Cerebral resuscitation after cardiac arrest: research initiatives and future directions.
At present, fewer than 10% of cardiopulmonary resuscitation (CPR) attempts prehospital or in hospitals outside special care units result in survival without brain damage. Minimizing response times and optimizing CPR performance would improve results. A breakthrough, however, can be expected to occur only when cerebral resuscitation research has achieved consistent conscious survival after normothermic cardiac arrest (no flow) times of not only five minutes but up to ten minutes. Most cerebral neurons and cardiac myocytes tolerate normothermic ischemic anoxia of up to 20 minutes. Particularly vulnerable neurons die, in part, because of the complex secondary post-reflow derangements in vital organs (the postresuscitation syndrome) which can be mitigated. Brain-orientation of CPR led to the cardiopulmonary-cerebral resuscitation (CPCR) system of basic, advanced, and prolonged life support. In large animal models with cardiac arrest of 10 to 15 minutes, external CPR, life support of at least three days, and outcome evaluation, the numbers of conscious survivors (although not with normal brain histology) have been increased with more effective reperfusion by open-chest CPR or emergency cardiopulmonary bypass, an early hypertensive bout, early post-arrest calcium entry blocker therapy, or mild cerebral hypothermia (34 C) immediately following cardiac arrest. More than ten drug treatments evaluated have not reproducibly mitigated brain damage in such animal models. Controlled clinical trials of novel CPCR treatments reveal feasibility and side effects but, in the absence of a breakthrough effect, may not discriminate between a treatment's ability to mitigate brain damage in selected cases and the absence of any treatment effect. More intensified, coordinated, multicenter cerebral resuscitation research is justified.