Nutrition & Rehabilitation Investigator’s ConsortiumClinical Evaluation Research UnitQueen’s University, Kingston General Hospital

Rupinder Dhaliwal, RD

Conflicts of Interest

I have received speaker honoraria or been paid from grants from the following companies:

– Nestlé Canada

– Fresenius Kabi AG

– Baxter

– Abbott Laboratories

Objectives

• Describe rationale for the novel components of the PEP uP protocol

Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients:

• Review results of cluster trial using PEP UP Protocol

• Describe strategies to effectively implement this protocol in the ICU

1 2 3 4 5 6 7 8 9 10 11 120

20

40

60

80

100

120

Mean of All Sites Best Performing Site Worst Performing Site

ICU Day

% r

ec

eiv

ed

/pre

sc

rib

ed

Current Practice in ICUs in 2011

n =211 ICUs, mean intake 56% prescribed calories

Heyland et al INS 2011 unpublished data

Optimal Amount of Calories for Critically Ill Patients: Depends on how you slice the cake!

Heyland DK, et al. Crit Care Med. 2011;39(12):2619-26.

Optimal amount =

80-85%

Association Between 12-day Caloric Adequacy

and 60-day Hospital Mortality

Failure Rate

Heyland et al Unpublished observations Results of 2011 International Nutrition Survey (INS)

% high risk patients who failed to meet minimal quality targets (80% overall energy adequacy)

75.6 78.1

91.2

75.1

87.0

69.8

79.9

A shift in the feeding paradigm is needed!

Can we do better?

PEP UP Protocol: components

Early enteral nutritionGoal rate feeding in stable patientsTrophic feeds Feeding unstable patientsMotility agentsHigher gastric residual volumesProtein supplementsSemi-elemental formulaMonitor nutritional adequacy

Early EN (within 24-48 Hours of Admission) Is Recommended!

Optimal amount of protein and calories for critically ill patients?

Initial Efficacy and Tolerability of Early EN with Immediate or Gradual Introduction in Intubated Patients

Desachy A, et al. Intensive Care Med. 2008;34(6):1054-9.

N = 100 ptsmechanically ventilated pts(not in shock) to immediate goal rate vs gradual ramp up

“Trophic Feeds”

Progressive atrophy of villous height and crypt depth in absence of EN.

Leads to increased permeability and decreased IgA** secretion.

Can be preserved by a minimum of 10-15% of goal calories.

Observational study of 66 critically ill patients suggests TPN†

+ trophic feeds associated with reduced infection and mortality compared to TPN alone1. A = No EN; B = 100% EN

1Marik. Crit Care & Shock. 2002;5:1-10;Ohta K, et al. Am J Surg. 2003;185(1):79-85.

Just say noto NPO

Rice TW, et al. JAMA. 2012;307(8):795-803.

Initial Tropic vs. Full EN in Patients with Acute Lung Injury

The EDEN randomized trial

Trophic vs. Full EN in Critically Ill Patients with Acute Respiratory Failure

Despite no differences in clinical outcomes……….

“Survivors who received initial full-energy EN were more likely to be discharged home with or without help as compared to a rehabilitation facility (68.3% for the full-energy group vs. 51.3% for the trophic group; p = .04).”

Rice TW, et al. Crit Care Med. 2011;39(5):967-74.

The EDEN randomized trial

Resuscitation is the priority

No sense in feeding someone dying of progressive circulatory failure

However, if resuscitated yet remaining on vasopressors:

What about feeding the hypotensive patient?

Safety and efficacy of EN??

Feeding the hypotensive patient?

Khalid I, et al. Am J Crit Care. 2010;19(3):261-8.

Prospectively collected multi-institutional ICU database of 1,174 patients who required mechanical ventilation for more than two days and were on vasopressor agents to support blood pressure.

The beneficial effect of early feeding is more evident in

the sickest patients, i.e., those on multiple

vasopressor agents

Pro-motility Agents

“Based on 1 level 1 study and 5 level 2 studies, in critically ill patients who experience feed intolerance (high gastric residuals, emesis), we recommend the use of a pro-motility agent”.

Conclusion:

1) Motility agents have no effect on mortality or infectious complications in critically ill patients

2) Motility agents may be associated with an increase in gastric emptying, a reduction in feeding intolerance and a greater caloric intake in critically ill patients

2009 Canadian CPGs www.criticalcarenutrition.com

It’s Not Just About Calories...

So in order to minimize this, we order: Protein supplement Beneprotein® 14 grams mixed

in 120 mls sterile water administered BID via NG

Loss of lean muscle mass

Inadequate protein intake

Immune dysfunction

Weak prolonged mechanical ventilation

113 select ICU patients with sepsis or burns

On average, receiving 1,900 kcal/day and 84 grams of protein

No significant relationship with energy intake but…

Allingstrup MJ, et al. Clin Nutr. 2012;31(4):462-8.

Begin 24 hour volume-based feeds. After initial tube placement confirmed, start Peptamen® 1.5. Total volume to receive in 24 hours =<write in 24 target volume>. Determine initial rate as per Volume Based Feeding Schedule. Monitor gastric residual volumes as per Adult Gastric Flow Chart and Volume Based Feeding Schedule. OR Begin Peptamen® 1.5 at 10 ml/h after initial tube placement confirmed. Reassess ability to transition to 24 hour volume-based feeds next day. {Intended for patient who is hemodynamically unstable (on high dose or escalating doses of vasopressors, or inadequately resuscitated) or not suitable for high volume EN (ruptured AAA, upper intestinal anastomosis, or impending intubation)}OR

NPO. Please write in reason: __________________ ______. (only if contraindication to EN present: bowel perforation, bowel obstruction, proximal high output fistula. Recent operation and high NG* output not a contraindication to EN.) Reassess ability to transition to 24 hour volume-based feeds next day.

Stable patients should be able to tolerate goal rate We use a concentrated

solution to maximize calories per ml

Doctors need to justify why they are keeping

patients NPO

If unstable or unsuitable, just use trophic feeds

We want to minimize the use of NPO but if selected, need

to reassess next day

The PEP uPProtocol

Note, there are only a few absolute

contraindications to EN

Note indications for trophic feeds

Single centre pilot study Heyland DK, et al. Crit Care 2010. 2010;14(2):R78

PEP UP Protocol: other components Gastric residual volume threshold 300 mls or more (REGANE

Study 500 ml vs 250 mls safe Montejo et al 2010 Int Care Med)

Protein supplement Beneprotein® 14 grams mixed in 120 mls sterile water administered BID via NG until full EN

Motility agents are started immediately, rather than started when there is a problem– Maxeran® 10 mg IV q 6h (halved in renal failure)

– Reassess need for motility agents daily

– If still develops high gastric residuals, add erythromycin 200 mg q 12h

– Can be used together for up to 7 days but should be discontinued when not needed any more

– Reassess need for motility agents daily

24 Hour Volume-based goal vs Hourly rate• Make up for missed hours over

the remaining hours• Max 150 ml/hr• RN latitude to adjust

A Change to Nursing Report

Adequacy of nutrition support =

24 hour volume of EN received

Volume prescribed to meet caloric requirements in 24 hours

Please report this % on

rounds as part of the GI

systems report

Efficacy of Enhanced Protein-Energy Provision via the Enteral Route in

Critically Ill Patients: The PEP uP Protocol

Daren K. HeylandProfessor of MedicineQueen’s UniversityKingston General HospitalKingston, Ontario

A multi-center cluster randomized trial

Research Questions

What is the effect of the new innovative feeding protocol, (PEP uP protocol), combined with a nursing educational intervention on EN intake compared to usual care?

What is the safety, feasibility and acceptability of the new PEP uP protocol?

Hypothesis: this aggressive feeding protocol combined with a nurse-directed nutrition educational intervention will be safe, acceptable, and effectively increase protein and energy delivery to critically ill patients.

Design

Protocol utilized in all patient mechanically intubated within the first 6 hours after ICU admission

Focus on those who remained mechanically ventilated > 72 hours

18 sites(low performing

from survey)

Control

Intervention

Baseline Follow-up6-9 months later

Bedside Written Materials Description

EN initiation orders Physician standardized order sheet for starting EN.

Gastric feeding flow chartFlow diagram illustrating the procedure for management of gastric residual volumes.

Volume-based feeding scheduleTable for determining goal rates of EN based on the 24 hour goal volume.

Daily monitoring checklist Excel spreadsheet used to monitor the progress of EN.

Materials to Increase Knowledge and Awareness

Study information sheetsInformation about the study rationale and guidelines for implementation of the PEP uP protocol. Three versions of the sheets were developed targeted at nurses, physicians, and patients’ family, respectively.

PowerPoint presentationsInformation about the study rationale and how to implement the PEP uP protocol. A long (30-40 minute) and short (10-15 minute) version were available.

Self-learning moduleInformation about the PEP uP protocol and case example to work through independently.

Posters A variety of posters were available to hang in the ICU during the study.

Frequently Asked Questions (FAQ) document Document addresses common questions about the PEP uP Protocol.

Electronic reminder messagesAnimated reminder messages about key elements of the PEP uP protocol to be displayed on a monitor in the ICU.

Monthly newsletters Monthly circular with updates about the study.

Tools to Operationalize the PEP uP Protocol

Analysis

3 overall analyses:

– ITT* involving all patients (n = 1,059)

– Efficacy analysis involving only those that remain mechanically ventilated for > 72 hours and receive the PEP uP protocol (n = 581)

– Those initiated on volume-based feeds (n = 57)

* ITT: intention to treat

Flow of Clusters (ICUs) and Patients

Through the Trial

45 ICUs with < 50% nutritional intake in 2009 International Nutrition Survey assessed for eligibility

18 Randomized

9 assigned to intervention group 9 assigned to control group

522 patients met eligibility requirements and were enrolled

and included in ITT analysis.

537 patients met eligibility requirements and were enrolled and included in ITT analysis.

306 patients included in efficacy analysis

231 on MV ≤ 72 hours 197 on MV ≤ 72 hours

54 did not receive the PEP uP protocol

271 patients included in efficacy analysis

57 patients initiated on 24 hour volume feeds

Participating Sites Intervention (n = 9) Control (n = 9) p-values

Hospital type Teaching

Non-teaching 4 (44.4%)5 (55.6%)

4 (44.4%)5 (55.6%)

1.00

Size of hospital (beds) Mean (range) 396.9 (139.0, 720.0) 448.7 (99.0, 1000.0) 0.97

ICU structure Open

Closed 3 (33.3%)6 (66.7%)

4 (44.4%)5 (55.6%)

1.00

Case type Medical

Neurological Surgical

Neurosurgical Trauma

Cardiac surgery Burns Other

9 (40.9%)3 (13.6%)5 (22.7%)2 (9.1%)1 (4.5%)0 (0.0%)1 (4.5%)1 (4.5%)

9 (36.0%)2 (8.0%)

8 (32.0%)2 (8.0%)2 (8.0%)1 (4.0%)1 (4.0%)0 (0.0%)

0.97

Size of ICU (beds) Mean (range) 12.6 (7.0, 20.0) 16.3 (8.0,25.0) 0.12

Full time equivalent dietician (per 10 beds)

Mean (range) 0.5 (0.3, 0.9) 0.4 (0.0, 0.6) 0.76

Regions Canada

USA4 (44.4%)5 (55.6%)

5 (55.6%)4 (44.4%)

1.00

Intervention Control

Baseline Follow-up Baseline Follow-up p-value

n 270 252 270 267

AgeMean ± SD 65.1 ± 15.5 64.1 ± 16.7 63.4 ± 15.1 61.4 ± 16.2 0.45

Sex Male (%) 157 (58.1%) 137 (54.4%) 170 (63.0%) 173 (64.8%)

0.56

Admission category Medical

Elective surgery Emergent surgery

230 (85.2%)

14 (5.2%)26 (9.6%)

222 (88.1%)12 (4.8%)18 (7.1%)

213 (78.9%)23 (8.5%)

34 (12.6%)

212 (79.4%)23 (8.6%)30 (11.2%)

0.24

Admission diagnosis Cardiovascular/vascular

Respiratory Gastrointestinal

Neurologic Sepsis

Trauma Metabolic

Hematologic Other non-operative conditions

Renal-operative Gynecologic-operative

Orthopedic-operative Other operative conditions

40 (14.8%)110 (40.7%)35 (13.0%)19 (7.0%)

37 (13.7%)0 (0.0%)11 (4.1%)1 (0.4%)7 (2.6%)2 (0.7%)1 (0.4%)1 (0.4%)6 (2.2%)

43 (17.1%)112 (44.4%)19 (7.5%)19 (7.5%)20 (7.9%)2 (0.8%)

15 (6.0%)0 (0.0%)

15 (6.0%)0 (0.0%)0 (0.0%)1 (0.4%)6 (2.4%)

31 (11.5%)78 (28.9%) 29 (10.7%) 30 (11.1%) 57 (21.1%)17 (6.3%)13 (4.8%)0 (0.0%)5 (1.9%)0 (0.0%)0 (0.0%)1 (0.4%)9 (3.3%)

51 (19.1%)81 (30.3%)29 (10.9%)28 (10.5%)25 (9.4%)18 (6.7%)6 ( 2.2%)1 (0.4%)7 (2.6%)3 (1.1%)1 (0.4%)3 (1.1%)

12 (4.5%)

undefined

APACHE II score Mean ± SD 23.0 ± 7.2 23.5 ± 7.1 21.1 ± 7.3 21.1 ± 7.3 0.53

Patient Characteristics

(n = 1,059)

Patient Nutrition Assessment Information (All patients – n = 1,059)

Intervention Control

Baseline Follow-up Baseline Follow-up p-value

n 270 252 270 267

Height Mean ± SD 1.7 ± 0.1 1.7 ± 0.1 1.7 ± 0.2 1.7 ± 0.1 0.55

Weight Mean ± SD 81.0 ± 25.3 81.4 ± 26.3 83.5 ± 26.5 83.7 ± 22.6 0.77

Body mass index (kg|m2)Mean ± SD 28.6 ± 8.2 28.6 ± 9.6 29.1 ± 8.1 28.6 ± 7.0 0.96

Prescribed energy intake (kcals)Mean ± SD 1,776.6 ± 352.4 1,774.8 ± 339.3 1,768.6 ± 412.1 1,784.4 ± 387.9 0.82

Prescribed protein intake (g)Mean ± SD 86.0±22.2 86.0 ± 19.8 99.9 ± 29.6 100.1 ± 27.8 0.09

Prescribed energy intake by weight (kcals|kg)

Mean ± SD 23.3 ± 5.9 23.2 ± 5.9 22.1 ± 4.9 22.3 ± 5.5 0.79

Prescribed protein intake by weight (g|kg)

Mean ± SD 1.1 ± 0.3 1.1 ± 0.3 1.2 ± 0.3 1.2 ± 0.3 0.26

Clinical Outcomes (All patients – n = 1,059)

Intervention Controlp-value

Baseline Follow-up Baseline Follow-up

Length of ICU stay (days)*

Median (IQR†)

6.1 (3.4,11.1)

7.2 (3.4,11.1)

6.4 (3.3,12.6)

5.7 (2.8,11.8) 0.35

Length of hospital stay (days)*

Median (IQR)

14.2 (8.1,29.8)

13.5 (8.1,28.4)

16.7 (7.5,27.7)

13.8 (7.1,26.6) 0.73

Length of mechanical ventilation (days)*

Median (IQR)

3.7 (1.6,9.1)

4.3 (1.3,9.9)

3.1 (1.4,8.4)

3 (1.4,7.3) 0.57

Patient died within 60 days of ICU admission

Yes 70 (25.9%)

68 (27.0%)

65 (24.1%)

63 (23.6%) 0.53

* Based on 60-day survivors only. Time before ICU admission is not counted.

† IQR: interquartile range

Change of Nutritional Intake from Baseline to Follow-up of All the Study Sites (All patients)

% Calories Received/Prescribed

% c

alo

rie

s r

ece

ive

d/p

rescri

be

d

326326

326326

331331

331331

360360

360360

371371

371371

372372372372

373373373373

374374

374374

375375

375375

390390

390390

Baseline Follow-up

20

30

40

50

60

70

80

p value <0.0001

Intervention sites

% c

alo

rie

s r

ece

ive

d/p

rescri

be

d

p value=0.65

327327 327327

p value=0.65p value=0.65

359359

359359

p value=0.65p value=0.65

362362

362362

p value=0.65p value=0.65p value=0.65p value=0.65p value=0.65p value=0.65

376376

376376

p value=0.65

377377

377377

p value=0.65

378378378378

p value=0.65

379379

379379

p value=0.65

380380

380380

p value=0.65p value=0.65

404404

404404

p value=0.65p value=0.65

Baseline Follow-up

20

30

40

50

60

70

80

Control sites

p value = 0.001 p value = 0.71

% p

rote

in r

ece

ive

d/p

rescri

be

d

326326

326326

331331

331331

360360

360360

371371

371371

372372

372372

373373 373373

374374

374374

375375

375375390390

390390

Baseline Follow-up

20

30

40

50

60

70

80

p value <0.0001

Intervention sites

% p

rote

in r

ece

ive

d/p

rescri

be

d

p value=0.78

327327 327327

p value=0.78p value=0.78

359359

359359

p value=0.78p value=0.78

362362 362362

p value=0.78p value=0.78p value=0.78p value=0.78p value=0.78p value=0.78

376376

376376

p value=0.78

377377

377377

p value=0.78

378378

378378

p value=0.78

379379

379379

p value=0.78

380380

380380

p value=0.78p value=0.78

404404

404404

p value=0.78p value=0.78

Baseline Follow-up

20

30

40

50

60

70

80

Control sites

% Protein Received/Prescribed

Change of Nutritional Intake from Baseline to Follow-up of All the Study Sites (All patients)

p value = 0.005 p value = 0.81

ICU Day

% c

alo

rie

s r

ece

ive

d/p

rescri

be

d

1 2 3 4 5 6 7 8 9 10 12

01

02

03

04

05

06

07

08

09

01

00

n ITTn Efficacyn FVF

24311357

21911357

19411357

17110854

15310552

1389646

1188340

1077535

835926

765223

594017

523514

ITTEfficacyFull volume feeds

ICU Day

% p

rote

in r

ece

ive

d/p

rescri

be

d

1 2 3 4 5 6 7 8 9 10 120

10

20

30

40

50

60

70

80

90

10

0

n ITTn Efficacyn FVF

24311357

21911357

19411357

17110854

15310552

1389646

1188340

1077535

835926

765223

594017

523514

ITTEfficacyFull volume feeds

Daily Proportion of Prescription Received by EN in ITT,Efficacy and Full Volume Feeds Subgroups

(Among Patients in the Intervention Follow-up Phase)

Compliance with PEP uP Protocol Components (All patients n = 1,059)

0

10

20

30

40

50

60

70

80

90

100

SupplementalProtein (ever)

SupplementalProtein

(first 48hrs)

Motility Agents(ever)

Motility Agents(first 48hrs)

Peptamen 1.5

Intervention - Baseline Intervention - Follow-up

Control - Baseline Control - Follow-up

Per

cen

t

Difference in Intervention baseline vs. follow up and vs. control all <0.05

-1

1

3

5

7

9

11

13

15

Vomiting Regurgitation Macro Aspiration Pneumonia

Intervention - Baseline Intervention - Follow-up

Control - Baseline Control - Follow-up

Complications (All patients – n = 1,059)

p > 0.05

Per

cen

t

Vomiting Regurgitation Macro Aspiration Pneumonia

Nurses’ Ratings of Acceptability

After GroupMean (Range)

24 hour volume based target 8.0 (1-10)

Starting at a high hourly rate 6.0 (1-10)

Starting motility agents right away 8.0 (1-10)

Starting protein supplements right away 9.0 (1-10)

Acceptability of the overall protocol 8.0 (1-10)

1 = totally unacceptable and 10 = totally acceptable

Overall, how acceptable is this new PEP uP feeding protocol to you?

Need more instructions to include all staff members Too much confusion over what protocol was supposed to be

May need a few adjustments however I think its overall acceptable

Good if everyone knows how to do it

Initial starting dose is too high

Maybe we needed more awareness by the MDs

Barriers to ImplementationDifficulties embed into EMR*

Non-comprehensive dissemination

of educational tools

Involvement of nurse educator (nurses owned it)

Ongoing bedside encouragement and coaching by site dietitian

* EMR: electronic medical records

Facilitators to Implementation

PEP uP Trial ConclusionStatistically significant improvements in

nutritional intake – Suboptimal effect related to suboptimal implementation

Safe

Acceptable

Merits further use

Can successfully be implemented in a broad range of ICUs in North America

Learning from the Trial : Next Steps

Change PEP uP protocol first day order to simplify (25 ml/hr for day 1)

Improve documentation of protein supplements (add to MAR!)

Develop PEP uP collaborative (community of practice)– PEP uP demonstration sites– Revise and disseminate tools

Audit practice again in early 2013

Call to action – is there room and interest to improve feeding practice in your ICU?

Identify nutrition champions – RNs, MDs, RDs

Feeding successfully requires a team approach

Education– Comprehensive education of the entire ICU team is essential – Tools and resources are available at criticalcarenutrition.com

Ongoing monitoring/feedback

Introduce PEP uP in YOUR ICU!

Education and Awareness Tools

PEP uP Pocket Guide PEP uP Poster

Protocol to Manage Interruptions to EN Due to Non-GI Reasons

Can be downloaded from www.criticalcarenutrition.com

PEP uP Monitoring Tool

Prompts for high risk patients improving calorie and protein intakes (≥ 80%

prescribed) starting motility agents, small bowel feeding, supplemental PN

Thanks Questions?