Therapeutic hypothermia for head injury

Induced hypothermia has been used in the treatment of head injury for many years. Encouraging results from small trials and laboratory studies led to renewed interest in the area and some larger trials.

To estimate the effects of mild induced hypothermia in moderate and severe head injury on mortality, long-term functional outcome, complications, and short-term control of intracranial pressure (ICP).

We searched the Injuries Group Specialised register (last searched in 2001), Medline, EMBASE and the Cochrane Controlled Trials Register. We handsearched conference proceedings and checked reference lists of relevant articles.

Randomised controlled trials of mild hypothermia to 34-35 Celsius for a t least 12 hours versus control (open or normothermia) in patients with any closed head injury requiring hospitalisation. Two reviewers independently assessed all trials.

Data on death, Glasgow Outcome Scale, complications and ICP were sought and extracted, either from published material or by contacting the investigators. Odds ratios and 95% confidence intervals were calculated for each trial on an intention-to-treat basis. Quantitative synthesis of data on complications other than pneumonia or ICP was not attempted. Trials of immediate and deferred hypothermia were analysed separately.

We found 12 trials with 812 participants. Active immediate hypothermia was associated with an odds ratio for death of 0.88, (771 patients, OR 0.88, 95% CI 0.63 to 1.21), and 0.75 for odds of being dead or severely disabled, (746 patients, OR 0.75, 95% CI 0.56 to 1.00). Hypothermia treatment was associated with a statistically significant increase in odds of pneumonia (281 patients, OR 1.95, 95% CI 1.18 to 3.23). The trial of deferred hypothermia (33 patients) reported a huge but not statistically significant reduction in the odds of death at 6 months, (OR 0.21, 95% CI 0.04 to 1.05). For death or severe disability deferred hypothermia was associated with an odds ratio of 0.10 (95% CI 0.01 to 1.00).

There is no evidence that hypothermia is beneficial in the treatment of head injury. The earlier, encouraging, trial results have not been repeated in larger trials. The reasons for this are unclear. Hypothermia increases the risk of pneumonia and has other potentially harmful side effects. Therefore, it would seem inappropriate to use this intervention outside of controlled trials in subgroups of patients for whom there is good reason to think the treatment would be beneficial.