Keeping body temperature at 33°C after hemicraniectomy for large middle cerebral artery (MCA) strokes didn’t improve early outcomes but did increase risks, a randomized clinical trial found.
Moderate hypothermia for 72 hours had a 65% higher relative risk of 14-day mortality compared with standard care in the small group of patients treated before suspension of the trial for safety concerns. The 19% rate (five of 26 patients) wasn’t significantly higher than the 13% (three of 24 patients, P=0.70).
More than twice as many patients had at least one adverse event at 14 days with hypothermia (46% vs 29%, P=0.26), reported Hermann Neugebauer, MD, MSc, of RKU–University and Rehabilitation Hospitals Ulm in Germany, and colleagues in JAMA Neurology.
Rates of adverse events continued to rise to 80% versus 43% among the standard care group out to 12 months, the investigators found.
Therapeutic hypothermia has worked in animal models following focal cerebra ischemia and on global cerebral ischemia following cardiac arrest.
Previous research suggested that outcomes in malignant MCA stroke might be better with simultaneous use of hypothermia following an improved protocol and early hemicraniectomy. “Key elements of hypothermia in such a protocol are (1) early initiation after hemicraniectomy, (2) target level of cooling between 32°C and 34°C, (3) duration of hypothermia at least 72 hours, and (4) controlled induction, maintenance, and rewarming by feedback systems,” the researchers wrote.
A small prior investigation combining hypothermia and hemicraniectomy did not demonstrate an increased risk of complications and severe adverse effects, Neugebauer’s group noted.
However, Neugebauer’s trial “convincingly demonstrates lack of benefit of hypothermia in patients treated with hemicraniectomy for malignant middle cerebral artery syndrome,” noted Mark Fisher, MD, of the University of California Irvine, who was not involved in the study.
“While there was some uncertainty on this issue based on several prior small scale studies, the findings of Neugebauer et al. do not encourage further investigation of the use of hypothermia in this patient population,” Fischer told MedPage Today.
Neugebauer’s group randomized 26 patients to the moderate hypothermia group and 24 patients to the control group at six German university hospitals, all of which had neurointensive care units. The participants were a mean age of 51.3 years, 56% were male, and all had malignant MCA stroke.
Patients were treated with hemicraniectomy, and then subsequently held at moderate hypothermia (temperature 33º C ± 1º C) for at least 72 hours.
At 12 month follow-up, there was no significant difference in functional outcomes.
Overall, the investigation was well-designed and likely generalizable for patients with malignant MCA syndrome, Fisher emphasized.
Despite the findings of this investigation, the researchers did not rule out the potential benefit of hypothermia in different settings of stroke treatment, including duration of target temperature or hypothermia, or in different stroke subtypes and initiation.
“Currently, the use of hypothermia cannot be recommended in patients with malignant MCA stroke outside clinical trials,” they concluded.
The study was funded by the Center for Stroke Research Berlin, Charité–Universitätsmedizin Berlin, and participating centers.
Neugebauer disclosed relationships with Boehringer Ingelheim, Bayer, and Daiichi-Sankyo.
Fisher reported no disclosures.