Fluid Therapy With Balanced Crystalloids Versus Normal Saline In Critically Ill Patients

Objective:We performed a systematic review and meta-analysis to evaluate whether the use of balanced crystalloids compared with saline reduce mortality and/or the occurrence of acute kidney injury(AKI)in intensive care unit(ICU)patients.Methods:A systematic search of PubMed,EMBASE,and the Cochrane Library was performed from database inception to December 31,2022.Randomized control trials(RCT)comparing balanced crystalloids and normal saline in ICU patients were selected.The primary outcome was mortality at the longest follow-up.Secondary outcomes included the incidence of AKI and new renal replacement therapy(RRT).The risk of bias of the included trials was assessed by the Cochrane risk-of-bias algorithm.The data were extracted and assessed according to Cochrane Handbook.Meta-analysis was conducted with RevMan 5.3 software.Trial sequential analysis(TSA)was conducted to control random errors for primary outcome and to estimate the required information size.Results:A total of 35,456 patients from eight studies were included.There was no significant difference between balanced crystalloids and saline in mortality(risk ratio[RR]: 0.96;95% confidence interval [CI]:0.92 – 1.01;P=0.09).TSA analysis indicated the cumulative Z-curve did not cross the conventional boundary and the TSA threshold line,and reached the required information size.This means that future studies that evaluate ICU patients will probably not change our conclusions.There were no significant differences between balanced crystalloids and saline in the outcomes of the incidence of AKI(RR: 0.97;95% CI 0.90–1.01;P=0.08)and new RRT(RR: 0.93;95% CI 0.93–1.02;P=0.11).We did subgroup meta-analyses on mortality by different diseases.Three RCTs including 1906 patients were enrolled traumatic brain injury(TBI)subgroup,and four RCTs including 31524 patients were enrolled non-TBI subgroup.The subgroup analysis with TBI showed lower mortality in patients receiving saline(RR:1.25;95% CI 1.02 – 1.50;P=0.03).However,in patients with non-TBI,balanced crystalloids achieved lower mortality than normal saline(RR: 0.94;95% CI 0.90–0.99;P=0.02).Four RCTs reported data of patients with sepsis,including 6501 sepsis patients and 26925 non-sepsis patients.The subgroup analysis with sepsis showed lower mortality in patients receiving balanced crystalloids(RR: 0.93;95% CI 0.87 – 1.00;P=0.04).However,there was statistically significant in non-sepsis subgroup(RR: 0.98;95% CI 0.92 –1.04;P=0.46).Conclusion:1.Compared with saline,balanced crystalloids may not improve the outcomes of ICU patients,and future studies that evaluate ICU patients will probably not change our conclusions.2.Balanced crystalloids increase the risk of death in patients with TBI.3.Future studies should focus on patients with specific diseases,such as TBI or sepsis,to evaluate which specific patient would most likely benefit from balanced crystalloids and which would benefit from saline.