Why Paracetamol is Used in Stroke Patients
Paracetamol (acetaminophen) is used in stroke patients primarily to treat fever when it occurs, as fever is strongly associated with worse outcomes and increased mortality, though evidence does not support its routine prophylactic use in normothermic patients. 1
The Rationale: Fever and Stroke Outcomes
Association Between Fever and Poor Outcomes
- Fever occurs in up to 50% of acute stroke patients and is strongly associated with death and disability in both ischemic stroke and intracerebral hemorrhage (ICH). 1
- Elevated body temperature may worsen outcomes through increased production of excitotoxins and oxygen radicals, destabilization of cellular membranes, and abnormal electrical depolarizations. 1
- Even subfebrile temperatures (36.5°C or higher) in the first days after stroke are associated with unfavorable outcomes. 2
What the Evidence Actually Shows
Treatment of Established Fever
- When fever is present, early treatment with antipyretics like paracetamol may be considered in clinical practice based on circumstantial evidence, though strong RCT evidence is lacking. 1
- The European Stroke Organisation guidelines state there is insufficient evidence to make strong recommendations on fever treatment, but note that fever treatment with antipyretics may be considered given the association between fever and poor outcomes. 1
Prophylactic Use is NOT Recommended
- The PAIS-1 trial (1400 patients, 11% with ICH) showed that prophylactic paracetamol did not improve outcomes overall (adjusted OR 1.20,95% CI 0.96-1.50) or in the ICH subgroup. 1
- For patients with acute ischemic stroke and normothermia, routine prevention of hyperthermia with antipyretics is NOT recommended as a means to improve functional outcome or survival. 1
- Retrospective analysis suggests prophylactic paracetamol in patients without fever (baseline temperature <37°C) was associated with worse outcomes (OR 0.58,95% CI 0.47-0.72). 3
Temperature Reduction Effects
- High-dose paracetamol (6000 mg daily) can reduce body temperature by approximately 0.3-0.4°C within 12-24 hours compared to placebo. 4
- The antipyretic effect begins within hours but may take up to 4 hours to reach maximum effect. 5
- Paracetamol may be less effective for temperatures exceeding 38°C. 5
Clinical Practice Algorithm
When to Use Paracetamol in Stroke:
If fever develops (temperature ≥38°C): Administer paracetamol to treat the fever and relieve patient discomfort, though evidence for improved outcomes is limited. 1
If normothermic at baseline: Do NOT use prophylactic paracetamol routinely, as this is not supported by evidence and may potentially worsen outcomes. 1, 3
Dosing when indicated: Standard dosing is 650-1000 mg every 4-6 hours (maximum 4000 mg daily in most patients; studies used up to 6000 mg daily). 5, 4
Important Caveats:
- The recommendation to treat fever is based on the strong association between fever and poor outcomes, not on direct evidence that treating fever improves outcomes. 1
- Preventive treatment of fever is not recommended outside of randomized controlled trials. 1
- The PAIS-2 trial was stopped prematurely due to slow recruitment, leaving the question of paracetamol's effect on functional outcomes uncertain. 2
Why NOT "Only" Paracetamol
The question implies paracetamol is the only option, but this is not accurate:
- Physical cooling methods (tepid sponging) can be used alongside or instead of pharmacological treatment. 1, 6
- NSAIDs like ibuprofen can be considered, though they carry risks in elderly patients (acute kidney injury, gastrointestinal complications) and require caution. 1, 6
- The choice of paracetamol over NSAIDs in stroke is often based on its better safety profile, particularly regarding bleeding risk in hemorrhagic stroke and renal/GI complications. 1