Temperature control in acute brain injury

Intensive Care Medicine: Published 20 April 2026

Purpose

Temperature is a key determinant of cerebral vulnerability after acute brain injury and a physiological variable that can be continuously monitored and actively controlled in the intensive care unit. Its therapeutic role has evolved from hypothermia-centred strategies toward early recognition of fever and controlled normothermia. This review examines the physiological rationale, clinical evidence, and contemporary practice of temperature management in neurocritical care.

Methods

We synthesised evidence from major randomised trials, observational studies, and international consensus recommendations across traumatic brain injury, acute vascular brain injury, and post-cardiac arrest encephalopathy, together with current monitoring and implementation approaches.

Results

Fever is consistently associated with worse neurological outcomes. In traumatic brain injury, hypothermia reduces intracranial pressure but does not improve functional outcome when used prophylactically and is reserved for refractory intracranial hypertension. In acute vascular brain injury, neutral trials and feasibility constraints have shifted practice toward early detection and treatment of fever rather than hypothermia. In post-cardiac arrest care, contemporary guidelines recommend protocolised temperature control with selection and maintenance of a constant target between 32°C and 37.5°C and active prevention of fever, rather than mandatory hypothermia.

Conclusions

Temperature control is a fundamental component of care aimed at protecting the injured brain through continuous monitoring, early detection of fever, and prevention of temperature-related harm.

 

Hypothermia versus normothermia in patients with cardiac arrest and shockable rhythm: a secondary analysis of the TTM-2 study

Critical Care volume 28, Article number: 335, Published: 15 October 2024

Background

The aim of this study was to assess whether hypothermia increased survival and improved functional outcome when compared with normothermia in out-of-hospital cardiac arrest (OHCA) patients with similar characteristics than in previous randomized studies showing benefits for hypothermia.

Methods

Post hoc analysis of a pragmatic, multicenter, randomized clinical trial (TTM-2, NCT02908308). In this analysis, the subset of patients included in the trial who had similar characteristics to patients included in one previous randomized trial and randomized to hypothermia at 33 °C or normothermia (i.e. target < 37.8 °C) were considered. The primary outcome was survival at 6 months; secondary outcomes included favorable functional outcome at 6 months, defined as a modified Rankin scale of 0–3. Time-to-death and the occurrence of adverse events were also reported.

Results

From a total of 1891 included in the TTM-2 study, 600 (31.7%) were included in the analysis, 294 in the hypothermia and 306 in the normothermia group. At 6 months, 207 of the 294 patients (70.4%) in the hypothermia group and 220 of the 306 patients (71.8%) in the normothermia group had survived (relative risk with hypothermia, 0.96; 95% confidence interval [CI], 0.81 to 1.15; P = 0.71). Also, 198 of the 294 (67.3%) in the hypothermia group and 202 of the 306 (66.0%) in the normothermia group had a favorable functional outcome (relative risk with hypothermia, 1.03; 95% CI, 0.87 to 1.23; P = 0.79). There was a significant increase in the occurrence of arrythmias in the hypothermia group (62/294, 21.2%) when compared to the normothermia group (43/306, 14.1%—OR 1.49, 95% CI 1.05–2.14; p = 0.026).

Conclusions

In this study, hypothermia at 33˚C did not improve survival or functional outcome in a subset of patients with similar cardiac arrest characteristics to patients in whom benefit from hypothermia was shown in prior studies.

 

Fever and hypothermia represent two populations of sepsis patients and are associated with outside temperature

 

by Daniel O. Thomas-Rüddel, Peter Hoffmann, Daniel Schwarzkopf, Christian Scheer, Friedhelm Bach, Marcus Komann, Herwig Gerlach, Manfred Weiss, Matthias Lindner, Hendrik Rüddel, Philipp Simon, Sven-Olaf Kuhn, Reinhard Wetzker, Michael Bauer, Konrad Reinhart and Frank Bloos 

 

Critical Care volume 25, Article number: 368 (2021) 

 

Background

Fever and hypothermia have been observed in septic patients. Their influence on prognosis is subject to ongoing debates.

Methods

We did a secondary analysis of a large clinical dataset from a quality improvement trial. A binary logistic regression model was calculated to assess the association of the thermal response with outcome and a multinomial regression model to assess factors associated with fever or hypothermia.

Results

With 6542 analyzable cases we observed a bimodal temperature response characterized by fever or hypothermia, normothermia was rare. Hypothermia and high fever were both associated with higher lactate values. Hypothermia was associated with higher mortality, but this association was reduced after adjustment for other risk factors. Age, community-acquired sepsis, lower BMI and lower outside temperatures were associated with hypothermia while bacteremia and higher procalcitonin values were associated with high fever.

Conclusions

Septic patients show either a hypothermic or a fever response. Whether hypothermia is a maladaptive response, as indicated by the higher mortality in hypothermic patients, or an adaptive response in patients with limited metabolic reserves under colder environmental conditions, remains an open question.

A lesson on induction of hypothermia and measurement of efficacy

A lesson on induction of hypothermia and measurement of efficacy. Critical Care 2014, 18:710

Harris, B.A. and Andrews, P.J.D.

http://ccforum.com/content/18/6/710

Brain injuries caused by stroke are common and costly in human and resource terms. The result of stroke is a cascade of molecular and physiological derangement, cell death, damage and inflammation in the brain. This, together with infection, if present, commonly results in patients having an increased temperature, which is associated with worse outcome. The usual clinical goal in stroke is therefore to reduce temperature to normal, or below normal (hypothermia) to reduce swelling if brain pressure is increased. However, research evidence does not yet conclusively show whether or not cooling patients after stroke improves their longer-term outcome (reduces death and disability). It is possible that complications of cooling outweigh the benefits. Cooling therapy may reduce damage and potentially improve outcome, and head cooling targets the site of injury and may have fewer side effects than systemic cooling, but the evidence base is unclear.

Revisiting therapeutic hypothermia for severe traumatic brain injury...again

Revisiting therapeutic hypothermia for severe traumatic brain injury...again. Critical Care 2014, 18: 160

Marion, D.W. and Regasa, L.E.

http://ccforum.com/content/18/3/160

Improved understanding of the molecular mechanisms of secondary brain injury has informed the optimum depth and duration of cooling and led to increased clinical interest in the therapeutic moderate hypothermia for severe traumatic brain injury over the past two decades. Although several large multi-center clinical trials have not found a treatment effect, multiple single-center trials have, and a recent meta-analysis by Crossley and colleagues now finds that the cumulative findings of those single-center trials dilute the multi-center trial results and show an overall reduction in mortality and poor outcomes associated with cooling. The need for consistent support of key physiologic parameters during cooling is emphasized by this finding.

A systematic review of therapeutic hypothermia for adult patients following traumatic brain injury

A systematic review of therapeutic hypothermia for adult patients following traumatic brain injury. Critical Care 2014, 18:R75

Crossley, S., et al.

http://ccforum.com/content/pdf/cc13835.pdf

Research into therapeutic hypothermia following traumatic brain injury has been 
characterised by small trials of poor methodological quality, producing variable results. The 
Cochrane review, published in 2009, now requires updating. The aim of this systematic 
review is to assess the effectiveness of the application of therapeutic hypothermia to reduce 
death and disability when administered to adult patients who have been admitted to hospital 
following traumatic brain injury. 

Therapeutic hypothermia: is it effective for non-VF/VT cardiac arrest?

Therapeutic hypothermia: is it effective for non-VF/VT cardiac arrest? Critical care, March 2013, 17: 215

Sandroni, C., et al.

http://ccforum.com/content/pdf/cc12524.pdf

Sudden cardiac death represents a major health problem. In adults, the prevalence of out-of-hospital cardiac arrest (OHCA) attended by the emergency medical services (EMS) ranges from 52 to 112 per 100,000 person-years in developed countries, whereas the prevalence of adult in-hospital cardiac arrest (IHCA) ranges from 1 to 5 per 1,000 patient admissions. Mortality from cardiac arrest exceeds 90 % in OHCA 
and 70 % in most studies on IHCA. Patients who have a shock able rhythm, i.e., ventricular fibrillation 
(VF) or pulseless ventricular tachycardia (VT), on initial electrocardiogram (EKG) have a consistently higher 
survival than those whose initial cardiac rhythm is nonshockable, i.e., asystole or pulseless electrical activity 
(PEA).

Hypothermia on arrival in the intensive care unit after surgery

Hypothermia on arrival in the intensive care unit after surgery
Author(s): Karalapillai , D . ; Story , D .
ISSUE: 2008 ; VOL 10 ; PART 2
Access: Critical Care and Resuscitation
Page: 116-119
Search the Web: [article] [author(s)]

Mild therapeutic hypothermia shortens intensive care unit stay of survivors after out-of-hospital cardiac arrest compared to historical controls

Research
Storm C, Steffen I, Schefold JC, Krueger A, Oppert M, Jörres A, Hasper D
Critical Care 2008, 12:R78 (14 June 2008)
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