Balanced crystalloid solutions versus normal saline in intensive care units: a systematic review and meta-analysis

Intravenous fluid therapy is important for pediatric and adult patients in intensive care units (ICUs). However, medical professionals continue to struggle to determine the most appropriate fluids to obtain the best possible outcomes for each patient.

We conducted a meta-analysis involving cohort studies and randomized controlled trials (RCTs) to compare the influence of balanced crystalloid solutions and normal saline among patients in ICUs.

Studies that compared balanced crystalloid solutions and saline in ICU patients from databases including PubMed, Embase, Web of Science, and Cochrane Library were systematically searched up to July 25, 2022. The primary outcomes were mortality and renal-related outcomes, which included major adverse kidney events within 30 days (MAKE30), acute kidney injury (AKI), new receipt of renal replacement therapy (RRT), maximum creatinine increasing, maximum creatinine level, and final creatinine level ≥ 200% of baseline. Service utilization including length of hospital stay, ICU stay, ICU-free days and ventilator-free days were also reported.

A total of 13 studies (10 RCTs and 3 cohort studies) involving 38,798 patients in ICUs met the selection criteria. Our analysis revealed that each subgroup had no significant difference in mortality outcomes among ICU patients between balanced crystalloid solutions and normal saline. A significant difference was detected between the adult groups (odds ratio [OR], 0.92; 95% confidence interval [CI], [0.86, 1.00]; p = 0.04) indicating that the AKI in the balanced crystalloid solutions group was lower than that in the normal saline group. Other renal-related outcomes, such as MAKE30, RRT, maximum creatinine increasing, maximum creatinine level, and final creatinine level ≥ 200% of baseline showed no significant difference between the two groups. Regarding secondary outcomes, the balanced crystalloid solution group had a longer ICU stay time (WMD, 0.02; 95% CI, [0.01, 0.03]; p = 0.0004 and I² = 0%; p = 0.96) than the normal saline group among adult patients. Furthermore, children treated with balanced crystalloid solution had a shorter hospital stay time (WMD, - 1.10; 95% CI, [- 2.10, - 0.10]; p = 0.03 and I² = 17%; p = 0.30) than those treated with saline.

Compared with saline, balanced crystalloid solutions could not reduce the risk of mortality and renal-related outcomes, including MAKE30, RRT, maximum creatinine increasing, maximum creatinine level, and final creatinine level ≥ 200% of baseline, but the solutions may reduce total AKI incidence among adult patients in ICUs. For service utilization outcomes, balanced crystalloid solutions were associated with a longer length of ICU stay in the adult group and shorter length of hospital stay in the pediatric group.