Correspondence

404 www.thelancet.com/neurology Vol 10 May 2011

Hypothermia in patients with brain injury: the way forward?

In the National Acute Brain Injury Study: Hypothermia II (NABIS: H II), re-ported by Guy Clifton and colleagues,1 the target temperature of 33°C was reached in 4·4 h, and patients in the hypothermia group were cooled for 48 h and then rewarmed by 0·5°C every 2 h. As a result, hypothermia did not improve outcome in these patients.

We agree with Maas and Stocchetti2 that a period of 48 h of hypothermia might be too short to have a benefi cial eff ect on outcome. We would like to emphasise that the rate of rewarming is also an important variable that infl uences the protective eff ects of hypothermic intervention after traumatic brain injury. Povlishock and Wei’s review3 showed that hypothermia followed by rapid rewarming not only reversed the protective eff ects associated with hypothermic intervention but also, in some cases, exacerbated the traumatically induced pathology and its functional consequences. Suehiro and Povlishock4 have shown that rapid rewarming could exacerbate the progression of traumatically induced axonal change in a rat model. Whether rewarming patients by 0·5°C every 2 h was appropriate is not clear, because the optimum rate is unknown. Reported rates of rewarming range from 0·5°C every 2 h to 1°C per day.5 However, we believe that a slower rewarming might be a better therapeutic strategy. We have no confl icts of interest.

Satoru Takeuchi, Hiroshi Nawashiro, Naoki Otanis.takeuchi@room.ocn.ne.jp

Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

1 Clifton GL, Valadka A, Zygun D, et al. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol 2011; 10: 131–39.

2 Maas A, Stocchetti N. Hypothermia and the complexity of trials in patients with traumatic brain injury. Lancet Neurol 2011; 10: 111–13.

3 Povlishock JT, Wei EP. Posthypothermic rewarming considerations following traumatic brain injury. J Neurotrauma 2009; 26: 333–40.

4 Suehiro E, Povlishock JT. Exacerbation of traumatically induced axonal injury by rapid posthypothermic rewarming and attenuation of axonal change by cyclosporin A. J Neurosurg 2001; 94: 493–98.

5 Sydenham E, Roberts I, Alderson P. Hypothermia for traumatic head injury. Cochrane Database Syst Rev 2009; 2: CD001048.

described in previous studies.2,4 Clifton and co-workers do not describe the timing of intracranial pressure increases. We urge them to review their data to assess whether these increases occurred during rewarming. Evidence suggests that in patients with traumatic brain injury the effi cacy of cooling crucially depends on treatment duration.2,4 Five meta-analyses have reported risk reductions of poor neurological outcome of 22–39%,2 and treatment duration of more than 48 h was a key factor for effi cacy.2,4

Brain oedema usually peaks 1–3 days after injury; rewarming while brain oedema is still present might result in intracranial pressure increases, reversing any potential benefi ts and possibly even worsening outcome.2 This notion could explain the trend to worse outcome in patients with diff use brain injury observed in this trial. Such rebound hypertension could be prevented by extending the treatment period until brain oedema has cleared and, importantly, by preventing post-hypothermia pyrexia.2 A large European trial using hypothermia to control intracranial pressure (Eurotherm3235Trial) is in progress, with treatment duration being determined by intracranial pressure.6 Knowledge of whether the hypothermia-associated increases in intracranial pressure reported in NABIS: H II did in fact occur during rewarming would be crucial for this ongoing study. We have no confl icts of interest.

Kees H Polderman, Peter J D Andrews k.polderman@tip.nl

Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA (KHP); and Centre for Clinical Brain Sciences,

University of Edinburgh, Edinburgh, UK (PJDA)

1 Clifton GL, Valadka A, Zygun D, et al. Very early hypothermia induction in patients with severe brain injury (National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol 2011; 10: 131–39.

2 Polderman KH. Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet 2008; 371: 1955–69.

Results of the National Acute Brain Injury Study: Hypothermia II (NABIS: H II) have shown that early induction of hypothermia did not improve out-come in patients with severe trau-matic brain injury, although apparent benefi ts were recorded in patients undergoing surgical evacuation of haematomas.1 Remarkably, and by contrast with previous studies of hypo thermia in traumatic brain injury,2–4 Guy Clifton and colleagues1 report that intracranial pressure was higher in the intervention group than in the control group. This rise in intracranial pressure occurred predominantly in patients with diff use injury rather than in those with evacuated haematomas. Indeed, a clear trend to worse outcome was detected in the intervention subgroup, largely balanced by better outcomes in patients with evacuated haematomas in whom intracranial pressure did not increase.1

The investigators attribute this surprising fi nding to their rigorous measures to reduce hypotension. To us, this explanation seems improbable. Previous hypothermia studies using rigorous measures to prevent hypotension have never reported increases in intracranial pressure associated with cooling.2,4,5 Furthermore, given that all study patients were treated according to the same protocol, why such rises occur predominantly in one subgroup is diffi cult to explain.

A more likely explanation would be a rise in intracranial pressure during rewarming—an occurrence