Lactate and pH as Independent Biomarkers for Prognosticating Meaningful Post-out-of-Hospital Cardiac Arrest Outcomes: A Systematic Review and Meta-Analysis

Abstract

Background/Objectives: To systematically review the literature and to characterize the utility of lactate and pH for predicting survival and long-term neurological outcomes after out-of-hospital cardiac arrest (OHCA). Methods: PRISMA guidelines were followed. PubMed, Embase, Web of Science, Cochrane Central, and Academic Search Premier were searched for relevant studies. The population included adults with OHCA. Studies with majority in-hospital cardiac arrest (>50%) and studies predicting return of spontaneous circulation (ROSC) were excluded. Pairs of investigators reviewed the studies for relevance. Data were extracted and risk of bias was assessed using the Newcastle-Ottawa Scale. Meta-analyses were performed to characterize the relationship between lactate and pH with survival and neurological outcomes. Results: We included 21,120 patients over 49 studies. Most studies (78%) included OHCA only. Mean lactate of 7.24 (95%CI:6.05-8.44) was associated with favorable survival (n = 9155; 21 studies), while mean lactate of 7.15 (95%CI:6.37-7.93) was associated with favorable neurological outcome (n = 7534; 21 studies). Mean pH of 7.22 (95%CI:7.10-7.33) was associated with favorable survival (n = 4077; 7 studies), while a mean pH of 7.22 (95%CI:7.17-7.27) was associated with favorable neurological outcome (n = 6701; 13 studies). Poor outcomes were associated with lower pH and higher lactate values. Risk of bias was generally low to medium, while heterogeneity was high. Conclusions: A direct correlation exists between pH with survival and neurological outcome; the likelihood of favorable outcomes increases as pH increases. Conversely, an inverse relationship exists between lactate with survival and neurological outcome; higher lactate is associated with poorer outcomes. For lactate, the threshold for survival was more lenient than for favorable neurological outcome.

Keywords: blood gas; hydrogen-ion concentration; lactic acid; out-of-hospital cardiac arrest; return of spontaneous circulation.

Figure 1

PRISMA diagram demonstrating the selection of articles during the review process. Out of 5504 screened articles, 147 articles underwent full-text analysis to determine eligibility, and 49 articles were ultimately included for data extraction. Of the included studies, 36 were retrospective cohort studies, 11 were prospective observational cohort studies, one was a combined retrospective and prospective cohort study, and one study was randomized.

Figure 2

Forest plots for survival (A) and neurological outcome (B) relative to lactate after outliers are removed. Forest plots for survival (C) and neurological outcome (D) relative to pH after outliers are removed. Favorable outcomes are on the left, and unfavorable outcomes are on the right. Abbreviations: CI, confidence interval; MRAW, raw mean; SD, standard deviation.