Probiotics for Preventing Ventilator-Associated Pneumonia in Mechanically Ventilated Patients: A Meta-Analysis with Trial Sequential Analysis

Abstract

Background and Objective: Ventilator-associated pneumonia (VAP) is still an important cause of morbidity and mortality in mechanically ventilated patients. The efficacy of the probiotics for preventing VAP is still controversial. Present study was conducted to comprehensively evaluate the effect of probiotics on VAP prevention in mechanically ventilated patients.Methods: PubMed, Embase, and CENTRAL were searched up to September 2016. Eligible trials designed with randomized controlled trials (RCTs) comparing probiotics with control in mechanically ventilated patients were included. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were estimated with fixed or random effects models. Trial sequential analysis (TSA) was performed using TSA 0.9beta software.Results: Thirteen RCTs (N = 1969) were included. Overall, probiotics were associated with reduced incidence of VAP (RR = 0.73, 95% CI = 0.60–0.89; P = 0.002), which was confirmed by TSA (TSA adjusted 95% CI = 0.55–0.96). However, no significant difference was observed in 90-day mortality (RR = 1.00, 95% CI = 0.72–1.37; P = 0.99), overall mortality (RR = 0.84, 95% CI = 0.70–1.02; P = 0.09), 28-day mortality (RR = 1.06, 95% CI = 0.72–1.57; P = 0.99), intensive care unit (ICU) mortality (RR = 0.97, 95% CI = 0.74–1.27; P = 0.82), hospital mortality (RR = 0.81, 95% CI = 0.65–1.02; P = 0.07), diarrhea (RR = 0.99, 95% CI = 0.83–1.19; P = 0.92), length of ICU stay (MD = −2.40 days, 95% CI = −6.75 to 1.95; P = 0.28), length of hospital stay (MD = −1.34 days, 95% CI = −6.21 to 3.54; P = 0.59), and duration of mechanical ventilation (MD = −3.32 days, 95% CI = −6.74 to 0.09; P = 0.06).Conclusions: In this meta-analysis, we found that probiotics could reduce the incidence of VAP in mechanically ventilated patients. It seems likely that probiotics provide clinical benefits for mechanically ventilated patients.

The Importance of the Microbiome in Critically Ill Patients: Role of Nutrition

“…Ventilator-associated pneumonia (VAP) is responsible for up to 47% of the infections acquired in the ICU [98], and is one of the main causes of mortality and morbidity [99]. Many strategies have been described to prevent it, but the results are not conclusive [98]. Recently, numerous studies have focused on the use of probiotics [23,98,99].…”

“…Many strategies have been described to prevent it, but the results are not conclusive [98]. Recently, numerous studies have focused on the use of probiotics [23,98,99].…”

“…They show that the use of probiotics in critically ill patients decreases the incidence of VAP, but has no impact on the mortality, duration of mechanical ventilation, or length of ICU stay. They also report that clinical heterogeneity and potential publication bias decrease solid clinical recommendations, and suggest the need for additional high-quality clinical trials to be able to show significant evidence of the possible therapeutic effects of the probiotics [98,100].…”

The gut microbiome alters immunophenotype and survival from sepsis

“…In addition, remaining microbes alter their own virulence factors in response to stress signals from the host (19). Further, intentionally altering the microbiomeby probiotics, fecal microbial transplant, or selective decontamination of the digestive tract-positively effects numerous outcomes in the intensive care unit (20)(21)(22). Together, the transition of a microbiome into a pathobiome has been hypothesized to be a driver of mortality from sepsis (23)(24)(25)(26), at least in part by the ability of invading bacteria to act as antigens and modulate the host immune response (7).…”

Critical illness and the role of the microbiome

“…Probiotics are selective exogenous bacteria given to the host. Meta‐analyses and multiple studies have indicated that probiotics are effective at decreasing ventilator‐associated pneumonia but do not alter length of stay or mortality. A clear limitation to the published works on probiotics is the significant heterogeneity between studies in dose, length, and bacteria given.…”