Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

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 DATA SOURCES: We searched MEDLINE, EMBASE, CENTRAL, and unpublished sources from inception to May 4, 2021.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.

Why Give My Surgical Patients Probiotics

“…There are no studies dedicated entirely to elective surgery patients who remained intubated for an extended period post-op; however, there are many meta-analysis of RCTs dealing with critically ill patients and with ventilatory-induced pneumonia, to whom probiotics were given with good results in relation to placebo [ 20 , 21 , 22 , 23 ].…”

What Surgeon Should Know about Probiotics

“…The physical trauma of surgery, augmented by the stress of anesthesia, pharmacologic manipulation (opioids, antibiotics, and acid-suppressing agents), alterations in tissue perfusion and pH, perioperative nutritional strategies, and the deprivation of gut motility, have been shown to cause gut microbial dysbiosis, inflammation and harmful disruption of the epithelial barrier, allowing so-called “bacterial translocation” in parallel with the depression of the host immune defense system [ 3 , 4 , 5 ]. Within this wide-ranging context, both the general health status of the patient scheduled for surgery and their own microbiome are of particular interest [ 6 ], while the most important pitfall remains the extensive heterogeneity in patient populations, the disease processes, different surgeries which may differently influence the gut microbiome (involving the colon or otherwise, clear operations such as hernia repair versus acute viscera inflammations, the presence of cirrhotic or congestive liver or obstructive jaundice), and treatment modalities in surgical settings [ 7 , 8 ].…”

Trial Sequential Analysis in Critical Care Medicine: The Way Forward

“…We congratulate Sharif et al ( 1 ) for their interesting systematic review and meta-analysis, published in a recent issue of Critical Care Medicine , of randomized clinical trials (RCTs) on probiotics in critical illness. They included 65 RCTs among adults and pediatric critically ill patients ( n = 8,483) and concluded that probiotics may reduce ventilator-associated pneumonia (VAP) with low certainty evidence.…”

“…The following vital variables were outlined: 1) proportion of events in the control group, 2) the assumed RRR of the experimental intervention, 3) the desired risk of type-I error alpha, 4) the desired risk of type-II error beta (from which the desired power can be calculated), and 5) the heterogeneity correction if a random effects model is chosen. Such variables should ideally be specified a priori in a systematic review registry or in a published protocol ( 4 ).…”

“…The authors reply: W e thank Lew et al (1) for their feedback on our recently published systematic review and meta-analysis in Critical Care Medicine comparing the safety and efficacy of probiotics versus placebo in critically ill patients (2). After careful review, there is an error in the published trial sequential analysis (TSA) for the ventilator-associated pneumonia (VAP) outcome.…”