Does atropine infusion cause fever in Organophosphate (OPC) poisoning?

Does Atropine Infusion Cause Fever in Organophosphate Poisoning?

Yes, atropine can cause fever in organophosphate poisoning, particularly with repeated or high-dose administration, but this is a recognized adverse effect that should not prevent appropriate atropinization for life-threatening toxicity.

Mechanism of Atropine-Induced Fever

• Atropine causes fever through suppression of sweat gland activity, particularly in infants and small children, leading to what is termed "atropine fever" 1
• The FDA drug label specifically notes that therapeutic doses may occasionally cause "atropine fever" due to suppression of sweat gland activity 1
• Repeated administration of atropine produces adverse central nervous system effects, including both hallucinations and fever 2

Clinical Context in Organophosphate Poisoning

• Atropine remains the immediate first-line treatment for severe organophosphate poisoning manifestations including bronchospasm, bronchorrhea, seizures, or significant bradycardia, regardless of fever risk 2, 3
• The American Heart Association gives atropine a Class 1 recommendation with Level A evidence for severe organophosphate poisoning 2
• Initial dosing should be 1-2 mg IV for adults (0.02 mg/kg for children), with doses doubled every 5 minutes until full atropinization is achieved 3

Distinguishing Fever Sources

• Fever in organophosphate poisoning may have multiple etiologies beyond atropine:
  • Atropine-induced suppression of sweating 1
  • Nicotinic effects causing muscle fasciculations and increased metabolic activity 2
  • Aspiration pneumonia from bronchorrhea 2
  • Rhabdomyolysis from prolonged muscle activity 3

Management Strategy When Fever Develops

• Do not stop atropine administration based solely on fever development - the therapeutic endpoint is control of life-threatening muscarinic symptoms (dry lungs, adequate oxygenation, dry mucous membranes, mydriasis) 3
• Monitor for signs of adequate atropinization rather than focusing on fever as a stopping point 3
• Implement cooling measures if fever becomes problematic while continuing atropine therapy 1
• Consider atropine infusion (400-600 mg/hour for adults or 10-20 mg/kg/hour for children) after initial bolus atropinization to maintain steady therapeutic levels and potentially reduce peak-related adverse effects 3

Evidence on Atropine Dosing Regimens

• A randomized trial in Bangladesh demonstrated that rapid incremental dose atropinization followed by continuous infusion reduced mortality (8% vs 22.5%) and atropine toxicity (12% vs 28.4%) compared to conventional bolus dosing 4
• The infusion approach achieved atropinization in mean 23.9 minutes versus 151.7 minutes with bolus dosing 4
• Maintenance atropine concentrations of approximately 5 nmol/L were sufficient when RBC-AChE activity was 10-30%, requiring only 0.005 mg/h/kg 5

Critical Pitfalls to Avoid

• Never withhold or prematurely discontinue atropine due to fever - inadequate atropinization leads to respiratory failure and death 2, 3
• Fever is an expected adverse effect with high-dose atropine therapy and does not indicate treatment failure 2, 1
• The risk of undertreating organophosphate poisoning far exceeds the risk of atropine-induced fever 2
• Always administer pralidoxime concurrently (Class 2a recommendation) as it addresses nicotinic effects that atropine cannot reverse 2, 3