Supplemental Digital Appendix A: Process for diagnosis of ventilator-associated pneumonia
Patients (in either the early nasojejunal or nasogastric nutrition groups) were diagnosed with clinically-suspected
VAP if they met the following criteria:

Had been receiving mechanical ventilation for > 72 hours, AND

Either New or worsening radiographic infiltrate and any use of new antibiotics

Or Persistent radiographic infiltrate and any use of new antibiotics in the absence of a clear non-pulmonary
source of sepsis, AND

At least one of the following:
(1) Temperature > 38.5°C or < 35.0°C
(2) Leukocyte count > 10 x 109/l or < 3 x 109/l
(3) Purulent sputum
(4) Isolation of bacteria from an endotracheal aspirate or bronchoalveolar lavage (defined as “growth on
culture of a named organism on the report, not including a light growth of oral, mixed respiratory or skin
flora”)
Any patient in either arm who met the definition of clinically-suspected VAP had additional clinical and diagnostic
information collected which was sent to the central site to be examined by the VAP-adjudication committee (made
up of 2 intensivists and 1 respiratory physician).
The committee reviewed the parameters of body temperature, serum white cell count, sputum amount and
purulence, PaO2/FiO2 ratios, microbiological culture results, antibiotic history and chest X-rays over the time period
from 3 days prior to 3 days after the development of clinically-suspected VAP. Chest X-rays had images of the
enteral tubes masked by electronic or physical means to allow this VAP-adjudication procedure to be blinded.
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The VAP-adjudication determined the diagnosis using several methods and then arrived at a final diagnosis of VAP
or not. These were:
(1) The clinically-suspected definition (as above).
(2) The Simplified Clinical Pulmonary Infection Score definition – the patient was considered to have VAP if they
scored 5 or more (from a maximum of 10 points using infiltrate, temperature, white cell count, sputum amount
and purulence, and PaO2/FiO2 ratio) at any time during the 3 days before, the day of, and the 3 days after clinicallysuspected VAP was diagnosed.
(3) The modified Memphis Ventilator-Associated Pneumonia Consensus Conference definition:

Definite VAP - if there was radiographic evidence of abscess and a positive needle aspirate, or if there was
histologic proof of pneumonia at biopsy or autopsy.

Probable VAP - if bronchoalveolar lavage yielded positive cultures, if there was a positive blood culture of an
organism found within 48 hours of isolation in the sputum, if there was a positive pleural-fluid culture of an
organism found within 48 hours of isolation in the sputum, or if histologic examination showed formation of
an abscess or consolidation with polymorphonuclear-cell infiltration.
In addition to using these 3 definitions, the VAP adjudication committee was asked to also use this information to
make their own best determination on whether or not the patient had VAP (by majority vote of the 3 members
adjudicating independently) and this determined the VAP status for this secondary outcome measure.
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Supplemental Digital Appendix B: Definition for diagnosis of hemorrhage related to enteral
tubes
Hemorrhage was defined as major or minor using the following criteria.
Major hemorrhage was epistaxis or overt GI hemorrhage, plus at least one of the following in the absence of other
causes:

A spontaneous drop of 20 mmHg or more in the systolic, diastolic or mean blood pressure within 24 hours
after upper GI bleeding

An increase in the pulse rate of 20 bpm and a decrease in the systolic blood pressure of 10mmHg upon the
patient assuming an upright position

A decrease in the hemoglobin concentration of at least 2 g/dL in 24 hours and the transfusion of 2 units of
packed red cells within 24 hours after bleeding

A spontaneous drop of 20 mmHg or more in the systolic, diastolic or mean blood pressure within 24 hours
after upper GI bleeding

Failure of the hemoglobin concentration (in g/dl) to increase after transfusion by at least the number of units
transfused minus 2
Minor hemorrhage was defined as epistaxis or overt GI hemorrhage in the absence of other causes that was not
defined as major.
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Supplemental Digital Appendix C: Organisms cultured from patients with confirmed VAP in
both nasogastric and early nasojejunal nutrition groups (number of patients in parentheses):
Nasogastric group
Acinetobacter sp. (1)
Aspergillis fumigatus (1)
Candida albicans (2)
Other Candid sp. (1)
Enterobacter cloacae (1)
Escherichia coli (5)
Hemophilus influenza (3)
Klebsiella oxytoca (1)
Klebsiella pneumoniae (1)
Mixed flora (1)
Other (2)
Penicillium sp (1)
Proteus mirabilis (1)
Pseudomonas aeruginosa (1)
Staphylococcus aureus (4)
Staphylococcus coagulase negative (1)
Staphylococcus epidermidis (2)
Staphylococcus hominis (1)
Stenotrophomonas maltophilia (2)
Streptococcus pneumonia (1)
4
Early jejunal group
Acinetobacter baumannii (2)
Bacillus sp. (1)
Candida albicans (3)
Other Candida sp. (1)
Enterobacter aerogenes (1)
Enterobacter cloacae (1)
Enterococcus faecalis (1)
Enterococcus faecium (1)
Escherichia coli (5)
Hemophilus influenza (3)
Mixed flora (1)
Peptococcus sp. (1)
Proteus mirabilis (1)
Pseudomonas aeruginosa (3)
Other pseudomonas sp. (1)
Staphylococcus aureus (5)
Staphylococcus coagulase negative (2)
Staphylococcus epidermidis (2)
Staphylococcus sp. (1)
Stenotrophomonas maltophilia (3)
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Supplemental Digital Appendix D: Per protocol analysis comparing early nasojejunal nutrition
group patients whose tubes reached the small bowel (79 patients; ie. excluding 12 patients
with tubes not advanced past the stomach) and nasogastric nutrition group patients (89).
Nasogastric
Early nasojejunal
nutrition
nutrition with small
(n=89)
bowel placement (n=91)
Age, years (mean, SD)
54 (18)
51 (19)
0.34
APACHE II score (mean, SD)
20 (8)
20 (7)
0.87
71% (19)
74% (21)
0.32
71% (19)
74% (22)
0.40
1444 (485)
1541 (517)
0.21
19 (21%)
15 (19%)
0.85
Minor GI hemorrhage (N, %)
3 (3%)
9 (11%)
0.04
Major GI hemorrhage (N, %)
2 (2%)
2 (3%)
0.90
Duration of MV, days (median, IQR)
8 (5-14)
9 (6-12)
0.68
Duration of ICU stay, days (median, IQR)
11 (7-16)
11 (7-15)
0.66
Duration of hospitalization, days (median, IQR)
24 (15-32)
20 (13-33)
0.51
12 (13%)
9 (11%)
0.68
Parameter
P value
Proportion of estimated energy requirements
delivered by EN for study period, (mean, SD)
Proportion of estimated energy requirements
delivered by EN over first 10 days (mean, SD)
Daily energy delivered, kcal (mean, SD)
VAP by blinded adjudication panel (N, %)
Hospital mortality (N, %)
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SD: standard deviation; APACHE II: acute physiology and chronic health evaluation; EN: enteral
nutrition; VAP: ventilator-associated pneumonia; N: number; GI: gastrointestinal; MV:
mechanical ventilation; IQR: interquartile range; ICU: intensive care unit
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