Four additional studies [48,52,55,58] observed a trend to improved outcome, but these differences were not statistically significant.In contrast, one of the two largest multi-centre randomised controlled trials (RCTs) failed to show that induced hypothermia http://www.selleckchem.com/products/MG132.html improved outcome at 6 months after TBI (relative risk [RR] of a poor outcome 1; 95% confidence interval [CI] 0.8 to 1.2; P = 0.99) [46]. Significantly more of the patients admitted to hospital with hypothermia who were randomly assigned to normothermia, and consequently re-warmed, had a poor outcome (78%, n = 31) compared with patients admitted with hypothermia and treated with hypothermia (61%, n = 38) (P = 0.09).
On subsequent analysis, it became clear that although this study was methodologically well designed, there was marked inter-centre variance in the treatment effect of hypothermia, age of participants, severity of illness scoring between groups, management of intracranial hypertension, and haemodynamic and fluid management [64]. Induced hypothermia in the hypothermia group was started relatively late with a slow speed of cooling (average time to target temperature of more than 8 hours) in all centres.Hypotension (lasting more than 2 hours) and hypovolaemia occurred three times more frequently in the hypothermia group. Bradycardia associated with hypotension occurred four times more frequently in this group, and electrolyte disorders and hyperglycaemia were also found more frequently in the hypothermia group [46]. All of these complications are known side effects of hypothermia.
Most are easily preventable with good intensive care and should not be regarded as inevitable consequences of hypothermia treatment. Since even very brief episodes of hypotension or hypovolaemia can adversely affect outcome in TBI, these and other issues may have significantly affected the results of this trial [65-67]. One possible problem was that some of the participating centres had little or no previous experience in using hypothermia. Large centres familiar with cooling showed apparently favourable neurological outcomes whereas smaller centres showed poor outcomes.Induction of hypothermiaThe most widely accepted use of hypothermia is after cardiac arrest. Two RCTs in this patient group have shown significant neurological improvements in patients who were treated with hypothermia many hours after injury and whose initial cardiac rhythm was ventricular fibrillation or ventricular tachycardia [68,69].
Subsequent data from a large study of patients after myocardial infarction suggest that infarct size was reduced in patients who were cooled to less than 35��C before coronary intervention [70], thus suggesting that faster cooling rates may be beneficial to patient outcome.Methods Cilengitide of cooling can be broadly divided into surface and core cooling techniques [71].