Abstract 6: Impact of Therapeutic Hypothermia Onset and Duration on Survival and Neurologic Function After Pulseless Electrical Activity/Asystole Cardiac Arrest
Introduction: Post-cardiac arrest therapeutic hypothermia (TH) improves survival and neurologic outcome in comatose survivors of witnessed out-of-hospital VF cardiac arrest. However, the efficacy of TH after non-VF cardiac arrest is less well documented. Furthermore, the optimal onset and duration of TH remain unknown. This study tests the hypothesis that the efficacy of TH after PEA/asystole cardiac arrest is dependent on the onset and duration of therapy.
Methods: Adult male Long Evans rats that achieved ROSC after a 10-min asphyxial cardiac arrest were block randomized to normothermia (37±1°C, n=32) or TH (33±1°C) initiated 0, 1, 4, or 8 hrs after ROSC and maintained for 24 or 48 hrs (8 groups, n=16 per group). Target temperature was achieved within 30 min of initiating TH, and rats were rewarmed at a rate of 0.25° C/hr. Core body temperature was regulated using a computerized telemetric feedback system that controls a fan, mister, and heating lamp. Primary outcomes were 7-day survival and survival with good neurologic function (GNF). GNF was defined as a neurologic function score ≥450 out of 500.
Results: Overall TH improved 7-day survival compared to normothermia (29% vs. 19%, p<0.05 log rank). Survival of rats treated with TH for 24 hrs vs. 48 hrs was not statistically different (31% vs. 25% p=0.51 log rank). TH initiated at 0, 1, 4, and 8 hours after ROSC resulted in survival rates of 41%, 28%, 31%, and 16% respectively. Only TH initiated immediately after ROSC was statistically different from normothermia (Cox model HR 0.52, 95% CI 0.29 to 0.94). Survival with GNF was 3% with normothermia, 11% with 24-hr TH, and 11% with 48-hr TH. TH initiated at 0, 1, 4, or 8 hrs after ROSC resulted in survival with GNF of 13%, 16%, 16%, and 0% respectively. Individual group differences were not statistically different.
Conclusions: Post-cardiac arrest TH improves survival after PEA/asystole cardiac arrest caused by asphyxia. We found no evidence that TH maintained for 48 hrs was superior to 24 hrs. TH initiated immediately after ROSC appeared to have the highest survival benefit while TH initiated 0, 1 or 4 hrs after ROSC resulted in equivalent survival with GNF.