Restrictive resuscitation in patients with sepsis and mortality: A systematic review and meta-analysis with trial sequential analysis

Study objective: Although fluid resuscitation is recommended by the Society of Critical Care Medicine Surviving Sepsis Campaign Guidelines, risks of volume overload persist.The objective of this systematic review is to assess the effects of a restrictive fluid resuscitation approach in the septic patient both during and after the initial resuscitation period (30 ml/kg).

Design: A systematic review and meta-analysis with trial sequential analysis (TSA) of randomized controlled trials was conducted. Two blinded reviewers independently assessed and included studies that evaluated adult patients with sepsis involving a comparator group with an effective restrictive fluid resuscitation approach. The primary outcome was mortality. Secondary outcomes included rates of acute kidney injury (AKI), renal replacement therapy (RRT), ventilator days, intensive care unit (ICU) and hospital length of stay (LOS), duration of vasopressor therapy, and limb (or digital) ischemia.

Setting: PubMed and Medline databases were queried for the search.

Patients: A total of eight trials in 2375 patients were included.

Intervention: Effective restrictive fluid resuscitation compared with standard of care.

Measurements and main results: The risk of bias was high in six studies and low in two studies, and all studies implemented fluid restriction after a 30-ml/kg infusion of fluids. Fluid restriction did not significantly reduce mortality in all studies compared to usual care (37% vs. 40% with usual care; risk ratio [RR] 0.90, 95% confidence interval [CI] 0.76-1.06, p = 0.23, I² = 24%) or by TSA findings. There were no significant differences in rates of AKI or RRT (5 studies), LOS in ICU (4 studies) or hospital (3 studies), duration of vasopressor therapy (6 studies), or incidence of limb or digital ischemia (3 studies). However, fluid restriction significantly reduced ventilator days as evaluated in seven studies (mean difference - 1.25 days, 95% CI -1.92 to -0.58 days, p = 0.0003, I² = 90%).

Conclusion: This study demonstrated that a restrictive 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.