• Fernando G Zampieri, Alexandre B Cavalcanti, Gian Luca Di Tanna, Lucas P Damiani, Naomi E Hammond, Flavia R Machado, Sharon Micallef, John Myburgh, Todd W Rice, Matthew W Semler, Paul J Young, and Simon Finfer.
• HCor Research Institute, São Paulo, Brazil.
• Crit Care Resusc. 2022 Jun 6; 24 (2): 128136128-136.

AbstractObjective: It remains unclear whether balanced solutions improve patient-centred outcomes in critically ill patients overall and whether the treatment effect is heterogeneous, with evidence that some populations of patients may be helped and others harmed. To provide the most up-to-date and comprehensive assessment of the totality of the evidence, we will perform an ongoing living systematic review with aggregated and individual patient data meta-analysis (IPDMA) comparing the use of balanced solutions with saline in critically ill adults. Design: Living systematic review using aggregated and individual patient data from randomised controlled trials. Data sources: We will conduct annual searches of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials. gov, the Australian New Zealand Clinical Trials Registry (ANZCTR), Japan's University Hospital Medical Information Network (UMIN) Center, and the Brazilian Registry of Clinical Trials (ReBEC). The first search was completed on 1 March 2022 and will be repeated annually. Authors of eligible trials will be invited to provide individual data for the IPDMA. The initial analysis will use all data received up to 30 June 2022. Review methods: We will include randomised controlled trials in adults treated in an intensive care unit that allocated individuals or clusters of patients to a balanced crystalloid solution or 0.9% saline for intravenous fluid therapy. Studies that used colloids as part of the intervention or that recruited only elective surgical patients will be excluded. The primary endpoint will be in-hospital mortality. The key secondary endpoint will be survival at longest follow-up for each trial. Data will be synthesised using both a random effect Bayesian meta-analysis and using hierarchical Bayesian models for individual patient data. Discussion: The use of balanced crystalloid solutions may reduce mortality and improve other outcomes in some critically ill patients. We will assess the totality of current and future evidence by performing an ongoing living systematic review with aggregated data and IPDMA. Protocol registration: CRD42022299282.© 2022 College of Intensive Care Medicine of Australia and New Zealand.

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