BACKGROUND:Intravenous thrombolysis is contraindicated in patients with ischaemic stroke with blood pressure higher than 185/110 mm Hg. Prevailing guidelines recommend to actively lower blood pressure with intravenous antihypertensive agents to allow for thrombolysis; however, there is no robust evidence for this strategy. Because rapid declines in blood pressure can also adversely affect clinical outcomes, several Dutch stroke centres use a conservative strategy that does not involve the reduction of blood pressure. We aimed to compare the clinical outcomes of both strategies. METHODS:Thrombolysis and Uncontrolled Hypertension (TRUTH) was a prospective, observational, cluster-based, parallel-group study conducted across 37 stroke centres in the Netherlands. Participating centres had to strictly adhere to an active blood-pressure-lowering strategy or to a non-lowering strategy. Eligible participants were adults (≥18 years) with ischaemic stroke who had blood pressure higher than 185/110 mm Hg but were otherwise eligible for intravenous thrombolysis. The primary outcome was functional status at 90 days, measured using the modified Rankin Scale and assessed through telephone interviews by trained research nurses. Secondary outcomes were symptomatic intracranial haemorrhage, the proportion of patients treated with intravenous thrombolysis, and door-to-needle time. All ordinal logistic regression analyses were adjusted for age, sex, stroke severity, endovascular thrombectomy, and baseline imbalances as fixed-effect variables and centre as a random-effect variable to account for the clustered design. Analyses were done according to the intention-to-treat principle, whereby all patients were analysed according to the treatment strategy of the participating centre at which they were treated. FINDINGS:Recruitment began on Jan 1, 2015, and was prematurely halted because of a declining inclusion rate and insufficient funding on Jan 5, 2022. Between these dates, we recruited 853 patients from 27 centres that followed an active blood-pressure-lowering strategy and 199 patients from ten centres that followed a non-lowering strategy. Baseline characteristics of participants from the two groups were similar. The 90-day mRS score was missing for 15 patients. The adjusted odds ratio (aOR) for a shift towards a worse 90-day functional outcome was 1·27 (95% CI 0·96-1·68) for active blood-pressure reduction compared with no active blood-pressure reduction. 798 (94%) of 853 patients in the active blood-pressure-lowering group were treated with intravenous thrombolysis, with a median door-to-needle time of 35 min (IQR 25-52), compared with 104 (52%) of 199 patients treated in the non-lowering group with a median time of 47 min (29-78). 42 (5%) of 852 patients in the active blood-pressure-lowering group had a symptomatic intracranial haemorrhage compared with six (3%) of 199 of those in the non-lowering group (aOR 1·28 [95% CI 0·62-2·62]). INTERPRETATION:Insufficient evidence was available to establish a difference between an active blood-pressure-lowering strategy-in which antihypertensive agents were administered to reduce blood pressure below 185/110 mm Hg-and a non-lowering strategy for the functional outcomes of patients with ischaemic stroke, despite higher intravenous thrombolysis rates and shorter door-to-needle times among those in the active blood-pressure-lowering group. Randomised controlled trials are needed to inform the use of an active blood-pressure-lowering strategy. FUNDING:Fonds NutsOhra.

Background and Purpose-Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of 36.5 degrees C. In the present trial, we aimed to confirm this finding. Methods-PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Results-Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Conclusions-Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed.

Introduction: Deficits in the ability to distinguish between the left and right side of the body can severely impair daily life functioning. The current study examined the relation between left right orientation (LRO) impairments and somatosensory related deficits, ranging from primary somatosensory impairments to body representation impairments, in patients who suffered a recent stroke. We also examined which areas in the brain are associated with LRO impairments using a Voxel-based Lesion Symptom Mapping (VLSM) analysis. Method: We tested 47 first-ever stroke patients and 48 age-matched healthy controls. LRO was assessed with the Bergen Right Left Discrimination Test (BRLD). Impairments on primary somatosensory function (touch perception, proprioception), higher order somatosensory function (finger gnosis, subjective sense of body ownership) and other cognitive functions (language, attention & working memory, visuospatial neglect) were entered as predictors in a logistic regression analyses. Outcome measures consisted of the BRLD-total performance which was further subdivided in performance for 1) first person perspective stimuli, 2) third person perspective stimuli, 3) alternating between first- and third person perspective. Results: Impairments on BRLD-total performance was predicted by impairments in finger gnosis and visuospatial neglect. For items placed in third person perspective, performance was predicted by body representation impairments; finger agnosia and the subjective sense of body ownership. VLSM analysis showed a significant association between LRO impairments and damage to the right insula. Discussion: The current study suggests that the somatosensory system is important for LRO. Furthermore, the results indicate that an affected body representation may hinder adopting a third person perspective that may subsequently also lead to LRO impairments. The right insular cortex appeared crucially involved in these processes. (C) 2017 Elsevier Ltd. All rights reserved.

Background and Purpose— Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. Methods— PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Results— Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74–1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Conclusions— Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed. Clinical Trial Registration— URL: http://www.trialregister.nl . Unique identifier: NTR2365.

RationaleIn the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 370 degrees C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 143; 95% confidence interval: 102-197). This relation was also found in the patients with a body temperature of 365 degrees C or higher (odds ratio 131; 95% confidence interval 101-168). These findings need confirmation.AimThe study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 365 degrees C or above on functional outcome.DesignThe Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 005 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 365 degrees C or above will be included within 12h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register.Study outcomesThe primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression.DiscussionIf high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be available for many patients with acute stroke worldwide.

Background: In observational studies, a high body temperature has been associated with unfavorable outcome. In in vitro studies, the fibrinolytic activity of alteplase decreased 5% per degree Celsius reduction in temperature. The modifying effect of body temperature on treatment with alteplase in patients with acute ischemic stroke is unclear. We assessed the influence of baseline body temperature on the effect of alteplase on functional outcome in patients with acute ischemic stroke, included in the Paracetamol (Acetaminophen) in Stroke (PAIS) trial. Methods: PAIS was a randomized, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke. For this study, we selected all patients with ischemic stroke and randomization within 6 h of symptom onset. We estimated the effect of treatment with alteplase on the modified Rankin Scale score at 3 months with ordinal logistic regression, stratified by baseline body temperature. We made adjustments for confounding factors and expressed associations as adjusted odds ratios (aOR) with 95% confidence intervals (CI). We also tested for interaction between treatment with alteplase and body temperature. Results: We included 647 of the 1,400 patients in PAIS in our study. Treatment with alteplase was associated with improved functional outcome at 3 months (aOR 1.51, 95% CI 1.09–2.08). In the 286 patients (44%) with a baseline body temperature of 37.0°C or higher, alteplase was associated with a larger effect (aOR 2.13, 95% CI 1.28–3.45) than in patients with a temperature below 37.0°C (aOR 1.11, 95% CI 0.71–1.69). A test for interaction between body temperature and alteplase did not reach statistical significance (p = 0.18). Conclusion: Patients with ischemic stroke and a high body temperature may have a larger benefit of treatment with alteplase than patients with lower body temperatures. These findings are in line with those from in vitro studies, in which lowering temperature decreased the fibrinolytic activity of the enzyme alteplase. This interaction should be explored further in randomized clinical trials of thrombolytic therapy or modification of body temperature. Trials of therapeutic hypothermia should be controlled for treatment with thrombolytics, and trials of thrombolytic treatment should consider body temperature as a potential effect modifier.

Subfebrile temperature or fever is present in about a third of patients on the first day after stroke onset and is associated with poor outcome. However, the temporal profile of this association is not well established. We aimed to assess the relationship between body temperature on admission as well as the change in body temperature from admission to 24 h thereafter and functional outcome and death. We analyzed data of 1,332 patients admitted within 12 h of stroke onset. The relation between body temperature on admission or the change in body temperature from admission to 24 h thereafter (adjusted for body temperature on admission) on the one hand and unfavorable outcome (death, or a modified Rankin Scale score >2) at 3 months on the other were expressed as odds ratio per 1.0°C increase in body temperature. Adjustments for potential confounders were made with a multiple logistic regression model. No relation was found between admission body temperature and poor outcome (aOR 1.06; 95% CI 0.85–1.32) and death (aOR 1.23; 95% CI 0.95–1.60). In contrast, increased body temperature in the first 24 h after stroke onset was associated with poor outcome (aOR 1.30; 95% CI 1.05–1.63) and death (aOR 1.51; 95% CI 1.15–1.98). An early rise in body temperature rather than high body temperature on admission is a risk factor for unfavorable outcome in patients with acute stroke.

An increase in body temperature in the first days following stroke is related to poor functional outcome. High-dose paracetamol (acetaminophen) reduces the body temperature by 0.3°C and can prevent fever. Paracetamol treatment is simple, cheap and has few side effects. In the first "Paracetamol (Acetaminophen) in Stroke" (PAIS) study, there was a beneficial effect of high-dose paracetamol on functional outcome in patients with stroke and a body temperature of 37.0°C or above. Because this result was found in a subgroup analysis, a new study is needed to confirm this finding. Recently the randomised PAIS 2 study was initiated. This study aims to assess the effect of high-dose paracetamol on functional outcome in patients with acute stoke and a body temperature of 37.0°C or above.

Background High body temperature in the first 12-24 h after stroke onset is associated with poor functional outcome. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial aimed to assess whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing body temperature and preventing fever.Methods In a multicentre, randomised, double-blind, placebo-controlled trial, patients with ischaemic stroke or intracerebral haemorrhage and body temperature between 36 degrees C and 39 degrees C were randomly assigned treatment with paracetamol (6 g daily) or placebo within 12 h from symptom onset. Treatment allocation was based on a computer-generated list of random numbers with varying block size. The primary outcome was improvement beyond expectation on the modified Rankin scale at 3 months, according to the sliding dichotomy approach. This trial is registered, number ISRCTN74418480.Findings Between March, 2003, and May, 2008, 1400 patients were randomly allocated treatment. 260 (37%) of 697 patients receiving paracetamol and 232 (33%) of 703 receiving placebo improved beyond expectation (adjusted odds ratio [OR] 1.20, 95% CI 0.96-1-50). In a post-hoc analysis of patients with baseline body temperature 37-39 degrees C, treatment with paracetamol was associated with improved outcome (1.43, 1.02-1.97). There were 55 serious adverse events in the paracetamol group (8%) and 70 in the placebo group (10%).Interpretation These 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 degrees C, but this post-hoc finding needs further study.

Background The Paracetamol (Acetaminophen) In Stroke (PAIS) study is a phase III multicenter, double blind, randomized, placebo-controlled clinical trial of high-dose acetaminophen in patients with acute stroke. The trial compares treatment with a daily dose of 6 g acetaminophen, started within 12 hours after the onset of symptoms, with matched placebo. The purpose of this study is to assess whether treatment with acetaminophen for 3 days will result in improved functional outcome through a modest reduction in body temperature and prevention of fever. The previously planned statistical analysis based on a dichotomization of the scores on the modified Rankin Scale (mRS) may not make the most efficient use of the available baseline information. Therefore, the planned primary analysis of the PAIS study has been changed from fixed dichotomization of the mRS to a sliding dichotomy analysis. Methods Instead of taking a single definition of good outcome for all patients, the definition is tailored to each individual patient's baseline prognosis on entry into the trial. Conclusion The protocol change was initiated because of both advances in statistical approaches and to increase the efficiency of the trial by improving statistical power. Trial Registration Current Controlled Trials [ISCRTN74418480]

HomeStrokeVol. 38, No. 11Acetaminophen for Temperature Reduction in Acute Stroke: Potential but Unproven Benefits Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBAcetaminophen for Temperature Reduction in Acute Stroke: Potential but Unproven Benefits Heleen M. den Hertog, MD H. Bart van der Worp, MD, PhD H. Maarten van Gemert, MD, PhD Diederik W. Dippel, MD, PhD Heleen M. den HertogHeleen M. den Hertog Erasmus MC University Medical Center, Rotterdam, The Netherlands H. Bart van der WorpH. Bart van der Worp University Medical Center, Utrecht, The Netherlands H. Maarten van GemertH. Maarten van Gemert Meander Medical Center, Amersfoort, The Netherlands Diederik W. DippelDiederik W. Dippel Erasmus MC University Medical Center, Rotterdam, The Netherlands Originally published13 Sep 2007https://doi.org/10.1161/STROKEAHA.107.485508Stroke. 2007;38:e131Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 13, 2007: Previous Version 1 To the Editor:We read with interest the review by Hemmen and Lyden on induced hypothermia for acute ischemic stroke.1 The review focuses on physical cooling methods in acute stroke. Some points, however, deserve in our opinion a more extensive discussion.The authors state that controlling body temperature below 36.5°C has been proven to correlate with good clinical outcome. They do not cite controlled clinical trials to support their point, but refer to 2 observational studies instead.Indeed, well-designed studies have shown a consistent relationship between increased body temperature measured within 12 to 24 hours after onset of stroke, and outcome, but not beyond that interval.2 These studies suggest that reductions in body temperature of 0.5°C might lead to a relative risk reduction in poor outcome of 10%. Reductions in body temperature of this magnitude have been proven feasible in 2 pilot studies of high-dose acetaminophen.3,4In our view, the uncontrolled studies and small randomized trials in acute ischemic stroke that have been conducted so far have not provided sufficient evidence of safety and feasibility of physical cooling methods. We need more randomized phase II studies with several cooling devices. These studies should explore the relationship between intensity of treatment, temperature reduction, and adverse events, such as arterial hypotension, infections, and cardiac arrhythmias. On the other hand, the risk of complications, the high costs of this mode of treatment, and other logistical barriers imply that there is a need for a simple medical intervention that may reduce body temperature to lesser extent, but is cheap and safe.Although several national and international guidelines recommend the use of acetaminophen in patients with fever after stroke, it is recognized that there is no evidence available of a therapeutic effect.5 Moreover, most patients develop fever after the first 24 hours, and it appears unlikely that late treatment will have an effect on outcome.Why not treat all patients early with high-dose acetaminophen? The main reason is that this treatment strategy has not yet been proven to improve functional outcome after stroke. In addition, acetaminophen can be dangerous in high doses and cause liver failure. Use of acetaminophen may delay the recognition of pneumonia and urinary tract infections, and thus lead to delayed treatment and poor outcome.We conclude that a large pragmatic placebo-controlled randomized clinical trial of acetaminophen in acute ischemic stroke is needed. Exactly such a trial is underway in the Netherlands, PAIS: Paracetamol (Acetaminophen) In Stroke. More than 1100 patients have been included in the trial as of January 2007. We expect to be able to present the trial's results in 2008.6DisclosuresNone.1 Hemmen TM, Lyden PD. Induced hypothermia for acute stroke. Stroke. 2007; 38: 794–799.LinkGoogle Scholar2 Reith J, Jorgensen HS, Pedersen PM, Nakayama H, Raaschou HO, Jeppesen LL, Olsen TS. Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet. 1996; 347: 422–425.CrossrefMedlineGoogle Scholar3 Dippel DW, van Breda EJ, van Gemert HM, van der Worp HB, Meijer RJ, Kappelle LJ, Koudstaal PJ. Effect of paracetamol (acetaminophen) on body temperature in acute ischemic stroke: a double-blind, randomized phase II clinical trial. Stroke. 2001; 32: 1607–1612.CrossrefMedlineGoogle Scholar4 Dippel DW, van Breda EJ, van Gemert HM, van der Worp HB, Meijer RJ, Kappelle LJ, Koudstaal PJ. Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial. BMC Cardiovasc Disord. 2003; 3: 2.CrossrefMedlineGoogle Scholar5 Adams H, Adams R, Del Zoppo G, MD, Goldstein LB. Guidelines for the early management of patients with ischemic stroke. 2005 guidelines update. A scientific statement from the Stroke Council of the American Heart Association/American Stroke Association. Stroke. 2005; 36: 916–923.LinkGoogle Scholar6 Van Breda EJ, van der Worp HB, van Gemert HM, Algra A, Kapelle LJ, Gijn J, Koudstaal PJ, Dippel DWJ. PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial [ISCRTN 74418480] BMC Cardiovasc Disord. 2005; 5: 24.CrossrefGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Simon A and Leffler A (2017) Antipyretika bei IntensivpatientenAntipyretics in intensive care patients, Der Anaesthesist, 10.1007/s00101-017-0301-9, 66:7, (511-517), Online publication date: 1-Jul-2017. November 2007Vol 38, Issue 11 Advertisement Article InformationMetrics https://doi.org/10.1161/STROKEAHA.107.485508PMID: 17872486 Originally publishedSeptember 13, 2007 PDF download Advertisement

Increased body temperatures are common in the acute phase of stroke. Experimental and clinical studies have suggested that increased body temperatures are related to poor outcome. In animal studies of focal cerebral ischemia, early hypothermia consistently reduced infarct volume. Based on these findings, several Phase II clinical trials have been performed to study physical methods to reduce body temperature in patients with acute stroke. The feasibility and safety of these methods have not yet been established with sufficient certainty. Pharmacological lowering of body temperature may be an attractive alternative approach. In guidelines for the treatment of acute stroke, antipyretics are generally recommended to reduce fever, although their effect on functional outcome is unknown. There is currently no evidence from randomized trials to support routine use of physical or pharmacological cooling in acute stroke. Large randomized clinical trials are needed to study the effect of both physical and medical cooling on functional outcome after stroke.

Abstract Background In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1°C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3°C (95% CI: 0.1–0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic. Methods/design Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level. Discussion This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one.

Background: Body temperature is a strong predictor of outcome in acute stroke. In a previous randomized trial we observed that treatment with high-dose acetaminophen (paracetamol) led to a reduction of body temperature in patients with acute ischemic stroke, even when they had no fever. The purpose of the present trial was to study whether this effect of acetaminophen could be reproduced, and whether ibuprofen would have a similar, or even stronger effect.Methods: Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 1000 mg acetaminophen, 400 mg ibuprofen, or placebo, given 6 times daily during 5 days. Treatment was started within 24 hours from the onset of symptoms. Body temperatures were measured at 2-hour intervals during the first 24 hours, and at 6-hour intervals thereafter.Results: No difference in body temperature at 24 hours was observed between the three treatment groups. However, treatment with high-dose acetaminophen resulted in a 0.3 degrees C larger reduction in body temperature from baseline than placebo treatment (95% CI: 0.0 to 0.6 degrees C). Acetaminophen had no significant effect on body temperature during the subsequent four days compared to placebo, and ibuprofen had no statistically significant effect on body temperature during the entire study period.Conclusions: Treatment with a daily dose of 6000 mg acetaminophen results in a small, but potentially worthwhile decrease in body temperature after acute ischemic stroke, even in normothermic and subfebrile patients. Further large randomized clinical trials are needed to study whether early reduction of body temperature leads to improved outcome.

During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily) and low dose (3 g daily) paracetamol (acetaminophen) in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied.