Early treatment with paracetamol could improve functional outcome for stroke patients with a body temperature of 37°C. The findings of the PAIS study are reported in an Article in the May edition of The Lancet Neurology, written by Dr Heleen M den Hertog, Erasmus MC, Rotterdam, The Netherlands, and colleagues from Erasmus MC, Rotterdam, UMC Utrecht, Utrecht and Meander MC, Amersfoort, The Netherlands.
High body temperature in the first 12 h after stroke onset is associated with poor functional outcome. About a third of patients have temperatures greater than 37•5°C within the first hours of stroke onset, and the odds of poor outcome are doubled for every degree increase in body temperature measured within 12 h of stroke onset. High body temperature might be a direct consequence of stroke or a result of accompanying infections. Paracetamol is usually well tolerated by patients with acute stroke and has almost no side-effects in doses up to 6 g per day. In patients with acute ischaemic stroke, paracetamol at a daily dose of 6 g reduces body temperature by about 0•3°C within 4 h from the start of treatment.
In this multicentre, randomised controlled trial, funded by The Netherlands Heart Foundation, 1400 patients with ischaemic stroke or intracerebral haemorrhage and body temperature of 36°C-39°C were randomly assigned treatment with paracetamol (6 g daily) or placebo within 12 h from symptom onset. The primary outcome was improvement beyond expectation on the modified Rankin Scale, which measures handicap after stroke. Patients were assigned to either paracetamol (697) or placebo (703). The researchers found that 37% of patients receiving paracetamol and 33% of those receiving placebo improved beyond expectation, but the difference was not statistically significant. However, in an analysis of patients with a baseline body temperature of 37°C, 40% of patients given paracetamol improved beyond expectation compared with 31% of placebo patients — a finding which was statistically significant. Thus one in every 11 patients treated with paracetamol would improve beyond expectation in this body temperature range. Importantly, analysis of this sub-group of patients was not pre-specified (ie, a post-hoc finding), so the results need further confirmation in a larger study.
The authors conclude: "Although the PAIS trial does not provide sufficient evidence to support routine use of high-dose paracetamol in patients with acute stroke, its results are promising. In patients with a baseline body temperature of 37°C, treatment with paracetamol resulted in a 9% absolute increase in the number of patients who improved beyond expectation, relating to a number needed to treat of only 11. This observation requires confirmation in an independent study. If such an effect can be confirmed, a simple, safe, and cheap treatment with a long time window for start of therapy will be available for patients with acute ischaemic stroke or intracerebral haemorrhage."
In an accompanying Reflection and Reaction comment, Dr Scott E Kasner, Comprehensive Stroke Center, University of Pennsylvania Medical Center, Philadelphia, USA, discusses how cost would be a major obstacle to a trial to confirm this finding, since it would need between 10,000 and 20,000 patients. He says: "Our funds, resources, and efforts may be better focused on more promising potential treatments of acute stroke. In clinical practice, existing data seem sufficient for us to comfortably conclude that paracetamol is safe and will lower high temperatures in patients with acute stroke, and that is exactly what we should use it for and what we should expect it to do."
Dr Heleen M den Hertog, Erasmus MC University Medical Centre, Netherlands T) +31 10 7040704 E) m.denhertog@erasmusmc.nl
Sylvia Marmelstein, Press Officer, Erasmus MC T) +31 107044537 E) s.marmelstein@erasmusmc.nl
Dr Scott E Kasner, Comprehensive Stroke Center, University of Pennsylvania Medical Center, Philadelphia, USA T) +1 215-662-3564 E) kasner@mail.med.upenn.edu
For full Article and Reflection and Reaction, see: http://press.thelancet.com/tlnparacetamolstroke.pdf
Journal
The Lancet Neurology