CEREBRAL RESUSCITATION FROM CARDIAC-ARREST - TREATMENT POTENTIALS

In 1961, in Pittsburgh, PA, ''cerebral'' was added to the cardiopulmon ary resuscitation system (CPR --> CPCR). Cerebral recovery is dependen t on arrest and cardiopulmonary resuscitation times, and numerous fact ors related to basic, advanced, and prolonged life support. Postischem ic-anoxic encephalopathy (the cerebral postresuscitation disease or sy ndrome) is complex and multifactorial. The prevention or mitigation of this syndrome requires that there be development and trials of specia l, multifaceted, combination treatments. The selection of therapies to mitigate the postresuscitation syndrome should continue to be based o n mechanistic rationale. Therapy based on a single mechanism, however, is unlikely to be maximally effective. For logistic reasons, the limi t for neurologic recovery after 5 mins of arrest must be extended to a chieve functionally and histologically normal human brains after 10 to 20 mins of circulatory arrest. This goal has been approached, but not quite reached. Treatment effects on process variables give clues, but long-term outcome evaluation is needed for documentation of efficacy and to improve clinical results. Goals have crystallized for clinicall y relevant cardiac arrest-intensive care outcome models in large anima ls. These studies are expensive, but essential, because positive treat ment effects cannot always be confirmed in the rat forebrain ischemia model. Except for a still-elusive breakthrough effect, randomized clin ical trials of CPCR are limited in their ability to statistically docu ment the effectiveness of treatments found to be beneficial in control led outcome models in large animals. Clinical studies of feasibility, side effects, and acceptability are essential. Hypertensive reperfusio n overcomes multifocal no-reflow and improves out come. Physical combi nation treatments, such as mild resuscitative (early postarrest) hypot hermia (34 degrees C) plus cerebral blood flow promotion (e.g., with h ypertension, hemodilution, and normocapnia), each having multiple bene ficial effects, achieved complete functional and near complete histolo gic recovery of the dog brain after 11 mins of normothermic, ventricul ar fibrillation cardiac arrest. Calcium entry blockers appear promisin g as a treat ment for postischemic anoxic encephalopathy. However, the majority of single or multiple drug treatments explored so far have f ailed to improve neurologic outcome. Assembling and evaluating combina tion treatments in further animal studies and determining clinical fea sibility inside and outside hospitals are challenges for the near futu re. Treatments without permanent beneficial effects may at least exten d the therapeutic window. All of these investigations will require coo rdinated efforts by multiple research groups, pursuing systematic, mul tilevel research-from cell cultures to rats, to large animals, and to clinical trials. There are still many gaps in our knowledge about opti mizing extracerebral life support for cerebral outcome.