What to Give When Fever Does Not Settle with Paracetamol
Ibuprofen is the first-line alternative when paracetamol fails to control fever, as it demonstrates superior antipyretic efficacy and longer duration of action. 1
Initial Optimization of Paracetamol Therapy
Before switching medications, ensure paracetamol is being used optimally:
- Verify adequate dosing: Use 15 mg/kg per dose (up to 1000 mg) every 4-6 hours, with maximum 4 g/day in adults 2, 3
- Check for dose reduction requirements: Elderly patients, those with hepatic insufficiency, alcohol abuse history, or dehydration require maximum daily dose reduction to 3000 mg (1000 mg every 8 hours) 4
- Allow sufficient time: Temperature reduction typically occurs over 60-90 minutes; standard-dose paracetamol takes longer (mean 97.5 minutes) compared to higher doses 5, 6
First-Line Alternative: Ibuprofen
When paracetamol fails to control fever, switch to ibuprofen as the primary antipyretic agent:
- Adult dosing: 400-600 mg every 6-8 hours 1
- Pediatric dosing: 6-10 mg/kg per dose 6
- Advantages: Faster temperature reduction and longer duration of fever control compared to paracetamol 1, 6
Critical Contraindications to Ibuprofen
Avoid ibuprofen in patients with:
- Impaired renal function (reduce dose if used) 1
- Concurrent aspirin therapy for antiplatelet effects (ibuprofen antagonizes aspirin's irreversible platelet inhibition) 1
- Active gastrointestinal bleeding or ulcer disease 1
- Severe COVID-19 with kidney, cardiac, or gastrointestinal injury 2
Combination Therapy Option
For bacterial fever specifically, paracetamol 500 mg/ibuprofen 150 mg combination demonstrates faster antipyretic effect at 1 hour compared to paracetamol alone (48.6% vs 33.6% achieving temperature reduction). 5
Adjunctive Non-Pharmacological Measures
When fever persists despite antipyretics:
- Maintain adequate hydration: No more than 2 liters per day in adults to avoid dehydration 2, 4
- Environmental modifications: During hot weather, uncover the patient and lower ambient temperature 2
- Avoid physical cooling methods: Tepid sponging and fanning cause patient discomfort without improving outcomes and should not be used 2
- Consider cooling devices: Only for refractory fevers unresponsive to antipyretics; set device to 37.5°C with continuous temperature monitoring 2
When to Escalate Care
Investigate underlying cause if fever persists beyond expected timeframe:
- Perform chest radiograph: Pneumonia is the most common infection causing fever in critically ill patients 2
- Consider imaging: CT of surgical area for post-operative patients with persistent fever 2
- Evaluate for: Pulmonary/urinary infections, sepsis, endocarditis, pulmonary embolism, drug fever 2
Special Clinical Contexts
Severe Traumatic Brain Injury
- Automated feedback-controlled temperature management devices are recommended over antipyretics alone, as antipyretics have limited efficacy in controlling fever and minimizing temperature variability in severe TBI 7
Critical Care Settings
- Antipyretics should be used primarily for symptomatic relief and patient comfort, not routinely to reduce temperature, as fever management does not improve 28-day mortality (RR 1.03; 95% CI 0.79-1.35) 2
Common Pitfall to Avoid
Do not continue ineffective paracetamol dosing for prolonged periods. If fever persists after 48-72 hours of appropriate paracetamol therapy, switch to ibuprofen rather than continuing the same ineffective regimen. 7, 5