In Excess – Death and Toxicology
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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

Dr Ian Whyte, FRACP

Hunter Area Toxicology Service


Clinical toxicology
Clinical Toxicology

  • Medical specialty concerned with the effects of drugs and toxins (poisons) on humans

    • paediatricians

    • accident and emergency specialists

    • occupational physicians

    • clinical pharmacologists


Paracelsus 1493 1541
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


Mle 32 years old
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


On arrival at hospital
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


Glasgow coma scale
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


Coma level
Coma level

  • Designed to assess current conscious level

  • Assesses

    • response to external stimuli

      • voice

      • touch

      • pain

    • blood pressure (BP)

    • breathing



Progress 19 7 94
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


Note detail
Note (detail)


Progress 19 7 941
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


Progress 20 7 94
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


Progress 20 7 94 cont
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


Progress 21 7 94
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



Evidence based toxicology
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


Hats database
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)


Hats database1
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



Coma level less than 6 hours
Coma level (less than 6 hours)


Coma level 6 hrs or more
Coma level (6 hrs or more)


Toxicoepidemiology
Toxicoepidemiology

  • Changes in drug regulation

    • Nembudeine removed

    • Chloral hydrate withdrawn

  • Relative toxicity

    • Differences in toxicity between

      • antidepressant drugs

      • sedative drugs

      • antihistamines


Repackaging
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)


Teaching toxicology
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


Paracetamol

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


Paracetamol deaths
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


Paracetamol deaths1
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


Paracetamol deaths2
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


The future
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


The future1
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


Admission
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)



Hats database2
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


Paracelsus
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


Paracelsus healthcare
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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