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Updated: Mar 7, 2026

Short-Duration Hypothermia Induction in Rats using Models for Studies examining Clinical Relevance and Mechanisms
Published on: March 3, 2021
Normothermia and Stroke
Jonathan Marehbian1, David M Greer2
1Department of Neurology, Division of Neurocritical Care and Emergency Neurology, Yale University School of Medicine, 15 York Street, Building LLCI, 10th Floor, Suite 1003, New Haven, CT, 06520, USA. jonathan.marehbian@yale.edu.
Opinion Statement:
In the past two decades, there has been much focus on the adverse effect of fever on neurologic outcome, the benefits of hypothermia on functional outcomes, and the interplay of associated complications. Despite decades of experience regarding randomized, safety and feasibility, case-controlled, retrospective studies, there has yet to be a large, randomized, multicenter, clinical trial with the appropriate power to address the potential benefits of targeted temperature modulation compared to hypothermia alone. What remains unanswered is the appropriate timing of initiation, duration, rewarming speed, and depth of targeted temperature management. We learn from the cardiac arrest literature that there is a neuroprotective value to hypothermia and, most recently, near normothermia (36 °C) as well. We have also established that increased depths of cooling are associated with increases in shivering, which warrant more aggressive pharmacologic management. Normothermia also has the advantage of allowing for more rapid clearance of sedating medications and less confounding of neuroprognostication. More difficult to quantify is the increased nursing and patient care complexity associated with moderate hypothermia compared to normothermia. It remains crucial, for those patients who are being considered for hypothermia/normothermia, to be cared for in an experienced ICU, driven under protocol, with aggressive shivering management and an expectation and acceptance of the complications associated with targeted temperature management. If targeted temperature management is not of consideration, then aggressive fever control should be undertaken pharmacologically and non-invasively, as they have been shown to be safe.
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