Isotonic Bicarbonate vs. Balanced Salt Solution as Resuscitation Fluid in Patients with Severe Metabolic Acidosis: A Randomized Controlled Trial

INTRODUCTION: Metabolic acidosis causes reduced myocardial performance and end organ hypoperfusion, which is associated with poor outcomes in critically ill patients. Previous studies showed that addition of bicarbonate in subset of patients with metabolic acidosis, led to improved clinical outcomes(1). However, the role of isotonic bicarbonate (ISB) as resuscitation fluid is unknown. OBJECTIVES: To compare the acid base status, hemodynamic variables and organ dysfunction, with the use of isotonic bicarbonate vs. balanced salt solution. METHODS: We conducted this prospective parallel group single blinded randomized controlled trail, in a tertiary care hospital, from September 2021 till July 2023 (CTRI/2021/07/035065). Patients aged≥18 years with severe acidosis [all of i) pH ≤ 7.2, ii) Serum bicarbonate ≤20 meq/L, iii) SOFA score ≥2 and iv). Lactate ≥2 at baseline] were randomized to receive either 1.35% bicarbonate solution (group ISB, prepared by mixing 150 meq of 8.4% bicarbonate in 1 litre 5% dextrose) or balanced salt solution (plasmalyte, group PL). Patients with any of the following were excluded-respiratory acidosis, acute heart failure, end stage chronic kidney disease, pregnant status and external acid ingestion. The fluid was administered in a protocolized manner, and primary aim was to compare lactate clearance (LC) at 6 hours of presentation. RESULTS: Out of 173 patients recruited, 156 patients (76 each group) were randomized and four patients in each group had a crossover to the other group. The overall median age of the population was 40 years (30-53.5, IQR) and SOFA score was 6 (3-11, IQR). As per modified intention to treat (ITT) analysis, ISB group had lower lactate clearance at 6 and 12 hours [18.8% (-18.6 to 40%) vs. 26.6% (1.85 to 53.16%, IQR, p=0.036 and 23.75 (-1.04 to 42.66) vs. 40 (14.17 to 67.43, p=0.013, respectively], lower serum bicarbonate levels at 2 and 6 hours and lower base excess (BE) at 2 hours. Subgroup analysis showed that patients with AKI had worse acidosis and LC at 6 hours. However, in patients with sepsis and SOFA ≥12, ISB led to greater lactate removal [33.33 (35.9) vs. 13.17(107) median (IQR as value)]. Hemodynamic parameters, vasopressor dosage, mortality <24 hours, incidence of new onset AKI, were similar between the groups. CONCLUSION: The use of isotonic bicarbonate as resuscitation fluid, as compared to balanced salt solution, failed to show improvement in acid base status in patients with severe metabolic acidosis and rather, was associated with worsening acid base status. Further large scale multicentric trials, aimed to compared hard outcomes like mortality should be conducted before establishing its safety as resuscitation fluid. ABBREVIATIONS: SOFA-sequential organ failure assessment score; AKI-acute kidney injury; IQR-interquartile range; ITT-intention to treat; LC-lactate clearnce.