It is difficult to match concerns about reperfusion injury during cardiopulmonary resuscitation (CPR) with specific proposals for alternative interventions. After all, no matter how harmful the effects of oxygenation may be, not restoring circulation in a patient in cardiac arrest is hardly a credible option. One alternative would be to restore circulation but withhold oxygen (or ventilate with room air). Another alternative would be to induce hypothermia during circulatory arrest before restoring circulation.

A recent paper in Resuscitation investigated the latter option and reports that delaying reperfusion  in mice until induction of mild hypothermia has been achieved can improve hemodynamics, survival and neurological outcome.  The time to drop the temperature from 37 degrees Celsius to 30 degrees Celsius was 90 seconds in mice. As the authors note, “this is not currently feasible in humans and it is likely that much longer resuscitation delays in the clinical setting might counteract the benefit of cooling before ROSC (return of spontaneous circulation)”.

Rapid partial cooling (as the authors suggest) may solve this problem but restoring circulation will result in moving warm blood to the very organs (such as the heart and the brain) that just had been cooled. Such an intervention will only work if some of the protective mechanisms of hypothermia, such as altered gene expression, are (partially) retained during subsequent rewarming.

One treatment modality that the authors did not research, but warrants investigation, would be to “mimic” intra-arrest hypothermia by restoring circulation and giving a cocktail of neuroprotective agents prior to restoring oxygenation. Such an approach may not eliminate all free radical injury upon restoring circulation, or eliminate other elements of reperfusion injury such as calcium overload and inflammatory responses, but it might be an interesting treatment to compare with induction of intra-arrest hypothermia and delayed CPR.