In a perfect medical examiner/coroner world, every decedent that requires an autopsy would be received shortly after death and unembalmed. However, there are instances where the decedent has already been embalmed, interred and there may be a need for the decedent to be exhumed and autopsied, such as the death investigation may be incomplete and/or suspicions of foul play, with allegations of poisoning. A significant question that may arise prior to an exhumation being ordered, if the issue is a potential poisoning: “Will drugs be detected after embalming and burial?” If the answer is no, the courts may be inclined not to disturb the sanctity of the grave.

A variety of cases are submitted to the Medical Examiner’s Office where there is little to no medical history and/or medical interventions prior to death. An awareness of the history or interventions may prevent a misinterpretation of the toxicological findings. Cocaine and tetrahydrocannabinol are on occasion used therapeutically, thus the detection of these drugs does not necessarily imply abuse. There are other drugs used therapeutically that also may be abused and/or suggest inappropriate use, without a complete history, there may be a misinterpretation of the findings. Gastric lavage, oxygen therapy, and fluid resuscitation all may alter the concentration of a drug or poison and may alter the significance of the toxicological finding. Some medical procedures utilizing contrast media may obscure or mask toxicological significant findings. End-of-life or hospice care and tissue procurement may add drugs that did not play a role if the death.

The determination of a fatal drug intoxication as the cause of death or drug intoxication as a contributing factor is a challenge for the toxicologist and pathologist. There are no hard “rules or guidelines” for the interpretation of postmortem toxicological results. As with the interpretation of any laboratory result, one must consider the case in totality. In the postmortem arena, this would include but is not limited to: prior medical history and intervention, scene investigation, anatomical findings or lack thereof, and toxicological results. There are other factors that come into play when interpreting postmortem toxicological results as well; clinical “therapeutic” versus postmortem “therapeutic” drug concentrations, whole blood to serum/plasma ratios, parent to metabolite ratios, postmortem redistribution, and tolerance. Drug–drug interaction further complicates the interpretation, one drug may induce metabolic enzymes and increase the clearance of the other drug or one drug may inhibit the metabolism of the other drug, leading to potentially toxic concentrations. The age and health of the decedent must also be included in the evaluation for they may impact drug clearance; both impacting the clearance of a drug.

Postmortem biochemical studies may be conducted along with the more common toxicological testing in conjunction with the autopsy. These studies in many cases are crucial for the determination of the cause and manner of death. Postmortem chemistries may be useful in a variety of cases; demonstrating a biochemical abnormality that is responsible for the death, assist in the evaluation of the physiological effects of recognized pathology, and some authors claim it may assist in the determination of the time of death. Chemical composition of vitreous fluid is more stable than blood or cerebral spinal fluid (CSF). In individuals dying of unexpected natural disease, the detection of vitreous urea nitrogen, glucose, and electrolytes abnormalities was found in over 5% of the cases.

The length of time and temperature of storage can potentially have a significant impact on the stability of the drug and its measured concentration. It is, therefore, imperative that one be aware of potential changes in drug concentrations due to instability when interpreting the toxicological result. Drug concentrations may increase or decrease during the storage interval; depending upon storage conditions, especially temperature and/or length of time, these changes may be substantial. The stability of drugs may be due to chemical instability and/or mediated by bacteriological activity. The chemical structure of the compound may be used to predict instability; drugs with ester linkages, containing a ringed heteroatom or have a functional group susceptible to oxidation or reduction may exhibit instability upon storage.

The postmortem concentrations of drugs have been demonstrated to exhibit a site (anatomical) dependency. Heart blood drug concentrations for many drugs are usually greater than the measured concentrations from peripheral sites; such as femoral veins. To further complicate the matter, the concentrations of drugs in postmortem specimens frequently increase with the increasing postmortem interval; especially heart blood specimens. The change in the peripheral specimens appears to be of less magnitude and at a slower rate than that of heart blood drug concentrations. Drugs in high concentrations in various tissue reservoirs; such as liver, lung, and heart will passively diffuse into adjacent tissue and central blood vasculature and increase the concentration the blood sample. Another reservoir with orally ingested drugs is the stomach. This process has been termed postmortem diffusion or postmortem redistribution. The chemical characteristics of the drug also play a major role in the propensity to undergo postmortem redistribution. Drugs with a high volume of distribution (Vd>3L/kg), weakly basic in chemical nature (pKa>7) and have a high octanol:water coefficient; that is are highly lipophilic make the drug more likely to redistribute. The longer the postmortem interval, the more likely there will be an increase in concentration for drugs that exhibit postmortem redistribution.

Toxicology is one of the oldest scientific disciples. History is replete with the evolution of toxicology, early challenges being the identification of poisons or foods that had been adulterated with or naturally contain a poison. The development of various analytical techniques over time improved one’s ability to detect drugs and poisons. In fact, the development of various medical examiner systems evolved out of the eventual detection of poisoners.

Tolerance is the body’s ability to adapt or acclimate to the effect(s) of a drug. A larger dose of the drug is required over time to achieve the initial or same effect of the drug at the previous dose due to a progressively decreased responsiveness to the drug. Tolerance can be divided into two types; innate and acquired. Innate tolerance is a genetically determined sensitivity or lack of sensitivity to a drug which is observed upon the first administration. Acquired tolerance may be categorized as physiological or adaptive (behavioral). Physiological tolerance may be further subcategorized into pharmacokinetic or metabolic and pharmacodynamic relating to a change in the receptor or its response to the drug. Adaptive tolerance is another category of acquired tolerance. These are learned compensatory actions to accommodate to the effects of a drug.

Drugs undergo a variety of oxidation, reduction, hydrolytic, and conjugation reactions during the course of their metabolism and elimination from the body. These reactions result in alterations in the chemical structure leading to the production of multiple and/or unique metabolites. Many of these metabolites, in some cases, will be at low concentrations and not detected in the course of routine toxicological analyses. However, in the case of a large ingestion of the parent drug they may be readily identifiable. Some of these “metabolites” are pharmacologically active and will enhance the overall pharmacological activity and/or duration of effect of the ingested drug. There may also be situations in which a particular metabolite may increase the toxicity of the ingested drug.

A thorough death scene investigation is a critical component of any death investigation. The death scene investigator serves as the “eyes” and “ears” of the pathologist. He or she can provide information to the forensic pathologist in the understanding of the totality of circumstances surrounding the death. Although not always appreciated, these observations and documentation of the physical surroundings of the death scene and the collection of physical evidence related to the death will provide, in many cases, valuable information to the toxicologist. The information could assist in determining what biological specimens to collect, type of analytical tests to be conducted, and aid in the interpretation of the toxicological results by the toxicologist and pathologist. The presence of drugs, drug paraphernalia may suggest a possible overdose. Toxic chemicals or monitors alarming may indicate an exposure to a toxic substance. Suicide notes found; written on paper, text messages, or found on a computer may suggest intent of the decedent. The investigator may find web-based searches or books on how to commit suicide, again suggesting possible mode and/or the intent of the decedent.