Benefits and harm of probiotics and synbiotics in adult critically ill patients. A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND & AIMS: Several systematic reviews and meta-analyses of randomized controlled trials concluded that probiotics administration in critically ill patients was safe and associated with reduced rates of ventilator-associated pneumonia and diarrhea. However, a recent large multicenter trial found probiotics administration, compared to placebo, was not efficacious and increased adverse events. An updated meta-analysis that controls for type-1 and -2 errors using trial sequential analysis, with a detailed account of adverse events associated with probiotic administration, is warranted to confirm the safety and efficacy of probiotic use in critically ill patients. METHODS: RCTs that compared probiotics or synbiotics to usual care or placebo and reported clinical and diarrheal outcomes were searched in 4 electronic databases from inception to March 8, 2022 without language restriction. Four reviewers independently extracted data and assessed the study qualities using the Critical Care Nutrition (CCN) Methodological Quality Scoring System. Random-effect meta-analysis and trial sequential analysis (TSA) were used to synthesize the results. The primary outcome was ventilator-associated pneumonia (VAP). The main subgroup analysis compared the effects of higher versus lower quality studies (based on median CCN score). RESULTS: Seventy-five studies with 71 unique trials (n = 8551) were included. In the overall analysis, probiotics significantly reduced VAP incidence (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.56-0.88; I2 = 65%; 16 studies). However, such benefits were demonstrated only in lower (RR 0.47, 95% CI 0.32, 0.69; I2 = 44%; 7 studies) but not higher quality studies (RR 0.89, 95% CI 0.73, 1.08; I2 = 43%; 9 studies), with significant test for subgroup differences (p = 0.004). Additionally, TSA showed that the VAP benefits of probiotics in the overall and subgroup analyses were type-1 errors. In higher quality trials, TSA found that future trials are unlikely to demonstrate any benefits of probiotics on infectious complications and diarrhea. Probiotics had higher adverse events than control (pooled risk difference: 0.01, 95% CI 0.01, 0.02; I2 = 0%; 22 studies). CONCLUSION: High-quality RCTs did not support a beneficial effect of probiotics on clinical or diarrheal outcomes in critically ill patients. Given the lack of benefits and the increased incidence of adverse events, probiotics should not be routinely administered to critically ill patients. PROSPERO REGISTRATION: CRD42022302278.

Nutrition therapy in the older critically ill patients: A scoping review.

INTRODUCTION: There is a lack of guidelines or formal systematic synthesis of evidence for nutrition therapy in older critically ill patients. This study is a scoping review to explore the state of evidence in this population. METHOD: MEDLINE and Embase were searched from inception until 9 February 2022 for studies that enrolled critically ill patients aged ≥60 years and investigated any area of nutrition therapy. No language or study design restrictions were applied. RESULTS: Thirty-two studies (5 randomised controlled trials) with 6 topics were identified: (1) nutrition screening and assessments, (2) muscle mass assessment, (3) route or timing of nutrition therapy, (4) determination of energy and protein requirements, (5) energy and protein intake, and (6) pharmaconutrition. Topics (1), (3) and (6) had similar findings among general adult intensive care unit (ICU) patients. Skeletal muscle mass at ICU admission was significantly lower in older versus young patients. Among older ICU patients, low muscularity at ICU admission increased the risk of adverse outcomes. Predicted energy requirements using weight-based equations significantly deviated from indirect calorimetry measurements in older vs younger patients. Older ICU patients required higher protein intake (>1.5g/kg/day) than younger patients to achieve nitrogen balance. However, at similar protein intake, older patients had a higher risk of azotaemia. CONCLUSION: Based on limited evidence, assessment of muscle mass, indirect calorimetry and careful monitoring of urea level may be important to guide nutrition therapy in older ICU patients. Other nutrition recommendations for general ICU patients may be used for older patients with sound clinical discretion.