October 2014 E-Journal Club



We hosted a great group of trainees for October traineeship, who hailed from North Carolina, California, the Philippines, and Hong Kong.  Our fall foliage was at its glorious peak and our guests were treated to the full range of Charlottesville fall weather: from near 80 degrees early in the week to near freezing by Friday night.

Our journal club article for October compared the use of early EN with early PN in the adult ICU.  I suspect this article will discussed at length during clinical nutrition week this year, and may be a source of controversy for some time to come.

October Citation:

Harvey SE, Parrott F, Harrison DA, et al. Trial of the Route of Early Nutritional Support in Critically Ill Adults. N Engl J Med. 2014;371(18):1673-1684.


This study was a “pragmatic”, multi-center, quazi-randomized*, unblinded trial comparing early enteral nutrition (EN) with early parenteral nutrition (PN) in a mixed adult ICU population.  Patients received either EN or PN within 36 hours after admission for 120 hours (5 days).  After the 120 hour intervention period, patients were changed to oral, EN, PN or any combination as deemed appropriate by the individual clinician.  Patients received PN through a “dedicated” central venous catheter (only used for PN).  Calorie goals were 25 kcals/kg actual weight and protein goals were determined by individual clinicians/usual practice.

The primary outcome of the study was all-cause mortality at 90 days.  Secondary outcomes included the duration of organ support, treated infectious and noninfectious complications, length of stay in the ICU and hospital, the duration of survival, mortality at the time of discharge from the ICU, from the hospital, at 90 days, and at 1 year.

* ( “a dynamic computer algorithm (minimization) with a random component, each patient being assigned with 80% probability to the group that would minimize the imbalance in the following factors: ICU; age (less than 65 years or 65 years and over); surgical status; and subjective assessment of severe malnutrition.”)

Inclusion and Exclusion Criteria were:

Inclusion criteria:

Unplanned ICU admission that was expected to last at least 3 days, age at least 18 years, expected to require nutrition support for at least 2 days as determined by a clinician within 36 hours after admission.

Exclusion criteria:

Previously enrolled in the study, admitted with thermal injury, receiving only palliative treatment, had received either EN or PN in the previous 7 days, admitted with percutaneous EN access, could not be fed through either EN or PN route, were pregnant, planned stay in the United Kingdom < 6 months.

Major Results:

A total of 2388 patients (1191 PN, 1197 EN) were analyzed out of the 11,108 patients that were screened (21.5%). There was no significant difference between groups in the primary study outcome of 30-day mortality, even after adjustment for baseline variables (393/1188 (33.1%) PN and 409/1195 (34.2%) EN).

There were no significant differences between the groups for 16 secondary outcomes, including mean number of infectious complications and 90-day mortality.  There were significantly less patients in the PN group reported to have hypoglycemia, compared to the EN group (PN 44 [3.7%] vs. EN 74 patients [6.2%]; 95% CI, 0.8 to 4.2; P = 0.006).  There were also significantly less episodes of emesis in the PN compared to the EN group (PN 100 patients [8.4%] vs. EN 194 patients [16.2%]; 95% CI, 5.2 to 10.4; P<0.001).

Crossover from PN to EN occurred in 81 patients (6.8%) and from EN to PN in 18 patients (1.5%) during the intervention period.  Patients receiving EN were more likely than those receiving PN to have complete days without nutrition (45 EN, 4 PN), have gastric residuals of 200-500 mL and receive prokinetic agents (426 EN, 26 PN).

Patients were reported to have received similar amounts of calories over the 120 hour intervention period (PN: avg. 17.8 kcals/kg/day, EN: 14.8 kcals/kg/day).  Average protein received was 1.0 gm/kg in the PN group and 0.7 gm/kg  in the EN group.

Author’s Conclusions:

“We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults.”


This study is remarkable in that the lack of significant difference in the primary outcome is not the most noteworthy result.  After all, it is difficult to impact ICU mortality with single interventions, which is why many ICU’s have critical care “bundles” to improve outcomes.  It would have been extraordinary if the route of nutrition for 5 days had an impact on patient mortality in a mixed adult ICU population.  Indeed, as others will undoubtedly comment, it is a shame that there was not a third group who did not receive any nutrition support so that we would finally have a better idea if early nutrition support via either route is advantageous.

Our group felt that the most notable part of this study was the lack of any difference in infectious complications between the EN and PN groups, which is a surprising result compared to previous evidence.

Several concerns that we discussed included the lack of information about how the amount of EN and PN that were actually received by the patient was determined/calculated.  Additionally, although the authors reported that EN was held more frequently than PN, including full days without EN, increased emesis and residuals – they reported that similar amounts of nutrition were provided to both groups.  Although previous studies, as well as this one, document that EN is frequently held and why, in this study it is unclear why the PN group ultimately only received about 70% of the nutrition goals.  In interpreting the results of this study we should remember that this is an investigation of short-term, hypocaloric PN (17 kcals/kg) – which may explain some of the differences in outcomes between this and previous EN/PN studies.

Another concern that we had is the use of vague and subjective definitions for several of the outcomes.  The definition of hypoglycemia provided by the supplemental tables was “any new episode of clinically significant hypoglycemia requiring active monitoring or treatment…” without giving any numeric value in mmol/L!  In a non-blinded study the lack of objective values is concerning – especially when it is one of the few adverse events that was significantly different between the 2 groups.

We also noted that supplemental nutrients were provided more frequently to the PN group.  Supplemental glutamine was provided to 4.2% of the PN group and none of the EN group, fish oils to 3.1% of the PN group and 0.1% of the EN group and supplemental selenium to 22.5% of the PN group and only 0.3% of the EN group.

Ultimately, we discussed that there was no mention of financial considerations.  Undoubtedly, this study will be used to support recommendations to have a lower threshold to begin PN in the ICU.  However, considering that PN is more expensive, and outcomes were not improved in the PN group, we will continue to reserve PN for patients with non-functioning GI tracts.  In the United States we have had so many recurring shortages, that it is especially important to reserve PN components for those patients that cannot live without it.

Our Take Home Message (s)

1.   Early, short-term (5 days or less) hypocaloric PN via a dedicated line with good glucose control does not appear to increase mortality or infectious complications compared to early EN in a well-nourished, mixed adult ICU population.

2.   Protein delivery was low in both groups…

3.   Results from this study should likely not be extrapolated to other populations, hypercaloric PN, longer periods of therapy, or perhaps, PN without supplemental selenium.

4.   When nutrition formulas or routes provide equivalent patient outcome, we have an obligation to use the most economical therapy in a faltering healthcare system rife with shortages.



Other News on the UVAHS GI Nutrition Website: (

Check out What’s New:

— “Nutrition Support Blog”

–“ Resources for the Nutrition Support Clinician

Latest Practical Gastroenterology article:

–Parrish CR, DiBaise J.  Part II: Nutrition Therapy for Short Bowel Syndrome in the Adult Patient.  Practical Gastroenterology 2014;XXXVIII(10):40.


Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD

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