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Table 2 Randomized controlled trials evaluating the effect of pre, pro or synbiotics on feeding tolerance of enterally fed critically ill patients

From: Effect of gut microbiota modulation on feeding tolerance of enterally fed critically ill adult patients: a systematic review

Author, year Population Design JADAD score EN protocol Type of intervention
Delivery vehicle Intervention /dose/duration control
Bleichner et al., 1997 [17] ICU patients
n=128
Parallel 5 NR NGT or jejunostomy EN (intact protein standard diet without fiber or lactose) + Saccharomyces boulardii /500 mg four times a day/limited to 21 days or to the withdrawal of EN EN (intact protein standard diet without fiber or lactose) + placebo
Schultz et al., 2000 [18] ICU patients
n=44
Parallel 2 NR Tube feeding Fiber containing formula+ pectin or fiber-free formula +pectin/ 20ml, twice daily/ 6 days Fiber containing formula+ placebo Or fiber-free formula +placebo
Spapen et al., 2001 [19] ICU patients with severe sepsis or septic shock
n= 25
Parallel 3 Start: first 24h, 25cc/h. Increase 25–35 cc/h to 80% target NGT EN+ partially hydrolyzed guar/ 22g/l / a maximum of 21 days or to the withdrawal of EN Fiber-free EN
Rushdi et al., 2004 [20] ICU patients with persistent diarrhea
n=20
Parallel 3 Start: first 18–24h. Target: 25–35 kcal/kg. First day: 50%, second day: 75%, third day: 100% NJT EN+ 2% soluble guar gum (Benefiber)/ 4 days Fiber-free EN
Knight et al., 2009 [21] ICU patients
n= 259
Parallel 5 Start: 30cc/h; max: 80cc/h; increase or decrease according to GRV NGT/ OGT EN (Nutrison Energy) + Synbiotic 2000 FORTE / twice a day/ to the earliest of the following time point:28 days after admission, death or discharge EN (Nutrison Energy) + placebo
Frohmader et al., 2010 [22] ICU patients
n= 45
Parallel 5 Start: first 24h, 20cc/h; increase: 20cc/4h to target. Target: 25–35 kcal/kg NGT/ OGT/ nasojejunostomy Fiber-free EN+ probiotic (VSL#3) /twice a day/ mean of 11.9 days Fiber-free EN+ placebo
Barraud et al., 2010 [23] ICU patients with MV
n=167
Parallel 5 Starting in the first 24h, 10 kcal/kg, increase to 30–35 kcal/kg NGT EN + multi-strain probiotic (Ergyphilus)/ once a day/ until successful weaning (maximum of 28 days) EN + placebo
Morrow et al., 2010 [24] ICU patients with MV
n=167
Parallel 5 NR NGT EN + probiotic (Lactobacillus rhamnosus GG) / twice a day/ EN+ inulin-based placebo
Ferrie and Daley, 2011 [25] ICU patients with diarrhea
n= 36
Parallel 5 NR Gastric tube Fiber containing EN+ probiotic (inulin-based Lactobacillus GG)/twice a day/ 7 days Fiber containing EN+ placebo (inulin)
Sanaie et al., 2014 [26] ICU patient
n= 40
Parallel 5 Start in first 24h, 25cc/h; increase 25cc/4h to target. Target: 25–30 kcal/kg NGT Fiber containing EN+ probiotic (VSL#3)/ twice daily/ 7 days Fiber containing EN+ placebo
Majid et al., 2014 [27] ICU patients
n= 22
Parallel 5 Energy estimation based on Schofield equation NGT Fiber containing EN+ additional oligofructose/inulin/ 7g per day/ 7days Fiber containing EN+ placebo
Malik et al., 2016 [28] ICU patients
n= 60
Parallel 5 25 kcal/kg. start in first 24–48h, with GRV management NGT EN+ multi-strain probiotic/ twice a day/ 7 days EN+ placebo
Fazilaty et al., 2018 [29] Multiple trauma ICU patients
n= 40
Parallel 5 Goal: 25–30 kcal/kg, 75% in the 48h NGT EN+ prebiotic (oat β-glucan)/ 3g per day/ 21 days EN+ placebo (maltodextrin)
Shimizu et al., 2018 [30] Septic ICU patients with MV
n= 72
Parallel 3 Start: 20cc/h; increase: 20cc/h/day to target. Target: 25–30 kcal/kg NGT EN +multi-strain probiotic (Yakult BL Seichoyaku) 3 g per day+ prebiotic (galactooligosaccharides) 10g per day/ until EN stop EN
Tuncay et al., 2018 [31] Neurocritical care patients
n=46
Parallel 1 Start: 10cc/h; increase: 10cc/8h till 20cc/h; requirement: Schofield equation+stress factor+activity factor+ ventilator support+fever+TEF Nasofeeding, gastrostomy/PEG EN with prebiotic content/ 21 days EN
  1. NR Not reported; NGT Nasogastric tube; EN Enteral nutrition; ICU Intensive care unit; OGT Orogastric tube; GRV Gastric residual volume; VSL#3, a single daily high dose probiotic preparation