January 16, 2019

Article Review – NEXT Journal Review Club

Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury.


Severe traumatic brain injury is a leading cause of neurologic disability, and approximately 50% of patients have long-term outcomes of death or severe disability [1-2-3]. The economic and social costs of severe traumatic brain injury are high [4]. The authors of this multicentre randomised trial investigated how an early Prophylactic Hypothermia can attenuate cerebral inflammatory and biochemical cascades, thereby limiting secondary brain injury [5-6]. This may, however, contribute to coagulopathy, immunosuppression, bleeding, infection, and dysrhythmias after trauma.

The aim of this investigation was to determine the effectiveness of early prophylactic hypothermia in terms of favourable neurologic outcomes or independent living (Glasgow Outcome Scale–Extended score, 5-8 [scale range, 1-8]) obtained by blinded assessors 6 months after injury.

Eligible patients with head injuries were estimated to be aged 18 to 60 years old, had a Glasgow Coma Scale (GCS) score of less than 9, and had current or imminent endotracheal intubation. Out-of-hospital exclusion criteria included significant bleeding suggested by systolic hypotension (<90 mm Hg) or sustained tachycardia (>120/min), suspected pregnancy, possible uncontrolled bleeding, GCS of 3 and unreactive pupils, or destination hospital not a study site.

Participants were randomly assigned 1:1 to prophylactic hypothermia or to controller normothermia. In the first group, the hypothermia was induced by a bolus of up to 2000 mL intravenous ice-cold 0.9% saline and surface-cooling wraps targeting an initial core temperature of 35°C. Once the significant risk factors for bleeding were excluded, a core temperature was reduced to 33°C ± 0.5°C. Intracranial pressure (ICP) monitors were inserted according to usual site practice and hypothermia was maintained at this target for at least 72 hours after randomisation.

If ICP < 20 mmHg, gradual controlled re-warming was commenced 0.25°C/h. If during re-warming ICP > 20 mmHg, the patient was re-cooled and then re-assessed regularly for suitability for re-warming. The maximum period of hypothermia was 7 days post randomisation. In the Normothermia Group, the temperature target was 37°C ± 0.5°C. Surface-cooling wraps could be used to manage pyrexia or refractory intracranial hypertension.

511 consecutive critically ill patients with severe traumatic brain injury, over an 8-year period, from 2010 to 2018, in six countries, both out-of-hospital and in emergency departments. 466 completed the primary outcome evaluation. Hypothermia was initiated rapidly after injury (median, 1.8 hours [IQR, 1.0-2.7 hours]) and re-warming occurred slowly (median, 22.5 hours [IQR, 16-27 hours]). In risk with Hypothermia, 0.99 [95%CI, 0.82-1.19]; P=0.94). In the Hypothermia and Normothermia groups. In the Hypothermia group, 33% of patients received less than 48 hours of Hypothermia (33°C-35°C), and 27% never reached the final target temperature of 33°C.



Favourable outcomes (Glasgow Outcome Scale–Extended score, 5-8) at 6 months occurred in 117 patients (48.8%) in the Hypothermia group and 111 (49.1%) in the Normothermia group (risk difference, 0.4% [95% CI, –9.4%to 8.7%]; relative, the rates of Pneumonia were 55.0% vs 51.3%, respectively, and rates of increased intracranial bleeding were 18.1% vs 15.4%, respectively.



Early Prophylactic Hypothermia compared with Normothermia did not improve neurologic outcomes at 6 months among patients with severe traumatic brain injury.


This article review was prepared and submitted by Temistocle Taccheri, Department of Anaesthesiology & Intensive Care Medicine, A Gemelli School of Medicine, University of Sacred Heart, Rome, on behalf of the ESICM NEXT Journal Review Club.


1) Maas AIR, Menon DK, Adelson PD, et al; InTBIR Participants and Investigators. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol.2017;16(12):987-1048. doi:10.1016/S1474-4422(17) 30371-X

2) Myburgh J, Cooper DJ, Finfer S, et al; SAFE Study Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group; Australian Red Cross Blood Service; George Institute for International Health. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med. 2007;357(9):874-884. doi:10.1056 /NEJMoa067514

3) Nichol A, French C, Little L, et al; EPO-TBI Investigators; ANZICS Clinical Trials Group. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. Lancet. 2015;386(10012):2499-2506. doi:10.1016/S0140-6736(15)00386-4

4) Access Economics Pty Limited for the Victorian Neurotrauma Initiative. The economic cost of spinal cord injury and traumatic brain injury in Australia.

5) Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009;37(7)(suppl): S186-S202. doi:10.1097/CCM.0b013e3181aa5241

6) Sahuquillo J, Vilalta A. Cooling the injured brain: how does moderate hypothermia influence the pathophysiology of traumatic brain injury? Curr Pharm Des. 2007;13(22):2310-2322. doi:10.2174/138161207781368756


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