Poisoning & Overdose

 

• Types

  • Poisoning can be acute or chronic, and deliberate or accidental. The route can be oral (drugs), inhaled (smoke), percutaneous (cyanide, organophosphates), or ocular (industrial chemicals).
  • Most poisoning involves deliberate self-harm, using oral drugs, in young adults. Poisoning in children, however, is usually accidental.
  • The commonest cause of toxicity in most developed countries is covered elsewhere: see paracetamol overdose

• Management

  Planning treatment:

  • Serum levels of the substance are important, but severity of symptoms usually determines management.
  • Toxbase is a useful resource.

  Methods

  Gastric decontamination:

  • Aims to reduce absorption.
  • Only used if there is a high risk of severe complications, and it is only useful within 1 hour of ingestion.
  • Activated charcoal is the commonest method. Gastric aspiration ± lavage ('stomach pump') is only used if charcoal is ineffective and it is a very large OD. Induced emesis is never used.
  • Cannot be used if there is reduced consciousness – due to risk of aspiration – unless the airway is protected.

  Increasing drug elimination:

  • Aims to reduce drug half life.
  • Multiple dose activated charcoal is the commonest method
  • Haemodialysis is also used, but is only effective if the drug is still in the blood. It is not always widely available. Used for ethylene glycol (antifreeze), salicylates, methanol, valproate, and lithium. Haemoperfusion is a related method which runs the blood past activated charcoal.

  Secondary prevention:

  • Avoid long-term prescriptions.
  • Switch to safer medications e.g. from TCA to SSRI.

• Activated charcoal

  Mechanism

  Adsorbs poison i.e. poison molecules adhere to its surface.

  Dose and route

  • Dose: 10 x the dose of the poison taken, up to 50 g.
  • Drunk PO in a solution. Can be given NG, but carries aspiration risk.

  Contraindications

  • Absent bowel sounds i.e. ileus.
  • Impaired gag reflex.
  • Unsafe swallow e.g. due to ↓consciousness.
  • Ineffective for iron, lithium, or alcohol overdoses.

  Complications

  • Aspiration pneumonitis.
  • ↓Absorption of therapeutic drugs.
  • Briquette formation leading to bowel obstruction.

  Multiple dose activated charcoal (MDAC)

  • Give further dose every 2 hours along with laxative to reduce enterohepatic circulation and osmotically draw toxin from blood back into bowel ('GI dialysis').
  • Effective for CBZ, phenobarbitone, theophylline, and quinine. May be useful for salicylates and phenytoin.

• Salicylate poisoning

  Pathophysiology

  • Usually aspirin.
  • Uncouples oxidative phosphorylation causing metabolic acidosis.
  • Also directly stimulates CNS respiratory centre causing ↑RR and respiratory alkalosis.

  Signs and symptoms

  ASA-DOSE:

  • Agitation or delirium.
  • Sweating
  • Auditory symptoms: tinnitus or deafness.
  • Dizziness
  • Overbreathing: ↑RR due to CNS effect or response to metabolic acidosis.
  • Seizures and coma.
  • Emesis

  Investigations

  • Plasma salicylate levels. Repeat every 2 hours until it peaks, which can take up to 6 hours.
  • U+E: ↓K+, AKI if severe.
  • ↓Glucose
  • ABG and HCO3-: initially alkalosis, later acidosis.

  Management

  ABCD:

  • Activated charcoal ± MDAC.
  • Sodium Bicarb for urine and serum alkalinisation: ionises salicylates so they can't cross blood-brain barrier, and can't escape renal tubules so are eliminated from circulation.
  • Correct glucose and K+ deficits.
  • Dialysis if: ↓pH, ↑↑salicylates, AKI.

• Tricyclic antidepressant (TCA) poisoning

  Epidemiology

  • TCA overdoses are rare – as the drug is not widely used now – but very dangerous.
  • In contrast, SSRI overdoses are commoner, but much less likely to be fatal.

  Signs and symptoms

  Anticholinergic effects:

  • Hot dry skin.
  • Mydriasis: dilated pupils.
  • ↑HR
  • Urinary retention.
  • Agitation and delirium.
  • Neurological: seizures, coma, hypertonia, hyperreflexia.

  Anti Na+ channel effects:

  • Arrhythmias, including VT and VF.
  • Cardiac arrest.
  • Heart block.

  Anti α-adrenergic effects:

  • ↓BP

  Investigations

  • ECG: wide QRS, long QT, increased PR. Continue to monitor if large OD or initial abnormality found.
  • U+E
  • Glucose
  • ABG: metabolic acidosis secondary to seizures and/or tissue hypoxia from ↓cardiac output.

  Management

  • Activated charcoal (± MDAC) if <2h since ingestion.
  • Sodium bicarbonate to reverse Na+ channel blockade if QRS >100 ms or there is ventricular arrhythmia.
  • DC cardioversion, lidocaine, or MgSO4 if bicarb fails. Most other anti-arrhythmic drugs are contraindicated.
  • Benzodiazepines if there are seizures.
  • Lipid emulsion if peri-arrest.

• Benzodiazepine poisoning

  Signs and symptoms

  • Drowsy. In severe cases, coma.
  • Neurological impairment, including motor impairment, diplopia, slurred speech, and ataxia.
  • Anterograde amnesia.
  • Rarely, paradoxical symptoms: anxiety, delirium.
  • ↓RR, which would suggest a combined OD.

  Management

  • Supportive treatment, especially airway.
  • Activated charcoal only if BZD taken in combo with something else.
  • Flumazenil is the antidote.

  Flumazenil

  Mechanism:

  • BZD receptor antagonist, which mainly acts to reverse CNS depression.

  Indications:

  • Severe OD – with marked impairment of consciousness or respiratory distress – in a first time or infrequent user.
  • In practice, it is most likely to be used for iatrogenic overdoses, when we can be sure that they are not long-term users and it is not a mixed overdose.

  Contraindications due to seizure risk:

  • BZD-dependant patients.
  • Mixed TCA OD.
  • Epilepsy history.

  Dose and administration:

  • Use the minimum effective dose.
  • Apply ECG monitoring when giving flumazenil as it may unmask an arrhythmia, especially if patient on TCA or carbamazepine.

  Half life is less than BZD, so may wear off first.

• Iron poisoning

  Rare but serious as iron is corrosive.

  Signs and symptoms

  • Early (0-6 hours): GI symptoms including nausea, vomiting, diarrhoea, and abdo pain.
  • Delayed (2-72 hours): black stools, circulatory collapse, and CNS symptoms including drowsiness, seizures, and coma.
  • Late (2-4 days): liver and kidney failure.
  • Very late (2-5 weeks): gastric stricture.

  Investigations

  • Establish amount of elemental iron from history.
  • Fe level, taken at least 4 hours after ingestion, then repeated 2-hourly.
  • ↑WBC
  • ↑Glucose
  • U+E and LFT.
  • Daily monitoring: clotting, HCO3-.

  Management

  • Gastric lavage.
  • Desferrioxamine is the antidote.

  Desferrioxamine (aka deferoxamine)

  • Chelates Fe, which is then excreted as red urine.
  • Indicated in severe OD, characterized by ↓consciousness, seizures, shock, metabolic acidosis, GI bleed.
  • Contraindicated in kidney failure.
  • Can cause ↓BP and pulmonary oedema.

• Organophosphate poisoning

  Pathophysiology and epidemiology

  • Relatively common suicide method in developing world, taken in the form of fertilizer. Also used as chemical weapon (sarin, VX).
  • Percutaneous or oral entry → cholinesterase inhibition → ↑acetylcholine (ACh) levels → parasympathetic activation, NMJ depolarization, and CNS dysregulation.

  Signs and symptoms

  DUMBELLS:

  • Diarrhoea
  • Urination
  • Miosis
  • Bradycardia, Bronchospasm, Bronchorrhea. The 'killer Bs' most likely to cause death.
  • Emesis
  • Lacrimation
  • Lethargy
  • Salivation

  Other symptoms:

  • Muscle: fasciculations and weakness.
  • Blurred vision.

  Investigations

  • ↓Serum and RBC cholinesterase.
  • Atropine therapeutic trial.

  Management

  • Decontaminate patient, while wearing personal protective equipment.
  • Atropine IV.
  • Contact public health authorities.
  • Pralidoxime – a cholinesterase reactivator – is the antidote. Use in severe poisoning.