Bicarbonate therapy: Resuscitating an old remedy with new evidence

Dear Editor,

Metabolic acidosis is a prevalent and serious condition in intensive care unit (ICU) patients, often seen upon admission and linked to poor clinical outcomes. It results from the buildup of non-volatile acids or the depletion of serum bicarbonate, usually due to renal or gastrointestinal losses. ¹ This acid-base imbalance results in a decrease in blood pH under the standard range of 7.35–7.45. A recent review indicated that moderate to severe metabolic acidosis impacts approximately 8%–14% of critically ill patients in the ICU and is associated with markedly elevated mortality rates. International studies, including hundreds of ICU patients, indicated that severe cases characterised by low pH, decreased bicarbonate levels and indications of organ failure had hospital mortality rates between 43% and 57%. ² Mortality in individuals with metabolic acidosis was more significant than in those with sepsis, underscoring its clinical severity.

Furthermore, metabolic acidosis is an independent risk factor for chronic kidney disease (CKD) patients with blood HCO₃ levels less than 22 mEq/L, and the proportion rises as kidney function deteriorates, adding to its clinical relevance.^1,2 These figures demonstrate the need for early identification and effective therapies in ICU patients. The conventional use of sodium bicarbonate treatment for the correction of acidosis has been contentious, with few data endorsing its efficacy in enhancing patient survival.

The latest study by Blank et al. ³ adds clarification by using target trial emulation. This sophisticated statistical method replicates the framework of a randomised clinical trial, using real-world data to reassess the effects of bicarbonate treatment on ICU patients. The research indicated that bicarbonate treatment correlated with a moderate but statistically significant decrease in 30-day ICU mortality (1.9% absolute risk reduction), especially in patients with acute renal damage, severe acidosis or receiving vasoactive support. The research indicated a decrease in the need for renal replacement treatment. These results are notable, particularly given that earlier studies, like the BICAR-ICU research, failed to demonstrate a definitive mortality advantage.

Furthermore, a prior meta-analysis found that bicarbonate therapy did not significantly lower mortality in critically ill patients with severe metabolic acidosis, primarily attributed to lactic acidosis. ⁴ Current randomised studies, such as BICARICU-2, SODa-BIC and MOSAICC, concentrate on specifically specified or high-risk populations, resulting in uncertainty over their broader applicability. ³ The retrospective approach, lack of granular data and possible unmeasured confounding factors limit the study’s results, which favour bicarbonate usage. Sodium bicarbonate’s therapeutic significance has long been debated, as it has been associated with delayed breathing cessation, fluid overload and paradoxical intracellular acidosis. Evidence supporting sodium bicarbonate use varies widely across different pathologies. Additional clinical trials are needed to evaluate better its benefit-risk profile in patients with diverse conditions. ⁵

The overarching consequence is evident: reviewing and improving conventional medicines using contemporary statistical methodologies may provide significant therapeutic advances. As ICU clinicians confront ever-intricate patient presentations, such evidence-based reevaluation of traditional techniques becomes crucial. Blank et al. ³ offer compelling evidence; however, randomised controlled trials are still required to validate these results, establish optimal administration strategies and promote their use beyond the limited populations of the current trials.

Nimra Khan Radiotherapy Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK