Under The Microscope: 'Like with Like'.

 

Many publications offer therapeutic, toxic and lethal ranges for a wide variety of poisonous substances, there is considerable variation in the quoted levels. These can be a source of confusion and sometimes dismay to the pathologist who, even with the advice of his local toxicologist, may find it difficult to decide whether a death can justifiably be attributed to a particular drug or other toxic substance. Even if he can so satisfy himself, he may be subjected to keen questioning, interrogation, doubt or criticism from colleagues, coroners, police, lawyers and others, who have access to different versions of toxic and fatal levels. The ultimate challenge may come in a criminal court, where opposing counsel may openly defy the pathologist's interpretations in cross-examination. There are some reasons for the variations found in such published data. He expresses the view that it is rather surprising that the order of disagreement is not greater, given the opportunities for disparity.

First, many of the published series are small, some being only individual case reports. Statistically, this is not a good foundation for establishing reference ranges, which are much better obtained from a database derived from the cumulative results of a large laboratory service, such as the British Home Office Forensic Science Service, which maintains a central computer store of all results from its laboratories. Second, analytical techniques vary widely, both in method and accuracy. The specificity varies from laboratory to laboratory so that there may be a lack of uniformity about what is actually being measured. For example, paracetamol may be measured by a non-specific method that picks up its metabolites as well as the native drug, which will then offer a different blood level in a fatal case from that found by more specific methods. In other words, one is not comparing 'like with like'.

The site of sampling may introduce wide errors. With some substances, a several-fold variation in concentration may be found between femoral vein and cardiac cavity blood. Last, errors occur because a 'fatal' level may be attributed to one substance without taking into account the level - or even the existence - of other toxic substances that the deceased may have taken, and of which the pathologist or analyst may not even have been aware. For example, the newer more potent benzodiazepines may be missed in a simple toxicological screen, but could well have contributed to the toxicological overload that caused the patient to die. In such a case, the level of the recognized drug would be blamed for the death, whereas in fact it may not have been a lethal dose in itself, though was recorded as such in any database or tables.

 

These facts highlight the dangers of limiting a request for analysis solely to the substance known or thought to have been taken. Often an efficient screen for other substances will reveal other unsuspected compounds, sometimes more toxic than the one originally suspected.

 

It has to be recognized, however, that, in many jurisdictions, the availability and expense of toxicological investigations may make it impossible to pursue a full analytical survey, especially if this is to be undertaken on a speculative basis rather than for quantification of a known or strongly suspected toxic agent. A full screen may only be practicable and justified in a suspected homicide, if laboratory facilities and fiscal support are severely restricted. In many countries homicide by poison is relatively rare and the funds to investigate accidental, suicidal and iatrogenic poisoning exhaustively may just not be available.

 

The autopsy in these circumstances can be amongst the most difficult of problems faced by a forensic pathologist - not in the technical procedure of the examination, but in the final evaluation of all the available information. The nature of the poisoning autopsy in Western countries has changed dramatically since the last century, when poisoning was a common method of homicide. There has been a marked change in the nature of poisons used in murder, suicide and accident: The corrosives, heavy metals and alkaloids commonly ingested in former years became relatively easy to detect, either by gross autopsy appearances or by straight-forward analytical methods. Further refinements of toxicological techniques, instead of the old methods in which large samples had to be tested because of the insensitivity of laboratory tests, the detection of nanogram quantities.

 

Acids, alkalis, phenols, arsenic, antimony and strychnine, for example, became easy to detect, and in the Western world these gave way to compounds that leave little or no gross, or even histological changes in the body. Most are pharmaceutical or agrochemical substances, active in low dose compared to the old 'blockbuster' poisons. As for the majority of drugs used in legitimate medical therapy, an added problem arises when low post-mortem levels are found - is this merely a therapeutic dose or the tail end of a declining lethal dose? In some parts of the world, such as South-east Asia, Africa and the Indian subcontinent, poisoning remains common and more physically damaging substances continue to be seen that leave obvious autopsy lesions. Some of these are described under the appropriate headings in the succeeding chapters, but in most poisonings the major function of the autopsy is to evaluate any other conditions present, both from trauma and natural disease - but also to collect suitable material for laboratory analysis. The proper retention of optimal samples, their correct preservation and dispatch to the toxicologist are of such fundamental importance that they are discussed in detail.

A considerable proportion of those who die from suspected poisoning will have died in hospital, and it is of prime importance that the medical records be obtained and studied before the autopsy begins. Even if poisoning was not confirmed or even suspected by the clinicians treating the patient, later information may have come to the pathologist to raise this possibility. Whether known or not, the results of ante-mortem investigations may be of considerable use to the pathologist. If poisoning was known or suspected before death, there may well have been toxicological analyses performed and the results of these may be of great value . Whether poisoning was suspected or not, there may still be ante-mortem blood or urine samples (taken for bio- chemical or haematological tests) stored in the hospital laboratory, which may be rescued for retrospective analysis. Such ante-mortem samples are likely to be of greater use than fluids drawn off at autopsy, because of sampling defects, post-mortem changes and because toxic levels are likely to have been higher during life, representing more accurately the maximum toxic concentrations. In addition, many patients dying in hospital from drug overdoses will have indwelling catheters in place. It is the common practice for the nursing staff to remove these at death and discard the urine. If it is possible to establish a practice in the wards where such terminal urine samples are saved, valuable material for analysis can be obtained.

The investigation of a death from suspected poisoning may stand or fall upon the correctness or otherwise of the sampling of fluids and tissues from the body. Unsuitable samples, inadequate amounts, incorrect sampling sites, poor containers, inadequate preservation methods, and delayed or unsatisfactory storage and transport to the laboratory may frustrate or distort proper analysis. The final outcome may be wrong, either in Failing to detect a poison actually present, in measuring only part of that originally present or - in some cases - even producing falsely high results that then lead to an incorrect cause of death. Not only must samples be in the optimal condition, but the accompanying information from the pathologist to the analyst needs to be as accurate and comprehensive as possible, so that the most appropriate techniques are used, and allowance made for any interfering substances that may be present.

 

In decomposed bodies infested with maggots, and in the absence of tissues or fluids normally taken for toxicology, Diptera and other arthropods can be used as alternative specimens for toxicological analyses. This relatively new field of forensic entomology is called entomotoxicology.

 

Acknowledgements:

www.politie.nl  Politiekorpschef  @Janny Knol©

www.aived.nl    AIVD – @Erik Akerboom ©

www.politie.nl WEB Politie - @Henk van Essen©

 

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