Clinical question: In critically ill adults with severe metabolic acidemia and moderate to severe acute kidney injury (AKI), does intravenous sodium bicarbonate reduce 90-day all-cause mortality?
Background: Severe metabolic acidemia (pH ≤7.20) frequently complicates critical illness with profound physiological consequences that may lead to hemodynamic instability, multi-organ dysfunction, and escalation of life support. Treatment with IV sodium bicarbonate in this population remains controversial. The BICARICU trial failed to demonstrate improved outcomes with IV sodium bicarbonate; however, analysis of subgroups with AKI showed reduced mortality and less need for kidney replacement therapy (KRT).
Study design: Multicenter, open-label, randomized controlled trial
Setting: 43 intensive care units in France
Synopsis: BICARICU-2 randomized 640 adults with pH up to 7.20 and Kidney Disease: Improving Global Outcomes Stage 2 to Stage 3 AKI to IV 4.2% sodium bicarbonate (target pH, ≥7.30) or usual care. Among the 627 patients analyzed, 90-day mortality was similar (62.1% versus 61.7%; absolute difference, 0.4%; 95% confidence interval [CI], 7.2 to 8.0; P=.91), with no difference at 28 or 180 days. Bicarbonate therapy reduced KRT use (35% versus 50%; absolute difference, −15.5%; 95% CI, −23.1 to −7.8) and delayed initiation without increased adverse events. The study was powered to detect a 10% absolute reduction in 90-day mortality and, therefore, was underpowered to detect possible, more modest effects on mortality. The trial’s open-label design, clinician-directed KRT initiation, crossover, and greater fluid exposure in the bicarbonate group introduced potential bias in dialysis-related outcomes.
For hospitalists involved in critical care, IV sodium bicarbonate may be considered as a temporizing strategy in selected patients with severe acidemia and AKI, but it should not be expected to improve survival.
Bottom line: IV sodium bicarbonate does not reduce 90-day mortality in severe metabolic acidemia with moderate-to-severe AKI but may decrease or delay KRT use.
Citation: Jung B, et al. Sodium bicarbonate for severe metabolic acidemia and acute kidney injury: the BICARICU-2 randomized clinical trial. JAMA. 2025;334(22):2000-2010. doi:10.1001/jama.2025.20231.
Dr. Kral is a hospitalist in the department of hospital medicine at the Cleveland Clinic and a clinical assistant professor and core faculty member of the Cleveland Clinic internal medicine residency program at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, both in Cleveland.