Mild resuscitative hypothermia in comatose patients of out-of-hospital cardiac arrest: A preliminary clinical feasibility trial

ABSTRACT

PURPOSE: No proven neuroprotective treatment exists for ischemic brain damage after cardiac arrest (CA). Although several animal studies have shown that mild to moderate hypothermia markedly mitigates ischemic brain damage after CA, the clinical safety and efficacy of mild hypothermia remain unproven. We conducted this preliminary study to evaluate the clinical feasibility and safety of mild resuscitative hypothermia (RH) for comatose patients of out-of-hospital CA. METHODS: We performed prospectively a preliminary, non-randomized, uncontrolled, clinical feasibility trial over four years in a university-based hospital. Consecutive patients admitted or transferred to the emergency medical center after out-of-hospital CA who met inclusion and exclusion criteria were enrolled. Hypothermia was induced as soon as possible after return of spontaneous circulation (ROSC) by using external surface cooling methods and cold saline gastric lavage at the target temperature (34 degrees C) and was maintained for 24 hours by using external surface cooling methods, which was followed by passive rewarming. RESULTS: Twelve patients were enrolled. Mean arrest time was 20+/-12 minutes (range 2 to 40); the mean advanced cardiac life support (ACLS) time was 12+/-8 minutes (range 4 to 27) and the mean time from start of ACLS to initiation of RH was 129 +/-113 minutes (range 40 to 420). Achieving the target temperature took 160+/-79 minutes (range 80 to 330) and the mean rewarming time was 605+/-190 minutes (range 360 to 960). One patient developed transient atrial fibrillation and premature ventricular complex during the induction period. Hypotension developed in six patients during hypothermia, pneumonia associated with induced hypothermia developed in four patients. Other complications, such as myoclonus (n=4), increased serum amylase (n=7), increased serum creatinine (n=2), and potassium abnormalities (n=2), also occurred. These complications occurred more frequently in patients with poor cardiac function after ROSC. No serious complications, such as ventricular fibrillation, bleeding, or sepsis, occurred. CONCLUSION: Mild RH after CA appears clinically feasible. However, induction with surface external cooling methods is slow, and maintenance of mild hypothermia was difficult. Future efforts to shorten the induction time and to develop more effective maintenance methods and more cautious applications to patients with poor cardiac function after ROSC are needed. Furthermore, well-designed, prospective, randomized, and controlled, multi-center efficacy trials are needed to evaluate the effect of mild RH.