Hypothermia in the Therapy of Ischemic Stroke

Abstract

The first clinical trial on the effect of mild hypothermia (MH; 33°C) in patients with severe middle cerebral artery (MCA) infarction was published in 1998. Hypothermia was induced at a mean of 14 h after symptom onset and maintained over 72 h. Mortality was only 44%, while survivors reached a favorable outcome, with a mean Barthel index of 70, despite the fact that all patients fulfilled the criteria for diagnosis of a “malignant” MCA infarction. Although hypothermia significantly reduced the intracranial pressure (ICP), a secondary rise of ICP, occasionally exceeding initial levels and requiring additional treatment with osmotherapeutics, was observed on rewarming. Similar results were recently published. from a multicenter observational study, which described 50 prospective patients with cerebral infarction involving at least the complete MCA territory treated with MH (33°C). Overall mortality was 38%, divided into 8% during hypothermia and 30% during rewarming, due to uncontrollable ICP increase. Neurological outcome was 28 (National Institutes of Health Stroke Scale; NIHSS) and 2.9 (Rankin Scale) 4 weeks and 3 months after stroke, respectively. Krieger et al. reported initial results from ten patients with acute ischemic stroke (NIHSS 19.8 ± 3.3), who were treated with MH (32°C) after thrombolysis. Mortality was 33%, while the mean modified Rankin Scale score at 3 months was 3.1 ± 2.3. Pneumonia was the only severe side effect of MH in the study of Schwab et al. The most frequent complications of MH encountered in the multicenter trial described above were thrombocytopenia (70%), bradycardia (62%) and pneumonia (48%). Four patients (8%) died during hypothermia, due to severe coagulopathy, cardiac failure, or uncontrollable intracranial hypertension. Hemicraniectomy (CE) and MH constitute promising treatment modalities for space-occupying cerebral infarction. To date, only one study has compared their effectivenes in controlling intracranial hypertension and reducing mortality. A total of 36 patients with severe acute ischemic stroke were treated with CE (n = 17) or MH (n = 19). Mortality was 12% for CE and 47% for MH, respectively, whereby 1 patient treated with MH died on treatment complications (sepsis) and 3 died on ICP crisis, which occurred during rewarming. It was concluded that in patients with acute ischemic stroke, CE results in a lower mortality and lower complication rates as compared to MH. However, this result remains to be confirmed in large-scale trials.