Lower vs. higher fluid volumes in sepsis-protocol for a systematic review with meta-analysis

Background: Intravenous fluid administration with crystalloids is recommended in the initial management of sepsis. However, the quality of evidence supporting the recommendation on fluid volumes is low, and clinical equipoise exists. Potential benefits of restricting fluid volumes has been suggested, but the overall benefit or harm in patients with sepsis is unknown. Accordingly, we aim to assess patient-important benefits and harms of lower vs. higher fluid volumes in resuscitation of adult patients with sepsis.

Methods/design: We will conduct a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials comparing different strategies to obtain separation in fluid volumes or balances during resuscitation of adult patients with sepsis. We will systematically search the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, BIOSIS and Epistemonikos for relevant literature. We will follow the recommendations by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The risk of systematic errors (bias) and random errors will be assessed, and the overall quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Discussion: The outlined systematic review will provide important data on how patient-important outcomes are affected by higher vs. lower resuscitation fluid volumes in adults with sepsis. Using trial sequential analysis to assess the risk of random errors will increase the validity of the summary estimates calculated and help estimate the required information size for future trials.