October 2013 E-Journal Club


We had another wonderful traineeship week in October, with trainees from Cooperstown, NY; Alexandria, VA; Lansdale, PA and Hong Kong (2).  Our weather is still mild here in C’ville, but fall rains dampened the latter half of the week.

Our October journal club article was the multi-center study of the PEP uP protocol.

October Citation:

Heyland DK, Murch L, Cahill N, et al.  Enhanced Protein-Energy Provision via the Enteral Route Feeding Protocol in Critically Ill Patients: Results of a Cluster Randomized Trial.  Crit Care Med. 2013 Aug 26. [Epub ahead of print]


This was a cluster randomized trial of 18 ICUs in North America to determine the effect of an “enhanced” enteral nutrition (EN) feeding protocol (PEP uP protocol) together with nurse-directed nutrition education, compared to the standard feeding protocol (usual care) on amount of protein and calories received.  The experimental protocol involved:

  • Starting EN at a higher initial target rate.
  • Changing from a mL/hr goal to volume-based (24-hour) goal, with instructions to nurses to increase feeding rates to meet the volume goal if feedings must be held.
  • An option to initiate “trophic feeds” at a low volume with a concentrated feeding solution, if the patient was deemed unsuitable for full feedings.
  • Semi-elemental feeding formula as the initial feeding formula.
  • Protein supplements are prescribed at the initiation of EN, then discontinued if not needed once EN reaches goal volume.
  • Begin prokinetic medication (metoclopramide) at the start of EN and then discontinue later if deemed unnecessary.
  • Increase the acceptable threshold for gastric residuals from 250 to 300mL (individual sites were able to use a gastric residual threshold between 250 and 500 mL), and decrease feeding rates (rather than stop) if residuals exceeded their threshold.

Half of the ICUs were randomized to implement the new feeding protocol and educational intervention, adequately train staff, and institute the use of preprinted orders, to enable the automatic utilization of this protocol upon ICU admission. In the other ICUs (control group), the usual feeding protocols continued to be operational.

Approximately 6 months later, when each intervention site had fully implemented the protocol, data collection was repeated in all participating ICUs. Daily nutrition information was recorded for a maximum of 12 days unless death or ICU discharge occurred sooner. All patients were followed until death, hospital discharge, or 60 days.

The primary endpoints of the study were:

a. The percentage of goal calories and protein actually received from EN over the first 12 days in the ICU

b.  the safety of the PEP uP protocol as defined by episodes of witnessed vomiting, regurgitation (gastric contents detected in the mouth), “macroaspiration” (defined as gastric contents detected in the airway), and ICU-acquired pneumonia as diagnosed by the individual hospital.

Inclusion and Exclusion Criteria:

Inclusion criteria:

Adult patients who were mechanically ventilated prior to, or within the first 6 hours, of ICU admission who remained mechanically ventilated for at least 72 hours.

Exclusion criteria:

Patients that had EN or PN started before the ICU admission and those intubated more than 6 hours after admission to the ICU.  All patients who died within the first 48 hours of ICU admission were excluded.

Major Results:

Ultimately there were 1,059 patients in the intention to treat analysis (all enrolled), 577 in the efficacy analysis (excluded patients on mechanical ventilation < 72 hours) and 57 in the intervention group that initially received 24-hour volume feeds as their first order.

The mean BMI was 29 and patients were prescribed an average of 1.2 g/kg/d of protein and 23 kcal/kg/d of calories.  Sixty-nine percent of the patients received EN, 6% received PN and 25% of study patients did not receive any nutrition support during their first 12 days in the ICU.  Patients remained on study protocol for an average of 6.3 days and had interruptions to their feeding protocol on 2.9 days during their ICU stay. The main reason for interrupting the feeding protocol was for procedures.

After the PEP uP protocol was implemented, patients in the intervention group received a significantly larger proportion of prescribed protein and calories from EN, compared to baseline (47 vs. 34%, p = 0.005 for protein; 44 vs. 32%, p = 0.001 for calories), but there were no significant changes achieved in the control group.  There was a noticeable variability in the success of the PEP up protocol between the different intervention sites ranging from 0% to 30% increase in protein adequacy and 5–28% in caloric adequacy.

Implementation of the PEP uP protocol was associated with a trend toward faster initiation of EN in the ICU compared to the control group (40.7–29.7 hr vs. 33.6–35.2 hr, p = 0.10).

In the intervention group there were more patients who received trophic feeds and 24-hour volume feeds in the follow up period, compared to baseline.  During the follow-up phase in the intervention group, only 48.5% of patients actually received motility agents in the first 48 hours, and only 31.7% received protein supplements. Of those started on EN, 67.5% were started on a semi-elemental formula. There were no significant differences in complication rates between the two groups.

Author’s Conclusions:

“….in ICUs with low baseline nutritional adequacy, the PEP uP protocol results in modest, but statistically significant increases in protein and calorie intake in critically ill patients.”


The realization that patients receive only a portion of the calories and protein prescribed in the adult ICU has led many facilities to re-evaluate their protocols for EN.  The PEP uP protocol uses strategies that are designed to enhance the delivery of EN combined with education strategies for caregivers.

The strengths of this study include the cluster randomized, multi-center design with a relatively large number of participants.  The authors point out several limitations of the study in the discussion section, including the fact that many patients received short-term mechanical ventilation and no EN.  Additionally, and perhaps most pertinent is that many facilities had ineffective implementation of the protocols (< ½ on prokinetics, < 1/3 on protein supplements).  Implementation of the study protocol increased average calorie and protein delivery to a very modest amount (about 200 kcals/day), which may have occurred due to noncompliance with the full protocols.

Our group discussed the PEP uP protocols and noted that several aspects are similar to our own efforts to enhance EN delivery.  However, we had some reservations about a policy that would place all patients receiving EN on automatic prokinetic medications.  We wondered if the lack of compliance with prokinetics at the study sites reflected a concern regarding the potential adverse effects of metoclopramide.  The study did not detect any negative effects of the protocol, but then again, less than ½ received prokinetics.  We also noted that there is no justification to use a far more expensive peptide-based formula, when available data does not demonstrate that feeding tolerance will be improved.1-3   We also noted (once again) how the inconsistent and partial delivery of nutrition in the real world, makes it a bit ridiculous to suggest a more complicated calculation for determining calorie goals could affect patient care.

Our Take Home Message (s)

  1. The PEP up protocol has a modest ability to decrease time to begin EN and increase nutrition delivery at facilities that do not already have an institutional culture favoring nutrition adequacy.
  2. It remains unclear if all of the components of the PEP uP protocol are necessary or advisable.



1.   Mowatt-Larssen CA, Brown RO, Wojtysiak SL, et al. Comparison of tolerance and nutritional outcome between a peptide and a standard enteral formula in critically ill, hypoalbuminemic patients.  JPEN J Parenter Enteral Nutr, 1992;16(1):20-24.

2.   Viall C, Porcelli K, Teran JC, et al. A double-blind clinical trial comparing the gastrointestinal side effects of two enteral feeding formulas. JPEN J Parenter Enteral Nutr, 1990;14(3):265-269.

3.   Heimburger DC, Geels VJ, Bilbrey J, et al. Effects of small-peptide and whole-protein enteral feedings on serum proteins and diarrhea in critically ill patients: a randomized trial. JPEN J Parenter Enteral Nutr, 1997;21(3):162-167.


Other News on the UVAHS GI Nutrition Website: (www.ginutrition.virginia.edu):

Upcoming Webinars 2013:

  • November 19:  Nutrition in ALS
  • December 10:  GI Nutrition Support Clinical Cases

Check out What’s New:

Latest Practical Gastroenterology article:

    –Thompson T, Thomas Grace T.  Gluten Content of Selected Labeled Gluten-Free Foods Sold in the US.  Practical Gastroenterology 2013;XXXVII(10):23.


Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD


PS – Please feel free to forward on to friends and colleagues.