SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

P64
THE USE OF CLUSTER ANALYSIS TO ESTABLISH A REFERENCE RANGE FOR BETA­
HYDROXYBUTYRATE CONCENTRATIONS IN POSTMORTEM BLOOD AND ITS
APPLICATION TO THE INVESTIGATION OF SUDDEN UNEXPECTED DEATH IN PROBLEM
DRINKERS
A Robert W Forrest* & Daniel Cooper. Forensic Pathology Unit, University of Sheffield, Medico-legal
Centre, Watery Street, Sheffield S3 7ES, UK
Alcoholic ketoacidosis is a relatively common cause of death in problem drinkers. (l) It should be
considered in every case of sudden unexpected death in a problem drinker, particularly if hepatic steatosis
(a fatty liver) is present and "routine" toxicology screening is unrevealing. An important clue may be a
trace of acetone apparent on the ethanol assay chromatogram in association with a low or zero alcohol
concentration. If the toxicologist or pathologist have any degree of suspicion that the death might be
associated with alcoholic ketoacidosis, then beta-hydroxybutyrate should be measured in post mortem
blood.
Whilst the diagnosis of alcoholic ketoacidosis is straightforward when the beta-hydroxy butyrate
concentration is grossly elevated in post mortem blood, the interpretation of the borderline result may be
difficult. In life, clinical laboratories typically quote the upper limit of normal for the fasting plasma betahydroxybutyrate
concentration as from 300 to 600 micromoles per litre. Unfortunately, whilst in principle it
should be a simple matter to establish a reference range for the beta-hydroxy butyrate concentration in postmortem
blood, in practice, for those working in England and Wales, this is fraught with difficulty. Most
post-mortem examinations are non-consensual, carried out under the direction of the coroner. In the
analysis of samples collected during such post-mortems, it is only permitted to carry out analyses directed
at establishing who the deceased was and where and when he came to his death without the specific
permission of the coroner and the relatives of the deceased. Whilst a "black letter" interpretation of the
present law is arguably more liberal, those who have retained specimens obtained at a coroner's postmortem
for research or teaching have been subject to considerable public criticism in the UK. (2). The
practicalities of obtaining permission from the relatives of the deceased who is about to be subject to a
coronial post mortem examination are daunting. If legislation currently before the UK Parliament becomes
law in its present form, then the researcher who analyses a post mortem blood sample without permission
will be liable to prosecution with a possible penalty of up to 3 years in prison on conviction. (3)
Consequently it is necessary to make the best possible use of the data obtained when investigating any
particular case to inform the interpretation of future cases. One approach that we have found useful is to use
cluster analysis of all of the data we have obtained in the investigation of possible cases ofalcoholic ketosis
to delineate normal, equivocal and elevated beta-hydroxybutyrate concentrations in post-mortem blood. We
further believe that the technique may be of more general application in the analysis of post-mortem
toxicology data. To illustrate the technique we present the analysis of our data in relation to the
investigation of alcoholic ketoacidosis and, more briefly, possible overdoses of diphenhydramine and
tramadol.
References:
I. Pounder DJ, Stevenson RJ, Taylor KK. Alcoholic ketoacidosis at autopsy. Journal of Forensic
Sciences 1998;43(4):812-6.
2. Metters J. Isaacs Report. London; 2003. http://www.publications.doh.gov.uklcmolisaacsreport/
3. Human Tissue Bill.
2003/4.http://www.publications.parliament.uklpalcm200304/cmbills/049!2004049.htm
Keywords: alcoholic ketoacidosis, beta-hydroxy butyrate, cluster analysis
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