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. 2023 Oct 11:19:783-799.
doi: 10.2147/TCRM.S416785. eCollection 2023.

Comparison of Balanced Crystalloids versus Normal Saline in Critically Ill Patients: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Yi Chen  1   2   3 , Yongli Gao  1   2   3
Affiliations

Comparison of Balanced Crystalloids versus Normal Saline in Critically Ill Patients: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Yi Chen et al. Ther Clin Risk Manag. .

Abstract

Background: Fluid resuscitation is routinely needed for critically ill patients. However, the optimal choice between crystalloids and normal saline is in heat debate.

Objective: To conduct a meta-analysis comparing normal saline and balanced crystalloids in the treatment of critically ill patients with composite mortality as the primary outcome.

Methods: PubMed, Embase, Medline, Web of Science, and Cochrane Library were searched from inception up to March 2022. Studies of critically ill adult patients assigned to receive normal saline or balanced crystalloids were included. We conducted a meta-analysis using an inverse variance, random-effects model in addition to trial sequential analysis (TSA). The primary outcome was composite mortality. Subgroup analyses were also conducted.

Results: Eighteen full-text studies (n=36,224) were included. Balanced crystalloids were associated with lower mortality compared with normal saline (risk ratio [RR]=0.96; 95% confidential interval [CI] 0.93, 1; p=0.03; I2=0) and lower incidence of acute kidney injury/acute renal failure (RR =0.93; 95% CI = 0.87, 0.99; p=0.03). No significant difference was observed in other outcomes. In the sepsis patients, the balanced crystalloid showed a lower composite mortality rate compared with normal saline (RR =0.91; 95% CI = 0.85, 0.99; p=0.02). TSA analysis demonstrated that, with 80% power, the effect of balanced crystalloid is not larger than a 10% relative decrease in composite mortality compared with normal saline.

Conclusion and relevance: This study demonstrated that balanced crystalloids could be an optimal choice over normal saline in critically ill patients to a reduced composite mortality rate. In patients with sepsis, the difference is especially significant. Nonetheless, the optimal resuscitation fluid option between saline and balanced crystalloid solutions should be investigated further with more evidence.

Keywords: balanced crystalloids; critically ill; meta-analysis; normal saline; systematic review.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The flowchart for the systematic search and the selection of studies.
Figure 2
Figure 2
The transitivity of potential effect modifiers. (A) The geography information of all included trials. (B). The frequency of fluid types published in clinical trials. (C). The frequency of patient groups published in clinical trials. (D) The mean age of all included patients.
Figure 3
Figure 3
Summary of risk of bias of the included randomized controlled trials.
Figure 4
Figure 4
The forest plot for outcomes. (A) Composite mortality. (B) The incidence of acute kidney injury. (C) The rate of requiring renal replacement therapy. (D) The hospitalization stays (E) The ventilator-free days.
Figure 5
Figure 5
The subgroup analysis of composite mortality.
Figure 6
Figure 6
The funnel plot for primary and secondary outcomes. (A) Composite mortality. (B) The incidence of acute kidney injury and acute renal failure. (C) The rate of requiring renal replacement therapy. (D) The hospitalization stays (E) The ventilator-free days.
Figure 7
Figure 7
Trial sequential analysis results. The required event size to demonstrate a 10% relative decrease in composite mortality with a control group proportion of 12%, an alpha of 5% and a beta of 20% is 4147 (vertical red line). The red lines represent the trial sequential monitoring boundaries and the futility boundaries. The dashed dark lines cross the y-axis at 1.96 and −1.96, which correspond to the nominal threshold for statistical significance. The blue line is the cumulative Z-curve.
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