After cardiac arrest, restoration of circulation is the first step toward survivorship. Extracorporeal CPR (ECPR), the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to restore circulation, is increasingly being used in refractory cardiac arrest. The Advanced Reperfusion Strategies for Patients With Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation (ARREST), Prague Out-of-Hospital, and Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest (INCEPTION) randomized controlled trials compared ECPR with conventional CPR for refractory out-of-hospital cardiac arrest (OHCA).¹ The 2 largest of these studies reported no difference in good functional outcome.^2,3 However, a subsequent Bayesian meta-analysis (modeled on a > 5% absolute increase in good functional outcome) reported a 71.1% posterior probability that ECPR was superior to conventional CPR.² The ability of VA-ECMO to impact functional outcome after OHCA may depend not only on restoration of circulation but also its effect on cerebral blood flow, arterial oxygenation, and Paco₂). Paco₂ may be tightly regulated on VA-ECMO by changes in fresh gas flow. If Paco₂ impacted functional outcome for cardiac arrest survivors managed with VA-ECMO, Paco₂ control may represent a potential therapeutic option.

There is a paucity of randomized controlled trials examining the effect of ECPR, which increases our reliance on registry data to inform practice. In this issue of CHEST, Izawa et al⁴ report a multicenter, retrospective observational study using the Japanese Association of Acute Medicine—Out-of-Hospital Cardiac Arrest (JAAM-OHCA) Registry.⁴ The investigators explored the association between both initial and 24 ± 6-hour Paco₂ levels and functional outcome in patients with OHCA managed with VA-ECMO. VA-ECMO was initiated before return of spontaneous circulation in three-quarters of patients. In comparison with high normocapnia (Paco₂, 40 to < 50 mm Hg), hypocapnia, low normocapnia, mild hypercapnia, and moderate to severe hypercapnia were all associated with a reduced probability of good functional outcome. A sensitivity analysis using 8 Paco₂ categories found a Paco₂ 40 to 45 mm Hg was associated with the highest rate of good functional outcome. These findings support Extracorporeal Life Support Organization (ELSO) guidelines, which recommend avoiding hypocarbia and expert consensus opinion, which recommends targeting a Paco₂ of 40 to 45 mm Hg.