Drug Toxicity 101

Paracetamol

  • There are various clinical presentations of acetaminophen overdose, including asymptomatic, vague nausea/vomiting, acute liver failure, and even coma. A thorough history, in combination with laboratory data, is crucial for diagnosis.
  • Rule of 150s =>
    • Toxic dose is approximately 150mg/kg
    • Treatment with NAC should be implemented if >150 mg/kg acetaminophen level at 4 hours of presentation
    • The initial dose of IV NAC is 150 mg/kg in the first hour.
  • If you are working in a community hospital, consider transfer to a transplant center early if the patient has evidence of severe toxicity (King’s College criteria) or if there is worsening clinical status despite treatment.

Aspirin

  • Start treatment for aspirin overdose at 40 mg/dL or signs of systemic illness with charcoal (if patient tolerates) and sodium bicarbonate
  • If salicylate levels > 90 mg/dL, AMS, significant organ dysfunction, pH < 7.2, or hemodynamic instability => emergent hemodialysis
  • If possible, avoid intubation! But if intubation is necessary, attempt to match the patient’s minute ventilation!

TCA Toxicity

  • TCA toxicity can present with seizures, tachycardia, hypotension, anticholinergic toxicity, and coma.
  • The most common dysrhythmia is sinus tachycardia but the classic EKG findings include cardiac conduction delays, terminal R wave in aVR, and a widened QRS.
  • Treat initially with IVF resuscitation and sodium bicarbonate when QRS > 100ms or for hemodynamic instability.
  • Last resort therapies for refractory arrhythmias with significant toxicity include lidocaine, magnesium, and intravenous lipid emulsion.

Iron Toxicity

  • Charcoal will NOT be beneficial in iron overdose.
  • Criteria for treatment with deferoxamine are hypotension/shock, CNS symptoms, AG metabolic acidosis, serum iron levels > 500 ug/dl or persistent GI symptoms
  • Deferoxamine has the potential for significant hypotension and pulmonary toxicity. Discuss treatment dosing and duration with your toxicologist.

 

Management of Iron Toxicity

The treatment of Fe overdose starts with attention to supportive care and adequate fluid resuscitation.

  1. Isotonic fluids: Numerous reasons account for hypovolemia and poor perfusion. Start fluid resuscitation with isotonic fluid boluses to restore hypovolemia.
  2. Activated charcoal (or other oral complexing agents): This is INEFFECTIVE at binding Fe to limit absorption.
  3. Whole bowel irrigation: This may be considered when Fe tablets are visualized on the KUB film. However, no controlled studies support the efficacy of WBI and so individual risks and benefits should be considered. WBI is achieved by administration of polyethylene glycol (PEG) solution via NG tube at recommended rates of 500 mL/hr in children and 1.5 – 2 L/hr in adolescents and adults.
  4. Gastric lavage: Generally NOT recommended