Restrictive fluids in sepsis: a systematic review and meta-analysis

Introduction: While large-volume fluid resuscitation as a part of early-goal directed therapy (EGDT) for sepsis has been widely adopted and endorsed by the SCCM Surviving Sepsis Guidelines, the risks of volume overload in the critically ill challenge this approach. The objective of this study is to assess the effects of a restrictive fluid resuscitation approach in sepsis given divergent results from randomized studies. Methods: A systematic review using a random effects meta-analysis with trial sequential analysis (TSA) of randomized controlled trials published from 2001 were evaluated. Studies were included if they evaluated adult patients with sepsis or septic shock involving a comparator group with an effective restrictive resuscitation approach. Two blinded reviewers independently assessed studies for inclusion and risk of bias and extracted data using Cochrane Collaborative methodology. The primary outcome was the incidence of mortality at the latest reported study period. Secondary outcomes included rates of acute kidney injury (AKI), ventilator days, intensive care unit (ICU) and hospital length of stay (LOS), duration of vasopressor therapy, and limb ischemia. Results: A total of 2,375 patients were included among the 8 trials analyzed. The risk of bias was high in 6 studies and low in 2 studies. All studies implemented fluid restriction after an initial 30 mL/kg volume. Use of a restrictive resuscitation approach did not significantly reduce mortality in all studies compared to usual care (37% vs 40% with usual care; risk ratio [RR] 0.94, 95% confidence interval [CI] 0.85–1.04, P=0.25, I2 = 24%) and was confirmed by TSA findings. There were no significant differences in rates of AKI (5 studies), LOS in ICU (4 studies) or hospital (2 studies), duration of vasopressor therapy (6 studies), or incidence of limb ischemia (3 studies). However, a restrictive resuscitation strategy significantly reduced ventilator days evaluated in 7 studies (mean difference -1.25 days, 95% CI -0.59 to -1.93 days, P=0.0003, I2 = 90%). Conclusions: This meta-analysis demonstrated that a restrictive fluid resuscitation strategy in sepsis resulted in no difference in mortality but may reduce ventilator days. Larger randomized trials are required to determine the optimal management of fluids in patients with sepsis.