Balanced crystalloids versus normal saline for fluid therapy in pediatrics diabetic ketoacidosis: a systematic review

Authors

  • Danny Alsalloum Department of Pediatrics, Medcare Women and Children Hospital, Dubai, UAE
  • Prabhakar Patil Department of Pediatrics, Al Zahra Hospital, Dubai, UAE

DOI:

https://doi.org/10.18203/2349-3291.ijcp20262972

Keywords:

Diabetic ketoacidosis, Pediatrics DKA, Balanced crystalloids, Ringer’s lactate, Plasma-lyte, Normal saline, Hyperchloremia, Acute kidney injury

Abstract

Fluid therapy is a cornerstone of management in paediatric diabetic ketoacidosis (DKA). Although normal saline has traditionally been the preferred resuscitation fluid, concerns regarding hyperchloremic metabolic acidosis have led to increasing interest in balanced crystalloids such as Ringer’s lactate and Plasma-lyte. However, evidence regarding their efficacy and safety in children with DKA remains limited and has not been comprehensively synthesized. A systematic review of the literature was conducted to evaluate balanced crystalloids versus normal saline for fluid therapy in paediatric DKA. PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane central register of controlled trials were searched from database inception to March 2026. Randomized controlled trials and comparative observational studies involving children and adolescents with DKA were included. Outcomes of interest included time to DKA resolution, resolution of acidosis, incidence of hyperchloremia, serum bicarbonate recovery, incidence of acute kidney injury (AKI), cerebral edema and duration hospital stay. Four comparative studies involving 49,920 paediatric patients were included in this systematic review. Out of these studies three were randomized controlled trials and one was retrospective observational study. Balanced crystalloids were consistently found to be associated with lower chloride accumulation, decreased incidence of hyperchloremia and improved bicarbonate recovery as compared to cases treated by normal saline. DKA and acidosis resolution demonstrated a trend toward earlier metabolic recovery with balanced crystalloids. No clear difference was observed in the incidence of AKI, intensive care unit stay, or hospital stay between treatment groups. One large observational study reported a lower rate of cerebral edema among children receiving Ringer’s lactate compared with normal saline. Balanced crystalloids appear to be safe and effective alternatives to normal saline for fluid therapy in paediatric DKA. They are associated with favorable clinical and biochemical outcomes specially with respect to chloride homeostasis and bicarbonate recovery. Larger multicenter randomized controlled trials are required to confirm these findings and determine their impact on clinically important outcomes.

References

Foti Randazzese S, La Rocca M, Bombaci B, Di Pisa A, Giliberto E, Inturri T, et al. Severe Diabetic Ketoacidosis in Children with Type 1 Diabetes: Ongoing Challenges in Care. Children (Basel). 2025;12(1):110.

Kostopoulou E, Sinopidis X, Fouzas S, Gkentzi D, Dassios T, Roupakias S, et al. Diabetic Ketoacidosis in Children and Adolescents; Diagnostic and Therapeutic Pitfalls. Diagnostics (Basel). 2023;13(15):2602.

Campos Magallón P, Royo Sesma I, Vázquez Gómez JA, Ruiz Del Campo M, Ruiz Del Prado MY. Types of fluid therapy for pediatric patients with diabetic ketoacidosis: a systematic review. Diabetes Res Clin Pract. 2025;229:112926.

Glaser N, Fritsch M, Priyambada L, Rewers A, Cherubini V, Estrada S, et al. ISPAD clinical practice consensus guidelines 2022: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes. 2022;23(7):835-56.

Yıldırımçakar D, Öcal M, Altıncık SA, Özhan B. Hyperchloremia and Prolonged Acidosis During Treatment for Pediatric Diabetic Ketoacidosis. Pediatr Emerg Care. 2024;40(12):856-60.

Gershkovich B, English SW, Doyle MA, Menon K, McIntyre L. Choice of crystalloid fluid in the treatment of hyperglycemic emergencies: a systematic review protocol. Syst Rev. 2019;8(1):228.

Yan JW, Slim A, Van Aarsen K, Choi YH, Byrne C, Poonai N, et al. Balanced crystalloids (RInger's lactate) versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department (BRISK-ED): a protocol for a pilot randomized controlled trial. Pilot Feasibility Stud. 2023;9(1):121.

Liu Y, Zhang J, Xu X, Zou X. Comparison of balanced crystalloids versus normal saline in patients with diabetic ketoacidosis: a meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne). 2024;15:1367916.

Rosenbloom AL. The management of diabetic ketoacidosis in children. Diabetes Ther. 2010;1(2):103-20.

Sagar N, Lohiya S. A Comprehensive Review of Chloride Management in Critically Ill Patients. Cureus. 2024;16(3):e55625.

Singhal D, Gupta S, Kumar V. Normal Saline Versus Ringer's Lactate for Intravenous Fluid Therapy in Children with Diabetic Ketoacidosis: A Randomized Controlled Trial. Indian J Pediatr. 2025;92(11):1181-7.

Agarwal A, Jayashree M, Nallasamy K, Dayal D, Attri SV. 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;13(2):e004623.

Williams V, Jayashree M, Nallasamy K, Dayal D, Rawat A. 0.9% Saline versus Plasma-Lyte as Initial Fluid in Children with Diabetic Ketoacidosis (SPinK Trial): A Double-Blind Randomized Controlled Trial. Crit Care. 2020;24:1-9.

Bergmann KR, Abuzzahab MJ, Nowak J, Arms J, Cutler G, Christensen E, et al. Resuscitation With Ringer's Lactate Compared With Normal Saline for Pediatric Diabetic Ketoacidosis. Pediatr Emerg Care. 2018;34(11).

Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. 2018;19:155-77.

Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-43.

Chua HR, Venkatesh B, Stachowski E, Schneider AG, Perkins K, Ladanyi S, et al. Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis. J Crit Care. 2012;27(2):138-45.

Van Zyl DG, Rheeder P, Delport E. Fluid management in diabetic-acidosis--Ringer's lactate versus normal saline: a randomized controlled trial. QJM. 2012;105(4):337-43.

Hammond NE, Zampieri FG, Di Tanna GL, Garside T, Adigbli D, Cavalcanti AB, et al. Balanced Crystalloids versus Saline in Critically Ill Adults - A Systematic Review with Meta-Analysis. NEJM Evid. 2022;1(2):EVIDoa2100010.

Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, et al; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018;378(9):829-39.

Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, et al; SALT-ED Investigators. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018;378(9):819-28.

Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012;308(15):1566-72.

Rochwerg B, Alhazzani W, Sindi A, Heels-Ansdell D, Thabane L, Fox-Robichaud A, et al; Fluids in Sepsis and Septic Shock Group. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med. 2014;161(5):347-55.

Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, et al; Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med. 2001;344(4):264-9.

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Published

2026-08-26

How to Cite

Alsalloum, D., & Patil, P. (2026). Balanced crystalloids versus normal saline for fluid therapy in pediatrics diabetic ketoacidosis: a systematic review. International Journal of Contemporary Pediatrics, 13(9), 1801–1809. https://doi.org/10.18203/2349-3291.ijcp20262972

Issue

Section

Systematic Reviews