Cooling for Acute Ischemic Brain Damage (COOL AID): Preliminary Efficacy Data of Moderate Hypothermia For Acute Ischemic Stroke

Abstract

114 Introduction: Pharmacological neuroprotection has not been shown to be effective in improving outcomes of patients with acute ischemic stroke. Hypothermia is effective experimentally in reducing infarct volumes and improving outcome. We present the preliminary efficacy data of moderate hypothermia in patients with severe middle cerebral artery (MCA) territory stroke. Methods: Patients with severe (NIHSS ≥ 15) MCA territory ischemic stroke who presented within 6 hours of onset were screened. Patients who failed to improve after thrombolysis or attempted thrombolysis (i.e. still had an NIHSS > 8) were enrolled and hypothermia initiated by cooling blanket and ice water-alcohol bath to a core temperature of 32° C ± 1°. Hypothermia was maintained for 12 to 72 hours depending on sonographic or angiographic MCA patency status. Follow-up modified Rankin Scale scores (mRS) were assessed at 3 months. Patients treated with hypothermia were compared with eligible patients who were screened for the study but excluded for logistical reasons. Results: Seventeen patients were screened between October, 1999 to June 2000 and 9 enrolled with a mean NIHSS score of 20.6 ± 3.0. The mean time to initiation of hypothermia from the time of stroke onset was 6.2 ± 1.3 hours and the mean duration of hypothermia was 48.6 ± 21.2 hours. Target temperature was achieved within 3.6 ± 1.6 hours. The mean NIHSS score of the control patients was 20.0 ± 2.7. Pre-hypothermia, the MCA was occluded in 3 patients and open in 6. Among control patients the MCA was occluded in 4, open in 4 and unknown in 1. The mean mRS score at 3 months was 2.8 ± 2.2 for the hypothermia patients. Five patients had a mRS score 0–2 (55.5 %) and 4 had a mRS ≥3 (44.5 %). Control patients had a mean mRS score of 4.4 ± 1.7 (p = 0.11). Only one control patient had a mRS score 0–2 (12.5 %) while 7 patients had a mRS ≥3 (87.5%, p=0.13). Conclusion: This pilot study suggests that adjunct moderate hypothermia may benefit patients with severe acute ischemic stroke. The efficacy of hypothermia combined with thrombolytic therapy needs to be tested in a Phase II randomized controlled trial.