Buffering Severe Acidemia in AKI: Fresh Data, New Caveats (The BICARICU-2 Trial)

Severe metabolic acidemia (pH ≤ 7.20) in the context of moderate to severe acute kidney injury (AKI) remains a persistent challenge in the intensive care unit. Acidemia impairs cardiac contractility, increases pulmonary vascular resistance, promotes vasodilation, and worsens renal perfusion and diaphragmatic function. Clinicians often turn to intravenous sodium bicarbonate (SB) as a buffering therapy, yet robust data supporting a survival benefit have been limited. The BICARICU-2 trial, recently published in JAMA, directly addressed this question by evaluating whether sodium bicarbonate infusion improves outcomes in patients with severe acidemia and AKI.

Conducted across 43 ICUs in France, the trial enrolled 640 adult patients who had a pH ≤ 7.20, serum bicarbonate ≤ 20 mEq/L, PaCO₂ ≤ 45 mm Hg, and AKI stage 2 or 3 per KDIGO criteria. Participants were randomized to receive 4.2% sodium bicarbonate infusion targeting a pH ≥ 7.30 or to a control group that received no bicarbonate therapy. The primary outcome was all-cause mortality at 90 days, with secondary outcomes including mortality at 28 and 180 days, use and timing of renal replacement therapy (RRT), organ support days, ICU and hospital length of stay, and major adverse kidney events.

At day 90, mortality was nearly identical between groups—62.1% in the bicarbonate group versus 61.7% in the control group—showing no significant difference. Mortality at day 28 and day 180 also did not differ. However, fewer patients in the bicarbonate group required RRT by day 28 compared with controls (35% versus 50%), and the time to RRT initiation was longer (median 30.9 hours versus 15.5 hours). There were no significant differences in ventilator-free days, vasopressor-free days, ICU length of stay, or major kidney events, and no signal of excess harm with sodium bicarbonate infusion.

In the accompanying JAMA editorial, Kusirisin and colleagues examined these results in the broader context of critical care practice. Although sodium bicarbonate therapy failed to improve survival, the authors noted that the lower and delayed use of RRT in the treatment arm is clinically meaningful. Avoiding or postponing RRT can reduce infection risk, limit exposure to hemodynamic instability, and conserve ICU resources. Nevertheless, the open-label design means clinicians knew which patients received bicarbonate, potentially influencing the threshold to initiate dialysis. RRT initiation criteria were not standardized, introducing an element of subjectivity that may confound interpretation of the secondary outcomes.

The editorial also highlighted that the trial may have been underpowered to detect smaller but clinically relevant survival benefits. Investigators had expected a control mortality near 80%, but the observed rate was around 62%, reducing statistical power. Moreover, the causes of acidemia were heterogeneous—ranging from high-anion-gap metabolic acidosis to lactic or mixed acidosis—and treatment effects might differ across these subgroups. Sub-phenotype analyses were not prespecified and remain unexplored.

For clinicians at the bedside, several practical lessons emerge. Sodium bicarbonate infusion appears safe and can be considered as a temporizing measure in patients with severe acidemia and advanced AKI. It may buy time before RRT initiation, particularly when the underlying process is potentially reversible or when logistical or resource constraints limit immediate dialysis. However, it should not be viewed as a therapy that improves mortality. Clinicians should monitor fluid balance closely, as bicarbonate administration increases volume load, and remain vigilant for masking of refractory acidemia, which could delay needed renal support.

The trial’s implications extend beyond bicarbonate itself. It underscores the need for precision in managing acid–base disturbances—matching the intervention to the metabolic derangement rather than adopting a universal approach. The data also reinforce that not all statistically negative trials are clinically irrelevant: a treatment that reduces or delays organ support without harm may still hold significant value in critical care, especially where resource use and iatrogenic risk are major concerns.

In summary, the BICARICU-2 trial shows that sodium bicarbonate infusion in patients with severe metabolic acidemia and moderate to severe AKI does not improve 90-day survival. Yet, it may meaningfully reduce or delay the need for dialysis. For critical care teams, the message is nuanced: bicarbonate remains a safe and potentially useful adjunct for correcting acidemia, not a mortality-reducing therapy. Its optimal use likely lies in carefully selected patients within a broader strategy of acid–base management, hemodynamic stabilization, and thoughtful timing of RRT initiation. Future studies should clarify which patient subgroups benefit most, the ideal dosing strategy, and how bicarbonate interacts with evolving approaches to renal support.

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References

Kusirisin P, Zampieri FG, Bagshaw SM. Sodium Bicarbonate in Severe Acidemia and Acute Kidney Injury—Turning the Tide or Chasing a Myth? JAMA. Published online October 29, 2025. doi:10.1001/jama.2025.20457

Jung B, Jabaudon M, De Jong A, et al. Sodium Bicarbonate for Severe Metabolic Acidemia and Acute Kidney Injury: The BICARICU-2 Randomized Clinical Trial. JAMA. Published online October 29, 2025. doi:10.1001/jama.2025.20231