Diclofenac Poisoning

Diclofenac poisoning causes gastrointestinal, renal, hepatic and neurological toxicity. Compared with ibuprofen, large overdoses are more likely to cause seizures, kidney injury, hepatitis and metabolic acidosis.

Diclofenac is widely used and sold over the counter in many countries. Serious toxicity is uncommon under about 50 mg/kg, but severe poisoning can occur above 100 mg/kg, and fatal cases are reported after intramuscular and large oral doses.

Risk factors for harm. Renal impairment, hypovolaemia, heart failure, cirrhosis, older age, concurrent nephrotoxic drugs, and mixed overdose.

Course. Symptoms develop within hours, and renal or hepatic injury appears at 24 to 72 hours. Most patients recover.

Pathophysiology.

Cyclo oxygenase inhibition reduces renal prostaglandins and gastric protection. Reactive metabolites may add idiosyncratic hepatotoxicity, and high doses impair mitochondrial function.

Acidosis and seizures occur in large doses through neuronal effects.

• Nausea, vomiting, abdominal pain, haematemesis and diarrhoea.
• Headache, dizziness, drowsiness, tinnitus, ataxia, seizures and coma in severe cases.
• Hypotension, tachycardia, anion gap acidosis and hypocalcaemia.
• Oliguria, raised creatinine, jaundice and raised transaminases at 24 to 72 hours.

Red flags.

• Seizures, coma or respiratory depression.
• Metabolic acidosis or hyperkalaemia.
• Oliguria, jaundice or gastrointestinal haemorrhage.

• History of dose, formulation (enteric coated or modified release), route and time; paracetamol and salicylate levels.
• Urea, creatinine, electrolytes, calcium, venous gas with lactate, glucose, liver function and full blood count.
• ECG in significant ingestions; no useful drug level.
• Repeat renal and liver function at 24 and 72 hours.

Differential diagnosis. Other NSAID overdose, salicylate poisoning, paracetamol poisoning, toxic alcohol ingestion and sepsis.

• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) if more than 50 mg/kg within 1 hour (2 hours for modified release) and the airway is protected. Monitor the airway for aspiration. Avoid with reduced consciousness, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Intravenous fluids (0.9% sodium chloride) to maintain urine output over 1 mL/kg/hour; avoid fluid overload.
• Seizures: lorazepam 0.1 mg/kg intravenously (maximum 4 mg for each dose) over 2 minutes, repeated once after 5 to 10 minutes if seizures continue. Maximum 8 mg in total. Monitor breathing, oxygen saturation, blood pressure and sedation. Use lower doses in older adults, respiratory disease and hepatic impairment; no renal adjustment; use only when needed in pregnancy.
• Gastrointestinal protection: omeprazole 40 mg intravenously or orally once daily (twice daily for active bleeding). Maximum 80 mg daily. Monitor haemoglobin and stool or vomit blood. Reduce dose to 20 mg in severe hepatic impairment; no renal adjustment; avoid with clopidogrel.
• Correct acidosis and electrolytes; sodium bicarbonate 8.4% 50 mL (50 mmol) intravenously over 20 minutes for pH under 7.1 with haemodynamic effect, repeated as needed. Maximum serum pH 7.55 and sodium 150 mmol/L. Monitor pH, potassium and sodium; avoid in heart failure with fluid overload.
• Kidney injury: avoid nephrotoxins and treat hyperkalaemia; renal replacement therapy for refractory acidosis, hyperkalaemia or fluid overload. Extracorporeal removal is ineffective because diclofenac is highly protein bound.
• Observe for 6 hours (12 hours for modified release) after significant ingestion.
• Psychiatric assessment in intentional ingestion.

Monitoring. Creatinine, electrolytes and liver function at 24 and 72 hours; urine output; ECG and gas as needed.

Referral and escalation. Poisons information centre for large ingestions; intensive care for seizures, coma or refractory acidosis; nephrology and hepatology as needed.

Special groups. Older adults and those with renal disease: lower threshold for admission and monitoring.