Paracetamol for stroke: easy in practice, but not in trials

Abstract

Hyperthermia exacerbates ischaemic neuronal injury and is associated with worse outcomes after stroke, including higher mortality, larger infarcts, and worse functional status. 1 Reith J Jorgensen HS Pedersen PM et al. Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet. 1996; 347: 422-425 Summary Full Text PDF PubMed Scopus (782) Google Scholar , 2 Azzimondi G Bassein L Nonino F et al. Fever in acute stroke worsens prognosis: a prospective study. Stroke. 1995; 26: 2040-2043 Crossref PubMed Scopus (407) Google Scholar , 3 Hajat C Hajat S Sharma P Effects of poststroke pyrexia on stroke outcome: a meta-analysis of studies in patients. Stroke. 2000; 31: 410-414 Crossref PubMed Scopus (376) Google Scholar , 4 Wang Y Lim LL Levi C Heller RF Fisher J Influence of admission body temperature on stroke mortality. Stroke. 2000; 31: 404-409 Crossref PubMed Scopus (191) Google Scholar Inducing hypothermia, or at least avoiding hyperthermia, would seem to be promising neuroprotective strategies in acute stroke, although achieving either easily, quickly, and effectively for the millions of people worldwide who have stroke each year has proven challenging. Technological advances have yielded indwelling central venous cooling catheters, surface-cooling pads, even intranasal cooling devices, all of which are being tested in stroke trials, but for much of the world, something simpler and cheaper is needed. Widely available, paracetamol is a possible part of the solution. Several small clinical trials have tested paracetamol as a treatment for acute stroke, finding a consistent reduction in temperature of only about 0·25°C and a possible small reduction in occurrence of fever but no effect on clinical outcome. 5 Dippel DW van Breda EJ van Gemert HM et al. Effect of paracetamol (acetaminophen) on body temperature in acute ischemic stroke: a double-blind, randomized phase II clinical trial. Stroke. 2001; 32: 1607-1612 Crossref PubMed Scopus (147) Google Scholar , 6 Kasner SE Wein T Piriyawat P et al. Acetaminophen for altering body temperature in acute stroke: a randomized clinical trial. Stroke. 2002; 33: 130-134 Crossref PubMed Scopus (159) Google Scholar , 7 Koennecke HC Leistner S Prophylactic antipyretic treatment with acetaminophen in acute ischemic stroke: a pilot study. Neurology. 2001; 57: 2301-2303 Crossref PubMed Scopus (58) Google Scholar , 8 Kalafut MA Llanes J Kidwell C Starkman S Saver JL Can prophylactic acetaminophen prevent hyperthermia in acute stroke? Results of the normothermia and stroke outcomes (NOTHOT) pilot clinical trial. Stroke. 2001; 32 (abstr).: 381 Google Scholar , 9 Dippel DW van Breda EJ van der Worp HB et al. Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690]. BMC Cardiovasc Disord. 2003; 3: 2 Crossref PubMed Scopus (91) Google Scholar The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trialThese results do not support routine use of high-dose paracetamol in patients with acute stroke. Paracetamol might have a beneficial effect on functional outcome in patients admitted with a body temperature 37–39°C, but this post-hoc finding needs further study. Full-Text PDF