Balanced Crystalloid Solution or Normal Saline in Fluid Resuscitation in Critically Ill Patients: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Abstract

Background: Both balanced crystalloid solution and normal saline are commonly used for fluid therapy in critically ill patients. However, the association between the types of crystalloid solution and patient outcomes remains inconclusive. Materials and Methods: The authors performed a search using Pubmed, Embase, and Cochrane Central Register through January 2022. Randomized controlled trials (RCTs) comparing balanced crystalloids and normal saline in non-perioperative fluid resuscitation for critically ill adult patients were included. The primary outcome was 30-day mortality. A trial sequential analysis (TSA) was performed to assess the effect of each type of fluid on the outcomes. Secondary outcomes included the incidence of acute kidney injury (AKI), renal replacement therapy (RRT), and other pre-specified outcomes. Results: Ten RCTs were identified and included 36,233 participants. Between the balanced crystalloids and the normal saline group, there were no significant differences in mortality at 30 days (relative risk [RR] 0.95, 95% confidence interval [CI] 0.89 to 1.02, I²=0), the incidence of AKI (RR 0.95, 95% CI 0.90 to 1.01, I²=0), and RRT (RR 0.93, 95% CI 0.86 to 1.01, I²=13). However, patients receiving balanced crystalloids demonstrated a significantly lower serum chloride level than the patients receiving normal saline (MD –1.95, 95% CI –3.45 to –0.45, I²=99). There was also no mortality difference in the sepsis and traumatic brain injury subgroups. The TSA confirmed the absence of an effect on mortality at 30 days and the incidence of AKI. Conclusion: In critically ill patients, the use of balanced crystalloids does not decrease 30-day mortality or the incidence of AKI and RRT. However, data in specific subgroups of patients were underpowered and further studies are required. There were signals of benefit and risk of the balanced salt solution in the subgroups of sepsis and traumatic brain injury. Trial registration: The present study was registered in the PROSPERO database, CRD42021275796. Keywords: Balanced crystalloid; Normal saline; Critically ill patients; Mortality; Acute kidney injury