Postmortem diffusion of drugs from the bladder into femoral venous blood

doi:10.1016/S0379-0738(01)00530-8

Forensic Science International

Volume 123, Issues 2–3, 1 December 2001, Pages 248-253

https://doi.org/10.1016/S0379-0738(01)00530-8 Get rights and content

Abstract

We describe significantly elevated drug concentrations in the femoral venous blood due probably to postmortem diffusion from the bladder. A 16-year-old deceased male was found in a shallow ditch in winter. The estimated postmortem interval was 9 days and putrefaction was not advanced. The cardiac chambers contained fluid and coagulated blood and a small amount of buffy coat clots. Diffused hemorrhages were found in the gastric mucosa. The bladder contained approximately 600 ml of clear urine. Gas chromatographic–mass spectrometric analysis of the urine disclosed allylisopropylacetylurea (a fatty acid ureide sedative), diphenhydramine, chlorpheniramine and dihydrocodeine. The cause of death was considered to be drowning due to a drug overdose and cold exposure. The concentrations of diphenhydramine, free dihydrocodeine and total dihydrocodeine in the femoral venous blood (1.89, 3.27 and 3.30 μg/ml, respectively) were much higher than those in blood from the right cardiac chambers (0.294, 0.237 and 0.240 μg/ml, respectively). Urine concentrations of diphenhydramine, free dihydrocodeine and total dihydrocodeine were 22.6, 37.3 and 43.1 μg/ml, respectively. The stomach contained negligible amounts of diphenhydramine, free dihydrocodeine and total dihydrocodeine (0.029, 0.018 and 0.024 mg, respectively); concentrations of these drugs in the femoral muscle were 0.270, 0.246 and 0.314 μg/g, respectively. These results indicate that postmortem diffusion of diphenhydramine and dihydrocodeine from the bladder resulted in the elevated concentrations of these drugs in the femoral venous blood. Not only high urinary drug concentrations but also a large volume of urine in the bladder might accelerate the postmortem diffusion.

Introduction

Postmortem blood drug concentrations are often site-dependent because of the postmortem release and redistribution of drugs from the lungs and liver [1], [2], diffusion of drugs from the stomach and trachea [3], [4], [5], [6], [7], [8] and postmortem metabolism or degradation of drugs [9], [10], [11], [12]. Drugs are usually quantified in peripheral, especially femoral venous blood, because it is generally affected to a lesser extent compared to so-called “central” blood by postmortem redistribution and diffusion [4], [5].

In this communication, we describe obviously elevated drug concentrations in the femoral venous blood due presumably to postmortem diffusion from the bladder.

Section snippets

Case history

A 16-year-old male (178 cm tall and weighing 77 kg) was found dead in a sitting position with the head facing the downstream in a concrete ditch (5 m wide and 1 m deep) in winter by a passer-by. His clothing was in order. Autopsy estimated the postmortem interval as 9 day, although putrefaction was not advanced. “Washerwoman’s” skin was apparent on the hands and feet. Subcutaneous hemorrhages were evident in the back of the hands and in the knees. No petechial hemorrhages were observed in the

Urine screen and confirmation

Urine was screened directly using Triage^TM Drugs of Abuse Panel plus Tricyclic Antidepressants (Biosite Diagnostic Inc., San Diego, CA) and processed for screening by gas chromatography (GC) and gas chromatography–mass spectrometry (GC–MS) as described [13].

A Shimadzu GC (GC-14B, Kyoto, Japan) was equipped with a TC-1 capillary column (dimethyl silicone, 15 m by 0.53 mm i.d., 1.5 μm film thickness (GL Sciences Inc., Tokyo, Japan)), a TC-5 capillary column (5% phenylmethyl silicone, 15 m by 0.53 mm

Results

The retention times were 3.9 and 11.0 min for allylisopropylacetylurea and the internal standard, respectively, on the quantitative TC-1 capillary column, 9.5, 11.1 and 12.0 min for diphenhydramine, chlorpheniramine and the internal standard, respectively, on the TC-17 column, and 9.4 and 9.8 min for trimethylsilyl derivatives of the internal standard and dihydrocodeine, respectively, on the TC-5 column. No peaks interfered with any of the tested specimens. Gas chromatograms of extracts from the

Discussion

High concentrations of drugs in the lungs and liver of corpses may be released postmortem into the blood vessels, and then blood containing these high concentrations may move into neighboring blood vessels to various degrees [2], [14]. Another factor affecting postmortem drug concentrations in blood in the torso and abdominal vessels is diffusion from the stomach [4], [5]. However, the contribution of this postmortem factor may be negligible in the present study because the stomach contained

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Regarding ethanol concentration in abdominal cavities, organs and vessels, this raises a question about the negative ethanol concentration in urine: why ethanol won’t be capable of crossing the bladder wall? To our knowledge, only one case report described PM diffusion of drugs (diphenhydramine and dihydrocodeine) from the bladder into venous blood [4], but no case has been described with diffusion from peripheral blood or from abdominal cavity into the bladder. In our case, diffusion of ethanol through the bladder wall may have been prevented by inhibiting factors such as refrigeration, and the absence of thinning of the bladder wall, because the bladder was relatively empty (only 45 ml of urine).
In the realm of forensic pathology, ethanol is one of the most frequently encountered xenobiotics. The determination of ethanol concentration in blood after death is of great interest in forensic settings. It is important to be able to determine the level of intoxication of the deceased at the time of death, which is directly correlated to the ability to act prior to death, especially when a suicide is suspected. This estimation is not always easy to establish owing to various artifacts that are important to know for a proper ethanol blood level interpretation, among them postmortem (PM) diffusion. We describe here a case of unusual ethanol distribution in body compartments and discuss the importance of PM diffusion and redistribution while performing complementary toxicological analysis, especially when the blood and urine samples seemed to be inconsistent after the first results.
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Due to a lack of reference values for blood concentration of metformin in the literature, the forensic evaluation of metformin findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested metformin amounts are often vague. Furthermore, post mortem evaluation of death due to lactic acidosis because of metformin is difficult since renal performance or lactate concentrations can not always reliably be determined after death.
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Postmortem concentrations of drugs do not necessarily reflect their concentrations at the time of death. They may vary according to the sampling site and the interval between death and the time of sample. These site- and time-dependent variations are called “postmortem redistribution”. The underlying mechanisms are complex and multifactorial. Passive drug release from drug reservoirs (e.g. gastro-intestinal tract, liver, lungs, myocardium) may occur immediately after death. Later, autolysis and putrefactive processes participate in the redistribution. The physicochemical and pharmacokinetic profile of xenobiotics appears to be a determining factor, but these aspects are less well known. The author presents the latest advances in the field.
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The methods for quantifying cocaine and its major metabolite benzoylecgonine, implemented in different biological matrices, make it possible to study distribution both analytes at postmortem. Among the studied matrices, the following neurological tissues are highlighted: the accumbens nucleus, the tegmental ventral area, and cerebrospinal fluid. Gas chromatography–mass spectrometry methods and statistical analysis are implemented to study the distributive behavior of cocaine and benzoylecgonine showing interesting correlations for the concentrations of cocaine and benzoylecgonine between the matrices of neurological tissues and other tissues more commonly used.
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The methods for quantifying cocaine and its major metabolite benzoylecgonine, implemented in different biological matrices, make it possible to study distribution both analytes at postmortem. Among the studied matrices, the following neurological tissues are highlighted: the accumbens nucleus, the tegmental ventral area, and cerebrospinal fluid. Gas chromatography–mass spectrometry methods and statistical analysis are implemented to study the distributive behavior of cocaine and benzoylecgonine showing interesting correlations for the concentrations of cocaine and benzoylecgonine between the matrices of neurological tissues and other tissues more commonly used.
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La correcta interpretación de los resultados toxicológicos post mórtem debe ser capaz de ofrecer una explicación sobre el significado y la trascendencia de los resultados analíticos obtenidos en el caso forense estudiado. El ajuste de la interpretación de resultados a la realidad de los hechos acontecidos será función de la calidad de la muestra analizada y de los resultados analíticos y del conocimiento de la existencia diversos fenómenos post mórtem y de las circunstancias en la que ocurrió la muerte. Todo el proceso está dificultado por la inexistencia de recomendaciones o protocolos que guíen al toxicólogo en el proceso de la interpretación. Constituye, por tanto, la etapa más compleja de la investigación toxicológica. Con el objetivo de ayudar al toxicólogo forense en esta tarea, se presenta esta revisión bibliográfica sobre los conocimientos existentes.
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Case reportPostmortem diffusion of drugs from the bladder into femoral venous blood

Abstract

Introduction

Section snippets

Case history

Urine screen and confirmation

Results

Discussion

Forensic Sci. Int.

Forensic Sci. Int.

Forensic Sci. Int.

Leg. Med.

Redistribution of basic drugs into cardiac blood from surrounding tissues during early-stages postmortem

J. Forensic Sci.

Postmortem diffusion of alcohol from the stomach

Am. J. Forensic Med. Pathol.

Postmortem diffusion of drugs from gastric residue: an experimental study

Am. J. Forensic Med. Pathol.

Differences between multisite postmortem ethanol concentrations as related to agonal events

J. Forensic Sci.

Postmortem diffusion of tracheal lidocaine into heart blood following intubation for cardiopulmonary resuscitation

J. Forensic Sci.

Case report
Postmortem diffusion of drugs from the bladder into femoral venous blood