Sodium Bicarbonate for Severe Metabolic Acidemia and Acute Kidney Injury: The BICARICU-2 Randomized Clinical Trial.

Importance: The effect of sodium bicarbonate infusion on outcome in patients with severe metabolic acidemia and moderate to severe acute kidney injury is unknown. Objective: To determine whether sodium bicarbonate infusion is associated with day 90 all-cause mortality in patients with severe metabolic acidemia and moderate to severe acute kidney injury. Design, Setting, and Participants: Randomized, open-label, clinical trial conducted with 640 patients in 43 French intensive care units from October 6, 2019, to December 19, 2023, with 90-day follow-up. The last date of follow-up was June 17, 2024. Adults with severe metabolic acidemia (defined as pH ≤7.20) and moderate to severe acute kidney injury were enrolled. Intervention: Patients were randomized 1:1 to receive either intravenous sodium bicarbonate infusion or no sodium bicarbonate to target an arterial pH of 7.30 or higher. Main Outcomes and Measures: The primary outcome was day 90 all-cause mortality. Secondary outcomes included day 28 and day 180 all-cause mortality; use of organ support therapy, vasopressors, or invasive mechanical ventilation; intensive care unit and hospital length of stay; intensive care unit-acquired infections; fluid balance; day-7 Sequential [Sepsis-related] Organ Failure Assessment score (6 organ systems' function is evaluated and scored from 0 [no dysfunction] to 4 [failure]; total score ranges from 0 [normal] to 24 [maximum failure]); and major adverse kidney events on day 90. Results: Among 640 randomly assigned patients, 627 were analyzed (313 in the control group and 314 in the bicarbonate group). The median age was 67 years (IQR, 59-74 years); 194 of 314 patients (62%) in the bicarbonate group and 185 of 313 controls (59%) were male. In the primary analysis, day 90 all-cause mortality was 195 of 314 patients (62.1%) in the bicarbonate group and 193 of 313 (61.7%) in the control group (absolute difference, 0.4; 95% CI, -7.2 to 8.0; P = .91). There was no evidence of a group effect on day 28 or day 180 all-cause mortality. Among 18 secondary outcomes, kidney replacement therapy was used in 109 of 314 (35%) bicarbonate group patients and 157 of 313 (50%) controls (absolute difference, -15.5; 95% CI, -23.1 to -7.8). No evidence of a group effect was found on other secondary outcomes, including adverse events. Conclusions and Relevance: For patients with severe metabolic acidemia and moderate to severe acute kidney injury, intravenous sodium bicarbonate did not affect mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT04010630.