Balanced Crystalloids Versus Normal Saline for Fluid Resuscitation in Patients With Diabetic Ketoacidosis: A...

Diabetic ketoacidosis (DKA) is a life-threatening metabolic complication of diabetes mellitus requiring aggressive intravenous fluid resuscitation. Although the recommended fluid has always been 0.9% normal saline (NS), its supraphysiological chloride load may induce hyperchloremic metabolic acidosis, potentially complicating DKA management. Balanced crystalloids (BCs), with electrolyte compositions more closely approximating human plasma, have emerged as potentially advantageous alternatives. This systematic review compares the clinical outcomes of NS with BCs for fluid resuscitation in patients with DKA. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Embase, and CENTRAL (2021-2026) following PRISMA guidelines. Studies that directly compared 0.9% NS with BCs (such as lactated Ringer's (LR) solution, Plasma-Lyte 148, Isolyte, Sterofundin, or other balanced electrolyte solutions (BES)) for DKA resuscitation were included. The outcomes of interest included time to DKA resolution, electrolyte profiles, insulin infusion duration, length of stay (LOS), acute kidney injury (AKI), and mortality. The risk of bias (ROB) was assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) (for non-randomized studies) and RoB 2 (for randomized controlled trials (RCTs)). Nine studies, four RCTs and five non-randomized studies, comprising 1416 patients, met the inclusion criteria. BCs consistently reduced hyperchloremia and improved bicarbonate profiles compared with NS. Insulin infusion duration was significantly shorter with BCs in two studies. Length-of-stay outcomes were mixed, with some studies showing shorter hospital or ICU stays with BCs. No significant differences in AKI incidence or mortality were observed between groups. The ROB ranged from moderate to substantial, although the RCTs demonstrated a lower ROB than the retrospective cohort studies. BCs demonstrated superior electrolyte profiles and comparable safety compared with NS in DKA. However, their effect on clinically meaningful outcomes such as time to DKA resolution remains uncertain. While the biochemical advantages support consideration of BC, definitive practice recommendations await higher-certainty evidence.