PACULit Daily Literature Update: Reevaluating bicarbonate therapy in pediatric DKA A propensity scorematched analysis of neurological and respiratory outcomes

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Reevaluating Bicarbonate Therapy in Pediatric DKA

Reevaluating bicarbonate therapy in pediatric DKA: A propensity score-matched analysis of neurological and respiratory outcomes

Patel M, Afifi AM, Hercher RL, et al. Am J Emerg Med. 2025 Jul;97:45-50. DOI: 10.1016/j.ajem.2025.07.033. PMID: 40683034.

Introduction

Diabetic ketoacidosis (DKA) is a severe, life-threatening complication of diabetes mellitus, particularly common in pediatric populations, contributing to significant morbidity and mortality worldwide. Historically, bicarbonate therapy has been employed in cases of severe pediatric DKA to rapidly correct acidosis. However, its use remains controversial due to the potential risk of adverse neurological events, especially cerebral edema, which is a feared and often fatal complication of pediatric DKA management.

Previous studies examining bicarbonate therapy have been limited by small sample sizes, lack of robust control for confounding variables, and short follow-up durations, leaving clinicians uncertain regarding its safety profile. This study leverages a large clinical dataset and utilizes propensity score matching to minimize bias and better elucidate the relationship between bicarbonate use and key neurological and respiratory outcomes in pediatric DKA.

Study Overview

This retrospective cohort study utilized the TriNetX global research network database compiling deidentified electronic health records. Pediatric patients <12 years old admitted with diabetic ketoacidosis were categorized into two groups: those treated with bicarbonate therapy and those without. Propensity score matching was applied to control for baseline differences and potential confounders, resulting in balanced cohorts of 211 patients each.

The primary outcome was the incidence of cerebral edema. Secondary outcomes included neurological complications such as coma, and respiratory complications including pulmonary edema and acute respiratory failure. Statistical analysis focused on risk difference (RD) and 95% confidence intervals (CI), with significance assessed using p-values.

Key Findings

No statistically significant difference in cerebral edema incidence was observed between bicarbonate-treated and non-treated groups (RD = 0.002; 95% CI: -0.039 to 0.044; p = 0.911), alleviating direct concerns about cerebral edema risk with bicarbonate.
Bicarbonate therapy was significantly associated with increased risks of coma (RD = 0.047; p = 0.001), pulmonary edema (RD = 0.048; p = 0.001), and acute respiratory failure (RD = 0.071; p = 0.008), highlighting neurologic and respiratory safety concerns.
These findings emphasize that risks beyond cerebral edema warrant careful consideration when deciding on bicarbonate use in pediatric DKA.

Evidence Synthesis

The results of Patel et al. (2025) are consistent with a growing clinical consensus and guideline recommendations that caution against routine bicarbonate therapy use in pediatric DKA except in select circumstances.

Key contextual points include:

Study / Guideline	Findings / Recommendations	Clinical Significance
Freeman et al., 2024	Bicarbonate use higher in community EDs but no increased cerebral edema or adverse outcomes compared to academic centers	Supports selective application of bicarbonate without increased complication rates in varied practice settings
Yıldırımçakar et al., 2024	Ringer’s lactate results in faster DKA resolution and less hyperchloremic acidosis compared to normal saline	Highlights benefit of balanced fluids over normal saline to reduce acid-base disturbances
Agarwal et al., 2025	Double-blind RCT demonstrated advantages of Ringer’s lactate for initial fluid therapy in pediatric DKA	Supports changing fluid management to improve metabolic outcomes and decrease need for bicarbonate
Rugg-Gunn et al., 2021 (UK Guidelines)	Guidance discourages routine bicarbonate use, recommending it only for rare, specific indications (e.g., life-threatening acidosis with cardiac compromise)	Endorses cautious, evidence-informed withholding of bicarbonate in most pediatric DKA cases
Veverka et al., 2016	Two-bag intravenous fluid protocol reduces insulin therapy duration and facilitates better DKA management without bicarbonate	Demonstrates effective alternative strategies minimizing bicarbonate necessity

Collectively, these findings advocate for sparing bicarbonate use, emphasizing safer alternatives and tailored fluid management protocols to optimize clinical outcomes in pediatric DKA.

Clinical Implications

Routine bicarbonate therapy should be avoided in pediatric DKA due to increased risks of coma and respiratory complications despite no increased cerebral edema risk.
Fluid management using balanced crystalloids like Ringer’s lactate may improve acid-base status and reduce the need for bicarbonate therapy.
Clinicians should adhere to established guidelines recommending bicarbonate only for specific severe acidosis with compromised cardiac function, ensuring vigilant monitoring for neurologic and respiratory complications.

Strengths & Limitations

Strengths	Limitations
Large sample size with 422 propensity score-matched patients enhancing comparability	Retrospective observational design limits causal inference
Use of propensity score matching to control for confounding baseline characteristics	Potential for unmeasured confounding and missing data inherent to electronic health records
Extended follow-up assessing neurological & respiratory outcomes beyond cerebral edema	Lack of granular clinical detail on bicarbonate dosing timing and indications

Future Directions

Prospective controlled trials are warranted to more definitively evaluate the safety profile and clinical benefits of bicarbonate therapy in pediatric DKA. Further research should explore optimized fluid management strategies and develop protocols incorporating balanced crystalloids and insulin dosing to reduce adverse complications without unnecessary bicarbonate use.

Despite no increased cerebral edema risk, bicarbonate therapy in pediatric DKA is linked to greater neurological and respiratory complications, warranting cautious use aligned with evolving clinical guidelines.

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References

Patel M, Afifi AM, Hercher RL, et al. Reevaluating bicarbonate therapy in pediatric DKA: A propensity score-matched analysis of neurological and respiratory outcomes. Am J Emerg Med. 2025 Jul;97:45-50.
Freeman JN, Giroux C, King T, et al. Variations in Management and Clinical Outcomes for Children With Diabetic Ketoacidosis in an Academic Pediatric Versus Community Emergency Department Setting. Pediatr Emerg Care. 2024 Aug 1;40(8):e133-e138.
Yıldırımçakar D, Öcal M, Altıncık SA, et al. Hyperchloremia and Prolonged Acidosis During Treatment for Pediatric Diabetic Ketoacidosis. Pediatr Emerg Care. 2024 Dec 1;40(12):856-860.
Agarwal A, Jayashree M, Nallasamy K, et al. 0.9% Saline versus Ringer’s lactate as initial fluid in children with diabetic ketoacidosis: a double-blind randomized controlled trial. BMJ Open Diabetes Res Care. 2025 Apr 7;13(2).
McGregor S, Metzger DL, Amed S, et al. Fluid management in children with diabetic ketoacidosis. Can Fam Physician. 2020 Nov;66(11):817-819.
Rugg-Gunn CE, Deakin M, Hawcutt DB. Update and harmonisation of guidance for the management of diabetic ketoacidosis in children and young people in the UK. BMJ Paediatr Open. 2021 Jun 4;5(1):e001079.
Veverka M, Marsh K, Norman S, et al. A Pediatric Diabetic Ketoacidosis Management Protocol Incorporating a Two-Bag Intravenous Fluid System Decreases Duration of Intravenous Insulin Therapy. J Pediatr Pharmacol Ther. 2016 Nov-Dec;21(6):512-517.

PACULit Literature Updates August 2025: Pediatrics

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