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

Background 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

1 “Use of a feeding protocol that incorporates motility agents and small bowel feeding tubes should be considered” What do Guidelines say? “Evaluating gastric residual volume (GRV) in critically ill patients is an optional part of a monitoring plan to assess tolerance of EN. “ “Use of enteral feeding protocols increases the overall percentage of goal calories provided and should be implemented”. Grade: C

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

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. 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 (EN % calories received/prescribed)  Adequacy of overall nutrition Purpose 1

Methods Data from two international, prospectively, observational cohort studies conducted in 2007 and 2008 from 269 ICUs across 28 countries 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  type and amount of nutrition received  strategies utilized to improve nutrition delivery  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

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

Primary Outcomes Objective To compare nutritional practices and outcome variables between ICUs with and without bedside feeding protocols. Outcomes Overall nutritional adequacy Enteral nutrition adequacy Overall nutritional adequacy = as the total amount of calories or protein received (from either EN or PN plus propofol)/prescribed x 100% 1

Data Analysis Data from 2007 and 2008 combined, 334 total sites, 65 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. 1

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 ICU structure Open Closed Other 48 (23.1%) 156 (75.0%) 4 (1.9%) 22 (36.1%) 39 (63.9%) 0 (0%) Medical Director196 (94.2%)54 (88.5%)0.15 Case Types Medical Surgical Other 189 (20.6%) 191 (20.8%) 537 (58.6%) 44 (19.1%) 49 (21.3%) 137 (59.6%) NR Size ICU17 (4-75)19 (5-48)0.50 Presence of ICU Dietitian168 (80.8%)46 (75.4%)0.37 FTE RD per 10 beds0.4 ( )0.3 ( )0.42 Avg. # eligible patients contributed/year 17.0 (range: 1-24)14.6 (range: 1-25)p=0.001

Results 269 ICUs participated from 28 countries with 5497 patients 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%) 29/61 (48%) of the non-protocolized sites being from the United States.

CharacteristicsTotal n=269 Feeding Protocol Yes208 (78%) Gastric Residual Volume Tolerated in Protocol Mean (range)213 ml (50, 500) Elements included in Protocol HOB Elevation71.2 % Motility agents68.5% Small bowel feeding55.2% Results: Feeding Protocols 15.2% using the recommended threshold volume of 250 ml 1

Results: Patients Table 2.ProtocolNo ProtocolP value Number of Patients n=4416 n=1081 age 59.6 (12-96) 58.8 (15-99)0.38 Gender1771 (40.1%)380 (35.2%)0.13 Admission category Medical Surgical 2792 (63.2%) 1624 (36.7%) 633 (58.6%) 448 (41.4%) 0.30 APACHE II22.4 (1-72)21.9 (1-46)0.31 Presence of ARDS554 (12.5%)137 (12.7%)0.96 Mechanical Ventilation median (IQR)8 (4-16.2)7 (3.6-14) Hospital LOS21.9 ( )20.7 ( )0.25 Mortality 60 day1280 (29.0%)295 (27.3%) Heyland JPEN 2010 ( in press)

Results: Nutrition outcomes Table 3.ProtocolNo ProtocolP value Number of Sites208/269 (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%) Time to start of EN from ICU admission 41.2 hrs57.1 hrs motility agents use in high GRVs 811 (64.3%) patients 103 (49.0%) patients average head of bead elevation 32.5 o 30.0 o small bowel feeding in high GRVs 177 (14.0 %) patients 35 (16.7%) patients Heyland JPEN 2010 ( in press)

Results: Nutrition Adequacy ProtocolNo Protocol Adequacy from EN45.4%34.7%,p< Overall nutritional adequacy 61.2 %51.7%,p= Heyland JPEN 2010 ( in press)

EN adequacy: multilevel model To control for the effect of significant patient and site level characteristics of EN adequacy The expected average EN adequacy over the first 12 ICU days UnadjustedAdjusted  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 1 Heyland JPEN 2010 ( in press)

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, nutrition adequacy delivered, and the use of motility agents. 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 2010 ( in press)

Strengths and Weaknesses 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. 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. 1

Acknowledgements 1 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. 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.

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