Is paracetamol (acetaminophen) effective for managing hyperthermia (high temperature)?

Paracetamol for High Temperature: Clinical Effectiveness and Recommendations

Paracetamol (acetaminophen) is effective for reducing fever in most clinical contexts, lowering body temperature by approximately 0.3-0.4°C within hours of administration, though it does not improve mortality or functional outcomes in conditions like stroke or sepsis. 1, 2, 3

Mechanism and Onset of Action

Paracetamol works as an antipyretic by inhibiting cyclooxygenase-3 and prostaglandin synthesis within the central nervous system, resetting the hypothalamic heat-regulation center. 4

Key timing considerations:

• The antipyretic effect begins within hours of administration 1
• Mean temperature reduction of 0.26-0.4°C occurs within 4-24 hours 1, 2, 3
• Higher doses (6000 mg daily) are more effective than lower doses (3900 mg daily) for temperature reduction 1, 2, 3

Dosing Recommendations

Standard fever management:

• Adults: 1000 mg every 6 hours (maximum 6000 mg daily) 2, 3, 5
• Pediatrics: 15 mg/kg every 4-6 hours 1, 6

The combination of paracetamol 500 mg/ibuprofen 150 mg may be more effective than paracetamol alone for bacterial fever, achieving the primary endpoint in 48.6% versus 33.6% of patients at one hour. 5

Clinical Context: When Paracetamol Does NOT Improve Outcomes

Acute ischemic stroke: The European Stroke Organisation guidelines explicitly recommend AGAINST routine prevention of hyperthermia with antipyretics in normothermic stroke patients, based on high-quality evidence from 1323 patients showing no improvement in functional outcome (RR: 1.02,95% CI: 0.94-1.10) or mortality (RR: 0.96,95% CI: 0.74-1.23). 7

Intracerebral hemorrhage: The PAIS-1 trial of 1400 patients (11% with ICH) found paracetamol was not superior overall (adjusted OR 1.20,95% CI 0.96-1.50) or in the ICH subgroup. 7 However, early treatment of established fever may still be considered based on circumstantial evidence, as fever is associated with worse outcomes. 7

Important Clinical Caveats

Paracetamol is relatively ineffective in patients with temperatures exceeding 38°C, who may be unresponsive to treatment. 1 In these cases, consider:

• Physical cooling methods (evaporative cooling with wet gauze and fans) 8
• Ice packs to axillae and groin 7
• Investigation for underlying infection source 1

Contraindications in specific hyperthermia syndromes:

• Malignant hyperthermia: Paracetamol is NOT mentioned in treatment protocols; management focuses on dantrolene (2 mg/kg IV), stopping trigger agents, and physical cooling measures 7
• Heatstroke: Avoid paracetamol and aspirin due to potential aggravation of coagulopathy and liver injury; use physical cooling as primary treatment 8

Practical Algorithm for Fever Management

For general fever (non-stroke, non-heatstroke):

1. Administer paracetamol 1000 mg (adults) or 15 mg/kg (pediatrics) 5, 6
2. Monitor temperature response at 1-4 hours 1
3. If temperature >38°C persists, add physical cooling methods 8
4. For bacterial fever, consider paracetamol/ibuprofen combination 5
5. Repeat dosing every 4-6 hours as needed, not exceeding maximum daily dose 1

For stroke patients:

• Only treat established fever (≥38°C), not prophylactically 7
• Paracetamol 1000 mg every 6 hours is reasonable for symptomatic relief despite lack of outcome benefit 7
• Focus on preventing fever sources (aspiration pneumonia, UTI, pressure ulcers) rather than prophylactic antipyretics 7

Key Clinical Pearls

• Paracetamol does NOT prevent febrile seizures in children, though it may improve comfort 8
• The medication is well-tolerated with adverse reactions <1/10,000 when used appropriately 6
• Intravenous formulation shows similar efficacy to oral/rectal routes with bioequivalent dosing 6
• Temperature reduction does not necessarily translate to improved clinical outcomes in critically ill patients 7, 4