Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the ICU
Lancet, 2018 · Multicenter randomized open-label controlled trial (n=389)
Clinical question
Does sodium bicarbonate infusion reduce mortality in ICU patients with severe metabolic acidemia?
What the trial found
The trial was neutral for its primary composite outcome overall. In the prespecified AKIN 2–3 subgroup, bicarbonate was associated with better 28-day survival and less renal replacement therapy; this subgroup result supports selective use rather than routine treatment of all severe acidemia.
Current guideline position
The 2026 Surviving Sepsis Campaign conditionally suggests bicarbonate in septic shock with pH <= 7.2 and AKIN 2-3 (very low certainty), while advising against its use solely to improve hemodynamics or reduce vasopressor requirements in hypoperfusion-induced lactic acidemia. BICARICU-2 should be taught alongside this recommendation because it found no mortality benefit but less kidney replacement therapy.
Clinical interpretation
The 2018 AKI-subgroup survival signal was hypothesis-generating. BICARICU-2 (JAMA 2025) subsequently found no mortality benefit in severe acidemia with moderate-to-severe AKI, although kidney replacement therapy was reduced. Do not present BICAR-ICU as proving a survival benefit.
Differential diagnosis (GOLD MARK vs HARDCARP), toxic alcohol osmolar gaps, Urine Anion Gap, and current sodium bicarbonate evidence including BICAR-ICU and BICARICU-2.
Stepwise 6-step interpretation algorithm, compensation formulas, albumin-corrected anion gap, delta ratio, and Stewart physicochemical (SID) principles.
Sepsis-AKI microcirculatory decoupling, KDIGO staging, Furosemide Stress Test (FST), urine microscopy, and the AEIOU dialysis threshold framework.
The subset of sepsis with profound circulatory and cellular/metabolic abnormality — clinically identified by a vasopressor requirement to maintain MAP ≥ 65 mmHg plus lactate > 2 mmol/L despite adequate fluid resuscitation.