Balanced crystalloids versus normal saline for initial fluid resuscitation in diabetic ketoacidosis: a systematic review and meta-analysis of randomized controlled trials.

Objective: To systematically synthesize evidence from RCTs that evaluate the efficacy and safety of balanced crystalloids compared with normal saline for initial fluid resuscitation of patients with DKA. Methods: This systematic review and meta-analysis were performed considering PRISMA guidelines and was registered in PROSPERO. A comprehensive search was performed to identify RCTs comparing balanced crystalloids with normal saline in adults and children with DKA. The risk of bias was assessed by using Cochrane RoB 2 tool. A random-effects meta-analysis was performed using R software to calculate pooled Mean Differences for continuous outcomes and Odds Ratios for dichotomous outcomes with 95% Confidence Intervals. Results: Eleven RCTs were included. In the quantitative synthesis of six RCTs (n = 491) using continuous time-to-event data, balanced crystalloids were not associated with a statistically significant reduction in time to DKA resolution compared with normal saline (Mean Difference [MD] = -1.50 hours; 95% CI: -3.79 to 0.79; p=0.15), with moderate heterogeneity (I2 = 36.2%). The 95% prediction interval ranged from -5.44 to 2.44 hours. However, balanced crystalloids resulted in a significantly greater increase in serum bicarbonate at 12 hours (MD = +2.50 mmol/L; 95% CI: 1.51 to 3.48; p=0.004; I2 = 0.0%). Subgroup analyses by fluid type, DKA severity, and age group showed no significant subgroup differences. Conclusion: Initial fluid resuscitation with balanced crystalloids was not associated with a shorter time to DKA resolution compared with normal saline, and they were associated with a rapid increase in serum bicarbonate levels; however, this biochemical improvement did not translate into a shorter time to DKA resolution or other clinical benefits. The choice of crystalloids for initial DKA resuscitation remains an area of clinical equipoise because of the substantial heterogeneity and methodological limitations of the available evidence, emphasizing the need for further high-quality research.