Sodium Bicarbonate Fails to Improve Kidney Outcomes in ICU

Sodium bicarbonate to correct metabolic acidosis in critically ill patients on vasopressors did not lower risks of major kidney outcomes, the randomized, double-blind SODa-BIC trial showed.

While the intervention rapidly corrected acidemia, there was no difference in the rate of major adverse kidney events — including death, use of renal-replacement therapy, or persistent renal dysfunction — in patients who received sodium bicarbonate versus placebo by day 30 (40.2% vs 39.4%, P=0.78), reported Ary Serpa Neto, MD, PhD, MSc, of Monash University in Melbourne, Australia, and colleagues.

Individually, rates of renal-replacement therapy (16.8% vs 20.9% for placebo) and in-hospital mortality (25.4% vs 24%) didn’t differ between groups at day 30, the authors wrote in the New England Journal of Medicine.

The findings were simultaneously presented at the 2026 Critical Care Reviews Meeting in Belfast, Ireland.

Adverse effects were slightly more common in patients who received sodium bicarbonate, occurring in four patients versus none who received placebo, a trend driven largely by hypokalemia.

While power was limited, Serpa Neto’s group found no evidence that outcomes differed in any prespecified subgroups either, such as patients with more severe acidosis (pH below 7.25) or those with advanced acute kidney injury (stage 2 or 3).

Metabolic acidosis is common in critically ill patients with sepsis, renal failure, or shock, and is tied to impaired myocardial contractility, reduced catecholamine responsiveness, and high risks of acute kidney injury, renal-replacement therapy use, and death.

“Early correction of acidemia may influence renal outcomes and organ-support requirements,” the authors noted. “Sodium bicarbonate is widely used to treat metabolic acidosis, but evidence supporting such use remains uncertain.”

“Although treatment with sodium bicarbonate did not improve outcomes, findings related to renal-replacement therapy should be interpreted in the context of clinical decision making,” the researchers noted. “Given that severe acidemia often triggers the initiation of renal-replacement therapy, deferral of therapy may reflect pH correction rather than improved kidney function.”

“Our findings do not rule out the possibility that sodium bicarbonate use may avoid the use of renal-replacement therapy, as suggested by the previous trials,” they wrote.

While the 2018 BICAR-ICU trial found that sodium bicarbonate did not improve 90-day mortality in patients with severe metabolic acidosis, it did reveal a lower risk of renal replacement therapy. The 2025 BICARICU-2 trial mirrored these findings in patients with acute kidney injury, reporting no change in mortality but a reduced need for kidney replacement interventions.

Though the prior trials hinted at renal benefits of sodium bicarbonate, they were open-label studies, the researchers pointed out.

“Moreover, these trials included patients with severe acidosis and therefore do not inform treatment decisions for the broader population of patients in the intensive care unit (ICU) who have less severe acidosis,” they explained. “Guideline recommendations on sodium bicarbonate use are based on low-certainty evidence and focused on narrow clinical scenarios.”

For the pragmatic, adaptive SODa-BIC trial, Serpa Neto’s group randomized 245 adult patients to receive sodium bicarbonate and 255 to receive placebo (5% dextrose). Participants were enrolled in 55 ICUs across seven countries from April 2023 through December 2025.

All had metabolic acidosis, defined as a pH below 7.30, a base excess of no more than -4 mmol/L, and a partial pressure of arterial carbon dioxide of no more than 45 mm Hg (without intubation) or no more than 50 mm Hg (with intubation).

The median patient age in the trial was 66 years and 43.2% were women. The median Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21 and Sequential Organ Failure Assessment (SOFA) score was 7. At enrollment, the median pH level was 7.26, base excess level was -9 mmol/L, and 46.2% had acute kidney injury.

Sodium bicarbonate or placebo was infused for up to 5 hours, with the infusion rate adjusted for a target pH of at least 7.30 and a base excess of at least 0 mmol/L.

The two groups had a similar incidence of acute kidney injury within 7 days and of persistent renal dysfunction within 30 days. The numbers of vasopressor-free days, renal-replacement therapy-free days, and ICU-free days at day 30, and the number of hospital-free days at day 90 were also similar between groups.

“Although enrollment was limited to patients receiving vasopressors, which decreases generalizability, this strategy provided prognostic enrichment and reflected a biologic rationale that the correction of acidemia may have greater physiological relevance in patients with hemodynamic instability than in patients without hemodynamic instability,” the group concluded.

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