Early sodium bicarbonate infusion was associated with improved outcome in critically ill patients with acute moderate metabolic acidosis: a retrospective observational study

Abstract

Background: Sodium bicarbonate (SB) infusion is widely administered for severe metabolic acidosis (MA). However, evidence supporting its effect on mortality in patients with acute moderate MA (MMA) has not yet been established. This study investigated the effect of early SB administration on mortality in critically ill patients with acute MMA and in other subgroups.

Methods: We retrospectively analyzed a large intensive care unit (ICU) database, Medical Information Mart for Intensive Care (MIMIC)-IV. Patients with acute MMA were identified using MIMIC-IV. Propensity score analysis (PSA) was performed to explain baseline differences in the probability of receiving SB. The marginal structural Cox model (MSCM) was developed to adjust for both baseline and time-varying confounding variables. The primary outcome was ICU mortality, and the secondary outcome was hospital mortality.

Results: In total, 1738 patients with acute MMA were identified; 484 were enrolled in the SB group and 1254 in the non-SB group. In the PSA, early SB infusion was not associated with reduced ICU mortality (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.67-1.14; P = 0.33) in the overall cohort. However, it was associated with improved ICU survival in patients with sepsis (HR: 0.69; 95% CI: 0.48-0.99; P < 0.05), sepsis shock (HR: 0.61; 95% CI: 0.40-0.93; P < 0.05), and sepsis and lactic acidosis (lactate >2.2 mmol/L; HR: 0.69; 95% CI: 0.48-0.99; P < 0.05). The results from MSCM were similar to those obtained for PSA.

Conclusion: Early SB infusion was associated with improved ICU survival outcomes in critically ill adult patients with sepsis, septic shock, and sepsis and lactic acidosis and acute MMA. Further large randomized controlled trials are required to confirm these results.

Keywords

Acute moderate metabolic acidosis / Critical care / Early sodium bicarbonate administration / Mortality

Conflict of interest statement

The authors declare no conflict of interest.

Author contributions

The study was designed by Feng C, who was also responsible for the data collection, analysis, interpretation, and drafting of the manuscript. Huang S, Zhu H, Peng Y, and Wang L contributed to data analysis and interpretation and drafted the manuscript. Wang L, Wang J, and Zhou X interpreted the data. Chen L and Yang B interpreted the data and reviewed the manuscript.

Funding

This research was funded by the National Natural Science Fund (No. 82072200, 82200169).

Ethical approval of studies and informed consent

This research strictly adhered to the Declaration of Helsinki (as revised in 2013) and received approval from the PLA General Hospital Ethics Committee (No. S2020-418-01, November 26, 2020). Retrospective data and clinical information were used for this study. The medical record collection process was safe and passive for patients. Informed consent was not required because no human subjects were included in this study. The Laboratory for MIT-LCP was responsible for database maintenance and granted permission for further analysis of the MIMIC-IV.

Acknowledgments

We are grateful to the team at the Laboratory for MIT-LCP, which maintained the MIMIC database.

References

[1] Jaber S, Paugam C, Futier E, 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; 392(10141):31-40. doi:10.1016/s0140-6736(18)31080-8

[2] Mochizuki K, Fujii T, Paul E, Anstey M, Bellomo R. Early metabolic acidosis in critically ill patients: a binational multicentre study. Crit Care Resusc. 2021; 23(1):67-75. doi:10.51893/2021.1.oa6

[3] Jung B, Rimmele T, Le Goff C, et al. Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. A prospective, multiple-center study. Crit Care. 2011; 15(5):R238. doi:10.1186/cc10487

[4] Kraut JA, Kurtz I. Use of base in the treatment of acute severe organic acidosis by nephrologists and critical care physicians: results of an online survey. Clin Exp Nephrol. 2006; 10(2):111-117. doi:10.1007/s10157-006-0408-9

[5] Parker MJ, Parshuram CS. Sodium bicarbonate use in shock and cardiac arrest: attitudes of pediatric acute care physicians. Crit Care Med. 2013; 41(9):2188-2195. doi:10.1097/CCM.0b013e31828a6669

[6] Zhang Z, Zhu C, Mo L, Hong Y. Effectiveness of sodium bicarbonate infusion on mortality in septic patients with metabolic acidosis. Intensive Care Med. 2018; 44(11):1888-1895. doi:10.1007/s00134-018-5379-2

[7] Fujii T, Udy AA, Nichol A, et al. Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: an international observational study. Crit Care. 2021; 25(1):45. doi:10.1186/s13054-020-03431-2

[8] Yagi K, Fujii T. Management of acute metabolic acidosis in the ICU: sodium bicarbonate and renal replacement therapy. Crit Care. 2021; 25(1):314. doi:10.1186/s13054-021-03677-4

[9] de Keyser CE, Leening MJ, Romio SA, et al. Comparing a marginal structural model with a Cox proportional hazard model to estimate the effect of time-dependent drug use in observational studies: statin use for primary prevention of cardiovascular disease as an example from the Rotterdam Study. Eur J Epidemiol. 2014; 29(11):841-850. doi:10.1007/s10654-014-9951-y

[10] Robins JM, Hernán MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology. 2000; 11(5):550-560. doi:10.1097/00001648-200009000-00011

[11] Karim ME, Gustafson P, Petkau J, et al. Marginal structural Cox models for estimating the association between β-interferon exposure and disease progression in a multiple sclerosis cohort. Am J Epidemiol. 2014; 180(2):160-171. doi:10.1093/aje/kwu125

[12] Johnson AE, Pollard TJ, Shen L, et al. MIMIC-III, a freely accessible critical care database. Sci Data. 2016; 3:160035. doi:10.1038/sdata.2016.35

[13] Johnson AE, Stone DJ, Celi LA, Pollard TJ. The MIMIC Code Repository: enabling reproducibility in critical care research. J Am Med Inform Assoc. 2018; 25(1):32-39. doi:10.1093/jamia/ocx084

[14] Johnson ABL, Pollard T, Horng S, Celi LA, Mark R. MIMIC-IV (version 0.4). Accessed December 12, 2022. https://www.physionet.org/

[15] Kellum JA, Lameire N; KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (part 1). Crit Care. 2013; 17(1):204. doi:10.1186/cc11454

[16] Allgöwer M, Burri C. Shock index. Dtsch Med Wochenschr. 1967; 92(43):1947-1950. doi:10.1055/s-0028-1106070

[17] Serpa Neto A, Deliberato RO, Johnson AEW, et al. Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts. Intensive Care Med. 2018; 44(11):1914-1922. doi:10.1007/s00134-018-5375-6

[18] Zhang Z. Propensity score method: a non-parametric technique to reduce model dependence. Ann Transl Med. 2017; 5(1):7. doi:10.21037/atm.2016.08.57

[19] Duhon B, Attridge RL, Franco-Martinez AC, Maxwell PR, Hughes DW. Intravenous sodium bicarbonate therapy in severely acidotic diabetic ketoacidosis. Ann Pharmacother. 2013; 47(7-8):970-975. doi:10.1345/aph.1S014

[20] Barbar SD, Clere-Jehl R, Bourredjem A, et al. Timing of renal-replacement therapy in patients with acute kidney injury and sepsis. N Engl J Med. 2018; 379(15):1431-1442. doi:10.1056/NEJMoa1803213

[21] Cooper DJ, Walley KR, Wiggs BR, Russell JA. Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study. Ann Intern Med. 1990; 112(7):492-498. doi:10.7326/0003-4819-112-7-492

[22] Mathieu D, Neviere R, Billard V, Fleyfel M, Wattel F. Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study. Crit Care Med. 1991; 19(11):1352-1356. doi:10.1097/00003246-199111000-00008