Comparison of balanced crystalloids versus normal saline in patients with diabetic ketoacidosis: a meta-analysis of randomized controlled trials

Abstract

Purpose: The optimal resuscitative fluid for patients with diabetic ketoacidosis (DKA) remains controversial. Therefore, our objective was to assess the effect of balanced crystalloids in contrast to normal saline on clinical outcomes among patients with DKA.

Methods: We searched electronic databases for randomized controlled trials comparing balanced crystalloids versus normal saline in patients with DKA, the search period was from inception through October 20^th, 2023. The outcomes were the time to resolution of DKA, major adverse kidney events, post-resuscitation chloride, and incidence of hypokalemia.

Results: Our meta-analysis encompassed 11 trials, incorporating a total of 753 patients with DKA. There was no significant difference between balanced crystalloids and normal saline group for the time to resolution of DKA (MD -1.49, 95%CI -4.29 to 1.31, P=0.30, I² = 65%), major adverse kidney events (RR 0.88, 95%CI 0.58 to 1.34, P=0.56, I² = 0%), and incidence of hypokalemia (RR 0.80, 95%CI 0.43 to 1.46, P=0.46, I² = 56%). However, there was a significant reduction in the post-resuscitation chloride (MD -3.16, 95%CI -5.82 to -0.49, P=0.02, I² = 73%) among patients received balanced crystalloids.

Conclusion: Among patients with DKA, the use of balanced crystalloids as compared to normal saline has no effect on the time to resolution of DKA, major adverse kidney events, and incidence of hypokalemia. However, the use of balanced crystalloids could reduce the post-resuscitation chloride.

Systematic review registration: https://osf.io, identifier c8f3d.

Keywords: balanced crystalloids; diabetic ketoacidosis; meta-analysis; normal saline; resuscitation.

Figure 1

PRISMA 2020 flow diagram for the meta analysis.

Figure 2

Assesment of quality by the Cochrane risk of bias tool. Red denotes high risk, yellow unclear risk and green low rsik.

Figure 3

Forest plot showing the effect of balanced crystalloids versus normal saline on the time of resolution to DKA.

Figure 4

Forest plot showing the effect of balanced crystalloids versus normal saline on the (A) major adverse kidney events, (B) incidence of hypokalemia.

Figure 5

Forest plot showing the effect of balanced crystalloids versus normal saline on the post-resuscitation chloride.

Figure 6

Trial Sequential Analysis of Clinical Outcomes. (A) time to resolution of DKA (6 studies, n=463); (B) major adverse kidney events (6 studies, n=451); (C) post-resuscitation chloride (4 studies, n=285); (D) incidence of hypokalemia (4 studies, n=380). The Z curve in blue measures the treatment effect (pooled relative risk). The parallel lines in green are the boundaries of conventional meta-analysis (alpha 5%), and the boundaries of benefit and harm are boundaries of conventional meta-analysis adjusted for between-trial heterogeneity and multiple statistical testing (TSA boundaries). A treatment effect outside the TSA boundaries of benefit/harm indicates reliable evidence for a treatment effect, and a treatment effect within the futility zone (the triangle between the parallel lines) indicates reliable evidence of no treatment effect.