Nutrition & Rehabilitation Investigator’s Consortium Clinical Evaluation Research Unit

1. Rupinder Dhaliwal, RD Nutrition & Rehabilitation Investigator’s Consortium Clinical Evaluation Research Unit Queen’s University, Kingston General Hospital

2. I have received speaker honoraria or been paid from grants from the following companies: Nestlé Canada Fresenius Kabi AG Baxter Abbott Laboratories Conflicts of Interest

3. Objectives • Describe rationale for the novel components of the PEP uPprotocol • 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

4. Current Practice in ICUs in 2011 • n =211 ICUs, mean intake 56% prescribed calories Heylandet al INS 2011 unpublished data

5. Optimal Amount of Calories for Critically Ill Patients: Depends on how you slice the cake! Association Between 12-day Caloric Adequacy and 60-day Hospital Mortality Optimal amount = 80-85% Heyland DK, et al. Crit Care Med. 2011;39(12):2619-26.

6. Failure Rate % high risk patients who failed to meet minimal quality targets (80% overall energy adequacy) 91.2 87.0 79.9 78.1 75.6 75.1 69.8 Heyland et al Unpublished observations Results of 2011 International Nutrition Survey (INS)

7. Can we do better? A shift in the feeding paradigm is needed!

8. PEP UP Protocol: components • Early enteral nutrition • Goal rate feeding in stable patients • Trophic feeds • Feeding unstable patients • Motility agents • Higher gastric residual volumes • Protein supplements • Semi-elemental formula • Monitor nutritional adequacy

9. Early EN (within 24-48 Hours of Admission) Is Recommended! Optimal amount of protein and calories for critically ill patients?

10. Initial Efficacy and Tolerability of Early EN with Immediate or Gradual Introduction in Intubated Patients N = 100 pts mechanically ventilated pts (not in shock) to immediate goal rate vs gradual ramp up DesachyA, et al. Intensive Care Med. 2008;34(6):1054-9.

11. 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. “Trophic Feeds” Just say no to NPO 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.

12. Initial Tropic vs. Full EN inPatients with Acute Lung Injury The EDEN randomized trial Rice TW, et al. JAMA. 2012;307(8):795-803.

13. Trophic vs. Full EN in Critically Ill Patients with Acute Respiratory Failure The EDEN randomized trial 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.

14. What about feeding the hypotensive patient? • Resuscitation is the priority • No sense in feeding someone dying of progressive circulatory failure • However, if resuscitated yet remaining on vasopressors: Safety and efficacy of EN??

15. Feeding the hypotensive patient? 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. Khalid I, et al. Am J Crit Care. 2010;19(3):261-8. The beneficial effect of early feeding is more evident in the sickest patients, i.e., those on multiple vasopressoragents

16. Pro-motility Agents Conclusion: Motility agents have no effect on mortality or infectious complications in critically ill patients 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 “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”. 2009 Canadian CPGs www.criticalcarenutrition.com

17. It’s Not Just About Calories... Inadequate protein intake Loss of lean muscle mass Immune dysfunction Weak prolonged mechanical ventilation • So in order to minimize this, we order: • Protein supplement Beneprotein® 14 grams mixed in 120 mls sterile water administered BID via NG

18. 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. ClinNutr. 2012;31(4):462-8.

19. We use a concentrated solution to maximize calories per ml If unstable or unsuitable, just use trophic feeds The PEP uPProtocol Stable patients should be able to tolerate goal rate 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 BeginPeptamen® 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. Note indications for trophic feeds Doctors need to justify why they are keeping patients NPO Note, there are only a few absolute contraindications to EN We want to minimize the use of NPO but if selected, need to reassess next day Single centre pilot study Heyland DK, et al. Crit Care 2010. 2010;14(2):R78

20. 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

21. 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

22. 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

23. Efficacy of Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients: The PEP uPProtocol A multi-center cluster randomized trial Daren K. Heyland Professor of Medicine Queen’s UniversityKingston General Hospital Kingston, Ontario

24. 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.

25. Design Control 6-9 months later 18 sites (low performing from survey) Baseline Follow-up Intervention • Protocol utilized in all patient mechanically intubated within the first 6 hours after ICU admission • Focus on those who remained mechanically ventilated > 72 hours

26. Tools to Operationalize the PEP uP Protocol

27. 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

28. Flow of Clusters (ICUs) andPatients 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. 231 on MV ≤ 72 hours 197 on MV ≤ 72 hours 54 did not receive the PEP uP protocol • 271 patients included in efficacy analysis • 306 patients included in efficacy analysis • 57 patients initiated on 24 hour volume feeds

29. Participating Sites

30. Patient Characteristics (n = 1,059)

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

32. Clinical Outcomes (All patients – n = 1,059) * Based on 60-day survivors only. Time before ICU admission is not counted. † IQR: interquartile range

33. Change of Nutritional Intake from Baseline to Follow-up of All the Study Sites (All patients) % Calories Received/Prescribed p value = 0.001 p value = 0.71

34. Change of Nutritional Intake from Baseline to Follow-up of All the Study Sites (All patients) % Protein Received/Prescribed p value = 0.005 p value = 0.81

35. Daily Proportion of Prescription Received by EN in ITT,Efficacy and Full Volume Feeds Subgroups (Among Patients in the Intervention Follow-up Phase)

36. Compliance with PEP uP Protocol Components (All patients n = 1,059) Percent Difference in Intervention baseline vs. follow up and vs. control all <0.05

37. Complications (All patients – n = 1,059) Percent Vomiting Regurgitation Macro Aspiration Pneumonia p> 0.05

38. Nurses’ Ratings of Acceptability 1 = totally unacceptable and 10 = totally acceptable

39. Overall, how acceptable is this new PEP uPfeeding 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

40. Barriers to Implementation Facilitators to Implementation • Involvement of nurse educator (nurses owned it) • Ongoing bedside encouragement and coaching by site dietitian * EMR: electronic medical records • Difficulties embed into EMR* • Non-comprehensive dissemination of educational tools

41. PEP uP Trial Conclusion • Statistically 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

42. 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

43. Introduce PEP uP in YOUR ICU! • 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

44. Education and Awareness Tools • PEP uP Pocket Guide • PEP uPPoster

45. Protocol to Manage Interruptions to EN Due to Non-GI Reasons Can be downloaded from www.criticalcarenutrition.com

46. PEP uP Monitoring Tool • Prompts for • high risk patients • improving calorie and protein intakes (≥ 80% prescribed) • starting motility agents, small bowel feeding, • supplemental PN

47. Thanks Questions?