A randomized controlled trial of therapeutic hypothermia in severe head-injured patients in Japan: Overview of the protocol

Protection against brain insults is one of the most difficult aspects of clinical practice. Recently, mild hypothermia has been applied to cardiopulmonary resuscitated victims and brain-protective effects were proved by two randomized, controlled trials (RCT). Clifton's group applied mild hypothermia therapy in severe head-injured cases (Glasgow Coma Scale; GCS < 8), but failed to prove any effectiveness. Our aim is to apply mild hypothermia therapy as a RCT in 300 traumatic brain injury cases in 40 medical centers in Japan. Inclusion criteria are: (1) GCS 4-8, except best motor response of 6; (2) core body temperature must be reduced to less than 35.5degreesC at 6 h after head injury in the mild hypothermia group; (3) age less than or equal to 15 to <70 years old. Patients are randomized into either a control group (35.5degrees-37.0degreesC, 100 patients) or a mild hypothermia group (32.0degrees-34.0degreesC, 200 patients). Core body temperature must be controlled for at least 72h in the two groups and may be prolonged, if necessary. Brain-oriented intensive care is required; physiologic parameters are qualified by cardiac index, as well as internal jugular venous oxygen saturation and temperature, which are recorded and stored in a computer in every 1 min. Evaluations of the effect of mild hypothermia therapy are carried out using the Glasgow Outcome Scale at 3 and 6 months, and by biochemical parameters such as cytokines, free radical products, and neurotoxic excitatory amino acids between the two groups. At this point in time, 74 patients have been enrolled.