Associations Between Fluid Balance and Outcomes in Critically Ill Children: A Protocol for a Systematic Review and Meta-analysis

BACKGROUND: Fluid therapy is a mainstay during the resuscitation of critically ill children. After initial stabilization, excessive fluid accumulation may lead to complications of fluid overload, which has been independently associated with increased risk for mortality and major morbidity in critically ill children. OBJECTIVES: Perform an evidence synthesis to describe the methods used to measure fluid balance, define fluid overload, and evaluate the association between fluid balance and outcomes in critically ill children. DESIGN: Systematic review and meta-analysis. MEASUREMENTS: Fluid balance, fluid accumulation, and fluid overload as defined by authors. METHODS: We will search Ovid MEDLINE, Ovid EMBASE, Cochrane Library, and ProQuest, Dissertations and Theses. In addition, we will search www.clinicaltrials.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and the proceedings of selected key conferences for ongoing and completed studies. Search strategy will be done in consultation with a research librarian. Clinical trials and observational studies (from database inception to present) in patients (<25 years) admitted to pediatric intensive care units (PICUs) reporting fluid balance, fluid accumulation, or fluid overload, and associated outcomes will be included. Language will not be restricted. Two reviewers will independently screen studies and extract data. Primary outcome is mortality, and secondary outcomes encompass critical care resource utilization. Quality of evidence and risk of bias will be assessed using the Newcastle-Ottawa Scale (NOS). Results will be synthesized qualitatively and pooled for meta-analysis if possible. LIMITATIONS: Quality of the included studies; lack of randomized trials; high degrees of expected heterogeneity; and variations in definitions of fluid balance and fluid overload between studies. CONCLUSION: We will comprehensively appraise and summarize the evidence of the association between fluid balance and outcomes in critically ill children, and in doing so attempt to harmonize definitions related to fluid balance, accumulation, and overload. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42016036209.