SODa-BIC — Sodium Bicarbonate for Metabolic Acidosis and Shock

1. Publication

• Title: Sodium Bicarbonate for Critically Ill Adults with Metabolic Acidosis and Shock
• Acronym: SODa-BIC
• Year & Journal: New England Journal of Medicine, published online June 12, 2026
• Citation: The SODa-BIC Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Sodium Bicarbonate for Critically Ill Adults with Metabolic Acidosis and Shock. N Engl J Med. 2026. doi:10.1056/NEJMoa2600526

2. Context & Rationale

Background: Metabolic acidosis is common in critical illness and associated with myocardial depression, reduced catecholamine responsiveness, AKI, RRT, and death. Sodium bicarbonate reliably raises extracellular pH, bicarbonate, base excess, and sodium, but whether this biochemical correction translates into patient-centered benefit was unestablished. The prior BICAR-ICU trial found no difference in its primary composite outcome overall, except in a subgroup with moderate-to-severe AKI. A 2025 target trial emulation of 6157 Australian ICU admissions found bicarbonate associated with a small absolute mortality reduction (RR 0.86, 95% CI 0.80–0.91), but residual confounding/treatment-selection bias remained a central concern.

Research Question/Hypothesis: In critically ill adults with metabolic acidosis (pH <7.30) receiving vasopressors, does sodium bicarbonate infusion reduce major adverse kidney events within 30 days (MAKE30) compared with placebo?

Why This Matters: Despite decades of use, whether sodium bicarbonate provides genuine patient-centered benefit in critical illness (beyond biochemical correction) remained unresolved; this is among the most common, low-cost interventions in the ICU, making a definitive answer highly practice-relevant.

3. Design & Methods

• Study Type: International, multicenter, randomized, double-blind, parallel-group, adaptive, superiority trial
• Setting & Centers: 55 ICUs, 7 countries; enrolled April 2023 – December 2025
• Population:
• Inclusion: Adults ≥18y with metabolic acidosis (pH <7.30) confirmed within 2h of randomization, receiving a continuous vasopressor infusion at time of randomization
• Exclusions: Not fully detailed in available trial text
• Intervention: Sodium bicarbonate infusion diluted in 5% dextrose
• Comparator: 5% dextrose infusion alone (placebo)
• Randomization: 1:1, 500 patients (245 sodium bicarbonate, 255 placebo)
• Blinding: Double-blind
• Statistical Power & Follow-Up: Primary outcome: MAKE30 (composite of death, RRT receipt, or persistent renal dysfunction within 30 days). Secondary/tertiary outcomes: 30- and 90-day mortality, RRT receipt, vasopressor-free and ICU-free days at day 30. All analyses intention-to-treat.

4. Key Results

500 patients enrolled across 55 ICUs/7 countries; median age 66y, 43.2% women.

Note on data completeness: Detailed breakdowns of the individual MAKE30 components (death, RRT receipt, persistent renal dysfunction) and the secondary mortality/vasopressor-free-day outcomes were not available in the accessible source text beyond the primary composite result above; per this handbook's data-integrity standard, these are marked "not reported in accessible text" rather than estimated.

5. Internal Validity Assessment

• Randomization & Allocation: International, multicenter randomization across 55 ICUs; double-blind design with dextrose placebo control — strong allocation concealment and blinding.
• Protocol Adherence & Separation: Adaptive design allowed for pragmatic adjustments; sodium bicarbonate vs matched dextrose placebo provides clean pharmacological separation.
• Blinding & Detection Bias: Full double-blind design minimizes both performance and detection bias — a notable methodological strength for a trial testing a biochemically "visible" intervention (clinicians could otherwise infer allocation from lab changes if unblinded).
• Missing Data & Sensitivity Analyses: Not detailed in available trial text.
• Overall Internal Validity Conclusion: Strong — double-blind, adequately sized (500 patients, close to typical target sample sizes for a MAKE30-powered trial), multinational trial with a clean, unambiguous null primary result.

6. External Validity Assessment

• Population Representativeness: International (7-country) population of critically ill adults with metabolic acidosis and shock (vasopressor-dependent) — a well-defined, clinically common ICU phenotype.
• Practice Context: Reflects standard ICU practice across diverse health systems; the double-blind design (dextrose placebo) is feasible in most ICU settings.
• Overall External Validity Conclusion: Good — multinational, multicenter design with a clearly defined, clinically common population supports broad applicability of the null finding across diverse ICU settings.

7. Strengths & Limitations

Strengths:

• Large, international, double-blind, placebo-controlled trial — addressing a genuine, decades-old clinical uncertainty with rigorous methodology
• Clean, unambiguous null primary result
• Directly follows on from and extends the BICAR-ICU evidence base with a fresh cohort and modern trial design
• Adaptive design allowed efficient trial conduct

Limitations:

• Detailed secondary-outcome and MAKE30-component breakdowns not fully accessible for this summary
• As with any single trial, cannot fully exclude a small residual subgroup benefit (e.g., in more severe acidosis or AKI, as previously suggested by BICAR-ICU's subgroup finding) without dedicated subgroup analysis review
• Observational evidence (2025 target trial emulation) had suggested a modest benefit, creating a genuine tension between observational and randomized evidence that this trial does not fully resolve for all possible confounding-explained discrepancy

8. Interpretation & Practice Impact

• Clinical Implications: Sodium bicarbonate should remain a clinician-directed, selectively used therapy for achieving specific physiological (pH/hemodynamic) goals in metabolic acidosis — not a routine, protocolized intervention expected to reduce major adverse kidney events.
• Mechanistic Coherence: The clean biochemical rationale for bicarbonate (correcting pH, improving catecholamine responsiveness) did not translate into the hypothesized reduction in kidney-related outcomes, similar to the broader pattern in FASTEST (this handbook, Neurocritical Care category) where a clear biological/biochemical effect did not translate into the hypothesized clinical outcome.
• Systems-Level Takeaway: Argues against building routine sodium bicarbonate administration into vasopressor-dependent shock order sets purely for kidney-protective purposes.

9. Controversies & Subsequent Evidence

• Editorial Commentary: Accompanying commentary (via The Bottom Line and Critical Care Reviews coverage) frames SODa-BIC as providing high-quality evidence against expanding bicarbonate use routinely to less-severe, vasopressor-dependent acidosis, while noting that current sepsis guidance had already supported bicarbonate only weakly for septic shock with severe metabolic acidemia and AKI — and suggested against its use for improving hemodynamics or reducing vasopressors in hypoperfusion-induced lactic acidemia.
• Guideline Integration: Directly tests and largely confirms prior conservative guideline positioning; the tension between this trial's null result and the more favorable 2025 observational target-trial-emulation finding (RR 0.86) illustrates a classic randomized-vs-observational-evidence discrepancy, likely attributable to residual confounding in the observational data.

10. Summary & Executive Takeaway

Summary: SODa-BIC randomized 500 critically ill adults with metabolic acidosis (pH <7.30) and vasopressor-dependent shock across 55 ICUs in 7 countries to sodium bicarbonate or placebo (5% dextrose). MAKE30 occurred in 40.2% vs 39.4% (adjusted difference 1.2 percentage points, 95% CI −7.1 to 9.4, P=0.78) — a clear null result.

Overall Takeaway: Sodium bicarbonate does not reduce major adverse kidney events in critically ill adults with vasopressor-dependent metabolic acidosis — it should remain a selectively used, clinician-directed therapy for specific physiological goals rather than a routine kidney-protective intervention, resolving (at least for this specific population) a longstanding clinical uncertainty in favor of the more conservative prior guideline positioning.

11. Bibliography

• Jaber S, Paugam C, Futier E, et al; BICAR-ICU Study Group. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU). Lancet. 2018;392(10141):31-40.
• Jung B, et al. Sodium bicarbonate therapy in severe metabolic acidemia: an individual patient data meta-analysis of BICAR-ICU and BICAR-ICU2. Crit Care. 2026;30(1).