5.4: Clinical Toxicology & Poisoning Management

General Resuscitation & Supportive Care

The primary directive in managing any poisoned patient is to treat the patient, not the poison. Resuscitation must follow the standard ABCDE (Airway, Breathing, Circulation, Disability, Exposure) algorithm. The vast majority of poisoned patients survive with high-quality supportive care alone. Key immediate priorities include:

• Airway Protection: Assessing the gag reflex and level of consciousness (Glasgow Coma Scale < 8 requires consideration for intubation, particularly if gastric decontamination is planned).
• Breathing: Monitoring oxygen saturation and respiratory rate, providing supplemental oxygen or mechanical ventilation if respiratory depression is present.
• Circulation: Establishing intravenous access, correcting hypotension with fluid resuscitation (e.g., 0.9% sodium chloride boluses), and monitoring cardiac rhythm.
• Disability: Correcting hypoglycaemia (checking blood glucose is mandatory in all altered conscious states) and managing seizures (first-line treatment is intravenous benzodiazepines, such as diazepam 5–10 mg or midazolam).
• Exposure: Removing contaminated clothing and washing skin to prevent ongoing dermal absorption.

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Gastric Decontamination: Indications & Contraindications

Gastric decontamination is no longer performed routinely. It is reserved for scenarios where the ingested substance is highly toxic, the presentation is early, and the airway is protected.

Single-Dose Activated Charcoal (SDAC)

Activated charcoal is a highly porous form of carbon that adsorbs toxins within the gastrointestinal lumen, preventing systemic absorption.

• Timing: Most effective if administered within 1 hour of ingestion. Beyond 1 hour, its efficacy decreases dramatically, though it may be considered for drugs that delay gastric emptying (e.g., opioids, anticholinergics) or for sustained-release formulations.
• Dose: Typically 50 g for adults (or 1 g/kg).
• Contraindications:
  • Unprotected airway (risk of aspiration, which leads to severe chemical pneumonitis).
  • Ingestion of corrosive substances (acids or alkalis) as it obscures endoscopic visualization and does not bind.
  • Ingestion of hydrocarbons (high risk of aspiration).
  • Inability to bind (the "PHAILS" mnemonic):
    • Pesticides / Petroleum distillates
    • Hydrocarbons
    • Acids / Alkalis (corrosives)
    • Iron
    • Lithium
    • Solvents / Alcohols (ethanol, methanol, ethylene glycol)

Whole Bowel Irrigation (WBI)

Whole bowel irrigation involves the administration of large volumes of an osmotically balanced polyethylene glycol (PEG) electrolyte solution (e.g., 1.5–2 L/hour for adults via nasogastric tube) to physically flush the gastrointestinal tract before the drug can be absorbed.

• Indications:
  • Ingestion of sustained-release or enteric-coated medications (e.g., calcium channel blockers, beta-blockers).
  • Ingestion of heavy metals not adsorbed by charcoal (e.g., iron, lead).
  • Ingestion of illicit drug packets ("body packers" or "body stuffers").
• Contraindications: Bowel obstruction, perforation, ileus, or haemodynamic instability.

Obsolete Methods

• Gastric Lavage ("Stomach Pumping"): Rarely indicated; associated with serious risks like aspiration, oesophageal perforation, and hypoxia. It is only considered within 1 hour of a life-threatening ingestion of a drug for which there is no antidote.
• Syrup of Ipecac: Strictly contraindicated in modern practice due to prolonged vomiting interfering with oral antidotes or activated charcoal, and risks of aspiration.

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Paracetamol Overdose & N-Acetylcysteine (NAC) Dosing

Paracetamol is the most common agent involved in pharmaceutical overdoses in Australia.

Pathophysiology of Hepatotoxicity

At therapeutic doses, paracetamol is primarily conjugated with sulfate and glucuronide to non-toxic metabolites. A small portion (approx. 5–10%) is oxidised by cytochrome P450 enzymes (mainly CYP2E1) to the highly reactive, electrophilic intermediate N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is immediately detoxified by conjugation with glutathione. In an acute overdose, the normal conjugation pathways become saturated, leading to increased production of NAPQI. Once hepatocellular glutathione stores are depleted by more than 70%, NAPQI binds covalently to hepatic cell proteins, causing acute centrilobular hepatic necrosis.

Risk Assessment & Nomogram Use

For a single, acute ingestion of immediate-release paracetamol:

1. Nomogram Application: The Rumack-Matthew nomogram (referred to in Australia as the paracetamol treatment nomogram) is used. The standard Australian treatment line starts at a concentration of 150 mg/L (1000 µmol/L) at 4 hours post-ingestion, and connects to 18.75 mg/L (125 µmol/L) at 15 hours.
2. Timing of Blood Level: Serum paracetamol must be measured no earlier than 4 hours post-ingestion. If measured before 4 hours, the result cannot be plotted on the nomogram as absorption may not be complete.
3. Treatment Initiation: If the serum paracetamol concentration is on or above the treatment line, N-acetylcysteine (NAC) must be commenced. If the ingestion occurred less than 8 hours ago, there is time to wait for the paracetamol level before starting NAC. If presentation is >8 hours post-ingestion or the history is unreliable, start NAC immediately and check the level. If the level comes back below the line, NAC can be discontinued.

Note: The nomogram is NOT valid for modified-release paracetamol (e.g., Panadol Osteo) or chronic repeated supratherapeutic ingestions.

The 2-Bag N-Acetylcysteine (NAC) Regimen

Australia transitioned from the traditional 3-bag protocol to a simplified 2-bag regimen to reduce the incidence of non-allergic anaphylactoid reactions (e.g., flushing, pruritus, bronchospasm, hypotension), which are common with rapid initial infusion rates.

• Total Dose: 300 mg/kg intravenously over 20 hours.
• Preparation: Infused in 5% glucose or 0.9% sodium chloride.

Note: For patients weighing over 110 kg, doses are capped at a maximum weight of 110 kg (i.e., Bag 1 cap is 22 g; Bag 2 cap is 11 g).

End of Infusion Criteria

Do not stop NAC automatically at 20 hours. Near the end of Bag 2 (approx. 2 hours before completion), bloods must be drawn to check:

1. ALT (Alanine Aminotransferase)
2. Serum paracetamol concentration

Criteria for stopping:

• Paracetamol concentration is < 10 mg/L (< 66 µmol/L) AND
• ALT is < 50 U/L (or if elevated, is clearly declining and stable) AND
• The patient is clinically well.

If these criteria are not met, the NAC infusion must be continued at the rate of Bag 2 (6.25 mg/kg/hour) and re-evaluated every 8 to 12 hours.

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Opioid Overdose & Naloxone

Opioid toxicity is characterized by the classic triad of respiratory depression, miosis (pinpoint pupils), and depressed consciousness.

Naloxone Therapy

Naloxone is a competitive opioid receptor antagonist that reverses both the therapeutic and toxic effects of opioids.

• Goal of Therapy: The goal is to restore adequate spontaneous ventilation (respiratory rate > 10–12 bpm, oxygenation > 95%), NOT to fully awaken the patient. Restoring full consciousness can precipitate acute, severe withdrawal syndrome, leading to agitation, vomiting, aspiration risk, and sympathetic surge.
• Dosing: Start with low doses (e.g., 40–100 micrograms IV) and titrate up every 2 minutes. Larger doses (e.g., 400 micrograms to 2 mg) are indicated if the patient is in cardiac or near-respiratory arrest.
• Rebound Toxicity (The "Half-Life Trap"): Naloxone has a short duration of action (30 to 90 minutes). Long-acting opioids (e.g., methadone, sustained-release oxycodone, or transdermal fentanyl) have half-lives extending to 24–48 hours. Patients resuscitated with naloxone must be monitored for at least 4 hours after the last dose of naloxone. If respiratory depression recurs, repeated doses or a continuous naloxone infusion (calculated as 2/3 of the initial reversing dose per hour) is required.
• Take-Home Naloxone (THN) in Australia: Under the National Take-Home Naloxone program, pharmacists can supply naloxone for free without a prescription to individuals at risk of experiencing or witnessing an opioid overdose. Available formulations include:
  • Nyxoid: Intranasal spray (1.8 mg per spray).
  • Prenoxad: Pre-filled syringe for intramuscular injection (1 mg/1 mL).

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Anticholinergic Toxicity

Anticholinergic toxidrome results from the blockade of muscarinic acetylcholine receptors. Common causative agents include tricyclic antidepressants (TCAs), antihistamines (diphenhydramine, promethazine), benztropine, atropine, and antipsychotics (olanzapine, clozapine).

Clinical Presentation (Toxidrome)

• "Blind as a bat" (Mydriasis, cycloplegia/blurred vision)
• "Mad as a hatter" (Delirium, confusion, hallucinations, agitation)
• "Red as a beet" (Flushed, warm skin due to cutaneous vasodilation)
• "Hot as a hare" (Hyperthermia due to loss of sweating)
• "Dry as a bone" (Dry mouth, dry skin, anhydrosis)
• "Bowel and bladder lose their tone" (Urinary retention, ileus/absent bowel sounds)
• Tachycardia (Loss of vagal tone)

Management

• Supportive Care: External cooling for hyperthermia, bladder catheterisation for urinary retention.
• Agitation Control: Benzodiazepines (e.g., diazepam) are first-line. Avoid haloperidol or phenothiazines as they possess intrinsic anticholinergic properties.
• TCA-Specific Toxicity (Sodium Channel Blockade): In TCA overdose, sodium channel blockade leads to cardiac toxicity (QRS prolongation > 100 ms, ventricular arrhythmias). If the QRS complex is wide (>100 ms on ECG), administer sodium bicarbonate (1–2 mmol/kg IV bolus) to increase extracellular sodium concentration and alkalinise the blood, which decreases drug binding to the active state of the sodium channel.
• Physostigmine: A reversible cholinesterase inhibitor that crosses the blood-brain barrier. It is reserved for severe, refractory central delirium. Contraindication: Never use physostigmine in suspected TCA overdose, as it can precipitate asystole and intractable seizures.

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Digoxin Toxicity & Digibind

Digoxin toxicity can occur acutely (e.g., deliberate self-poisoning) or chronically (e.g., renal decline in an elderly patient on maintenance therapy).

Presentation

Nausea, vomiting, diarrhoea, abdominal pain, bradycardia, heart blocks, and visual changes (classic xanthopsia — yellow-green halo vision).

Hyperkalaemia

Digoxin inhibits the Na+/K+-ATPase pump. In acute toxicity, this leads to profound extracellular accumulation of potassium. A serum potassium level > 5.0 mmol/L in acute digoxin poisoning is a powerful predictor of mortality and is an absolute indication for antidote administration.

Antidote: DigiFab / Digibind

Digoxin-specific antibody fragments bind to free digoxin, pulling it from tissue sites and forming a complex that is excreted renally.

• Indications for DigiFab:
  1. Cardiac arrest or life-threatening arrhythmias.
  2. Severe progressive bradyarrhythmias unresponsive to atropine.
  3. Serum potassium > 5.0 mmol/L in acute poisoning.
  4. Acute ingestion of > 10 mg in adults (or > 4 mg in children).
  5. Steady-state serum digoxin concentration > 15 nmol/L (or > 12 ng/mL).
• Dosing Calculation:
  • If the ingested dose is known: Number of vials = Ingested dose (mg) / 0.5 mg (each vial of DigiFab binds 0.5 mg of digoxin).
  • If the steady-state serum concentration is known: Number of vials = [Serum digoxin (nmol/L) * Patient weight (kg)] / 100.
  • If unknown: Administer 5 to 10 vials empirically for acute toxicity; 1 to 2 vials for chronic toxicity.
• Monitoring Trap: Do NOT measure serum digoxin levels after administering DigiFab. Standard assays measure both free and antibody-bound digoxin, leading to falsely elevated, misleading results. Monitor ECG and potassium levels instead.

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Iron Poisoning

Iron poisoning is a common and potentially lethal paediatric ingestion. Toxicity is determined by the amount of elemental iron ingested, not the salt weight.

Calculating Elemental Iron

• Ferrous sulfate: 20% elemental iron (e.g., a 325 mg tablet contains 65 mg of elemental iron).
• Ferrous fumarate: 33% elemental iron.
• Ferrous gluconate: 12% elemental iron.

Toxicity Thresholds

• < 20 mg/kg: Generally non-toxic.
• 20–60 mg/kg: Mild to moderate gastrointestinal toxicity.
• > 60 mg/kg: High risk of severe systemic toxicity, shock, and organ failure.

Clinical Stages of Iron Toxicity

1. Stage 1 (Gastrointestinal - 0.5 to 6 hours): Corrosive effect on the mucosa. Vomiting, haematemesis, abdominal pain, diarrhoea. The absence of GI symptoms in the first 6 hours rules out significant iron toxicity.
2. Stage 2 (Latent - 6 to 24 hours): Apparent clinical improvement. The patient seems to recover, but subclinical cellular damage is occurring.
3. Stage 3 (Systemic / Shock - 12 to 48 hours): Severe cellular toxicity. Profound lactic acidosis, cardiovascular collapse/shock, acute kidney injury, seizures, and coma.
4. Stage 4 (Hepatotoxicity - 2 to 5 days): Acute hepatic necrosis, jaundice, and coagulopathy.
5. Stage 5 (Gastric Scarring - 2 to 6 weeks): Scarring of the pylorus or duodenum, leading to gastric outlet obstruction.

Management

• Decontamination: Activated charcoal does not adsorb iron. If a toxic dose (>60 mg/kg) is ingested and tablets are visible on abdominal X-ray, perform Whole Bowel Irrigation (WBI).
• Antidote: Desferrioxamine (deferoxamine) is an iron chelator administered intravenously. It binds to ferric iron (Fe3+) in systemic circulation to form ferrioxamine, which is renally excreted.
  • Indications: Shock, metabolic acidosis, severe lethargy, or serum iron levels > 90 µmol/L (or > 60 µmol/L with systemic symptoms).
  • End Point: Resolution of symptoms, correction of acidosis, and clearance of the "vin rosé" (reddish-pink) discolouration of urine.

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Urinary Alkalinisation

Urinary alkalinisation is an elimination enhancement technique that utilizes the principle of ion trapping.

Mechanism

By infusing intravenous sodium bicarbonate, the pH of the urine is raised to 7.5–8.5. For weakly acidic drugs (e.g., salicylates, methotrexate), an alkaline environment shifts the chemical equilibrium towards the ionised, conjugate base form. Because ionised molecules are highly polar, they cannot cross the lipid membrane of the renal tubule cells back into systemic circulation. Thus, they remain "trapped" in the urine and are excreted.

Clinical Applications

1. Salicylate (Aspirin) Overdose:
   • Alkalinisation of both the blood (target pH 7.45–7.55) and urine (target pH 7.5–8.5) is critical.
   • Blood alkalinisation: Prevents salicylate from crossing the blood-brain barrier into the central nervous system (where it causes neurotoxicity, cerebral oedema, and death).
   • Urine alkalinisation: Enhances renal clearance.
2. Methotrexate Toxicity: Prevents the precipitation of methotrexate and its metabolites in the acidic environment of the renal tubules, avoiding crystalline nephropathy and acute kidney injury.

Monitoring & Electrolyte Traps

• Potassium Monitoring: Hypokalaemia must be corrected before starting or during urinary alkalinisation. If the patient is hypokalaemic, the kidneys will actively reabsorb potassium ions from the distal tubules in exchange for hydrogen ions. This excretion of hydrogen ions acidifies the urine (paradoxical aciduria), rendering urinary alkalinisation impossible.
• Monitoring parameters: Urine pH (hourly), blood pH (do not allow arterial pH to exceed 7.55 to avoid severe metabolic alkalosis), serum potassium, and fluid balance (avoid fluid overload).