Impact of normocapnia vs. mild hypercapnia on prognosis after cardiac arrest: A systematic review and meta-analysis

Objective: To explore the impact of mild hypercapnia or normocapnia on the prognosis of patients after the return of spontaneous circulation (ROSC) following cardiac arrest (CA).

Methods: This systematic review and meta-analysis followed the guidelines in the PROSPERO report. Information was retrieved in PubMed, Cochrane Library, Embase, and Web of Science to collect all publications in English from January 1, 2000, to March 1, 2024, involving post-CA with mild hypercapnia. Study selection and data extraction were performed by two authors using Review Manager 5.4 software. The primary/secondary outcomes, including overall or ICU mortality, were evaluated.

Results: 6 studies, including 4 observational studies, were ultimately enrolled in this study. A total of 19,025 patients were included in the studies, with 6899 receiving therapeutic mild hypercapnia and 12,126 maintaining normocapnia. Three studies focused on out-of-hospital patients, one study on in-hospital patients, one study on both in-hospital and out-of-hospital patients, and one study not specifying the type of CA. Compared to normocapnia, there was no significant difference in overall mortality among patients with mild hypercapnia (P = 0.51, OR = 1.13, 95 % CI: 0.93-1.38) and the proportion of patients with favorable neurological prognosis was not altered (OR:0.95, 95 % CI:0.80-1.14, P = 0.52). The overall ICU mortality rate was not significantly different between mild hypercapnia and normocapnia (OR:1.08,95 % CI:0.89-1.32, P = 0.42), and subgroup analysis showed that the results of randomized controlled trials and observational studies were consistent.

Conclusion: The presented meta-analysis suggests that mild hypercapnia is not associated with improvements in overall survival, ICU survival, or neurological prognosis compared to normocapnia in patients with CA.

Implications for clinical practice: This is the first meta-analysis specifically to compare the clinical outcome of CA with mild hypercapnia or normocapnia and find that mild hypercapnia may not be detrimental to the prognosis of patients after CA. It is unnecessary to control the mild hypercapnia intensively to normal range of PaCO₂ in clinics.