Table 1.
Summary of randomised controlled trials of nutrition interventions on muscle mass, strength or function
| Author, year, country | Population | Intervention | Control | Muscle mass, strength or functional outcome | Summary of results |
|---|---|---|---|---|---|
| Allingstrup, 2017, Denmark [41] | 199 pts, MV, expected to stay >3d in ICU | Early goal-directed nutrition (based on indirect calorimetry and 24-h urinary urea) | Standard care (25 kcal/kg/day via EN) | Primary: SF-36 PCS score at 6 months | No difference in SF-36 PCS score between groups, mean, control vs intervention: 23 vs 22.9, diff (95% CI) 0.0 (−5.9–5.8), p = 0.99; data available for n = 88 vs 88 pts |
| Casaer, 2011, Belgium [42] | 4640 pts, at nutritional risk (NRS ≥ 3) | Early PN (by day 3) | Delayed PN (by day 8) | Secondary: 6MWT iADLs |
No difference in 6MWT, control vs intervention: median 277 (IQR: 210–345) vs 283 (205–336) metres, p = 0.57; data available for n = 624 vs 603 pts No difference in n (%) iADLs (control vs intervention: 779 (73.5%) vs 752 (75.5%), p = 0.31); data available for n = 1060 vs 996 pts |
| Doig, 2013, Australia [43] | 1372 pts, contraindications to early EN, expected to stay in ICU >2 d | Early PN | Standard care | Secondary: D60 SF-36 physical function | No difference in SF-36 physical function, mean±SD: control vs intervention: 40.7±29.6 vs 42.5±30.8, diff (95% CI) 1.8 (1.85–5.52), p = 0.33; data available for n = 513 vs 524 pts |
| Doig, 2015, Australia [44] | 474 pts, expected to stay in ICU >2 d | 100 g/day IV amino acid supplementation | Standard care | Secondary: D90 SF-36 general health status and physical function |
No difference in SF-36 General Health, mean±SD, control vs intervention: 52.8±25.9 vs 50.5±27.2, diff (95% CI) 2.3 (−3.1–7.7), p = 0.41; data available for n = 180 vs 192 pts No difference in SF-36 Physical Function, mean±SD, control vs intervention: 53.2±33.0 vs 47.7±33.7, diff (95% CI) 5.5 (−1.31–12.3), p = 0.11; data available for n = 180 vs 192 pts |
| Dresen, 2021, Germany [45•] | 42 pts, MV, haemodynamically stable, expected to require >28 d organ support | 1.8 g protein/kg/day | 1.2 g protein/kg/day | Primary: change in ultrasound-derived QMLT from study inclusion to weeks 2 and 4 | No difference in muscle loss between groups; change in mean QMLT, control vs intervention: −0.28±0.08 vs −0.15±0.08 mm; p=0.368 |
| Ferrie, 2016, Australia [46] | 119 pts, receiving PN, expected to receive ≥3 d of the intervention | 1.2 g/kg IV amino acid | 0.8 g/kg IV amino acid |
Primary: handgrip strength at ICU discharge Secondary: ultrasound-derived muscle thickness of quadriceps, forearm and mid-upper arm at D7 |
No difference in handgrip strength, mean±SD, control vs intervention: 15.8±10.3 vs 18.5±10.4 cm; p = 0.054 Greater ultrasound-derived forearm muscle thickness at D7 with intervention, mean±SD, control vs intervention: 2.8±0.4 vs 3.2±0.4 cm; p < 0.0001 |
|
Fetterplace, 2018, Australia [47] Pilot RCT |
60 pts, MV <48 h, anticipated to remain MV ≥72 h | Volume-based EN with protein supplementation | Usual care (continuous hourly rate EN) | Secondary: change in ultrasound-derived QMLT from ICU admission to discharge | Greater amelioration of QMLT loss with intervention, control vs intervention: mean diff (95% CI) 0.22 (0.06–0.38) cm, p = 0.01 |
| McNelly, 2020, UK [48•] | 121 pts, expected MV ≥48 h, requiring gastric EN, multiorgan failure, likely ICU stay ≥7 d and likely survival ≥10 d | Intermittent EN | Continuous EN | Primary: change in ultrasound-derived RF-CSA over 10 days |
No difference in RF-CSA, mean±SD, control vs intervention: −19.8±14.2 vs −17.4±14.6 cm, diff (95% CI) −2.4 (−9.7–4.8), p = 0.505 Change to day 10: mean difference (95% CI): −1.1 (−6.1–4.0) %; p = 0.676 |
| Nakamura, 2020, Japan [49•] | 50 pts, receiving EN, haemodynamically stable | Standard EN + 3 g HMB, 14 g arginine, 14 g glutamine | Standard EN | Primary: rate of CT-derived femoral muscle volume loss from day 1 to 10 | No difference in CT-derived femoral muscle loss, control vs intervention: 14.4±1.6 vs 11.4±1.6 %; p = 0.18 |
| Ridley, 2018, Australia [50] | 100 pts, ≥16 y, adm to ICU in previous 48–72 g, receiving MV and expected to continue until day after randomisation, central venous access, ≥1 defined organ system failure | Supplemental PN | Standard care |
Secondary: ICU mobility scale (or 6MWT where possible) at hospital discharge HGS at hospital discharge MAMC at hospital discharge |
No difference in ICU mobility scale, median [IQR], control vs intervention: 8 [4–10] vs 9 [5–10], p = 0.58; data available for n = 33 vs 25 pts No difference in handgrip strength, mean±SD, control vs intervention: 20±8 vs 19±13.5 kg, p = 0.71; data available for n=24 vs 19 pts No difference in MAMC, mean±SD, control vs intervention: 30±5 vs 30±5 cm, p = 0.91; data available for n = 25 vs 22 pts |
| Viana, 2021, Switzerland [51•] | 30 pts, MV, likely survival ≥7 d | HMB | Placebo (maltodextrin) | Primary: magnitude of loss of ultrasound-derived quadriceps muscle CSA from day 4 to 15 | No difference in muscle loss between groups; mean skeletal muscle area (control D1 114 (95% CI 43–185.8) to D14 100.4 (95% CI 32.6–168.2) cm2 vs intervention D1 110.5 (95% CI 43.7–177.3) to D14 99.32 (95% CI 25.7–172.92) cm2, p = 0.86 |
|
Wischmeyer, 2017, USA Pilot RCT [52] |
125 pts, acute respiratory failure, expected to require MV >72, BMI <25 or ≥35 | Standard EN + supplemental PN | Standard EN |
Secondary: Barthel Index at hospital discharge HGS at discharge 6MWT at discharge SF-36 PCS at 3 months and 6 months |
Barthel Index, mean±SD, control vs intervention: 46.5±32.1 vs 61.1±32.4, p = 0.08; data available for n = 41 vs 28 pts SF-36 PCS at 3 months, mean±SD, control vs intervention: 35.3±10.8 vs 33.3±10.1, p = 0.38; data available for n = 27 vs 22 pts SF-36 PCS at 6 months, mean±SD, control vs intervention: 35.8±11.2 vs 39.3±10.2, p = 0.17; data available for n = 30 vs 20 pts |
6MWT, 6-minute walk test; BMI, body mass index; CSA, cross-sectional area; CT, computed tomography; EN, enteral nutrition; D, day; HGS, handgrip strength; HMB, B-hydroxy-B-methylbutyrate; iADLs, independent with activities of daily living; IV, intravenous; MV, mechanical ventilation; PCS, physical component summary; PN, parenteral nutrition; QMLT, quadriceps muscle layer thickness; RCT, randomised controlled trial; SF-36, Short Form 36