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In Excess – Death and Toxicology The interface between clinical toxicology, forensic sciences and the law

In Excess – Death and Toxicology The interface between clinical toxicology, forensic sciences and the law. Dr Ian Whyte, FRACP Hunter Area Toxicology Service. Clinical Toxicology. Medical specialty concerned with the effects of drugs and toxins (poisons) on humans paediatricians

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In Excess – Death and Toxicology The interface between clinical toxicology, forensic sciences and the law

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  1. In Excess – Death and Toxicology The interface between clinical toxicology, forensic sciences and the law Dr Ian Whyte, FRACP Hunter Area Toxicology Service

  2. Clinical Toxicology • Medical specialty concerned with the effects of drugs and toxins (poisons) on humans • paediatricians • accident and emergency specialists • occupational physicians • clinical pharmacologists

  3. Paracelsus (1493–1541) • All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy • Justice is like poison; whether it kills or heals depends on the dosage • Stephen J. Nardi, US criminal defence lawyer • http://www.nocolpa.com/quotes.html

  4. MLE (32 years old) • Alcoholic father killed his mother (MVA) when he was 3 • State ward in multiple institutions with repeated physical and sexual abuse • Cerebral aneurysm rupture in 1988 • on carbamazepine (Tegretol) for seizures • Alcoholic for 15 years – 18–36 cans of beer a day

  5. On arrival at hospital • 19/7/94 1440 hours • Arrived by ambulance • Found unconscious in police cell • No response to Naloxone • ? Stroke, ? Drug overdose • Unconscious • Coma level 2 • Glasgow coma scale 3/15

  6. Glasgow coma scale • Developed in Scotland to help predict long term outcome of head injury • Assesses • eye response (Nil, 1 – Spontaneous, 4) • motor response (Nil, 1 – Obeys, 6) • voice response (Nil, 1 – Oriented, 5) • Maximum 15/15 • Minimum 3/15

  7. Coma level • Designed to assess current conscious level • Assesses • response to external stimuli • voice • touch • pain • blood pressure (BP) • breathing

  8. Coma level

  9. Progress 19/7/94 • 1800 hours • Carbamazepine concentration 335 μmol/L • therapeutic range 20–50 μmol/L • 2100 hours • Police phone call concerning a note found in the patient’s wallet

  10. Note (detail)

  11. Progress 19/7/94 • 2210 hours • gastroscopy performed because of delayed absorption • small amounts of dispersible white powder throughout stomach • 2230 hours • stomach washed out and activated charcoal given regularly to bind the carbamazepine

  12. Progress 20/7/94 • Stable during day • 1700 hours • rapid irregular heart rhythm disturbance with partial response to usual treatment • given more potent drugs to slow heart • 1815 hours • slow rhythm disturbance and low blood pressure

  13. Progress 20/7/94 cont • 1845 hours • drugs to increase blood pressure to counteract drugs to slow heart rate • blood pressure and pulse now “stable” • 2300 hours • blood pressure began to fall slowly in spite of drug treatment and without rhythm problems

  14. Progress 21/7/94 • 0100 hours • began having multiple epileptic seizures • seizures stopped • blood pressure fell very low • heart stopped • unable to be restarted • 0130 hours • deceased

  15. Carbamazepine

  16. Evidence based toxicology • If this single case was our only experience of carbamazepine poisoning then incorrect conclusions would be inevitable • Timely, accurate collection of data on multiple cases is essential • The Hunter Area Toxicology Service has been collecting such data on all admissions for poisoning since 1987

  17. HATS database • Database written in 1986 and began collecting data on 13/1/1987 • Since then there have been 6125 admissions • Of these, 5181 admissions were for deliberate self harm (drug overdose)

  18. HATS database • Of the 5181 admissions for deliberate self harm, 117 were for overdose of carbamazepine • Of these, 2 (1.7%) died • Overall 32 of 5181 (0.6%) died

  19. Time from overdose to admission

  20. Coma level (less than 6 hours)

  21. Coma level (6 hrs or more)

  22. Toxicoepidemiology • Changes in drug regulation • Nembudeine removed • Chloral hydrate withdrawn • Relative toxicity • Differences in toxicity between • antidepressant drugs • sedative drugs • antihistamines

  23. Repackaging • In 1993 the company changed from supplying carbamazepine in bottles of 100 tablets to blister packing • The median overdose before the change was 21 tablets (3–180) • The median overdose after the change was 12 tablets (1–200)

  24. Teaching toxicology • To assign cause of death when drugs or toxins are involved requires an understanding of toxicology • Lack of understanding will lead to errors

  25. Very safe in standard doses In overdose, more toxic compounds are produced than can be handled Signs of liver damage appear at 24 hours and peak at 2–3 days 85–95% Non–toxic compounds PARACETAMOL 5–15% Liver toxic compound SH Non–toxic compounds Paracetamol

  26. Paracetamol deaths • National Coronial data collection in the United Kingdom • Coroners’ returns to the Registrar General • Office of Population Censuses and Surveys • In 1990, 547 deaths were reported where paracetamol was mentioned

  27. Paracetamol deaths • Of the 547, 331 were found dead or were dead on arrival at hospital • These deaths are very unlikely to be due to paracetamol • A further 66 died in hospital but did not have any evidence of liver injury at autopsy • These deaths were not paracetamol

  28. Paracetamol deaths • Paracetamol is frequently combined with other pain relieving agents • codeine • dextropropoxyphene • is rapidly converted to a compound toxic to the heart • is the most likely cause of the early deaths • Paracetamol likely to have caused 150 deaths

  29. The future • National data collection and linkage • health services • toxicologists • accident and emergency departments • coroners • NCIS • forensic pathologists • MEMO project • http://www.ctlu.se/CTLU_MEMO.html

  30. The future • Better communication between services • Education in basic principles of toxicology for coroners and those assisting • More rigorous research in toxicology • Less reliance on reports of rare, if interesting, cases

  31. Admission • Had an epileptic seizure • CAT scan of head excluded a stroke • Admitted to the Intensive Care Unit • Intubated and ventilated • Thought to be a sedative drug overdose • Carbamazepine (Tegretol) • Diazepam (Valium)

  32. Carbamazepine (PJS)

  33. HATS database • Database began 13/1/1987 • We have had 6125 admissions • Of these, 5181 were for deliberate self harm (drug overdose) • Of these, 117 were for overdose of carbamazepine • Of these, 2 (1.7%) died • Overall 32 of 5181 (0.6%) died

  34. Paracelsus • All things are poisons, and nothing is without toxicity. Only the dose permits anything not to be poisonous. For example, every food and every drink is a poison if consumed in more than the usual amount: which proves the point. I admit that a poison is a poison; but that is no reason for condemning it outright

  35. Paracelsus Healthcare • Paracelsus Healthcare Corp. will pay $3 million to settle allegations that the hospital chain ran a revolving door drug rehabilitation clinic where some patients never saw a physician, said the U.S. Justice Department

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