An article in the May edition of The Lancet Neurology written by Dr Heleen M den Hertog, Erasmus MC, Rotterdam, The Netherlands, and collaborators from Erasmus MC, Rotterdam, UMC Utrecht, Utrecht and Meander MC, Amersfoort, The Netherlands, points out findings from the PAIS study concluding that stroke early treatment with paracetamol for stroke patients with a body temperature of 37 to 39 degrees Celsius could improve functional outcome.

In the first twelve to twenty four hours after a stroke, high body temperature is linked to poor functional outcome. Within the first hours of the beginning of a stroke, about a third of patients have temperatures above 37.5°C. The chances of poorer results are multiplied by two for every degree increased in body temperature measured within the twelve hours of stroke onset. High body temperature may be directly caused by the stroke or by associated infections. Patients with severe strokes generally have a good acceptance for paracetamol. In daily doses of up to 6 g, it produces nearly no side-effects. Within four hours from the start of the treatment, in patients with severe ischaemic stroke, doses of paracetamol of 6 g per day reduce body temperature by about 0.3°C.

The Netherlands Heart Foundation funded this multicentre, randomized controlled trial which included 1,400 patients with ischaemic stroke or intracerebral haemorrhage and body temperature between 36 to 39°C. Within twelve hours of symptom onset, they were assigned to random treatment with daily doses of 6 g of paracetamol (697 patients) or placebo (703 patients). On the modified Rankin Scale that measures handicap after a stroke, improvement beyond what was anticipated was the most important outcome. Findings showed that 37 percent of patients receiving paracetamol and 33 percent receiving placebo improved beyond expectations, but the variation was not statistically important.

An examination of patients with a baseline body temperature between 37 and 39°C showed that 40 percent of patients who received paracetamol improved beyond expectation compared with 31 percent of placebo patients. In this case the finding was statistically significant. As a result, one in every eleven patients treated with paracetamol would improve beyond expectation in this body temperature range. It is important to point out that findings need further verification since the analysis of this sub-group of patients was not pre-defined and could result from coincidental correlation.

The authors write in conclusion: “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 37-39°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 associated remark, Dr Scott E Kasner, Comprehensive Stroke Center, University of Pennsylvania Medical Center, Philadelphia, USA, explains how a trial to verify this finding would be difficult to carry out because of its cost, since it would require between 10,000 and 20,000 patients. He writes: “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.”

“Paracetamol for stroke: easy in practice, but not in trials.”
Scott Kasner
The Lancet Neurology, Volume 8, Issue 5, Pages 415 – 416, May 2009

Written by Stephanie Brunner (B.A.)