Table 1 Randomized studies evaluating probiotics in critically ill patients
From: Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis
Study | Population | Methods score | Type of probiotic/intervention | |||
|---|---|---|---|---|---|---|
Delivery vehicle | Intervention/dose/duration | Control | ||||
1 | Tempe 1983 [30] | ICU patients n = 40 | C.Random: yes ITT: yes Blinding: double Score: 10 Viability (intervention): NR | EN tube | EN (unknown) + Ultra-Levure (Saccharomyces boulardii), 1010/1 L solution for 11–21 days | EN (unknown) + placebo (sterile solution) |
2 | Schlotterer 1987 [31] | Patients with burns n = 18 | C.Random: no ITT: no Blinding: double Score: 8 Viability (intervention): NR | NG tube | EN (Polydiet or Nutrigil) + Saccharomyces boulardi 500 mg QID for 8-28 days | EN (Polydiet or Nutrigil) + placebo |
3 | Heimburger 1994 [32] | Mixed ICU patients: 83 % received antibiotics n = 62 | C.Random: no ITT: no Blinding: double Score: 9 Viability (intervention): NR | EN tube | EN (standard) + 1 g of Lactinex (Lactobacillus acidophilus and Lactobaccilus bulgaricus) 2 × 106TID for 5–10 days | EN (standard) + placebo (0.5 g dextrose + 0.5 g lactose) |
4 | Bleichner 1997 [33] | Mixed ICU patients n = 128 | C.Random: not sure ITT: yes Blinding: double Score: 13 Viability (intervention): NR | EN tube | EN (unknown) + Saccharomyces boulardii 500 mg QID for 21 days or until EN stopped | EN (unknown) + placebo (powder) |
5 | Kecskes 2003 [34] | ICU patients on antibiotics n = 45 | C.Random: no ITT: no Blinding: double Score: 8 Viability (intervention): yes | NJ tube | EN (Nutrison fiber) + fermented oatmeal formula with Lactobacillus plantarum 299 10 9 BID and fiber for 7 days | EN (Nutrison fiber) + heat-killed Lactobacillus plantarum 299 BID + fiber (non-viable) |
6 | Jain 2004 [36] | ICU patients n = 90 | C.Random: no ITT: yes Blinding: double Score: 10 Viability (intervention): NR | Oral or NG tube | EN or PN + Trevis™ 1 capsule TID + 7.5 g Raftilose (oligofructose) BID until hospital discharge | EN or PN + placebo (powdered sucrose capsules) |
7 | Lu 2004 [35] | Patients with burns n = 40 | C.Random: no ITT: yes Blinding: double Score: 9 Viability (intervention): NR | NR | EN + synbiotics (4 types of probiotics + 4 types of unspecified prebiotics) for 21 days | EN + 4 types of prebiotics |
8 | Klarin 2005 [37] | Critically ill patients on antibiotics n = 17 | C.Random: no ITT: no Blinding: no Score: 6 Viability (intervention): NR | Mixed in fermented oatmeal, given via NG tube | EN + Lactobacillus plantarum 299v, 109/day 50 ml every 6 h × 3 days then 25 ml every 6 h until ICU discharge | EN (Impact or Nutrodrip fiber). Some patients needed PN |
9 | McNaught 2005 [38] | ICU patients on antibiotics n = 130 | C.Random: no ITT: yes Blinding: no Score: 7 Viability (intervention): NR | Oral, NJ tube | EN or PN + Proviva, (oatmeal and fruit drink) 5 × 107 CFU/ml of L. plantarum 299 v × 500 mls until hospital discharge or beyond | EN or PN alone |
10 | Kotzampassi 2006 [39] | Patients with multiple trauma from 5 ICUs n = 77 | C.Random: no ITT: no Blinding: double Score: 8 Viability (intervention): NR VAP determination: clinical | Endoscopic gastrostomy or NG tube | EN or PN + Synbiotic 2000 Forte 1011, 1 sachet/day for 15 days until ICU discharge | EN or PN + placebo (maltodextrin), mixed in tap water |
11 | Alberda 2007 [40] | ICU patients n = 28 | C.Random: no ITT: yes; Blinding: double Score: 10 Viability (intervention): No for VSL # 3; Yes for bacteria sonicates | NG tube | Jevity Plus (EN) (10 g fructooligosaccharides/1000 mL and 12 g of soluble and insoluble fiber blend) + VSL # 3, 1 package BID, 9 × 1011 /day for 7 days until ICU discharge or EN discontinuation | Jevity Plus + placebo |
12 | Li 2007 [41] | Patients with severe acute pancreatitis n = 25 | C.Random: no ITT: yes Blinding: no Score: 7 Viability (intervention): NR | Given enterally | Jinshuangqi (bifidobacteria, lactobacillus and streptococcus) 2.0 g TID on basis of traditional treatment Duration: NR | Traditional treatment |
13 | Olah 2007 [42] | Patients with severe acute pancreatitis n = 83 | C.Random: no ITT: no Blinding: no Score: 9 Viability (intervention): NR | NJ tube | EN (Nutricion fiber) + Synbiotic 2000, 4 × 1010 CFU for 7 days | EN (Nutricion fiber) + 10 g plant fibers ((2.5 g each of Betaglucan, inulin, pectin and resistant starch) (prebiotics) BID for at least 2 days |
14 | Forestier 2008 [44] | Mixed ICU patients, 50 % on antibiotics n = 208 | C.Random: not sure ITT: no Blinding: double Score: 8 Viability (intervention): NR VAP determination: objective | NG tube or oral (after tube removal) | Lactobacillus casei rhamnosum, 109 CFU BID until ICU discharge | Placebo (growth medium never exposed to bacteria). |
15 | Besselink 2008 [43] | Patients with severe acute pancreatitis from 15 ICUs n = 298 | C.Random: not sure ITT: yes Blinding: double Score:11 Viability (intervention): NR VAP determination: clinical | NJ tube or oral | EN (Nutrison multifiber) + Ecologic 641 1010 CFU BID for 28 days | EN (Nutrison multifiber) + placebo (cornstarch + maltodextrins) |
16 | Klarin 2008 [45] | ICU patients from 5 ICUs, on antibiotics for C. Difficile n = 68 | C.Random: yes ITT: no Blinding: double Score: 10 Viability (intervention): NR | Mixed in fermented oatmeal added to enteral feeds NG tube | 299 Lactobacillus plantarum, 8 × 108 CFU/ml given as 6 × 100 ml doses every 12 h and after 50 ml given BID until ICU discharge | Same oatmeal gruel mixed with lactic acid |
17 | Knight 2009 [46] | General ICU patients n = 300 | C.Random: yes ITT: no Blinding: double Score: 10 Viability (intervention): NR VAP determination: clinical | NJ or OG (orogastric) tube | EN (Nutrition Energy) + Synbiotic 2000 FORTE 4 × 1011 species/sachet BID for 28 days or ICU discharge | EN (Nutrison Energy) + Placebo |
18 | Barraud 2010 [47] | Mechanically ventilated ICU patients, 80 % on antibiotics n = 167 | C.Random: yes ITT: yes; Blinding: double Score: 12 Viability (intervention): NR VAP determination: objective | NG tube | EN (Fresubin) + Ergyphilus 2 × 1010 per capsule + potato starch 5 capsules/day for 28 days | EN (fresubin) + placebo capsules (excipient of potato starch) |
19 | Morrow 2010 [10] | ICU patients n = 146 | C.Random: no; ITT: yes; Blinding: double; Score:10 Viability (intervention): yes VAP determination: objective | Oropharynx and NG tube | EN (routine care) + Lactobacillus rhamnosus GG, 2 × 109 BID as lubricant and mixed with water until extubation | EN (routine care) + inert plant starch inulin (prebiotic) BID as lubricant and mixed with water |
20 | Frohmader 2010 [48] | General ICU patients on antibiotics n = 45 | C.Random: yes ITT: yes Blinding: double Score: 11 Viability (intervention): yes | NG or NJ tube | EN (Standard) + VSL #3 mixed in nutritional supplement (Sustagen), BID until hospital discharge | EN (Standard) + placebo mixed in nutritional supplement (Sustagen), BID |
21 | Ferrie 2011 [49] | Critically ill patients with diarrhea, n = 36 | C.Random: no ITT: yes Blinding: double Score: 10 Viability (intervention): yes | NG tube | EN (Standard) + Culturelle (Lactobacillus rhamnosus GG), 1010 species/capsule +280 mg inulin powder for 7 days | EN (Standard) + Raftiline, gelatin capsule with 280 mg inulin powder (prebiotic) |
22 | Sharma 2011 [50] | Patients with acute pancreatitis n = 50 | C.Random: yes ITT: yes Blinding: double Score: 11 Viability (intervention): yes | Oral, NJ or NG | EN (standard) or oral 4 sachets each 2.5 × 109 Lactobacillus acidophilus, Bifidobacterium longus, Bifidobacterium bifidum & Bifidobacterium infantalis + 25 gms fructose for 7 days | EN (Standard) + placebo |
23 | Tan 2011 [51] | Patients with closed head injury n = 52 | C.Random: yes ITT: yes Blinding: single Score: 10 Viability (intervention): yes VAP determination: clinical | NG tube | EN (standard) total of 109 bacteria i.e., 7 sachets each 0.5 × 108 Bifidobacterium longum, 0.5 × 1071 Lactobacillus bulgaricus and 0.5 × 107 Streptococcus thermophilus for 21 days | EN (standard) |
24 | Cui 2013 [20] | Patients with severe acute pancreatitis n = 70 | C.Random: no ITT: yes Blinding: no Score: 9 Viability (intervention): yes | EN | EN + bifidobacterium, 4 capsules (each 210 mg, 2.604 × 109) every 12 h, given through nasal gastric tube. Total dose per day 20.832 × 109 | EN |
25 | Tan 2013 [21] | Severe craniocerebral trauma n = 52 | C.Random: no ITT: other Blinding: no Score: 11 Viability (intervention): yes | NG tube | EN + 1 × 109 bacteria of viable probiotics (Golden Bifid, 3.5 g 3 times per day) per day for 21 days. | EN (standard) |
26 | Wang 2013 [22] | Severe acute pancreatitis with intestinal ileus or abdominal distention. n = 183 | C.Random: no ITT: yes Blinding: no Score: 6 Viability (intervention): NR | SBFT | EN (standard) + capsules 0.5 g TID containing Bacillus subtilis and Enterococcus faecium (5.0 × 107Bacillus subtilis and 4.5 × 108 Enterococcus faecium per 250 g capsule). Unclear timeframe. | EN (standard) |
27 | Lopez de Toro 2014 [23] | Medical and surgical ICU patients with multi-organ failure n = 89 | C.Random: yes ITT: yes Blinding: no Score: 11 Viability (intervention): NR | EN | EN + symbiotic drink with streptococcus Thermophilus, lactobacillus bulgaricus, Lactobacillus casei, lactobacillus acidophilus, bifidobacterium, Escherichia coli, coliformes × 7 days (max 4.8 × 109 UFC/ml). | EN and PN |
28 | Sanaie 2014 [24] | Critically ill pts, SIRS, expected length of stay ≥7 days n = 40 | C.Random: yes ITT: yes Blinding: double Score: 9 Viability (intervention): yes | NG tube | EN (standard) + 2 sachets VSL#3 BID × 7 days. | EN (standard) + placebo |
29 | Rongrungruang 2015 [25] | Critically ill patients, expected to receive mechanical ventilation at least 72 h and had no VAP at enrollment n = 150 | C.Random: no ITT: no Blinding: no Score: 6 Viability (intervention): yes | EN | 80 ml of 8 × 109 cfu of Lactobacillus casei (Shirota strain) (Yakult) for oral care after the standard oral care once daily An additional 80 ml of the product was given via enteral feeding once daily for 28 days or when their endotracheal tubes were removed | EN (standard) + oral care with 2 % chlorhexidine solution 4 times per day |
30 | Zeng 2016 [26] | Critically ill patients, expected to receive mechanical ventilation at least 48 h n = 235 | C.Random: yes ITT: no Blinding: no Score: 5 Viability (intervention): yes | NG tube | 1 capsule (Medilac-S, China) 0.5 g three times daily. Each probiotic capsule contained active Bacillus subtilis and Enterococcus faecalis at a concentration of 4.5 × 109 /0.25 g and 0.5 × 109/0.25 g, respectively | EN (standard) |