0.9% Sodium chloride solution versus Plasma-Lyte 148 versus compound sodium lacTate solution in children admitted to PICU—a randomized controlled trial (SPLYT-P): study protocol for an intravenous fluid therapy trial

Abstract

Background Intravenous fluid therapy represents the most common intervention critically ill patients are exposed to. Hyperchloremia and metabolic acidosis associated with 0.9% sodium chloride have been observed to lead to worse outcomes, including mortality. Balanced solutions, such as Plasma-Lyte 148 and Compound Sodium Lactate, represent potential alternatives but the evidence on optimal fluid choices in critically ill children remains scarce. This study aims to demonstrate whether balanced solutions, when used as intravenous fluid therapy, are able to reduce the incidence of a rise in serum chloride level compared to 0.9% sodium chloride in critically ill children. Methods This is a single-centre, open-label randomized controlled trial with parallel 1:1:1 assignment into three groups: 0.9% sodium chloride, Plasma-Lyte 148, and Compound Sodium Lactate solutions for intravenous fluid therapy. The intervention includes both maintenance and bolus fluid therapy. Children aged < 16 years admitted to intensive care and receiving intravenous fluid therapy during the first 4 h of admission are eligible. The primary outcome measure is a ≥ 5mmol/L increase in serum chloride level within 48 h post-randomization. The enrolment target is 480 patients. The main analyses will be intention-to-treat. Discussion This study tests three types of intravenous fluid therapy in order to compare the risk of hyperchloremia associated with normal saline versus balanced solutions. This pragmatic study is thereby assessing the most common intervention in paediatric critical care. This is a single-centre open-label study with no blinding at the level of delivery of the intervention. Certain paediatric intensive care unit (PICU) patient groups such as those admitted with a cardiac condition or following a traumatic brain injury are excluded from this study. Trial registration The study has received ethical approval (HREC/19/QCHQ/53177: 06/06/2019). It is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619001244190) from 9th September 2019. Recruitment commenced on 12th November 2019. The primary results manuscript will be published in a peer-reviewed journal.

Acetate‐ versus lactate‐buffered crystalloid solutions: A systematic review with meta‐analysis and trial sequential analysis

“…[22][23][24][25] In addition, we identified three on-going trials. [36][37][38] The main reasons for excluding trials were wrong study design and wrong outcome measures (Figure 1-PRISMA flowchart).…”

“…A total of four trials ( n = 288) could be included in the meta‐analyses 22–25 . In addition, we identified three on‐going trials 36–38 . The main reasons for excluding trials were wrong study design and wrong outcome measures (Figure 1—PRISMA flowchart).…”

“…52,53 Considering the vast use of buffered crystalloid solutions in clinical practice, the lack of data comparing their individual effects on patientimportant outcomes is surprising. Importantly, we identified three on-going trials [36][37][38] investigating the effects of acetate-versus lactatebuffered solutions on patient-important outcome measures, including the large "BASE" pilot trial (Semler et al expected n = 2093), 36 which will contribute markedly to the existing body of evidence.…”

Effect of Saline vs Gluconate/Acetate–Buffered Solution vs Lactate-Buffered Solution on Serum Chloride Among Children in the Pediatric Intensive Care Unit

“…A detailed description of the prespecified outcomes has been previously published. 18 Baseline demographic data, study treatments, and outcomes were manually collected, with additional data (including intravenous fluid therapy data, components to calculate organ dysfunction scores, biochemical data) extracted from the electronic health records. A prespecified data monitoring plan was executed throughout the trial to ensure accurate data collection (eMethods 4 in Supplement 2).…”

“…The study was registered with the Australia New Zealand Clinical Trial Registry before commencement of recruitment. The study protocol including composition of the study fluids and the statistical analysis plan was published before completion of enrollment 18 and is available in Supplement 1. Ethics approval was ob-tained before commencement of the trial (HREC/19/QCHQ/ 53177; eMethods 1 in Supplement 2).…”