Therapeutic hypercapnia after cardiac arrest: still promising or time to move on?

Post-cardiac arrest care remains challenging, with persistently poor neurological and survival outcomes. Accordingly, novel adjunctive interventions are needed. While maintaining normocapnia is the current standard, hypercapnia has been proposed as a potential intervention. However, its role and potential benefits remain unclear. This comprehensive review summarizes current evidence on the use of hypercapnia in post-cardiac arrest care, focusing on neurological, cardiovascular, and survival outcomes, underlying mechanisms, and directions for future clinical investigations. Observational studies have sparked interest in the potential benefits of hypercapnia during the post-cardiac arrest period, including in specific populations. Methodological variations and conflicting findings from earlier studies have prompted the conduct of controlled trials and animal experiments to clarify its effects. Mild hypercapnia appears to be a practical and clinically safe approach, improving cerebral oxygenation without major adverse events. However, no improvement in long-term neurological recovery or survival has been demonstrated. Moreover, the effects on the cardiovascular and other organ systems, as well as mechanisms at the cellular level, remain inconclusive. Although mild hypercapnia may be considered part of a comprehensive post-cardiac arrest care strategy, further studies are needed to define its optimal application, potential synergy with other interventions, the populations most likely to benefit, and its underlying mechanisms.