1. The Impact of Enteral Feeding Protocols on Enteral Nutrition Delivery: Results of a multicenter observational study
Rupinder Dhaliwal, RD
Daren K. Heyland, MD
Naomi E Cahill, RD
Xiaoqun Sun, MSc
Andrew G Day, MSc
Stephen A. McClave, MD 1

2. Background Components of feeding protocols may include orders for
Feeding protocols are considered to be an effective strategy
to maximize the benefits and minimize the risks of enteral nutrition
in critically ill patients.
Components of feeding protocols may include orders for
Early initiation of enteral nutrition
Use of motility agents
Gastric residual volumes
Head of the bed elevation
Use of small bowel feeding tubes
The benefits of such protocols would be:
to standardize the delivery of EN
to automate the provision of EN 1

3. What do Guidelines say?
“Use of a feeding protocol that incorporates prokinetics at initiation, higher GRVs (250 mls) and use of post pyloric feeding tubes should be considered”
“Evaluating gastric residual volume (GRV) in critically ill patients is an optional part of a monitoring plan to assess tolerance of EN. “ Avoid holding EN when GRV < 250 mls.
Consensus, imperative
Rupinder to update
“Use of enteral feeding protocols increases the overall percentage of goal calories provided and should be implemented.” Avoid holding EN for GRVs < 500 mls. Grade: C, B 1 3

4. Taylor et al Crit Care Med 1999; Martin CMAJ 2004; Doig GS JAMA 2008
RCT Level of Evidence
RCTs of aggressive feeding protocols
Results in better protein-energy intake
Associated with reduced complications and improved survival
Taylor et al Crit Care Med 1999; Martin CMAJ 2004; Doig GS JAMA 2008
However, the estimates of their effectiveness are limited due to:
the nature of small single-center studies
the bundling with many other interventions in cluster
randomized controlled trials. 1

5. Purpose
To evaluate the effect of an ICU site-based feeding protocol on nutrition practices and outcomes in the context of an international multicenter, observational study.
Objective
To compare the following performance criteria between sites that did or did not use a feeding protocol:
Use of EN
Time to start EN
Adequacy of enteral nutrition
Adequacy of overall nutrition
Clinical outcomes 1

6. Overall nutritional adequacy Enteral nutrition adequacy
Primary Outcomes
Overall nutritional adequacy
Enteral nutrition adequacy
Overall nutritional adequacy = as the total amount of calories or protein received (from EN + appropriate PN + propofol) /prescribed x 100%
Overall EN adequacy = as the total amount of calories or protein received (from EN) /prescribed x 100%
Our primary objective was to compare nutrition practices between sites that protocol or not.
Outcomes were: overall nutritional adequacy as the total amount of calories or protein received (from either EN or PN plus propofol) over the first 12 ICU days, divided by the amount prescribed and expressed as a percentage. Days without EN or PN were included and counted as 0% adequacy. Days following permanent progression to exclusive oral intake were excluded from the calculation of adequacy. EN adequacy was calculated similarly but included only the calories or protein received by the EN route. 1

7. Methods 1 Each participating ICU aimed to recruit 20 patients.
Data from two international, prospectively, observational cohort studies
conducted in 2007 and 2008 were combined.
Patients:
Consecutively enrolled mechanically ventilated adults
In ICU > 3 days
Data was collected from ICU admission to a maximum of 12 days:
sites recorded the presence or absence of a feeding protocol
timing, type and amount of nutrition received
strategies utilized to improve nutrition delivery (m. agents, small bowel feeds, HOB)
60 day mortality, hospital and ICU length of stay and duration of mechanical ventilation
Each participating ICU aimed to recruit 20 patients.
Nutrition practices and clinical outcomes were compared between ICUs that
used a feeding protocol and those who did not. 1

8. Data Management
Data entered on to our secure online edcs, built-in range checks
and data query process. 1

9. Data Analysis
Data from 2007 and 2008 combined, 334 total sites, sites participated both years, 269 unique ICUs
Hospital and ICU characteristics compared at the site level
All other variables were compared at the patient level
Clustered 2 stage sample design: patient and site, so potential for heterogeneity between ICUs.
Advanced statistical methods were done to account for heterogeneity (adjusted chi square tests, multilevel modelling).
To reduce the potential heterogeneity between ICUs due to the clustered 2 stage sample design, variables such as medical/surgical, yes/no options (categorical) were compared between the groups cy Chi square test (Rao method) that adjusts for clustering.
Categorical variables (Yes/no, medical/surgical, etc) were compared between
the 2 groups using the adjusted Chi-Squared method
Continuous variables (age, BMI, etc) were compared between the 2 groups
using multilevel modelling that accounted for the heterogeneity between same ICU
across years
Three level multi-modelling, where patients are nested within an ICU by year,
which are nested in ICUs 1

10. 269 ICUs participated from 28 countries
Results
269 ICUs participated from 28 countries
2007: 128/167 (77%) used protocol
2008: 132/167 (79%) used protocol
Protocol
No Protocol
208/269 (77%)
61/269 (23%)

11. Results 269 ICUs participated from 28 countries
Canada 46/57 (80.7%)
USA 48/77 (62.3%) UK
19/19 (100%)
Australia
28/28 (100%)
New Zealand
6/7 (85.7%)
India
5/9 (55.5%)
Brazil
2/4 (50%)
China
16/25 (64%)
Italy
7/7 (100%)
Ireland
7/7
(100%)
feeding protocols varied significantly between countries
29/61 (48%) of the non-protocolized sites being from the United States.

12. Results: Site Characteristics
Table 1.
Protocol (n=208)
(77%)
No Protocol (n=61) (23%)
P value
Hospital Type
Teaching
Non Teaching
162 (77.9%)
46 (22.1%)
51 (83.6%)
10 (16.3%)
0.38
Size hospital
mean (range)
606 ( )
791 ( )
0.004
Multiple ICUs in hospital
yes
107 (51.4%)
45 (73.8%)
0.002
ICU structure
Open
Closed
Other
48 (23.1%)
156 (75.0%)
4 (1.9%)
22 (36.1%)
39 (63.9%)
0 (0%)
0.099
Medical Director
196 (94.2%)
54 (88.5%)
0.15
Case Types
Medical
Surgical
189 (91%)
191 (92%)
44 (72%)
49 (80%)
0.0004
0.017
Size ICU
17 (4-75)
19 (5-48)
0.50
Presence of ICU Dietitian
168 (80.8%)
46 (75.4%)
0.37
FTE RD per 10 beds
0.4 ( )
0.3 ( )
0.42
Avg. # eligible patients contributed/year
17.0 (range: 1-24)
14.6 (range: 1-25)
p=0.001
Characteristics of the 269 unique ICUs are presented in table 1 where only the 2008 values are reported for sites participating in both years.
Protocols were more often used in closed ICUs from smaller, single ICU hospitals. 12

13. Results: Feeding Protocols
Characteristics
Total n=269
Feeding Protocol
Yes
208 (77%)
Gastric Residual Volume Tolerated in Protocol
Mean (range)
213 ml (50, 500)
Elements included in Protocol
HOB Elevation
71.2 %
Motility agents
68.5%
Small bowel feeding
55.2%
15.2% using the recommended threshold volume of 250 ml 1 13

14. Results: Patients n = 5497 Table 2. Protocol No Protocol P value 1
Number of Patients
n=4416
n=1081
age
59.6 (12-96)
58.8 (15-99)
0.38
Gender
1771 (40.1%)
380 (35.2%)
0.013
Admission category
Medical
Surgical
2792 (63.2%)
1624 (36.7%)
633 (58.6%)
448 (41.4%)
0.30
APACHE II
22.4 (1-72)
21.9 (1-46)
0.31
Presence of ARDS
554 (12.5%)
137 (12.7%)
0.96
Mechanical Ventilation
median (IQR)
8 (4-16.2)
7 (3.6-14)
0.089
Hospital LOS
21.9 ( )
20.7 ( )
0.25
Mortality 60 day
1280 (29.0%)
295 (27.3%)
0.37
Protocolized ICUs had a higher proportion of female patients (40.1% versus 35.2% p=0.013), but otherwise patient characteristics and clinical outcomes were similar between sites with and without bedside feeding protocols (table 2). 1
Heyland JPEN ( in press) 14

15. Results: Nutrition outcomes
Table 3.
Protocol
No Protocol
P value
Number of Sites
208/269 (77%)
61/269 (23%)
EN alone PN
EN + PN
None
3108 (70.4%)
322 (7.3%)
785 (17.8%)
201 (4.6%)
688 (63.6% )
116 (10.7%)
184 (17.0%)
93 (8.6%)
0.0036
Time to start of EN from ICU admission
41.2 hrs
57.1 hrs
0.0003
motility agents use in high GRVs
811 (64.3%) patients
103 (49.0%) patients
0.0028
average head of bead elevation
32.5o
30.0o
0.017
small bowel feeding in high GRVs
177 (14.0 %)
patients
35 (16.7%)
0.45
On average, EN was initiated earlier in sites with protocols compared to those without protocols (41.2. hours from admission to ICU vs. 57.1, p=0.0003).
In patients with high gastric residual volumes, more patients in protocolized sites received motility agents (64.3% of patients vs. 49.0%, p=0.0028) compared to sites that did not use a feeding protocol.
There was no difference in the use of small bowel feeding tubes in patients with high gastric residual volumes between sites (14.0 vs 16.7% of patients, p=0.45). The average head of bead elevation was slightly higher (32.5 versus 30.0 p=0.017) at sites that used feeding protocols (see Table 3). 1
Heyland JPEN ( in press) 15

16. Results: Nutrition Adequacy
Overall nutritional adequacy (61.2 % of patient’s caloric requirements vs 51.7%) and adequacy from EN (45.4% of requirements vs 34.7%) was higher in protocolized sites compared to non-protocolized sites.
Protocol
No Protocol
Adequacy from EN
45.4%
34.7%
p<0.0001
Overall nutritional adequacy
61.2 %
51.7%
p=0.0003 1
Heyland JPEN ( in press) 16

17. EN adequacy: multilevel model
After adjusting for the effect of:
significant patient characteristics (age, BMI, gender, # days in ICU, surgical vs. Medical, APACHE II)
site level characteristics of EN adequacy (year of survey, vs. Non teaching, closed, RD, glycemic protocols)
The expected average EN adequacy over the first 12 ICU days
Unadjusted
Adjusted
 by 7.4%
(SE=1.8%, p<0.0001) in patients from sites with protocols
by 4.1%
(SE=1.8%, p=0.021) in patients at sites with protocols
Expected average EN adequacy over first 12 days
greater for patients from sites with feeding protocols (53.2% SE=1.0% versus 45.8% SE=1.7%). by 7.4% (SE=1.8%, p<0.0001)
BMI, days in hospital prior to admission and ICU days were modelled as categorical variables due to the statistically significant non-linearity of the relationship between these variables and EN adequacy (all p<0.01). No patient or ICU level variables (BMI, age, days iN ICU prior to admission, interacted significantly with feeding protocol use (all p>0.05). 1
Heyland JPEN ( in press)

18. Conclusions
There is great variation in the use of feeding protocols in ICUs across the World.
The presence of an enteral feeding protocol is associated with significant improvements in the use of EN, timing of initiation of EN, the use of motility agents and nutrition adequacy delivered.
We suggest that the use of feeding protocols become standard of care in ICUs.
Despite the use of protocols, overall nutrition adequacy is still below target, further refinement and optimization of the characteristics of feeding protocols is warranted.
The positive effect of feeding protocols on clinical outcomes is yet to be established. 1
Heyland JPEN ( in press)

19. Strengths and Weaknesses
observational nature of the study design
did not standardize the specific nutrition interventions included in the feeding protocols
did not optimize the utilization of protocols at each site. We are unable to comment on the quality of these existing protocols or the level of compliance at the bed-side.
Strengths
large number of participating sites from around the world
Use of a structured, validated data capture system, which enhances the generalizability and validity of the observations.
As such, our observed estimate reflects the ‘real world’ experience. 1
Heyland JPEN ( in press)

20. Efficacy of Enhanced Protein-Energy Provision via the Enteral Route
in Critically Ill Patients:
The PEP uP Protocol
A Single center feasibility trial
Daren K. Heyland
Professor of Medicine
Queen’s University, Kingston General Hospital
Kingston, ON Canada
SP14 20

21. Acknowledgements
The authors are grateful to the critical care practitioners from all participating ICU sites for their dedication and commitment to collecting data for this study.
Colleagues at the Clinical Evaluation Research Unit
Naomi Cahill currently holds a Canadian Institutes
for Health Research (CIHR) Fellowship in
Knowledge Translation.
All authors declare no conflicts of interest relevant to the subject of this manuscript. 1