Sodium bicarbonate administration for metabolic acidosis in the intensive care unit: a target trial emulation

Abstract

Purpose: Sodium bicarbonate is commonly administered to treat metabolic acidosis in intensive care units (ICUs). There is limited evidence from randomized trials to support this practice, and observational studies show conflicting results. Our aim was to perform a target trial emulation evaluating the effect of bicarbonate therapy on mortality.

Methods: Retrospective cohort study using data from 12 Australian ICUs. Inclusion criteria were adults with pH < 7.3 and PCO₂ ≤ 45 mmHg within the first three days. We excluded repeat admissions, toxicology, diabetic ketoacidosis, and pre-existing end-stage renal failure. The treatment intervention was sodium-bicarbonate administration, and the primary outcome was 30-day ICU mortality with ICU discharge as a competing event. We evaluated multiple subgroups, including patients with acute kidney injury, requirement for vasoactive therapy, and pH < 7.2. The primary model utilized a parametric g-computation and rolling entry matching was performed as a sensitivity analysis.

Results: We identified 6157 eligible admissions, of which 1764 (29%) received sodium bicarbonate. Bicarbonate therapy was associated with a 1.9% absolute mortality reduction for the primary analysis [risk ratio 0.86, 95% confidence interval (CI) 0.80 to 0.91], and significant benefits were seen across all subgroups evaluated. A similar point estimate of 2.1% was observed in the sensitivity analysis, with a sustained mortality reduction seen at 30 days.

Conclusion: In this target trial emulation, bicarbonate administration was associated with a small but statistically significant reduction in mortality for patients with metabolic acidosis. Large sample sizes would be required to demonstrate this effect in a randomized trial.

Keywords: Acute kidney injury; Critical care; Metabolic acidosis; Sodium bicarbonate.

Fig. 1

Unadjusted ICU mortality^a in patients who did or did not receive sodium bicarbonate. ^aICU mortality with ICU discharge as a competing event

Fig. 2

Effect of bicarbonate administration on primary and secondary outcomes. *Subgroup with 7.2 ≤ pH < 7.3, no acute kidney injury or requirement for vasoactive support. RD absolute risk difference in estimated mortality, RR risk ratio, CI confidence interval. AKI acute kidney injury, REM rolling entry matching, RRT renal replacement therapy. Vasoactive support = mean daily vasoactive-inotropic score ≥ 10, equivalent to 0.1mcg/kg/min noradrenaline. E value indicates the strength of unmeasured confounding that would be required to invalidate the results. For context: in this dataset, commencing renal replacement confers an RR of 1.52 for 30-day ICU mortality

Fig. 3

Marginal ICU mortality according to use of bicarbonate therapy—g-computation. Modeled survival curves comparing treatment algorithms where no patient received bicarbonate treatment, all patients receiving treatment, or the “natural course” (i.e., the treatment which was actually administered to the patient cohort)

Fig. 4

Estimated 30-day survival according to use of bicarbonate therapy—rolling entry matching