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

Abstract

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. 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. 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. 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.