If you have issues viewing or accessing this file contact us at NCJRS.gov. ------~--------- CHAPTER 4 Treatment for Survival Prior to Death and Interpretation of Postmortem 'Toxicologic Findings Eric G. Comstock, M.D, The protocol for postmortem examination not detectable at postmortem examination. in the medical examiner's or coroner's office Substances detected may be found to have should provide for a minimum toxicologic been administered medicinally and to have no examination in every death. Specimens to be causative role whatsoever. Concentrations of collected for t0xicologic evaluation should drugs for which tolerance develops may be so include: (a) gastric contents with notation of high as to be considered an unequivocal cause the total volume, (b) heart blood, (c) urine, of death in a pharmacologically naive individ­ (d) bile, and (e) selected tissues, such as liver, ual, while they may have played no role what­ lung, and kidney. soever in a chronic drug user. The minimum toxicologic examination The purpose of this discussion is to direct should provide for qualitative screening with attention to the circumstances which influ­ quantitation when the qualitative procedures ence the interpretation of toxicologic findings are positive. Minimum routine screening pro­ at postmortem examination. cedures should include a test for volatile organics and screening procedures for detec­ tion of a variety of groups of drugs. Circum­ CIRCUMSTANCES INFLUENCING stances of death may dictate a more elaborate INTERPRETATION protocol or suggest specific substances or groups of substances that should be assessed.1 Statistical parameters, such as "the lethal The only significance that routinely can be dose 50 percent" or "the lethal concentration attached to positive toxicologic findings is 50 percent," permit the determination of the that a detected substance is present. It is ex­ relative toxicity of a substance for various tremely rare that causal significance can be species or for subgroups within a single attributed to a substance on the basis of analy­ species. The relative toxicity of various sub­ tical data alone. More commonly, the results stances may be compared using these con­ of toxicologic findings must be interpreted cepts. They are, however, not applicable to with consideration given to investigations of single individuals within a population except the scene, activities of the decedent inunedi­ for approximation of the order of magnitude ately prior to death, first aid or treatment of susceptibility of the individual to the sub­ efforts provided by laymen or by medical stance under consideration. personnel, and long-term drug use history. When discussions of susceptibility are limited to single individuals, statistical con­ These investigations may result in the Cause of cepts lose validity. It becomes necessary to death being attributed to a su?stance which is examine the factors that influence variation in susceptibility of individuals within the The author acknowledges the support of the population. While many of these variables National Institute 011 Drug Abuse (grant #aH81 DA 01466·0 lSI) for part of the research underlying the have not 'been defined, some have been the discussion in this chapter. subject of investigation. Individual differences in susceptibility to 1For further discussion of topics treated here, see also chapter 3, "Postmortem Examination," and toxic substances are determined in part by chapter 5, "Forensic Toxicology in Death Investiga­ genetic factors. Differences in enzymatic tion." armamentaria which determine efficacy of 23 24 COMSTOCK detoxification are slow and fast acetylation, drug which would unequivocally be fatal for glucose-6-phosphate dehydrogenase deficien­ the phalmaC,)logically naive individual. cies, acetylcholinesterase deficiencies, and Interpretation of ihe toxicologic findings in metabolic correlates with the hemoglobin­ postmortem examination requires consider­ opathies, such as sickle cell disease. Defects ation of the genetic variable in susceptibility, in amino acid metabolism also may alter sus­ appraisal of preexisting pathology, and assess­ ceptibility to some toxic substances. The ment of the phalmacologic experience of the occurrence of these genetically determined decedent. variations in metabolism may place the indi­ vidual significantly outside the normal curve of susceptibility, influencing interpretation of TREATMENT PRIOR TO DEATH postmortem findings. An individual may be made more suscep­ The phrase "treatment prior to death" is tible to some substances by preexisting path­ used to describe occurrences during the inter­ ology. Susceptibility to carbon monoxide val between exposure and death. This includes may be increased by coexisting pathological first aid given by laymen as well as treat­ processes limiting exchange of oxygen in the ment administered by the medical community. lung or in a target organ, such as brain or Implicit is a survival interval between the heart. Acquired end-organ susceptibility is exposure and the occurrence of death. During illustrated by chronic exposure to anticholi­ this interval, the pharmacodynamics of redis­ nesterase insecticides. Reduction of choli­ tribution or disposition influence the interpre­ nesterase levels results in significant increase tation of the chemical findings at p0stmortem in response to administration of succinyl examination. choline. Impairment of liver function in­ Attempts at first aid may include the creases the relative susceptibility to sub­ mechanical induction of vomiting with conse­ stances dependent upon hepatic enzymes for quent aspiration asphyxia resulting in death detoxification. Significantly impaired renal unrelated to the concentration of toxic sub­ function increases susceptibility to sub­ stances present in the body. Efforts to induce stances normally excreted by the kidneY in a vomiting with sodium chloride are not un­ pharmacologically active form. common, and where vomiting has failed to Tolerance may develop to make an individ­ occur, death from hypernatrernia has occurred ual less susceptible to the lethal effects of in the presence of drugs of no toxicologic certain drugs. Dispositional tolerance is ex­ significance. Utilization of street treatment emplified by hepatic microsomal enzyme in­ folklore may result in intravenous injections duction. Experience with a toxic substance of milk or intravenous injections of table salt. over a period of time may result in increasing Other drugs that may be used in a treatment the rate of detoxification by increasing the effort include administration of ampheta­ activity of enzymes that effect the biotrans­ mines for barbiturate overdose and adminis­ formation of the substance to a nontoxic tration of chlorpromazine for amphetamine metabolite. Dispositional tolerance does not overdose. increase the concentration of toxic substance Once a patient finds his way to medical that can be tolerated at the target end organ. care, interpretation of subsequent postmortem Comparison of a tolerant individual with a findings may become very complicated. pharmacologically naive individual after a Administration of supportive care for pul­ similar survival interval shows lower tissue monary or cardiovascular failure may result concentrations of the substance in the toler­ in survival after the time that the original ant individual. "End-organ tolerance" des­ offending substance has been cleared from the cribes the adaptive procedure by which the body, with death due to injury incurred while target organ becomes less responsive to the the toxic substance was present. The per­ phalmacologic efhct of the substance. Devel­ formance of gastric lavage alters the interpre­ opment of end-organ tolerance permits an tation of postmortem examination of gastric individual to survive tissue concentrations of a contents and may add the complications of TREATMENT PRIOR TO DEATH AND POSTMORTEM TOXICOLOGIC FINDINGS 25 aspiration asphyxia or aspiration pneumonitis variety of complicating circumstances, any of of chemical or of infectious origin. In the which could be contributing factors in delayed treatment effort a variety of other drugs death. such as central nervous system and respiratory stimulants and pressor amines may be admin­ istered. Not only do these substances compli­ PHARMACODYNAMICS OF HOST­ cate interpretation of postmortem findings, SUBSTANCE RELATIONSHIPS but they may contribute to the lethality of the situation by adding the hazard of over­ Understanding the pharmacodynamics oc­ dose with these therapeutic agents. Other cm'ring with exposure to a toxic substance is possible complications that may occur during essential to interpretation of postmortem the treatment process include protracted findings. Figure 1 presents a schematic model hyperventilation; overcompensation of acid/ of the major ev~nts in absorption, redistribu­ base disturbances; dehydration and over­ tion, biotransformation, and excretion of· hydration in attempts at forced diuresis; toxic substances in the body. The substances obstruction of a main stem bronchus causing are absorbed through mucous membranes of collapse of the lung, arteriovenous shunting, the lung or the gastrointestinal tract i11to the and hypoxemia; and rupture of an emphyse­ systemic circulation. Water-soluble substances matous bleb with tension pneumothorax. may be excreted directly by the kidney. Monitoring of central venous pressure by way Lipid-soluble substances may be excreted by of a subclavian puncture has