🗝️ Key Points
- 🔬 Main objective: BICARICU‑2 evaluated whether sodium bicarbonate infusion improves outcomes in septic shock with severe metabolic acidosis.
- 🙅♂️ No mortality benefit: This trial like its predecessor trial found overall no statistically significant mortality benefit, despite physiologic correction of pH.
- ⚠️Possibly some kidney protection: Bicarbonate may have shown reduction to time to kidney replacement therapy (KRT) as well as rates of KRT, however this also needs further review as results are ripe for skepticism.
- 💭Encourages rethinking: Findings challenge the reflexive use of bicarbonate in severe acidosis and reinforce that treating the underlying shock remains the priority.
📝 Introduction
Medical providers have debated whether sodium bicarbonate should be used to correct this acidosis. The theorized physiological benefit is straight forward: raise the pH, improve hemodynamics, and stabilize the patient. The earlier BICARICU‑1 trial suggested a possible benefit in patients with severe acidosis and AKI. The BICARICU-1 trial was covered with excellent breakdown and take away points in a prior REBEL EM post. The authors of the following randomized clinical study sought to further investigate this question in the setting of a modern septic shock population.
🧾 Paper
Jung B, et al. Sodium Bicarbonate for Severe Metabolic Acidemia and Acute Kidney Injury: The BICARICU-2 Randomized Clinical Trial. JAMA. 2025;334(22):2000-2010. PMID: 41159812
🔙PREVIOUSLY COVERED ON REBEL EM:
- BICAR-ICU: How Should this Study Affect Care in the ED?
- Effectiveness of Sodium Bicarbonate Administration on Mortality in Cardiac Arrest Patients: A Systematic Review and Meta-Analysis
- The Kompas Trial: Sodium Bicarbonate Prehydration in Adults with CKD Prior to Contrast-Enhanced CT
- Sodium Bicarbonate in Cardiac Arrest Management
⚙️ What They Did
📈 Results
💥 Critical Results
💪🏽 Strengths
- Stratified Randomization: Stratification of center, age, and severity of acidemia allowed for the mean/medium characteristics to be balanced between the intervention and control groups.
- Focused Population: In the BICARICU-1 trial there seemed to be a benefit when isolating for severe metabolic acidemia with AKI. BICARICU-2 specifically studied patients with these criteria to directly focus on the subgroup that may have seen a benefit in the predecessor trial.
- Patient-focused outcome: The primary endpoint of 90-days all cause mortality and secondary endpoints of 28 days and 180 days is meaningful and objective outcome to measure.
- No Loss to Follow-Up: For the primary outcome, per the article there was 0% lost to follow up,ensuring the integrity of the primary outcome data.
⚠️ Limitations
- Open-Label Design: Blinding in this trial is understandably difficult as clinicians need to assess progression of critical patients. However, treatment bias can play a factor as KRT initiation was a clinician dependent outcome that was measured including time to onset of KRT as well as duration of KRT.
- Treatment Crossover: 47 patients in the control group received sodium bicarbonate. This could potentially undermine the real treatment effects. But noted by the authors the per-protocol review still showed no mortality benefit
- Isolated-country Population: All patients were from 43 ICUs only in France. Practice patterns when pertaining to KRT, ICU admission, sodium bicarbonate use, as well as other medical management may have different practice patterns and limit generalizability to North American EDs and ICUs.
- Non-standardized Dosing: Rather than a weight based dosing or calculated deficit dosing, treatment was titrated to achieve a pH ≥7.30. Without standardized dosing it makes it hard to provide reasonable set reproducible dosing of sodium bicarbonate.
- KRT reduction uncertainty: The significant reduction in KRT was noted by the authors and they commented specifically on this. Due to treatment directly increasing pH it may have delayed or completely avoided patients that had met the criteria of refractory acidemia from starting KRT. It may have given a falsehood of true renal function.
🗣️ Discussion
- BICARICU-2 answers an unresolved finding leftover by the BICARICU-1 trial. The original trial suggested patients with severe metabolic acidemia and AKI might represent a subgroup that could see benefit from sodium bicarbonate. BICARICU-2 targeted this population; however, despite targeting this population with suspected benefit, bicarbonate did not improve mortality at either day 28, 90, or 180 days.
- Mortality results are consistent, with consistency on mortality curves at day 28, 90, and 180 days. The per-protocol analysis was still noted to show no mortality benefit. This further makes it hard to contradict that routine use of bicarbonate provides survival benefit for severe metabolic acidemia.
- Substantial reduction in KRT with an absolute difference of 15.5% and an NNT of 7 to avoid one patient receiving KRT provides the most interesting new revelation. An inexpensive and readily available medication, being able to stave off KRT to a significant rate may be seen as impressive. However, as the authors also alluded to was this a true difference of treatment bias. The article being open-label allows for further bias that may be added on top of the treatment bias. Acidemia being an indicator clinicians could initiate KRT allows for treatment bias that sodium bicarbonate raises arterial pH and treating one of the indicators for KRT.
- The reduction of ICU-acquired bloodstream infections with an absolute difference of -4.5% provides another intriguing discussion. My suspicion is that it is secondary to reduced need for KRT lines and reduced overall line maintenance. Interestingly, with a statistically significant increase in bloodstream infections there was still no notable change in mortality.
- From an Emergency Medicine perspective this should establish that bicarbonate should not be part of the immediate management of severe septic patients with metabolic acidemia and AKI. Rather the goal of correcting the pH should be accomplished with correcting the disease process rather than bandaging it with bicarbonate.
- Overall the BICARICU-2 trial should further shift the conversation away from “Does bicarb save lives?” to “Can bicarb avoid or delay progression to dialysis?”. BICARICU-2 and its predecessor trial have seemingly, convincingly answered that question: No.
- BICARICU‑2 challenges the long‑standing belief that correcting metabolic acidosis with bicarbonate improves outcomes in septic shock. Focusing on the effects it may have on progression to dialysis and what benefit may reduced/delayed dialysis can provide to patients can provide interesting debate.
📘 Author's Conclusion
“For critically ill patients who had both severe metabolic acidemia and moderate to severe AKI, sodium bicarbonate therapy did not significantly decrease day 90 all-cause mortality.”
💬 Our Conclusion
The BICARICU-2 trial demonstrates that sodium bicarbonate as a medical management to aid in the care of septic shock patients with severe metabolic acidosis does not improve mortality. It offers a statistically significant reduction in the hours prior to starting KRT, as well as it may offer a moderate reduction to ICU acquired bloodstream infections, it fails to provide mortality benefit. Furthermore, this shows the importance of source control and hemodynamic optimization rather than chasing a pH number in septic shock patients with severe metabolic acidosis.
🚨 Clinical Bottom Line
BICARICU‑2 shows that bicarbonate does not improve survival or organ failure in septic shock with severe metabolic acidosis. Correcting the number does not correct the shock.
Post Peer Reviewed By: Mark Ramzy, DO (X: @MRamzyDO)
📚 References
- Jung B, et al.
Sodium Bicarbonate for Severe Metabolic Acidemia and Acute Kidney Injury: The BICARICU-2 Randomized Clinical Trial. JAMA. 2025;334(22):2000-2010.
PMID: 41159812 - Jaber S, et al.
Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet. 2018
PMID: 29910040 - Bryant, R.
“BICAR-ICU: How Should this Study Affect Care in the ED? – REBEL EM – Emergency Medicine Blog.” REBEL EM – Emergency Medicine Blog, 10 Sep. 2018
Full Blog Post Here
Meet the Authors
Francis Han, DO
Eli Johnson, DO
🔎 Your Deep-Dive Starts Here
Effectiveness of Sodium Bicarbonate Administration on Mortality in Cardiac Arrest Patients: A Systematic Review and Meta-Analysis
Background/Introduction: The use of Sodium Bicarbonate (SB) in cardiac arrest has ...
The Kompas Trial: Sodium Bicarbonate Prehydration in Adults with CKD Prior to Contrast-Enhanced CT
Background: Most guidelines recommend prehydration prior to iodine-based contrast media ...
BICAR-ICU: How Should this Study Affect Care in the ED?
During a busy resuscitation it behooves the ED resuscitationist to ...
Sodium Bicarbonate in Cardiac Arrest Management
Background: As with all medications in cardiac arrest (i.e. epinephrine, amiodarone) ...
