Sodium Bicarbonate for Severe Metabolic Acidemia and Acute Kidney Injury: Insights from the BICARICU-2 Trial

Summary of the BICARICU-2 Trial

The BICARICU-2 trial is a follow-up to the original BICARICU trial. It suggested that the targeted use of sodium bicarbonate in critically ill patients with metabolic acidemia may improve survival rates and reduce the need for renal replacement therapy (RRT). This recent trial was conducted in France as an open-label randomized controlled trial (RCT). It enrolled 640 patients from 43 intensive care units (ICUs).

Included patients presented with severe metabolic acidosis and acute kidney injury (AKI). Both per-protocol and intention-to-treat (ITT) analyses were performed. The primary outcome, which was mortality, showed no significant difference between the groups. However, the need for renal replacement therapy was lower in the intervention group, with a number needed to treat (NNT) of 7. All other secondary outcomes and adverse effects were similar in both groups.

PICOTT Framework

• Population: ICU patients with severe metabolic acidosis and severe AKI.

• Intervention: Intravenous 4.2% sodium bicarbonate to target a pH > 7.3 for 28 days or until ICU discharge.

• Comparison: No intervention (no placebo).

• Outcomes: Primary outcome was 90-day mortality.

• Type of Question: Therapy.

• Type of Study: RCT.

  
  

Interpretation of the Study

Unsurprisingly, the study found no difference in mortality rates with the administration of sodium bicarbonate. The reduction in renal replacement therapy (RRT) needs makes sense, as acidemia is a clear indication for RRT. Once RRT is initiated, patients are less likely to be RRT-free by 28 days.

Sodium bicarbonate is a safe and inexpensive intervention that has consistently helped avoid RRT in critically ill patients. All other secondary outcomes are hypothesis-generating and should be interpreted cautiously. Interestingly, the overall mortality in both groups (62%) is higher than expected for septic shock patients in other studies, which average around 30%. Notably, 30% of patients were in surgical ICUs, which typically have even lower mortality rates.

The absolute risk reduction (ARR) for RRT is 15% (50% control event rate - 35% experimental event rate), resulting in a NNT of 7, consistent with findings from the BICARICU-1 trial.

Overall Risk of Bias

Risk of bias assessment - BICARICU-2

Pros and Cons

Pros: Both ITT and per-protocol analyses were conducted. The results were similar, adding strength to the findings.

Cons: The trial was open-label, and there was no placebo. Additionally, 47 patients in the control group crossed over to the experimental group. This crossover is problematic and likely worsened the outcomes seen in the experimental group, as crossovers tend to be sicker than other patients. However, this was not clearly reflected in the supplementary data, as the groups appeared similar.

Context of the Findings

The data aligns with previous thoughts regarding the use of sodium bicarbonate in the ICU and emphasizes the importance of avoiding RRT when possible. This is consistent with findings from both BICARICU-1 and STARRT AKI studies.

Teaching Points

• Understanding outcome measures is crucial.

• Familiarity with relative risk and risk difference (ARR) is important.

• Knowing the number needed to treat (NNT) can guide clinical decisions.

• Distinguishing between intention-to-treat analysis and per-protocol/as-treated analysis is essential.

• Recognizing the importance of blinding in clinical trials.

  
  

Conclusion

The findings from the BICARICU-2 trial provide valuable insights into the use of sodium bicarbonate in critically ill patients. While the mortality rates did not differ significantly, the reduction in the need for renal replacement therapy is noteworthy. This study somewhat settles the debate but may evolve with more data in the future.

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