Introduction
Methods
Trial design and oversight
Participants
Randomization and masking
Implementation of the feeding guideline
Data collection
Trial outcomes
Statistical analysis
Results
Results of recruitment
Baseline characteristics
Characteristics | Feeding guideline 48 ICUs, 1399 pts | Control 49 ICU, 1373 pts | P value |
---|---|---|---|
ICU-level characteristics | |||
Tertiary, No. (%) | 34 (70.8) | 37 (75.5) | 0.61 |
ICU type, No. (%) | 0.97 | ||
Emergency | 2 (4.2) | 2 (4.1) | |
Medical | 1 (2.1) | 1 (2) | |
Neuro | 1 (2.1) | 1 (2) | |
Surgical | 2 (4.2) | 2 (4.1) | |
General | 42 (87.5) | 43 (87.8) | |
Patient-level characteristics | |||
Age, mean ± SD, y | 61.0 ± 17.6 | 60.1 ± 17.7 | 0.98 |
Male, No. (%) | 938 (67.0%) | 928 (67.6%) | 0.56 |
BMI, mean ± SD, kg/m2 | 22.8 ± 3.2 | 23.1 ± 3.2 | 0.27 |
APACHE II score, mean ± SD | 18.3 ± 6.8 | 18.6 ± 7.6 | 0.63 |
mNUTRIC score, mean ± SD | 4.28 ± 1.96 | 4.30 ± 2.05 | 0.97 |
SOFA score, mean ± SD | 7.5 ± 3.4 | 8.1 ± 3.7 | 0.07 |
Proportion of organ failure (SOFA score for individual system ≥ 2), No. (%) | |||
Respiration | 968 (72.1%) | 1043 (78.4%) | 0.10 |
Renal | 284 (21.2%) | 316 (23.7%) | 0.46 |
Cardiovascular | 384 (28.6%) | 450 (33.8%) | 0.52 |
Proportion of patients receiving organ support, No. (%) | |||
Mechanical ventilation | 921 (68.6%) | 966 (72.5%) | 0.242 |
Renal replacement therapy | 127 (9.5%) | 204 (15.3%) | 0.018 |
Vasoactive drugs | 401 (29.9%) | 523 (39.3%) | 0.051 |
Gastrointestinal function, No. (%) | 0.09 | ||
AGI-I | 1019 (75.9%) | 888 (66.5%) | |
AGI-II | 236 (17.6%) | 290 (21.7%) | |
AGI-III | 50 (3.7%) | 126 (9.4%) | |
AGI-IV | 37 (2.8%) | 31 (2.3%) | |
Comorbidities, No. (%) | |||
Hypertension | 617 (44.1%) | 574 (41.8%) | 0.36 |
Coronary disease | 214 (15.3%) | 250 (18.2%) | 0.31 |
Diabetes | 236 (16.9%) | 265 (19.3%) | 0.20 |
Chronic Respiratory diseases | 146 (10.4%) | 122 (8.9%) | 0.31 |
Stroke | 211 (15.1%) | 175 (12.7%) | 0.42 |
Gastrointestinal disease | 76 (5.4%) | 125 (9.1%) | 0.13 |
Malignant tumor | 43 (3.1%) | 59 (4.3%) | 0.44 |
Others | 524 (37.5%) | 497 (36.2%) | 0.84 |
Process measures
Process Measures | Feeding guideline 48 ICUs, 1399 pts | Controls 49 ICU, 1373 pts | Difference (95% CI) | P |
---|---|---|---|---|
Mean time from enrollment to EN initiation, d, mean ± SD | 1.20 ± 1.42 | 1.55 ± 1.64 | − 0.40 [− 0.71, − 0.09] | 0.01 |
Mean time to from enrollment to PN initiation, d, mean ± SD | 1.29 ± 1.74 | 0.80 ± 1.40 | 1.06 [ 0.44, 1.67] | 0.001 |
Mean nutrition support days within first seven days after enrollment /10 patient-days, mean ± SD | ||||
EN and/or PN | 8.29 ± 2.26 | 8.34 ± 2.43 | 0.10 [− 0.44, 0.65] | 0.71 |
EN (either alone or combined with PN) | 7.51 ± 2.82 | 6.49 ± 3.42 | 1.09 [0.46, 1.73] | 0.001 |
PN(either alone or combined with EN) | 1.66 ± 3.12 | 3.72 ± 4.18 | − 1.68 [− 2.86, − 0.49] | 0.006 |
Mean energy delivered for patients within first seven days after enrollment / fed patient*-days, kcal, mean ± SD | ||||
EN | 1070.8 ± 500.6 | 1015.9 ± 423.5 | 64.45 [− 49.13,178.04] | 0.26 |
PN | 776.5 ± 472.9 | 829.9 ± 611.1 | − 43.21 [− 245.8,159.41] | 0.67 |
Patients never fed during first seven days, No. (%) | 7(0.6%) | 12(0.9%) | 0.2% [− 0.6%; 1.0%] | 0.67 |
Patients received EN during first two days after enrollment, No. (%) | 883(65.8%) | 687(51.4%) | 16.5% [ 7.0%; 25.9%] | < 0.001 |
Patients received PN during first two days after enrollment, No. (%) | 250(18.6%) | 555(41.5%) | − 19.5% [− 33.1%; − 5.9%] | 0.005 |
Patients fed during first two days after enrollment, No. (%) | 1036(77.2%) | 1042(78.0%) | 0.7% [− 8.4%; 9.9%] | 0.87 |
Patients received EN or PN first two days after enrollment, No. (%) | 1022(76.2%) | 1006(75.3%) | 3.2% [− 6.0%; 12.5%] | 0.49 |
EN tolerance score after enrollments, mean ± SD | ||||
Day 1 | 0.2 ± 0.8 | 0.2 ± 0.8 | − 0.03 [− 0.23, 0.16] | 0.74 |
Day 2 | 0.3 ± 0.9 | 0.3 ± 1.0 | − 0.05 [− 0.24, 0.14] | 0.62 |
Day 3 | 0.4 ± 1.0 | 0.4 ± 1.0 | − 0.02 [− 0.20, 0.16] | 0.85 |
Day 4 | 0.3 ± 0.9 | 0.4 ± 1.1 | − 0.06 [− 0.23, 0.11] | 0.47 |
Day 5 | 0.3 ± 0.9 | 0.4 ± 1.1 | − 0.11 [− 0.25, 0.04] | 0.16 |
Day 6 | 0.3 ± 0.9 | 0.4 ± 1.0 | − 0.08 [− 0.23, 0.07] | 0.30 |
Day 7 | 0.3 ± 0.9 | 0.4 ± 1.0 | − 0.10 [− 0.25, 0.05] | 0.18 |
Days requiring prokinetic agents within first seven days enrollment /10 patient-days, mean ± SD | 1.1 ± 2.7 | 1.0 ± 2.5 | 0.37 [− 0.29, 1.03] | 0.26 |
Proportion of patients who received a post-pyloric feeding tube (patients receiving EN) within first seven days after enrollment, No. (%) | 91(6.5%) | 149(10.9%) | − 3.1% [− 9.3%; 3.1%] | 0.32 |
Primary outcome and other clinical outcomes
Outcome measure | Feeding guideline 48 ICUs, 1399 pts | Control 49 ICU, 1373 pts | Difference (95% CI) | P value | ICC or design effect | |
---|---|---|---|---|---|---|
Feeding guideline | Control | |||||
All-cause mortality at day 28, No (%) | 188 (14.2%) | 205 (15.2%) | − 1.59% [− 4.34%, 1.15%] | 0.42 | 0.11 | 0.05 |
ICU-free days within 28 days, d | 9.1 ± 8.9 | 8.7 ± 8.8 | 0.48 [− 1.02, 1.98] | 0.53 | 0.13 | 0.14 |
Incidence of new infections in ICU, No (%) | 97 (6.9%) | 92 (6.7%) | 0.13% [− 1.87%, 2.13%] | 0.93 | 0.21 | 0.26 |
Adverse events, no./total no. of events | 6 | 11 | 0.47 | |||
Gastrointestinal events | 4 | 3 | 0.66 | |||
Others* | 2 | 8 | 0.32 | |||
Serious adverse events#, no./total no. of patients | 1 | 3 | 0.38 |