Abstract

Most combat fatalities result from rapid exsanguination in the field and resuscitation via fluid administration is generally unsuccessful. In a series of experiments over the past 5 years, we have developed a novel approach targeting the use of rapid induction of profound hypothermia by aortic flush to produce a state of suspended animation for delayed resuscitation after experimental exsanguination cardiac arrest in dogs. In over 200 experiments in dogs, exsanguination cardiac arrest was induced by rapid hemorrhage over ~5 min. After the 5-min hemorrhage and an additional 2 min of cardiac arrest, hypothermia (8°–34°C, tympanic temperature) was induced by aortic or femoral flush of ice-cold saline via a balloon catheter. Cardiac arrest was then continued for durations ranging between 15 and 120 min. The specific duration and temperature selected depended on the goals of the specific study. Delayed resuscitation after the predefined suspended animation interval was achieved using cardiopulmonary bypass (for 1–2h), mild hypothermia (34°C to 12h), and 72–90 h of continuous intensive care. In some studies, the insult also included laparotomy, splenectomy, and thoracotomy, to simulate trauma. In other studies, pharmacological agents were combined with hypothermia to test for therapeutic synergy. Final neurologic outcome was assessed at 72–96 h by overall performance category and neurological deficit scores. Brain histopathology was also evaluated. Normal neurologic outcome with minimal histopathologic damage was routinely achieved after a cardiac arrest of 90 min using this suspended animation approach. In some dogs, good neurologic outcome was achieved even after a cardiac arrest of 120 min. A delay of 5–8 min in the induction of suspended animation attenuated its preservative effect. Of 14 drugs tested, only the antioxidant tempol produced a synergistic effect with hypothermia. The addition of trauma worsened organ function without affecting brain histopathology. Suspended animation with delayed resuscitation represents a revolutionary approach to resuscitation of the trauma victim with otherwise lethal exsanguination cardiac arrest. Our studies suggest additional benefit from the combination of antioxidants with hypothermia, and challenge the previously posed limits of hypothermic protection and preservation of the brain. In ongoing studies we are testing suspended animation after prolonged shock, evaluating the mechanisms of hypothermic protection using proteomics, and probing beyond the 2-h theoretical limit for cardiac arrest duration with intact survival.

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