Adult patients with early MV were identified (n = 27,887), of which 16,772 (60.1%) received early EN. The number of surgical patients was 14,531 (52.1%) of whom 7,756 (53.4%) received early EN, and the number of medical patients was 13,356 (47.9%) of whom 9,016 (67.5%) received early EN. The mean age was not significantly different between the early and late EN groups (60.1 ± 16.5 vs. 60.4 ± 16.1 years, respectively; p=0.10). Additionally, the VW score was not significantly different between the early and late EN cohorts (10.3 ± 8.3 vs. 10.4 ± 10.4, p>0.05). Further details on the baseline socio-demographic characteristics are outlined in Table 1.
Regression analyses after IPTW showed that the early EN group was associated with lower hospital mortality (OR=0.88, 95% CI 0.82 to 0.94), higher home discharge (OR=1.47, 95% CI 1.38 to 1.56), fewer MV days (HR=1.23; 95% CI, 1.11 to 1.37), shorter hospital LOS (HR=1.43; 95% CI, 1.33 to 1.54) and ICU LOS (HR=1.36; 95% CI, 1.27 to 1.46), and lower cost (-$21,226; 95% CI, -$23,605 to -$18,848) compared to the late EN group (Table 2).
Table 1. Patient demographics before and after inverse probability treatment weighting
|
Original
|
After IPTW
|
|
Late
|
Early
|
SAMD
|
Late
|
Early
|
SAMD
|
|
N=11115
|
N=16772
|
|
|
|
|
Age, ± SD (yr)
|
60.4 ± 16.1
|
60.1 ± 16.5
|
-0.02
|
60.1 ± 20.3
|
60.1 ± 16.5
|
0.00
|
vW score, ± SD *
|
10.6 ± 8.5
|
10.3 ± 8.4
|
-0.03
|
10.4 ± 10.4
|
10.3 ± 8.3
|
-0.01
|
Male (no. [%])
|
6600 (59.4)
|
9666 (57.6)
|
-0.04
|
9697 (57.7)
|
9663 (57.6)
|
0.00
|
Race (no. [%])
|
|
|
|
|
|
|
Asian
|
255 (2.3)
|
541 (3.2)
|
0.06
|
532 (3.2)
|
540 (3.2)
|
0.00
|
Black
|
2189 (19.7)
|
3227 (19.2)
|
-0.01
|
3220 (19.2)
|
3225 (19.2)
|
0.00
|
White
|
7423 (66.8)
|
11118 (66.2)
|
-0.01
|
11124 (66.2)
|
11108 (66.2)
|
0.00
|
Other
|
1250 (11.2)
|
1899 (11.3)
|
0.00
|
1928 (11.5)
|
1898 (11.3)
|
0.00
|
Payer category (no. [%])
|
|
|
|
|
|
|
Managed care organization
|
1261 (11.3)
|
1727 (10.3)
|
-0.03
|
1698 (10.1)
|
1724 (10.3)
|
0.01
|
Medicaid
|
2053 (18.5)
|
3084 (18.4)
|
0.00
|
3095 (18.4)
|
3075 (18.3)
|
0.00
|
Medicare
|
5951 (53.5)
|
9167 (54.6)
|
0.02
|
9207 (54.8)
|
9166 (54.7)
|
0.00
|
Other
|
1852 (16.7)
|
2807 (16.7)
|
0.00
|
2804 (16.7)
|
2806 (16.7)
|
0.00
|
Admission category (no. [%])
|
|
|
|
|
|
|
Cardiac
|
1724 (15.5)
|
1411 (8.4)
|
-0.22
|
1397 (8.3)
|
1411 (8.4)
|
0.00
|
Gastrointestinal
|
486 (4.4)
|
335 (2)
|
-0.14
|
332 (2)
|
335 (2)
|
0.00
|
Infectious
|
3584 (32.2)
|
5230 (31.2)
|
-0.02
|
5222 (31.1)
|
5230 (31.2)
|
0.00
|
Neurologic
|
1751 (15.8)
|
3405 (20.3)
|
0.12
|
3484 (20.7)
|
3405 (20.3)
|
-0.01
|
Other
|
1407 (12.7)
|
2180 (13)
|
0.01
|
2157 (12.8)
|
2167 (12.9)
|
0.00
|
Respiratory
|
1747 (15.7)
|
3669 (21.9)
|
0.16
|
3654 (21.7)
|
3668 (21.9)
|
0.00
|
Trauma
|
418 (3.8)
|
555 (3.3)
|
-0.02
|
557 (3.3)
|
555 (3.3)
|
0.00
|
Elective admission (no. [%])
|
1249 (11.2)
|
1215 (7.2)
|
-0.14
|
1233 (7.3)
|
1213 (7.2)
|
0.00
|
Surgical admission (no. [%])
|
6775 (61)
|
7756 (46.2)
|
-0.30
|
7691 (45.8)
|
7756 (46.2)
|
0.01
|
Vasopressor (no. [%])
|
6740 (60.6)
|
8551 (50.9)
|
-0.20
|
8507 (50.6)
|
8544 (50.9)
|
0.01
|
Dialysis (no. [%])
|
1181 (10.6)
|
1280 (7.6)
|
-0.10
|
1296 (7.7)
|
1280 (7.6)
|
0.00
|
Hospital characteristics (no. [%])
|
|
|
|
|
|
|
Teaching
|
7025 (63.2)
|
11034 (65.7)
|
0.05
|
11028 (65.6)
|
11027 (65.8)
|
0.00
|
Rural hospital
|
2087 (18.8)
|
2768 (16.5)
|
-0.06
|
2827 (16.8)
|
2761 (16.5)
|
-0.01
|
Bed size
|
|
|
|
|
|
|
000-099
|
80 (0.7)
|
168 (1)
|
0.03
|
168 (1)
|
168 (1)
|
0.00
|
100-199
|
656 (5.9)
|
1369 (8.2)
|
0.09
|
1354 (8.1)
|
1367 (8.2)
|
0.00
|
200-299
|
1628 (14.6)
|
2633 (15.7)
|
0.03
|
2685 (16)
|
2632 (15.7)
|
-0.01
|
300-399
|
1827 (16.4)
|
2468 (14.7)
|
-0.05
|
2543 (15.1)
|
2465 (14.7)
|
-0.01
|
400-499
|
1763 (15.9)
|
2519 (15)
|
-0.02
|
2600 (15.5)
|
2518 (15)
|
-0.01
|
500+
|
5163 (46.4)
|
7628 (45.4)
|
-0.02
|
7454 (44.4)
|
7621 (45.4)
|
0.02
|
Year (no. [%])
|
|
|
|
|
|
|
2018
|
4415 (39.7)
|
7268 (43.3)
|
0.07
|
7390 (44)
|
7258 (43.3)
|
-0.01
|
2019
|
3689 (33.2)
|
5195 (31)
|
-0.05
|
5117 (30.5)
|
5195 (31)
|
0.01
|
2020
|
3013 (27.1)
|
4322 (25.7)
|
-0.03
|
4296 (25.6)
|
4318 (25.7)
|
0.00
|
IPTW, inverse probability treatment weighting; SD, standard deviation; SAMD, standardized absolute mean difference.
* A weighted summary score based on the 30 comorbidities.
Table 2. Unadjusted outcomes and regression analyses after inverse probability treatment weighting
|
Unadjusted outcomes after IPTW
|
Regression analysis
|
|
|
|
Early EN
|
Late EN
|
Yes
|
P value
|
|
|
|
|
(Reference = Late EN)
|
|
|
Discharge disposition, n (%)
|
|
|
OR (95% CI)
|
|
|
Hospital mortality
|
2611 (15.6)
|
3255 (19.4)
|
0.88 (0.82, 0.94)
|
<0.0001
|
|
Home
|
4610 (27.5)
|
3394 (20.2)
|
1.47 (1.38, 1.56)
|
<0.0001
|
|
Other
|
9550 (56.9)
|
10155 (60.4)
|
Reference
|
|
|
|
|
|
HR (95% CI)
|
|
|
LOS, days, mean (SD)
|
18.3 ± 17.8
|
23.7 ± 33.5
|
1.43 (1.33, 1.54)
|
<0.0001
|
|
ICU LOS, days, mean (SD)
|
10.7 ± 10.3
|
13.5 ± 16
|
1.36 (1.27, 1.46)
|
<0.0001
|
|
MV days, mean (SD)
|
9.6 ± 10.2
|
11.8 ± 24.9
|
1.23 (1.11, 1.37)
|
<0.0001
|
|
|
|
|
Estimate (95% CI)
|
|
|
Total cost, mean ± SD
|
67644 ± 72873
|
88216 ± 134984
|
-21227 (-23605, -18848)
|
<0.0001
|
|
Abbreviations: EN enteral nutrition; LOS, length of stay; ICU, intensive care unit; MV, mechanical ventilation; IQR, interquartile range; OR, odds ratio; HR, hazard ratio, SD, standard deviation.
HR >1 means the hazard of discharge alive is shorter in early EN compared to late EN.
In subgroup analyses, the baseline characteristics were adjusted using IPTW (See Table 3 for medical patients and table 4 for surgical patients). In the medical cohort, early EN was associated with a decreased risk of hospital mortality (OR=0.79; 95% CI, 0.72 to 0.87), increased likelihood of home discharge (OR=1.47; 95% CI 1.35 to 1.60), shorter hospital LOS (HR 1.55; 95% CI, 1.42 to 1.69), shorter ICU LOS (HR 1.42; 95% CI, 1.31 to 1.55), fewer MV days (HR 1.32; 95% CI, 1.16 to 1.50), and lower costs (-$15,127.8; 95% CI, -$17,892.8 to -$12,362.8) (Table 5). In the surgical cohort, early EN was associated with discharge to home (OR 1.45; 95% CI 1.33 to 1.57), shorter hospital LOS (HR 1.4; 95% CI, 1.3 to 1.5), shorter ICU LOS (HR 1.36; 95% CI, 1.26 to 1.46), fewer MV days (HR 1.2; 95% CI, 1.08 to 1.34), and lower costs (-$26,954.4; 95% CI, -$30,466.7 to -$23,442.2) (Table 6). The consistency of findings across these cohorts indicates that early EN positively impacted patients across both medical and surgical ICU settings.
Table 3. Patient demographics before and after inverse probability treatment weighting in medical patients.
|
Original
|
After IPTW
|
|
Late
|
Early
|
SAMD
|
Late
|
Early
|
SAMD
|
|
N=4340
|
N=9016
|
|
|
|
|
Age, ± SD (yr)
|
62.6 ± 15.4
|
61.7 ± 16
|
-0.05
|
61.8 ± 23.1
|
61.7 ± 16
|
0.00
|
vW score, ± SD *
|
12.1 ± 8.6
|
11 ± 8.4
|
-0.12
|
11 ± 12.2
|
11 ± 8.4
|
0.00
|
Male (no. [%])
|
2473 (57)
|
4959 (55)
|
-0.04
|
4941 (54.9)
|
4958 (55)
|
0.00
|
Race (no. [%])
|
|
|
|
|
|
|
Asian
|
89 (2.1)
|
284 (3.1)
|
0.07
|
277 (3.1)
|
284 (3.2)
|
0.00
|
Black
|
914 (21.1)
|
1817 (20.2)
|
-0.02
|
1804 (20)
|
1817 (20.2)
|
0.00
|
White
|
2841 (65.5)
|
5895 (65.4)
|
0.00
|
5901 (65.5)
|
5894 (65.4)
|
0.00
|
Other
|
496 (11.4)
|
1020 (11.3)
|
0.00
|
1024 (11.4)
|
1020 (11.3)
|
0.00
|
Payer category (no. [%])
|
|
|
|
|
|
|
Managed care organization
|
330 (7.6)
|
708 (7.9)
|
0.01
|
705 (7.8)
|
707 (7.8)
|
0.00
|
Medicaid
|
761 (17.5)
|
1569 (17.4)
|
0.00
|
1559 (17.3)
|
1569 (17.4)
|
0.00
|
Medicare
|
2671 (61.5)
|
5493 (60.9)
|
-0.01
|
5500 (61.1)
|
5493 (60.9)
|
0.00
|
Other
|
578 (13.3)
|
1246 (13.8)
|
0.01
|
1243 (13.8)
|
1246 (13.8)
|
0.00
|
Admission category (no. [%])
|
|
|
|
|
|
|
Cardiac
|
285 (6.6)
|
451 (5)
|
-0.07
|
455 (5.1)
|
451 (5)
|
0.00
|
Gastrointestinal
|
95 (2.2)
|
108 (1.2)
|
-0.08
|
104 (1.2)
|
108 (1.2)
|
0.00
|
Infectious
|
1895 (43.7)
|
3460 (38.4)
|
-0.11
|
3460 (38.4)
|
3460 (38.4)
|
0.00
|
Neurologic
|
487 (11.2)
|
1123 (12.5)
|
0.04
|
1121 (12.4)
|
1123 (12.5)
|
0.00
|
Other
|
499 (11.5)
|
1087 (12.1)
|
0.02
|
1076 (11.9)
|
1087 (12.1)
|
0.00
|
Respiratory
|
1038 (23.9)
|
2701 (30)
|
0.14
|
2705 (30)
|
2700 (30)
|
0.00
|
Trauma
|
41 (0.9)
|
86 (1)
|
0.00
|
86 (1)
|
86 (1)
|
0.00
|
Elective admission (no. [%])
|
237 (5.5)
|
365 (4)
|
-0.07
|
370 (4.1)
|
365 (4)
|
0.00
|
Vasopressor (no. [%])
|
2096 (48.3)
|
3694 (41)
|
-0.15
|
3693 (41)
|
3694 (41)
|
0.00
|
Dialysis (no. [%])
|
484 (11.2)
|
693 (7.7)
|
-0.12
|
703 (7.8)
|
693 (7.7)
|
0.00
|
Hospital characteristics (no. [%])
|
|
|
|
|
|
|
Teaching
|
2503 (57.7)
|
5407 (60)
|
0.05
|
5383 (59.8)
|
5407 (60)
|
0.00
|
Rural hospital
|
874 (20.1)
|
1669 (18.5)
|
-0.04
|
1714 (19)
|
1668 (18.5)
|
-0.01
|
Bed size
|
|
|
|
|
|
|
000-099
|
55 (1.3)
|
124 (1.4)
|
0.01
|
123 (1.4)
|
124 (1.4)
|
0.00
|
100-199
|
322 (7.4)
|
946 (10.5)
|
0.11
|
944 (10.5)
|
945 (10.5)
|
0.00
|
200-299
|
778 (17.9)
|
1614 (17.9)
|
0.00
|
1617 (17.9)
|
1614 (17.9)
|
0.00
|
300-399
|
715 (16.5)
|
1345 (14.9)
|
-0.04
|
1370 (15.2)
|
1345 (14.9)
|
-0.01
|
400-499
|
649 (15)
|
1207 (13.4)
|
-0.04
|
1244 (13.8)
|
1207 (13.4)
|
-0.01
|
500+
|
1821 (42)
|
3780 (41.9)
|
0.00
|
3709 (41.2)
|
3780 (41.9)
|
0.02
|
Year
|
|
|
|
|
|
|
2018
|
1638 (37.7)
|
3619 (40.1)
|
0.05
|
3631 (40.3)
|
3618 (40.1)
|
0.00
|
2019
|
1439 (33.2)
|
2888 (32)
|
-0.02
|
2872 (31.9)
|
2888 (32)
|
0.00
|
2020
|
1263 (29.1)
|
2509 (27.8)
|
-0.03
|
2503 (27.8)
|
2509 (27.8)
|
0.00
|
IPTW, inverse probability treatment weighting; SD, standard deviation; SAMD, standardized absolute mean difference.
* A weighted summary score based on the 30 comorbidities.
Table 4. Patient demographics before and after inverse probability treatment weighting in surgical patients.
|
Original
|
After IPTW
|
|
Late
|
Early
|
SAMD
|
Late
|
Early
|
SAMD
|
|
N=6775
|
N=7756
|
|
|
|
|
Age, ± SD (yr)
|
59 ± 16.3
|
58.2 ± 16.8
|
-0.05
|
58 ± 18
|
58.2 ± 16.8
|
0.01
|
vW score, ± SD *
|
9.6 ± 8.2
|
9.5 ± 8.2
|
-0.01
|
9.5 ± 8.8
|
9.5 ± 8.2
|
0.00
|
Male (no. [%])
|
4127 (60.9)
|
4705 (60.7)
|
-0.01
|
4712 (60.9)
|
4705 (60.7)
|
0.00
|
Race (no. [%])
|
|
|
|
|
|
|
Asian
|
166 (2.5)
|
256 (3.3)
|
0.05
|
258 (3.3)
|
256 (3.3)
|
0.00
|
Black
|
1275 (18.8)
|
1408 (18.2)
|
-0.02
|
1403 (18.1)
|
1408 (18.2)
|
0.00
|
White
|
4581 (67.6)
|
5214 (67.2)
|
-0.01
|
5183 (67)
|
5214 (67.2)
|
0.01
|
Other
|
753 (11.1)
|
878 (11.3)
|
0.01
|
898 (11.6)
|
878 (11.3)
|
-0.01
|
Payer category (no. [%])
|
|
|
|
|
|
|
Managed care organization
|
930 (13.7)
|
1017 (13.1)
|
-0.02
|
1008 (13)
|
1017 (13.1)
|
0.00
|
Medicaid
|
1292 (19.1)
|
1506 (19.4)
|
0.01
|
1527 (19.7)
|
1506 (19.4)
|
-0.01
|
Medicare
|
3279 (48.4)
|
3673 (47.4)
|
-0.02
|
3640 (47)
|
3673 (47.4)
|
0.01
|
Other
|
1274 (18.8)
|
1560 (20.1)
|
0.03
|
1566 (20.2)
|
1560 (20.1)
|
0.00
|
Admission category (no. [%])
|
|
|
|
|
|
|
Cardiac
|
1439 (21.2)
|
960 (12.4)
|
-0.24
|
968 (12.5)
|
960 (12.4)
|
0.00
|
Gastrointestinal
|
391 (5.8)
|
227 (2.9)
|
-0.14
|
229 (3)
|
227 (2.9)
|
0.00
|
Infectious
|
1689 (24.9)
|
1770 (22.8)
|
-0.05
|
1769 (22.9)
|
1770 (22.8)
|
0.00
|
Neurologic
|
1264 (18.7)
|
2282 (29.4)
|
0.25
|
2245 (29)
|
2282 (29.4)
|
0.01
|
Other
|
906 (13.4)
|
1080 (13.9)
|
0.02
|
1083 (14)
|
1080 (13.9)
|
0.00
|
Respiratory
|
709 (10.5)
|
968 (12.5)
|
0.06
|
975 (12.6)
|
968 (12.5)
|
0.00
|
Trauma
|
377 (5.6)
|
469 (6)
|
0.02
|
472 (6.1)
|
469 (6)
|
0.00
|
Elective admission (no. [%])
|
1012 (14.9)
|
848 (10.9)
|
-0.12
|
844 (10.9)
|
848 (10.9)
|
0.00
|
Vasopressor (no. [%])
|
4642 (68.5)
|
4850 (62.5)
|
-0.13
|
4790 (61.9)
|
4850 (62.5)
|
0.01
|
Dialysis (no. [%])
|
697 (10.3)
|
587 (7.6)
|
-0.10
|
589 (7.6)
|
587 (7.6)
|
0.00
|
Hospital characteristics (no. [%])
|
|
|
|
|
|
|
Teaching
|
4522 (66.7)
|
5620 (72.5)
|
0.12
|
5578 (72.1)
|
5620 (72.5)
|
0.01
|
Rural hospital
|
1212 (17.9)
|
1093 (14.1)
|
-0.10
|
1135 (14.7)
|
1093 (14.1)
|
-0.02
|
Bed size
|
|
|
|
|
|
|
000-099
|
25 (0.4)
|
44 (0.6)
|
0.03
|
44 (0.6)
|
44 (0.6)
|
0.00
|
100-199
|
334 (4.9)
|
422 (5.4)
|
0.02
|
428 (5.5)
|
422 (5.4)
|
0.00
|
200-299
|
850 (12.5)
|
1018 (13.1)
|
0.02
|
1029 (13.3)
|
1018 (13.1)
|
-0.01
|
300-399
|
1110 (16.4)
|
1120 (14.4)
|
-0.05
|
1190 (15.4)
|
1120 (14.4)
|
-0.03
|
400-499
|
1114 (16.4)
|
1311 (16.9)
|
0.01
|
1315 (17)
|
1311 (16.9)
|
0.00
|
500+
|
3342 (49.3)
|
3841 (49.5)
|
0.00
|
3735 (48.2)
|
3841 (49.5)
|
0.03
|
Year (no. [%])
|
|
|
|
|
|
|
2018
|
2776 (41)
|
3640 (46.9)
|
0.12
|
3654 (47.2)
|
3640 (46.9)
|
-0.01
|
2019
|
2250 (33.2)
|
2307 (29.7)
|
-0.07
|
2278 (29.4)
|
2307 (29.7)
|
0.01
|
2020
|
1749 (25.8)
|
1809 (23.3)
|
-0.06
|
1810 (23.4)
|
1809 (23.3)
|
0.00
|
IPTW, inverse probability treatment weighting; SD, standard deviation; SAMD, standardized absolute mean difference.
* A weighted summary score based on the 30 comorbidities.
Table 5. Unadjusted outcomes and regression analyses after inverse probability treatment weighting in medical patients.
|
Crude outcomes after IPTW
|
Regression analysis
|
|
|
|
Early EN
|
Late EN
|
Yes
|
P value
|
|
|
|
|
(Reference = Late EN)
|
|
|
Discharge disposition, n (%)
|
|
|
OR (95% CI)
|
|
|
Hospital mortality
|
1487 (16.5)
|
2025 (22.5)
|
0.79 (0.72, 0.87)
|
<0.0001
|
|
Home
|
2882 (32)
|
2074 (23)
|
1.47 (1.35, 1.60)
|
<0.0001
|
|
Other
|
4646 (51.5)
|
4907 (54.5)
|
Reference
|
|
|
|
|
|
HR (95% CI)
|
|
|
LOS, days, mean (SD)
|
13.7 ± 10.5
|
18.4 ± 35
|
1.55 (1.42, 1.69)
|
<0.0001
|
|
ICU LOS, days, mean (SD)
|
7.9 ± 5.7
|
9.9 ± 11.9
|
1.42 (1.31, 1.55)
|
<0.0001
|
|
MV days, mean (SD)
|
7.3 ± 7.0
|
9.4 ± 29.4
|
1.32 (1.16, 1.50)
|
<0.0001
|
|
|
|
|
Estimate (95% CI)
|
|
|
Total cost, mean ± SD
|
43043 ± 33813
|
58264 ± 128248
|
-15128 (-17893, -12363)
|
<0.0001
|
|
Abbreviations: EN enteral nutrition; LOS, length of stay; ICU, intensive care unit; MV, mechanical ventilation; IQR, interquartile range; OR, odds ratio; HR, hazard ratio, SD, standard deviation.
HR >1 means the hazard of discharge alive is shorter in early EN compared to late EN.
Table 6. Unadjusted outcomes and regression analyses after inverse probability treatment weighting in surgical patients.
|
Crude outcomes after IPTW
|
Regression analysis
|
|
|
|
Early EN
|
Late EN
|
Yes
|
P value
|
|
|
|
|
(Reference = Late EN)
|
|
|
Discharge disposition, n (%)
|
|
|
OR (95% CI)
|
|
|
Hospital mortality
|
1124 (14.5)
|
1238 (16)
|
0.98 (0.89, 1.07)
|
0.60
|
|
Home
|
1728 (22.3)
|
1335 (17.2)
|
1.45 (1.33, 1.57)
|
<0.0001
|
|
Other
|
4904 (63.2)
|
5169 (66.8)
|
Reference
|
|
|
|
|
|
HR (95% CI)
|
|
|
LOS, days, mean (SD)
|
23.7 ± 22.5
|
30 ± 30.5
|
1.4 (1.3, 1.5)
|
<0.0001
|
|
ICU LOS, days, mean (SD)
|
13.9 ± 13.2
|
17.7 ± 17.1
|
1.36 (1.26, 1.46)
|
<0.0001
|
|
MV days, mean (SD)
|
12.3 ± 12.4
|
14.6 ± 20.2
|
1.2 (1.08, 1.34)
|
0.001
|
|
|
|
|
Estimate (95% CI)
|
|
|
Total cost, mean ± SD
|
96238 ± 92917
|
123094 ± 127672
|
-26954 (-30467, -23442)
|
<0.0001
|
|
Abbreviations: EN enteral nutrition; LOS, length of stay; ICU, intensive care unit; MV, mechanical ventilation; IQR, interquartile range; OR, odds ratio; HR, hazard ratio, SD, standard deviation.
HR >1 means the hazard of discharge alive is shorter in early EN compared to late EN.