Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial*

Abstract

OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution (n = 351) versus 0.9% saline (n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3–9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49–0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusion-related AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization.

Running Wide Open: Strong Evidence for Bolus Fluids Selection in Pediatric Sepsis*

“…The work by Sankar et al (18), published in this issue of Critical Care Medicine, is a particularly welldesigned trial demonstrating the benefit of BC over NS. In their multicenter, double-blind RCT of over 700 patients, their patients received either PlasmaLyte A or 0.9% saline for bolus fluids.…”

“…This article's important findings are tempered by certain limitations in design. First, although a large study by pediatric critical care standards, the study by Sankar et al (18) enrolled only one-tenth of the number of patients in the adult SMART trial, which increases the likelihood of biases, especially selection bias. Maintenance fluid was not controlled in the study by Sankar et al (18), and although there was a similar proportion of bolus to maintenance administered-35% and 34% in the first 24 hours in the NS and BC group, respectively-there remains the significant confounding factor of bolus fluids being a minority of overall fluids administered.…”

“…First, although a large study by pediatric critical care standards, the study by Sankar et al (18) enrolled only one-tenth of the number of patients in the adult SMART trial, which increases the likelihood of biases, especially selection bias. Maintenance fluid was not controlled in the study by Sankar et al (18), and although there was a similar proportion of bolus to maintenance administered-35% and 34% in the first 24 hours in the NS and BC group, respectively-there remains the significant confounding factor of bolus fluids being a minority of overall fluids administered. Last, it is notable that the principal findings in this trial were substantially similar to the SMART trial: increased risk of new or progressive AKI, and increased risk of RRT with NS bolus administration.…”

“…However, entrenched does not mean permanent; our own institution's Pharmacy and Therapeutics Committee updated their guidance on bolus administration to encourage consideration of BCs in January 2021, with local practice patterns shifting heavily toward BC since. Sankar et al (18) have added a strong body of evidence supporting institutional change from NS to BC for bolus administration in pediatric septic patients. Further studies are required to expand the population size evaluated, and to determine if a mortality benefit exists as it does in the adult population, indeed one large RCT is currently underway (19).…”

“…Ultimately, this will beg the question: should NS be reserved for specialty cases, as opposed to the default choice? Change in healthcare deserves to be promoted rapidly when the interventions are evidence-based, safe, cheap, and scalable; Sankar et al (18) have presented compelling data to move us in the direction of BCs.…”