Sodium bicarbonate therapy in severe metabolic acidemia: an individual patient data meta-analysis of the BICAR-ICU and BICAR-ICU2 trials
Abstract
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.
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BibTeX
@article{fosset2026sodium,
title = {{Sodium bicarbonate therapy in severe metabolic acidemia: an individual patient data meta-analysis of the BICAR-ICU and BICAR-ICU2 trials}},
author = {Maxime Fosset and Joris Pensier and Matthieu Jabaudon and Laurent Bitker and Audrey de Jong and Gerald Chanques and Helena Huguet and Nicolas Molinari and Samir Jaber and Boris Jung},
journal = {Critical Care},
year = {2026},
month = oct,
doi = {10.1186/s13054-026-06206-3},
url = {https://hal.science/hal-05702027v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sodium bicarbonate therapy in severe metabolic acidemia: an individual patient data meta-analysis of the BICAR-ICU and BICAR-ICU2 trials
AU - Maxime Fosset
AU - Joris Pensier
AU - Matthieu Jabaudon
AU - Laurent Bitker
AU - Audrey de Jong
AU - Gerald Chanques
AU - Helena Huguet
AU - Nicolas Molinari
AU - Samir Jaber
AU - Boris Jung
PY - 2026
DA - 2026/10/22
JO - Critical Care
DO - 10.1186/s13054-026-06206-3
UR - https://hal.science/hal-05702027v1
AB - 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.
SN - 1364-8535
SN - 1466-609X
ER -