Poisons and Poisoning

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Poisons and Poisoning

• Dr Ian Wilkinson
• Clinical Pharmacology Unit

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Accidental?
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Deliberate?
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Suicides in the UK

• 6,300 suicides pa
• 20 of deaths in young people
• 140,000 attempted suicides (parasuicides)
• Most common 15-19 year old females
• Most common method is poisoning
• 50 paracetamol

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General Comments

• Try and get as much history as possible including
  witnesses
• People truly wanting to commit suicide often lie
• Remember the ABCs
• Airway Clear mouth throat, gag reflex
• Breathing O2 saturation, ABGs
• Circulation Venous access, IV fluids if shocked
• Assess GCS
• Examination

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History

• When, what, how much ?
• Why?
• Circumstances
• PMHx, Drug history
• Psychiatric history
• Assess mental status and capacity

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Care with names!

• Distalgesic
• Anadin

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Investigations

• Always check blood glucose.
• Send blood urine for toxicology screening.
• ALWAYS measure paracetamol salicylate levels
• Failure to diagnose treat is negligent.
• UEs, LFTs, glucose, ABG, clotting, bicarbonate
• ECG, CXR
• Specific blood levels

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Management

• Supportive
• Correct hypoxia, hypotension, dehydration, hypo-
  hyperthermia, and acidosis
• Control seizures
• Monitor
• TPR, BP, ECG, Oxygenation, GCS
• General
• ? Absorption
• ? Elimination
• Specific antidotes

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? Absorption

• NEVER Ipecacuanha
• Gastric lavage
• Only if within 1 hour life-threatening amount
• Never for corrosives
• If ? LOC intubate
• Activated charcoal
• 50 g single or repeated dose (? elimination)
• Doesnt bind heavy metals, ethanol, acids

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? Elimination

• Multiple dose activated charcoal
• Quinine, phenobarbitone
• Charcoal haemoperfusion
• Barbiturates, theophylline
• Diuresis
• Urinary alkalinization
• Dialysis

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Paracetamol Overdose

• Most common drug taken in overdose
• Few symptoms or early signs
• As little as 12g can be fatal
• Hepatic and renal toxin
• Centrolobular necrosis
• More toxic if liver enzymes induced or reduced
  ability to conjugate toxin

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Paracetamol Metabolism
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Management

• General measures including
• UEs, LFTs, glucose, clotting ABG, bicarbonate,
  paracetamol and salicylate levels
• Activated charcoal
• lt8 hours
• Take level after four hours
• Start N-aceylcysteine if above treatment line
• Patients are usually declared fit for discharge
  from medical care on completion of its
  administration. However, check INR, creatinine
  and ALT before discharge. Patients should be
  advised to return to hospital if vomiting or
  abdominal pain develop or recur

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Management 2

• gt8 hours
• Urgent action required because the efficacy of
  NAC declines progressively from 8 hours after the
  overdose
• Therefore, if gt 150mg/kg or gt 12g (whichever is
  the smaller) has been ingested, start NAC
  immediately, without waiting for the result of
  the plasma paracetamol concentration
• gt24 hours
• Still benefit from starting NAC

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Treatment Graph
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N-acetylcysteine

• Supplies glutathione
• Dosage for NAC infusion - ADULT
• (1) 150mg/kg IV infusion in 200ml 5 dextrose
  over 15 minutes, then
• (2) 50mg/kg IV infusion in 500ml 5 dextrose over
  4 hours, then
• (3) 100mg/kg IV infusion in 1000ml 5 dextrose
  over 16 hours
• Side-effects
• Flushing, hypotension, wheezing, anaphylactoid
  reaction
• Alternative is methionine PO (lt12 hours)

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Aspirin Overdose

• Early features
• hyperventilation, sweating, tremor, tinnitus,
  nausea / vomiting, or hyperpyrexia
• Metabolic features
• Hypo- or hyper-glycaemia, hypokalaemia,
  respiratory alkalosis, metabolic acidosis
• Others
• renal failure, pulmonary oedema, seizures, coma,
  death

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Management

• General measures
• Bloods
• Salicylate (paracetamol) level gt2 hours, and
  after 2hrs
• gt700 potentially lethal
• gt500 moderate-severe poisoning
• UEs, glucose, ABG, bicarbonate
• Activated charcoal
• Rehydrate, monitor glucose, correct acidosis and
  K
• If levels gt500mg/L alkalanize urine (HCO3-)
• Levels gt 700 mg/L before rehydration, renal
  failure or pulmonary oedema consider
  haemodialysis

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TCAs -Introduction

• Potentially fatal (2.5 to 3.5g of amitriptyline)
• Neurological and cardiac problems common
• Toxicity due to anticholinergic actions, and
  direct quinidine-like effect on the myocardium
• Serious toxicity results from-
• Ventricular dysrhythmias
• Seizures
• Hypotension
• Respiratory depression
• Initial symptoms at presentation may be trivial,
  and most major problems occur within 6hrs

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TCAs-Features of poisoning

• Peripheral
• Sinus tachycardia, hot dry skin, dry mouth,
  urinary retention, hypotension and hypothermia
  may occur
• CNS
• Dilated pupils, ataxia, nystagmus, squint, ?LOC,
  coma, seizures, respiratory depression, ?tone, ?
  ?reflexes, ? plantars
• ECG
• prolonged PR and QRS interval, ? QT
• ventricular dysrhythmias

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TCAs -Management

• GCS and QRS, best indicators of toxicity
• Supportive
• do not use flumazenil if benzo taken
• Check airway, maintain ventilation, correct
  hypoxia
• Check ABG, if ? CO2 requires ventilation
• Correct hypotension (crystalloids)
• Gastric lavage if within 1 hr, and activated
  charcoal
• Rx fits and agitation with diazepam
• Rewarm slowly if hypothermic
• Close monitoring for 24hrs

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TCAs- Dysrhythmias

• Carful ECG monitoring is required
• QRS interval is a guide to cardiac toxicity
  (gt100ms)
• Avoid antidysrhythmic drugs. They may make
  matters worse
• Correct hypoxia and acidosis. Aim for a pH of
  7.45-7.50 (no higher)
• use iv boluses of sodium bicarbonate
• Sodium loading may also help
• Prolonged CPR may be of use

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Tricyclic OD Initial ECG
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Tricyclic OD Recovery ECG
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Benzodiazepine Overdose

• Deaths from poisoning with benzodiazepines alone
  are rare, but may be lethal in combination with
  other CNS depressants
• Treatment is supportive and aimed at maintaining
  adequate ventilation whilst supporting
  cardiovascular depression
• Flumazenil (specific benzodiazepine antidote) is
  not licensed (in the UK) for routine use in
  benzodiazepine overdoses
• Flumazenil may induce seizures particularly
  dangerous where tricyclic antidepressants have
  been taken
• Flumazenil, may however, be used in the
  differential diagnosis of unclear cases of
  multiple overdoses but expert advice is ESSENTIAL.

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Other agents

• Opiates Naloxone
• Iron Desferrioxamine
• Lead Sodium EDTA
• Digoxin FAB
• Calcium blockers Calcium
• Ethylene glycol Ethanol
• Lithium Dialysis