Is sodium bicarbonate beneficial for rescue therapy or ph normalizing-strategy for metabolic acidosis? an insight from meta-analysis

Abstract Background and Aims Metabolic acidosis is a major acid-base derangement observed in critical ill patients with poor prognosis. Sodium Bicarbonate (SB) commonly used for metabolic acidosis, but its risk–benefit profile on clinically important outcomes remains uncertain. This study aimed to inquire beneficial of SB administration for metabolic acidosis therapy. Methods Following PRISMA Guidelines, a meta-analysis was performed after systematic search with prespecified subgroup analyses by study design. Risk of bias was assessed using ROB 2 and ROBINS-I. The predefined outcomes are 30-day mortality, vasopressor-free days, ventilator-free days, Renal-Replacement Therapy (RRT)-free days, and ICU length of stay. Results We included 9 studies encompassing 10,092 patients with moderate-to-severe metabolic acidosis. Overall, sodium bicarbonate did not reduce mortality (OR 1.25, 95% CI 0.84–1.86; I²=83%). In RCTs, mortality was neutral (OR 0.82, 95% CI 0.55–1.21; I²=44%), while cohorts suggested higher mortality (OR 1.76, 95% CI 1.55–2.01; I²=0%; subgroup difference p=0.0003). RCTs showed reduced RRT requirement with SB (OR 0.53, 95% CI 0.41–0.67; I²=0%), whereas cohorts showed increased RRT performed (OR 2.05, 95% CI 1.67–2.51; I²=42%; subgroup difference p<0.00001). Secondary outcomes showed no consistent benefit and substantial heterogeneity. RCTs had low risk/some concerns, while observational studies were moderate-to-critical risk of bias, mainly due to confounding. Conclusion SB administration does not improve overall survival but might delay or avoid unnecessary early RRT in moderate-to-severe metabolic acidosis based on consistent randomized evidences. Discordant observational findings likely reflect confounding by indication, supporting bicarbonate as a selective rescue therapy rather than a routine pH-normalizing strategy.