New Research in the Field of Stroke: Therapeutic Hypothermia after Cardiac Arrest

Abstract

Therapeutic hypothermia as a potential treatment for stroke, cerebral ischemia, and other neurological diseases has gained momentum since the initial discovery that relatively small differences in intraischemic brain temperature critically determine ischemic neuronal vulnerability.1 Since that time, laboratories throughout the world have investigated the potential use of mild-to-moderate hypothermia in many ischemia models.2,3 Various studies have also investigated potential mechanisms contributing to hypothermic protection. Pathomechanisms sensitive to intra- and postischemic temperature reductions and elevations include glutamate release, stabilization of the blood-brain barrier, oxygen radical production, intracellular signal conduction, protein synthesis, ischemic depolarization, reduced cerebral metabolism, membrane stabilization, inflammation, activation of protein kinases, cytoskeletal breakdown, and early gene expression.2,4 Because the pathophysiology of ischemic brain injury is complex, the fact that many injury mechanisms have been reported to be temperature sensitive may account for the dramatic effects of temperature on ischemic outcome. Thus, therapeutic hypothermia has the necessary support from preclinical data to initiate well-designed clinical studies targeting various patient populations. In a recent issue of The New England Journal of Medicine , the results of 2 randomized clinical trials showed clearly that mild hypothermia improves neurologic outcome and reduces overall mortality in survivors of out-of-hospital–witnessed cardiac arrest.5,6 In the study from Australia, a total of 77 patients who remained comatose after the return of spontaneous circulation (ROSC) were randomized to receive 12 hours of hypothermia or standard normothermic temperature management.5 In that study, surface cooling was begun in the field and the target temperature of 32°C to 34°C was reached within 2 hours of ROSC. Forty-nine percent of those treated with hypothermia were discharged home or to a rehabilitation facility, as compared with 26% of those not treated with hypothermia ( P =0.046). In the second study from Europe, 9 centers in 5 countries participated, with …