Sodium bicarbonate therapy in severe metabolic acidemia: an individual patient data meta-analysis of the BICAR-ICU and BICAR-ICU2 trials

BACKGROUND: Two randomized trials (BICAR-ICU and BICAR-ICU2) evaluated intravenous sodium bicarbonate therapy in patients with severe metabolic acidemia but yielded inconclusive results. We performed an individual patient data meta-analysis to assess its effects on 90-day mortality and renal replacement therapy (RRT) use, and search for heterogeneity of treatment effects across prespecified subgroups. METHODS: We performed an individual patient data meta-analysis of the BICAR-ICU and BICAR-ICU2 trials, including adults with severe metabolic acidemia (pH ≤ 7.20). Patients were randomized to receive intravenous sodium bicarbonate titrated to a pH ≥ 7.30 or no sodium bicarbonate. The primary outcome was 90-day mortality. Secondary outcomes included RRT initiation and dialysis-free days. Prespecified subgroup analyses explored treatment-effect heterogeneity by acidemia depth (pH ≤ 7.10 vs. > 7.10), severe acute kidney injury (AKI) status, and serum lactate (< 2mmol/L vs. ≥2mmol/L). RESULTS: A total of 1,016 patients was included (509 sodium bicarbonate, 507 control). Sodium bicarbonate therapy did not significantly reduce 90-day mortality compared to control (58.3% vs. 60.6%; risk ratio [RR], 0.96; 95%CI, 0.86-1.07; p = 0.51). However, it significantly reduced RRT initiation (34.8% vs. 50.7%; RR, 0.69; 95%CI, 0.60-0.79; p < 0.001, number needed to treat: 6.3) and increased dialysis-free days (incidence rate ratio, 1.10; 95%CI, 1.06-1.14; p < 0.001). A significant interaction was observed with acidemia depth (p-for-interaction = 0.006): in patients with pH ≤ 7.10, sodium bicarbonate reduced 90-day mortality (RR, 0.80; 95%CI, 0.68-0.93; p = 0.004); no benefit was seen with pH > 7.10 (RR, 1.05; 95%CI, 0.92-1.21; p = 0.47). No significant interactions were observed for severe AKI status (p-for-interaction = 0.11) nor serum lactate (p-for-interaction = 0.22). CONCLUSIONS: Sodium bicarbonate therapy did not reduce overall 90-day mortality but decreased RRT use and suggested a mortality benefit in patients with the most profound acidemia (pH ≤ 7.10). These findings invite a reconsideration of current paradigms, suggesting timely correction of severe metabolic acidemia to avoid RRT in some patients.