Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
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OBJECTIVES:To determine the safety and efficacy of probiotics or synbiotics on morbidity and mortality in critically ill adults and children.DATA SOURCES:We searched MEDLINE, EMBASE, CENTRAL, and unpublished sources from inception to May 4, 2021.STUDY SELECTION:We performed a systematic search for randomized controlled trials (RCTs) that compared enteral probiotics or synbiotics to placebo or no treatment in critically ill patients. We screened studies independently and in duplicate.DATA EXTRACTION:Independent reviewers extracted data in duplicate. A random-effects model was used to pool data. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development, and Evaluation approach.DATA SYNTHESIS:Sixty-five RCTs enrolled 8,483 patients. Probiotics may reduce ventilator-associated pneumonia (VAP) (relative risk [RR], 0.72; 95% CI, 0.59 to 0.89 and risk difference [RD], 6.9% reduction; 95% CI, 2.7–10.2% fewer; low certainty), healthcare-associated pneumonia (HAP) (RR, 0.70; 95% CI, 0.55–0.89; RD, 5.5% reduction; 95% CI, 8.2–2.0% fewer; low certainty), ICU length of stay (LOS) (mean difference [MD], 1.38 days fewer; 95% CI, 0.57–2.19 d fewer; low certainty), hospital LOS (MD, 2.21 d fewer; 95% CI, 1.18–3.24 d fewer; low certainty), and duration of invasive mechanical ventilation (MD, 2.53 d fewer; 95% CI, 1.31–3.74 d fewer; low certainty). Probiotics probably have no effect on mortality (RR, 0.95; 95% CI, 0.87–1.04 and RD, 1.1% reduction; 95% CI, 2.8% reduction to 0.8% increase; moderate certainty). Post hoc sensitivity analyses without high risk of bias studies negated the effect of probiotics on VAP, HAP, and hospital LOS.CONCLUSIONS:Low certainty RCT evidence suggests that probiotics or synbiotics during critical illness may reduce VAP, HAP, ICU and hospital LOS but probably have no effect on mortality.
