Table 4.
Relevant outcome parameters of included randomized studies of enteral glutamine supplementation in critically ill patients
| Study | Methods | Intervention | Mortality, n (%)a | Infections, n (%)b | Hospital stay (days) | ICU LOS (days) | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Score | Dose (g/kg/day) | Experimental | Control | Experimental | Control | Experimental | Control | Experimental | Control | |
| Type of feeding | ||||||||||
| Houdijk et al. [24] | C. random: Yes | >0.25 | 4/41 (9.8) | 3/39 (7.7) | 20/35 (57.1) | 26/37 (70.2) | 32.7 ± 17.1 | 33.0 ± 23.8 | NA | NA |
| ITT: No | Altira Q (glutamine-enriched formula) vs. isonitrogenous control (added amino acids) | |||||||||
| Blinding: Yes | ||||||||||
| 10 | ||||||||||
| Same volume of feeding received in both groups | ||||||||||
| Jones et al. [25] | C. random: Yes | 0.16 | Hospital | Hospital | NA | NA | NA | NA | 11 (4–54) | 16.5 (5–66) |
| ITT: No | Protina Torre MP (Fresenius Kabi, Bad Homburg, Germany) + glutamine (10–15 g/day nitrogen) vs. isonitrogenous control (11–14 g/day nitrogen) | 10/26 (38.5) | 9/24 (37.5) | |||||||
| Blinding: Yes | ICU | ICU | ||||||||
| 8 | 9/26 (35) | 9/24 (38) | ||||||||
| 6 months | 6 months | |||||||||
| 12/26 (46) | 10/24 (42) | |||||||||
| Brantley and Pierce [26] | C. random: Not sure | 0.50 | 0/31 (0.0) | 0/41 (0.0) | NA | NA | 19.5 ± 8.8 | 20.8 ± 11.5 | 11.4 | 11.1 |
| ITT: No | Glutamine-supplemented enteral formula vs. standard formula (isonitrogenous) protein given 1.5 g/kg/day | |||||||||
| Blinding: No | ||||||||||
| 4 | ||||||||||
| Hall et al. [27] | C. random: Yes | 0.27 | Hospital | Hospital | 38/179 (21) | 43/184 (23) | 25 (16–42)c | 30 (19–45)c | 11 (7–19) (excluding deaths) | 13 (8–19) (excluding deaths) |
| ITT: Yes | Isocal (Nestlé Health Science, Lutry, Switzerland) + glutamine (66 g/day protein) vs. isonitrogenous formula Isocal + glycine (64 g/day protein) | 24/179 (13) | 23/184 (13) | |||||||
| Blinding: Yes | ICU | ICU | ||||||||
| 13 | 16/179 (9) | 14/184 (8) | ||||||||
| 30 days | 30 days | |||||||||
| 26/179 (15) | 25/184 (14) | |||||||||
| 6 months | 6 months | |||||||||
| 27/179 (15) | 30/184 (16) | |||||||||
| Hall et al. [27] | C. random: Yes | 0.27 | 7/76 (9) | 6/78 (8) | Sepsis | Sepsis | NA | NA | NA | NA |
| Trauma subgroup | ITT: Yes | Isocal + glutamine (66 g/day protein) vs. isonitrogenous formula Isocal + glycine (64 g/day protein) | 7/76 (9) | 11/78 (14) | ||||||
| Blinding: Yes | ||||||||||
| 13 | ||||||||||
| Garrel et al. [28] | C. random: Yes | 0.28 | 2/21 (10) | 12/24 (50) | Positive blood cultures | Positive blood cultures | 33 ± 17 (16)d | 29 ± 17 (19)d | NA | NA |
| ITT: yes | Sandosource (Nestlé Health Science) + glutamine (2.15 g/kg/day protein) vs. Sandosource + amino acids (isonitrogenous), 1.97 g/kg/day protein | 7/19 (37) | 10/22 (45) | |||||||
| Blinding: Yes | ||||||||||
| 11 | ||||||||||
| Zhou et al. [29] | C. random: Yes | 0.35 | 0/20 | 0/20 | 2/20 (10) | 6/20 (30) | 67 ± 4 (20) | 73 ± 6 (20) | NA | NA |
| ITT: No | Ensure (NutriDrinks, Perivale, UK) + glutamine vs. Ensure + amino acids (isonitrogenous) | |||||||||
| Blinding: Double-blind | ||||||||||
| 8 | ||||||||||
| Peng et al. [30] | C. random: Not sure | 0.5 | NA | NA | NA | NA | 46.6 ± 12.9 (25) | 55.7 ± 17.4 (23) | NA | NA |
| ITT: Yes | Oral glutamine granules vs. placebo (isocaloric, isonitrogenous) 2.0 g/kg/day protein | |||||||||
| Blinding: No | ||||||||||
| 7 | ||||||||||
| Luo et al.e [31] | C. random: Not sure | 0.32 | ICU | ICU | NA | NA | NA | NA | 8.1 ± 0.4 (12) | 6.9 ± 0.9 (9) |
| ITT: No | Glutamine + IV saline + vs. Nutren (Nestlé Health Science) + 15 % Clinisol (Baxter Healthcare, Deerfield, IL, USA) (placebo) (isocaloric, isonitrogenous) | 1/12 | 0 /9 | |||||||
| Blinding: Double-blind | 28 days | 28 days | ||||||||
| 9 | 1.7 g/kg/d protein | 1/12 | 0 /9 | |||||||
| McQuiggan et al. [32] | C. random: Not sure | 0.5 (actual 0.4) IMPACT (Nestlé Health Science) + Glutasolve (Nestlé Health Science) via NJ tube (1.3 g/kg/day protein), bolus with H2O vs. Impact + protein supplements (isonitrogenous, isocaloric) 0.85 g/kg/day protein | 0/10 | 2/10 (20) | NA | NA | 32 ± 13.6 (10) | 39.3 ± 33.6 (10) | 4.8 ± 6.7 (10) | 10.4 ± 6.2 (10) |
| ITT: Yes | ||||||||||
| Blinding: No | ||||||||||
| 10 | ||||||||||
| Pattanshetti et al. [33] | C. random: Not sure | Enteral isonitrogenous mixture + EN glutamine + “regular” nutrition vs. enteral isonitrogenous mixture + “regular” nutrition | 0/15 | 2/15 | Number of times positive blood cultures | Number of times positive blood cultures | 22.73 ± 9.13 | 39.73 ± 18.27 | NA | NA |
| ITT: Yes | ||||||||||
| Blinding: Single-blind (outcomes) | ||||||||||
| 8 | 0.20 ± 0.41 | 0.73 ± 0.96 | ||||||||
| van Zanten et al. [14] | C. random: Yes | 0.28 (mean intake) glutamine, omega-3, antioxidant-enriched EN (experimental product) vs. isonitrogenous, isocaloric high-protein EN (Nutrison Advanced Protison; Nutricia Advanced Medical Nutrition, Amsterdam, the Netherlands) | Hospital | Hospital | 80/152 (53) | 78/149 (52) | 38.2 ± 28.9 | 37.7 ± 27.5 | 23.7 ± 22.4 | 25.6 ± 24.0 |
| ITT: Yes | 38/152 (25) | 33/149 (22) | ||||||||
| Blinding: Double-blind | ICU | ICU | ||||||||
| 12 | 30/152 (20) | 29/149 (20) | ||||||||
| 28 days | 28 days | |||||||||
| 31/152 (20) | 25/149 (17) | |||||||||
| 6 months | 6 months | |||||||||
| 53/152 (35) | 42/149 (29) | |||||||||
| van Zanten et al. [14] trauma subgroup | C. random: Yes | 0.28 (mean intake) glutamine, omega-3, antioxidant-enriched EN (experimental product) vs. isonitrogenous, isocaloric high-protein EN (Nutrison Advanced Protison) | Hospital | Hospital | 32/55 (58) | 36/54 (67) | 44.4 ± 31.2 | 39.8 ± 25.3 | 31.3 ± 30.3 | 32.5 ± 27.5 |
| ITT: Yes | 6/55 (11) | 6/54 (11) | ||||||||
| Blinding: Double-blind | ICU | ICU | ||||||||
| 12 | 5/55 (9) | 6/54 (11) | ||||||||
| 28 days | 28 days | |||||||||
| 4/55 (7) | 2/54 (4) | |||||||||
| 6 months | 6 months | |||||||||
| 8/55 (15) | 59/54 (17) | |||||||||
C. random concealed randomization median (range), EN enteral nutrition, ITT intent to treat, IV intravenous, NA not applicable, NJ nasojejunal, TPN total parenteral nutrition
Data are presented as mean ± standard deviation or number (%), as appropriate
aHospital mortality unless otherwise stated
bNumber of patients with infections unless otherwise stated
cMedian and range hence not included in meta-analysis (Hall et al. 2003 [27]; p = not significant)
dSubgroup of patients, hence not included in the meta-analyses [28]
eData from parenteral glutamine group not shown here