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Review
. 2022 Apr 1;11(7):1971.
doi: 10.3390/jcm11071971.

Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis

Azizullah Beran  1 , Nehaya Altorok  1 , Omar Srour  1 , Saif-Eddin Malhas  1 , Waleed Khokher  1 , Mohammed Mhanna  1 , Hazem Ayesh  1 , Nameer Aladamat  2 , Ziad Abuhelwa  1 , Khaled Srour  3 , Asif Mahmood  1 , Nezam Altorok  1   4 , Mohammad Taleb  5 , Ragheb Assaly  1   5
Affiliations
Review

Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis

Azizullah Beran et al. J Clin Med. .

Abstract

The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81-0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79-0.95), and AKI (RR 0.85, 95% CI 0.77-0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90-1.03), need for RRT (RR 0.91, 95% CI 0.76-1.08), and ICU LOS (MD -0.25 days, 95% CI -3.44, 2.95), were observed between the two groups. However, subgroup analysis of randomized controlled trials (RCTs) showed no statistically significant differences in overall mortality (RR 0.92, 95% CI 0.82-1.02), AKI (RR 0.71, 95% CI 0.47-1.06), and need for RRT (RR 0.71, 95% CI 0.36-1.41). Our meta-analysis demonstrates that overall BC was associated with reduced mortality and AKI in sepsis compared to NS among patients with sepsis. However, subgroup analysis of RCTs showed no significant differences in both overall mortality and AKI between the groups. There was no significant difference in the need for RRT or ICU LOS between BC and NS. Pending further data, our study supports using BC over NS for fluid resuscitation in adults with sepsis. Further large-scale RCTs are necessary to validate our findings.

Keywords: balanced crystalloids; lactated ringer; normal saline; plasmalyte; sepsis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram for the selection of studies.
Figure 2
Figure 2
(A) Forest plot comparing balanced crystalloids and normal saline regarding overall mortality. (B) Subgroup analysis based on the study design (RCTs vs. observational studies) for overall mortality. (C) Subgroup analysis based on enrollment location (ED vs. ICU) for overall mortality.
Figure 3
Figure 3
Subgroup analysis based on the type of balanced crystalloids: (A) lactated ringer and (B) Plasmalyte for overall mortality. Forest plots comparing balanced crystalloids and normal saline regarding: (C) 28/30-day mortality and (D) 90-day mortality.
Figure 4
Figure 4
Forest plots comparing balanced crystalloids and normal saline regarding: (A) acute kidney injury, (C) need for renal replacement therapy, and (E) intensive care unit length of stay. Subgroup analysis based on study design (RCTs vs. observational studies) for (B) acute kidney injury and (D) need for renal replacement therapy.
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