TABLE 2.
Description of included studies.
| ID | Author | Intervention | Details of intervention | Dose or volume of intervention | Nutritional initiation | Duration of intervention | Drug administration |
| 1 | Caparros | Prebiotics + EPN |
Prebiotics: fiber (8.9 g/L). EPN: Stresson Multifiber [75 g of proteins, with an 83:1 non-protein-calories-to-nitrogen ratio, and had a high content of arginine (11.8%), MCT (40%)] |
Prebiotics: NR EPN: 25 kcal/kg per day. |
<24 h | Until hospital discharge | Gastric or jejunal |
| EPN | EPN: Nutrison Protein Plus (per liter, 62.5 g of proteins with a 102:1 non-protein calories-to-nitrogen ratio and was free of MCT and fiber) | EPN: 25 kcal/kg per day. | |||||
| 2 | Kotzampassi | Synbiotics + EPN | Synbiotics 2000 Forte Probiotics: Pediococcus pentosaceus 5–33:3, Leuconostoc mesenteroides 32–77:1, L. paracasei ssp 19, L. plantarum 2,362 Prebiotics: inulin, oat bran, pectin, resistant starch EPN: NR |
Probiotics: 4 × 1011 CFUs QD Prebiotics:10 g QD EPN: NR |
<24 h | 15 days | Endoscopic gastrostomy or NG tube |
| Placebo + EPN |
Placebo: Maltodextrin EPN: NR |
Placebo: Maltodextrin QD EPN: NR |
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| 3 | Radrizzani | EPN | EN: Perative (55% carbohydrate, 25% fat, 21% protein, 1.3 kcal/ml, containing per 100 ml: 0.8 g l-arginine, 0.15 g ω-3 fatty acids, 0.7 g ω-6 fatty acids, 2.9 mg vitamin E, 0.75 mg β-carotene, 2.2 mg zinc, and 7 μg selenium) | 25–28 kcal/kg body weight per day | <24 h | NR | NR |
| TPN | TPN: 59% carbohydrate, 23% fat, 18% protein, 1.2 kcal/ml | Central venous catheter | |||||
| 4 | Spindler-Vesel | Synbiotics + EPN | Synbiotics 2000 Probiotics: Lactobacillus: Pediococcus pentosaceus 5–33:3, Lactococcus raffinolactis 32–77:1, Lactobacillus paracasei subsp paracasei 19, Lactobacillus plantarum 2362 Prebiotics: glucan, inulin, pectin, resistant starch EPN: Nutricomp standard (3.7 g protein, 13.7 g carbohydrate, 3.3 g fat per 100 mL) |
Probiotics: 4 × 1011 CFUs QD Prebiotics:10 g QD EPN: 0.2 and 0.3 gN/kg body weight/d and an average of 25 non-protein kcal/kg body weight/d |
<24 h | 7 consecutive days. Until ICU discharge or EN discontinuation | NG tube feeding |
| Prebiotics + EPN |
Prebiotics: Nova Source (fermentable fibers) EPN: Nova Source (4.1 g protein, 14.4 g carbohydrate, 3.5 g fat, 2.2 g fermentable fibers as fermentable guar gum per 100 mL) |
Prebiotics: NR EPN: 0.2 and 0.3 gN/kg body weight/d and an average of 25 non-protein kcal/kg body weight/d |
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| EPN | EPN: Nutricomp peptide (4.5 g hydrolyzed protein, 16.8 g carbohydrate, 1.7 g fat per 100 mL), Alitraq (5.25 g protein, 16.5 g carbohydrate, 1.55 g fat and 1.55 g glutamine, 446 mg arginine, 154 mg ?-linolenic acid per 100 mL) | EPN: 0.2 and 0.3 gN/kg body weight/d and an average of 25 non-protein kcal/kg body weight/d | |||||
| 5 | Abdulmeguid | EPN | EN: standard feeding formula, which is a 1-calorie per mL | 20–35 kcal/kg/day | <24 h | NR | NR |
| TPN | TPN: NR | Central venous catheter | |||||
| 6 | Forestier | Probiotics + EPN | Probiotics: Lactobacillus casei rhamnosus | Probiotics:1 × 109 CFUs BID | <72 h | From the third day after admission to the ICU until discharge or death. | NG tube or oral after tube removal |
| Placebo + EPN | Placebo: Growth medium without bacteria |
Placebo: BID EPN: NR |
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| 7 | Giamarellos-Bourboulis | Synbiotics + EPN | Synbiotics 2000 Forte Probiotics: Pediococcus pentosaceus 5–33:3, Leuconostoc mesenteroides 32–77:1, L. paracasei ssp 19, L. plantarum 2,362 Prebiotics: inulin, oat bran, pectin, resistant starch EPN: Intestamin |
Probiotics: 4 × 1011 CFUs QD Prebiotics: 10 g QD EPN: NR |
<24 h | 15 days | NG/gastrostomy tube |
| EPN | EPN: Intestamin | EPN: NR | |||||
| 8 | Knight | Synbiotics + EPN | Synbiotics 2000 Forte® Probiotics: Pediococcus pentosaceus 5–33:3, Leuconostoc mesenteroides 32–77:1, L. paracasei ssp 19, L. plantarum 2,362 Prebiotics: inulin, oat bran, pectin, resistant starch EPN: Nutrison Energy |
Probiotics: 4 × 1010 CFUs BID Prebiotics:10 g BID EPN: NR |
<24 h | A maximum of 28 days or ICU discharge or death | NG/OG tube |
| Placebo + EPN |
Placebo: Crystalline cellulose EPN: Nutrison Energy |
Placebo: BID EPN: NR |
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| 9 | Moses | EPN | EPN: Hypocaloric EN | Maximum of 1000 cal/d and protein 28.32 g | <48 h | From the time of intubation to either the time of tracheostomy or extubation or transfer out of the medical ICU to the ward or death. | NG feeding |
| TPN | TPN: Glucose and electrolyte | Maximum of 1000 cal/d and protein 28.32g | Central venous catheter | ||||
| 10 | Barraud | Probiotics + EPN |
Probiotics: Ergyphilus capsules (Lactobacillus rhamnosus GG, Lactobacillus casei, Lactobacillus acidophilus, Bifidobacterium bifidum) EPN: Fresubin® |
Probiotics: 2 × 1010 CFUs QD EPN: 30–35 kcal/kg |
<24 h | The entire period of mechanical ventilation but for a duration not exceeding 28 days | NG tube |
| Placebo + EPN |
Placebo: Excipient EPN: Fresubin® |
Placebo: QD EPN: 30–35 kcal/kg |
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| 11 | Frohmader | Probiotics + EPN |
Probiotics: VSL#3 (Lactobacillus, Bifidobacterium, Streptococcus salivarius subsp. thermophilus) EPN: Isosource or Renal or Diabetic Resource (Novartis, Melbourne, Australia) |
Probiotics: 4.5 × 1011 CFUs BID EPN: 5 to 35 cal/kg per day and 0.8 to 1.5 g protein per kilogram per day. |
<48 h | Until hospital discharge | NG/NJ tube |
| Placebo + EPN |
Placebo: Free of fiber and prebiotics additives EPN: Isosource or Renal or Diabetic Resource (Novartis, Melbourne, Australia) |
Placebo: BID EPN: 25 to 35 cal/kg per day and 0.8 to 1.5 g protein per |
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| 12 | Morrow | Probiotics + EPN |
Probiotics:
Lactobacillus rhamnosus GG EPN: NR |
Probiotics: 1 × 109 CFUs BID EPN: NR |
<48 h | Until extubation, tracheostomy placement, or death | Mixed with water Oropharynx and NG tube |
| Placebo + EPN |
Placebo: Inert inulin EPN: NR |
Placebo: Inert inulin BID EPN: NR |
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| 13 | Altintas | EPN | EN: standard feeding formula, which is a 1-calorie per mL | 25–30 kcal kg–1 d–1, Protein requirement was calculated as 1.2–1.5 g/kg/d (ideal body weight) | <48 h | NR | Gastric and postpyloric feeding |
| TPN | TPN: 70% of the non-protein calories were met by carbohydrates and 30% by lipids. | Central or peripheral route | |||||
| 14 | Tan | Probiotics + EPN |
Probiotics: Golden Bifid: 0.5 × 108 CFUs Bifidobacterium longum, 0.5 × 107 CFUs Lactobacillus bulgaricus, 0.5 × 107 CFUs Streptococcus thermophilus EPN: 3.8 g protein, 13.8 g carbohydrate, 3.4 g fat/100 ml, osmolarity 250 mOsm/l, no fibers |
Probiotics:109 CFUs per day EPN: 30 kcal/kg body weight/day and 0.2 gN/kg body weight/day |
<48 h | 21 days | NG tube |
| EPN | EPN: 3.8 g protein, 13.8 g carbohydrate, 3.4 g fat/100 ml, osmolarity 250 mOsm/l, no fibers | EPN: 30 kcal/kg body weight/day and 0.2 gN/kg body weight/day | |||||
| 15 | Aydoğmuş | EPN |
EN: first-line enteral nutrition (45% carbohydrate, 35% lipid and 20% protein) PN: NR |
25–30 kcal kg–1 d–1 | NR | NR | NG tube feeding |
| TPN | TPN: a concentration of 1 mL/kcal that contained 20–30% dextrose, 20% lipid and 5.4–10% amino acid. | Central venous catheterization | |||||
| 16 | Rongrungruang | Probiotics + EPN |
Probiotics:
Lactobacillus casei (Yakult) (Shirota strain) EPN:NR |
Probiotics: 8 × 109 CFUs for oral care after standard oral care QD. 8 × 109 CFUs enteral feeding QD EPN: NR |
NR | 28 days or endotracheal tubes were removed | Feeding tube |
| EPN | EPN: NR | EPN: NR | |||||
| 17 | Malik | Probiotics + EPN |
Probiotics:
Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus lactis, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium infantis EPN: Osmolite 1 cal (standard formula), Glucerna (glucose intolerance formula), Peptamen (semielemental formula), and Novasource Renal (electrolyte and fluid restriction). |
Probiotics:3 × 109 CFUs BID EPN:25 kcal kg–1 d–1 |
<48 h | 7 days | NG tube feeding |
| Placebo + EPN |
Placebo: Similar appearance and taste EPN: Osmolite 1 cal (standard formula), Glucerna (glucose intolerance formula), Peptamen (semielemental formula), and Novasource Renal (electrolyte and fluid restriction). |
Placebo: 3g BID EPN:25 kcal kg–1 d–1 |
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| 18 | ZarinfarN | Probiotics + EPN | Probiotics: Lactobacillus GG | TID | NR | NR | NG tube feeding |
| Placebo + EPN | Placebo: NR | TID | |||||
| 19 | Zeng | Probiotics + EPN |
Probiotics: Medilac-S: Bacillus subtilis 4.5 × 109 CFUs/0.25 g and Enterococcus faecalis 0.5 × 109 CFUs/0.25 g EPN: NR |
Probiotics:0.5 g (1 × 1010 CFUs) TID EPN: NR |
<24 h | Until tracheal extubation, discharge from the hospital or death, with a maximum duration of 14 days | NG tube feeding |
| EPN | EPN: NR | EPN: NR | |||||
| 20 | Fazilaty | Prebiotics + EPN |
Prebiotics: oat β-glucan EPN: high-protein enteral diet (20% protein, 30% lipid, and 50% carbohydrate) |
Prebiotics: 3 g QD EPN: 25–30 kcal kg–1 d–1 based on weight and metabolic condition. |
<48 h | NR | NG tube feeding |
| Placebo + EPN |
Placebo: maltodextrin EPN: high-protein enteral diet (20% protein, 30% lipid, and 50% carbohydrate) |
Prebiotics: 3g QD EPN: 25–30 kcal kg–1 d–1 based on weight and metabolic condition. |
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| 21 | Kooshk | Prebiotics + EPN |
Prebiotics: Fenugreek seed powder EPN: NR |
Prebiotics:3 g BID EPN: NR |
<24 h | NR | NG tube feeding |
| EPN | EPN: NR | EPN: NR | |||||
| 22 | Reignier | EPN |
EN: first-line enteral nutrition Isosmotic, isocaloric, normal-protein, polymeric preparations. PN: NR |
Daily calorie target in kcal/kg of actual bodyweight was 20–25 during the first 7 days then 25–30 from day 8 to extubation. | <72 h | Until tracheal extubation or death | NG tube feeding |
| TPN | TPN: NR | Central venous catheterization | |||||
| 23 | Shimizu | Synbiotics + EPN |
Probiotics: Yakult BL Seichoyaku (1 × 108 CFUs/g B. breve strain/g and 1 × 108 cfu/g L. casei strain Shirota) Prebiotics: galactooligosaccharides (Oligomate S-HP) EPN: standard polymeric diet Glucerna®-Ex 1 kcal/mL; 51:17:32 ratio of carbohydrate, protein, and fat; fiber 1.4 g/100 mL |
Probiotics: 3 g (2 × 108 CFUs) QD Prebiotics: 10 g QD EPN: 25–30 kcal/kg ideal body weight per day as the calorie goal. |
<72 h | Until oral intake was initiated | Nasal tube |
| EPN | EPN: standard polymeric diet Glucerna®-Ex 1 kcal/mL; 51:17:32 ratio of carbohydrate, protein, and fat; fiber 1.4 g/100 mL | EPN: 25–30 kcal/kg ideal body weight per day as the calorie goal. | |||||
| 24 | Mahmoodpoor | Probiotics + EPN |
Probiotics: Lactocare: Lactobacillus species (casei, acidophilus, rhamnosus, bulgaricus), Bifidobacterium species (breve, longum), Streptococcus thermophilus. EPN: Standard formula (1 kcal/mL; Ensure) |
Probiotics:1010 CFUs BID EPN:25 kcal/kg |
<48 h | 14 days or death | NG tube feeding |
| Placebo + EPN |
Placebo: Starch capsule EPN: Standard formula (1 kcal/mL; Ensure) |
Placebo: BID EPN:25 kcal/kg |
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| 25 | Anandaraj | Probiotics + EPN |
Probiotics:
Lactobacillus rhamnosus EPN: NR |
Probiotics: 2 × 109 CFUs BID EPN: NR |
NR | For a total of seven days or until extubation, whichever was earlier. | NG tube feeding |
| Placebo + EPN |
Placebo: Starch capsule EPN: NR |
Placebo: BID EPN: NR |
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| 26 | Jin | Probiotics + EPN |
Probiotics: Golden Bifid 0.5 g/tablet (0.5 × 107 CFUs Bifidobacterium longum, 0.5 × 106 CFUs Lactobacillus bulgaricus, 0.5 × 106 CFUs Streptococcus thermophilus) EPN: TP-HE, TPF-T, TPF-D |
Probiotics: 2 g (2.1 × 107 CFUs) TID EPN: 25 kcal/kg ideal body weight per day as the calorie goal. |
<48 h | NR | Nasal feeding |
| EPN | EPN: TP-HE, TPF-T, TPF-D | EPN: 25 kcal/kg ideal body weight per day as the calorie goal. | |||||
| 27 | Nseir | EPN |
EN: first-line enteral nutrition Isosmotic, isocaloric, normal-protein, polymeric preparations. PN: NR |
Daily calorie target in kcal/kg of actual bodyweight was 20–25 during the first 7 days then 25–30 from day 8 to extubation. | <72 h | Until tracheal extubation or death | NG tube feeding |
| TPN | TPN: NR | Central venous catheterization | |||||
| 28 | Habib | Probiotics + EPN |
Probiotics: Lacteol Forte®
Lactobacillus LB (Lactobacillus delbrueckii and Lactobacillus fermentum) EPN: NR |
Probiotics:1 × 109 CFUs TID EPN: NR |
<24 h | NR | OG/NG tube feeding |
| Placebo + EPN |
Placebo: Starch capsule EPN: NR |
Placebo: TID EPN: NR |
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| 29 | Nazari | Probiotics + EPN |
Probiotics: Lactocare: Lactobacillus species (casei, acidophilus, rhamnosus, bulgaricus), Bifidobacterium species (breve, longum), Streptococcus thermophilus. EPN: NR |
Probiotics: 1 × 1010 CFUs Q12h EPN: NR |
NR | NR | NG tube feeding |
| Placebo + EPN |
Placebo: Starch capsule EPN: NR |
Placebo: Q12h EPN: NR |
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| 30 | Johnstone | Probiotics + EPN |
Probiotics: L rhamnosus GG EPN: NR |
Probiotics:1 × 1010 CFUs BID EPN: NR |
<24 h | Up to 60 days or until discharge from the ICU or until Lactobacillus species was isolated from a sterile site or cultured as the sole or predominant organism from a non-sterile site | Enteral feeding |
| Placebo + EPN |
Placebo: Microcrystalline cellulose EPN: NR |
Placebo: BID EPN: NR |
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| 31 | Maria | Probiotics + EPN |
Probiotics:
L. acidophilus LA-5, L. plantarum UBLP-40, B. animalis subsp. lactis BB-12, S. boulardii Unique-28 EPN: NR |
Probiotics:
L. acidophilus LA-5 (1.75 × 109 CFUs), L. plantarum UBLP-40 (0.5 × 109 CFUs), B. animalis subsp. lactis BB-12 (1.75 × 109 CFUs), S. boulardii Unique-28 (1.5 × 10109 CFUs) BID EPN: NR |
<24 h | 15 days | Nasogastric or gastrostomy tube |
| Placebo + EPN |
Placebo: Powdered glucose polymer EPN: NR |
Placebo: BID EPN: NR |
CFUs, colony forming units; EN, enteral nutrition; EPN, enteral nutrition and/or adjuvant peripheral parenteral nutrition; MCT, medium-chain triglycerides; NG, nasogastric; NR, not reported; OG, orogastric; PN, parenteral nutrition; TPN, total parenteral nutrition; TBI, traumatic brain injuries; TPN, total parenteral nutrition.