrations.^{23,38,66,76, 77, and 78,85, 86, and 87}

During putrefaction, bacteria cause fermentation of endogenous carbohydrates, resulting in ethanol formation. In decedents without gross evidence of putrefaction, especially those in cool, dry environments, endogenous ethanol production is minimal.^18,22 With a longer postmortem interval or in an environment that is more conducive to ethanol production, the distinction between endogenous and exogenous sources of ethanol becomes more difficult. Sampling from multiple sites is often useful in making the distinction.¹⁰¹ A comprehensive review of interpreting postmortem ethanol concentrations is available elsewhere.⁶⁶

Handling of the Body or Samples.

Inappropriate handling of the body may result in artifacts.^91,93 In one reported case, methanol was detected in the vitreous humor of a decedent after embalming.¹² The methanol was subsequently traced to a spray cleanser that likely settled on the surface of open eyes during washing of the body.

In addition, inappropriate handling of samples may affect xenobiotic concentrations. In one study, autopsy blood was obtained from a diabetic man who died of bronchopneumonia. The samples were stored at 40°F (4°C) and tested at 2 and 5 days postmortem. The blood ethanol increased from 0.4 to 3.5 g/L because of an inadequate addition of fluoride preservative to the samples. The combination of inadequate preservation, hyperglycemia (vitreous glucose of 996 mg/dL), and bacterial sepsis created an ideal environment for ethanol production via fermentation.⁶⁶

In the United States, preservatives containing metals are currently banned for use in embalming because they may contaminate subsequent evaluation for metal poisoning. Formalin may also affect stability or quantitative identification of some xenobiotics. When necessary, an analysis of embalming fluid used by the mortician or soil sampling around disinterred bodies may facilitate the toxicologic investigation.^{19,34,107,109,110}

Autopsy Findings.

In many xenobiotic-related deaths, the anatomic findings are nonspecific.¹⁰⁸ In some cases, the autopsy reveals confirmatory or supportive findings. A large quantity of undigested pills in the stomach is consistent with an intentional overdose, and suicide should be considered. Centrilobular hepatic necrosis may be found in decedents with a history of APAP overdose. The autopsy may also reveal other findings such as coronary artery narrowing, chronic hypertension, renal abnormalities, or a clinically silent myocardial injury. Such information may be useful to assess the potential effects of a xenobiotic in a patient with previously undiagnosed conditions. In other cases, the absence of a chronic condition may be strongly suggestive of a xenobiotic-related death. For example, a decedent with an autopsy finding of aortic dissection in the absence of chronic hypertensive findings or other predisposing conditions may suggest a xenobiotic-induced hypertensive crisis as may occur from use of cocaine or other sympathomimetics.

Artifacts Related to Sampling Sites.

Site-specific differences in postmortem xenobiotic blood concentrations are common.³⁵ For example, blood obtained from femoral vessels may have low glucose concentrations because of postmortem glycolysis, but the blood glucose concentration removed from the right heart chambers may be high as a result of perimortem release of liver glycogen stores. As noted above, hyperglycemic conditions are more reliably assessed from sampling the vitreous humor as vitreous is a relatively protected environment in the early postmortem interval. An elevated vitreous glucose concentration suggests antemortem hyperglycemia. The individual interpreting the toxicologic report must know the exact site from which the sample was taken.^20,60

Ideally, samples from more than one site would be available for comparison; unfortunately, multiple blood samples are not often routinely obtained. Comparison of concentrations from different sites may reveal important information regarding the extent of xenobiotic absorption at the time of death and acute versus chronic exposure.^{9, 10, and 11,20,26,30,52,67,72,80,82,85,88, 89, and 90,95,96,101,103}

Other Considerations.

Published therapeutic, toxic, and fatal postmortem xenobiotic concentrations are available to aid in the interpretation of postmortem specimens.^4,70 However, the conditions associated with reported concentrations do not necessarily permit comparisons with the concentrations of the particular case under investigation. Thus, these resources are valuable but should be used mainly as representative of prior attempts at rigorous analysis and not accepted as absolute values that define either toxic or therapeutic concentrations. Similarly, formulas available for assessing xenobiotic doses or concentrations in the living are not usually applicable when analyzing postmortem samples.

Other Limitations

Although there are generalized standards of practice in forensic investigations, specimen collection and laboratory methodologies may vary.^2,4 Some xenobiotic concentrations may be falsely elevated or depressed depending on the chosen methodology.^32,72 Descriptions of specific toxicology laboratory techniques are beyond the scope of this chapter, but these variables must also be given consideration in the interpretations of results. Other limitations may include a lack of information relating to the circumstances of death and possible compromises in specimen handling because of the required protocols for the maintenance of proper chain of custody often of paramount importance in forensic autopsies.^37,38

• Accurate interpretation of postmortem toxicologic reports requires an understanding of potential biochemical changes and other artifacts that affect postmortem testing.

• It is exceptionally difficult to absolutely correlate postmortem xenobiotic blood and tissue concentrations to those at the actual time of death.

• Postmortem toxicology is an evolving discipline that may permit only the most likely cause and manner of xenobiotic-related death to be identified.

• Progress in this field will depend on the continued collaboration between the treating physicians, medical and forensic toxicologists, and forensic pathologists.

References