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Original Investigation
January 18, 2019

Outcomes of Hypothermia in Addition to Decompressive Hemicraniectomy in Treatment of Malignant Middle Cerebral Artery Stroke: A Randomized Clinical Trial

Author Affiliations
  • 1Department of Neurology, RKU–University and Rehabilitation Hospitals Ulm, University of Ulm, Ulm, Germany
  • 2Department of Neurology, University Hospital, Technische Universität Dresden, Dresden, Germany
  • 3Department of Neurology, Universitätsklinikum Augsburg, Augsburg, Germany
  • 4Department of Neurology, University of Heidelberg, Heidelberg, Germany
  • 5Department of Neurology, Klinikum Kassel, Kassel, Germany
  • 6Department of Neurology, University of Leipzig, Leipzig, Germany
  • 7Klinikum Saalekreis, Merseburg, Germany
  • 8Department of Neurology, University of Tübingen, Tübingen, Germany
  • 9Department of Neurology, University of Erlangen, Erlangen, Germany
  • 10Department of Neurology and Neurointensive Care, Klinikum Darmstadt, Darmstadt, Germany
  • 11Department of Neurology and Center for Stroke Research Berlin, Charité–Universitätsmedizin Berlin, Berlin, Germany
  • 12Department of Neurology, Johanna-Etienne-Krankenhaus Neuss, Neuss, Germany
  • 13Department of Neurosurgery, Charité–Universitätsmedizin Berlin, Berlin, Germany
  • 14Center for Stroke Research Berlin, Charité–Universitätsmedizin Berlin, Berlin, Germany
  • 15Institute of Statistics, University of Ulm, Ulm, Germany
  • 16Institute for Clinical Epidemiology and Biometry, Comprehensive Heart Failure Centre, University of Würzburg, Würzburg, Germany
  • 17Clinical Trial Center, University Hospital Würzburg, Würzburg, Germany
  • 18Department of Neurology, Ostalb-Klinikum Aalen, Aalen, Germany
JAMA Neurol. 2019;76(5):571-579. doi:10.1001/jamaneurol.2018.4822
Key Points

Question  Does moderate hypothermia after decompressive hemicraniectomy reduce early mortality in patients with malignant stroke?

Findings  This randomized clinical trial investigated the effects and safety of moderate hypothermia (temperature, 33°C ± 1°C) after hemicraniectomy in 50 patients 60 years and younger who had malignant stroke. Mortality at day 14 was not significantly different between the hypothermia group and the control group; the trial was terminated early for safety reasons because of a higher rate of serious adverse events in the hypothermia group.

Meaning  Moderate hypothermia after hemicraniectomy did not improve early mortality but may be harmful to patients with malignant stroke.

Abstract

Importance  Moderate hypothermia in addition to early decompressive hemicraniectomy has been suggested to further reduce mortality and improve functional outcome in patients with malignant middle cerebral artery (MCA) stroke.

Objective  To investigate whether moderate hypothermia vs standard treatment after early hemicraniectomy reduces mortality at day 14 in patients with malignant MCA stroke.

Design, Setting, and Participants  This randomized clinical trial recruited patients from August 2011 through September 2015 at 6 German university hospitals with dedicated neurointensive care units. Of the patients treated with hemicraniectomy and assessed for eligibility, patients were randomly assigned to either standard care or moderate hypothermia. Data analysis was completed from December 2016 to June 2018.

Interventions  Moderate hypothermia (temperature, 33.0 ± 1.0°C) was maintained for at least 72 hours immediately after hemicraniectomy.

Main Outcomes and Measures  The primary outcome was mortality rate at day 14 compared with the Fisher exact test and expressed as odds ratio (ORs) with 95% CIs. Rates of patients with serious adverse events were estimated for the period of the first 14 days after hemicraniectomy and 12 months of follow-up. Secondary outcome measures included functional outcome at 12 months.

Results  Of the 50 study participants, 24 were assigned to standard care and 26 to moderate hypothermia. Twenty-eight were male (56%); the mean (SD) patient age was 51.3 (6.6) years. Recruitment was suspended for safety concerns: 12 of 26 patients (46%) in the hypothermia group and 7 of 24 patients (29%) receiving standard care had at least 1 serious adverse event within 14 days (OR, 2.05 [95% CI, 0.56-8.00]; P = .26); after 12 months, rates of serious adverse events were 80% (n = 20 of 25) in the hypothermia group and 43% (n = 10 of 23) in the standard care group (hazard ratio, 2.54 [95% CI, 1.29-5.00]; P = .005). The mortality rate at day 14 was 19% (5 of 26 patients) in the hypothermia group and 13% (3 of 24 patients) in the group receiving standard care (OR, 1.65 [95% CI, 0.28-12.01]; P = .70). There was no significant difference regarding functional outcome after 12 months of follow-up.

Interpretation  In patients with malignant MCA stroke, moderate hypothermia early after hemicraniectomy did not improve mortality and functional outcome compared with standard care, but may cause serious harm in this specific setting.

Trial Registration  http://www.drks.de, identifier DRKS00000623

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