April 2015 E-Journal Club


It finally feels like spring in Virginia, and our visitors to UVA were treated to (mostly) fair weather and our Dogwoods and Redbuds in bloom.  Our April trainees hailed from Highlands Ranch, Colorado and Montego Bay, Jamaica.  Our April journal club dealt with the topic of EPA/GLA/antioxidant-enriched EN – but this time in trauma patients.

April Citation:

Kagan I, Cohen J, Stein M, et al.  Preemptive enteral nutrition enriched with eicosapentaenoic acid, gamma-linolenic acid and antioxidants in severe multiple trauma: a prospective, randomized, double-blind study.  Intensive Care Med. 2015;41(3):460-469.


This was a single center, randomized, double-blind study of the effects of pre-emptive enteral nutrition (EN) enriched with EPA, GLA and antioxidants (Oxepa) on oxygenation and the incidence of ALI/ARDS in trauma patients, as compared to a control EN formula (Pulmocare). The control formula had similar macronutrient distribution as the trial product, with 55% of calories from lipid, except the control product was rich in omega-6 fatty acids (96.8 % corn oil, 3.2 % soy lecithin).  EN was provided within 48 hours of randomization to provide at least 80% of energy expenditure, as determined by indirect calorimetry.

The primary outcomes were the level of oxygenation (PaO2/FiO2 ratio on days 4 and 8), the incidence of ALI/ARDS and the length of ventilation. Secondary outcomes included the incidence of new organ failure (SOFA score), rate of new infections, bacteremia, ventilator-associated pneumonia, length of ICU stay, length of hospital stay and 28-day mortality.  A per-protocol analysis was planned that excluded patients that did not tolerate EN or who received mechanical ventilation < 48 hours.  A power analysis found that at least 60 patients in each group would be required to detect a statistically significant difference in oxygenation on days 4 and 8 of the study.

Inclusion and Exclusion Criteria were:

Inclusion criteria:

Patients between the ages of 18–90 years with a diagnosis of multiple trauma, or isolated head trauma who required mechanical ventilation and had an anticipated ICU stay of ≥2 days were included in the study.

Exclusion criteria:

Any contraindication for commencing EN within 36 hours of ICU admission, treatment with immunosuppressive drugs, second-/third-degree burns covering >66 % of body surface area or pregnancy.

Major Results:

A total of 195 patients were screened with 120 patients randomized and 21 patients subsequently excluded (16 early extubation and 5 failure to reach >500 mL EN by day 3). The per-protocol analysis included 99 patients (47 control and 52 study group).

The study and control groups were not similar after randomization with significantly more multiple trauma patients in the study group (n=57) compared to the control (n=45), and significantly more patients with isolated head trauma in the control group (n=13) compared to the study group (n=5).

There were no significant differences in the primary outcomes of ventilatory parameters, P/F ratio or incidence of ALI/ARDS between the intention to treat (all randomized) or per-protocol populations. There were no significant differences in most of the secondary outcomes between the control and study group, except there were significantly more bacteremias in the study group compared to control (14 vs. 3; P = 0.008).  In addition, study patients received significantly more packed RBC transfusions than controls (189 vs. 77 units, respectively; P = 0.03).  When the 5 study and 13 control patients with isolated head trauma were analyzed separately, there were no significant differences in any of the parameters studied.

The study group showed a significant increase in both EPA and GLA concentrations at day 4 (P = 0.05) and at day 8 (P < 0.001) when compared to baseline. No changes in any of the fatty acids studied were noted in the control group apart from a significant decrease in the DHA concentration on day 4.

Author’s Conclusions:

The authors concluded that the pre-emptive administration of EPA and GLA did not result in improved outcomes in mechanically ventilated patients with multiple trauma despite their demonstrated integration into the membrane of RBCs. Studies titrating the dose of EPA and GLA in specific populations with the aim of determining an effective dosage should be planned.


The strengths of this study include randomization, the double-blind design, and the use of a control formula with similar macronutrient distribution as the study formula.

Unfortunately, the study was marginally powered to detect differences in oxygenation, and as evidenced by the significantly unequal distribution of multi-trauma and head injured patients, there was a breakdown of the randomization right from the start.  The failure to provide homogenous groups of patients prevents any kind of strong conclusions from this study.  The increased bacteremias in the study group may simply be related to increased need for transfusions in multi-trauma patients.  It was very surprising that the authors would analyze the subgroup of 18 isolated head injured patients, especially when they were significantly more who received the control formula, and only 5 patients who received the study formula.

The authors mention in the discussion section that the EPA/DHA content of red cells did not reach the 8% goal used for evaluation of cardiovascular risk.  There is justification for future studies to evaluate the potential of products with increased omega-3 fatty acid content, but they will require larger numbers of patients randomized to be able to evaluate morbidity and mortality outcomes in critically ill patients.

The authors also suggest that this study provides evidence that EN products with increased omega-6 fatty acid content do not increase risk of morbidity and mortality.  However, considering that the study was not adequately powered for most morbidity and mortality outcomes, the lack of comparison to a reduced-fat, standard feeding product, and the breakdown of randomization with uneven groups of patients in this study, no valid conclusions can be formed about increased omega-6 fat nutrition in the ICU from the results of this study.

Finally, the average age of patients was 42 years, which is a younger population than we usually see, so at least for us, this study’s results may not have been transferable to our population.

Our Take Home Message (s)

  1. The small number of patients enrolled and the breakdown of the randomization prevents any firm conclusions about the effects of EPA/DHA/GLA-antioxidant enriched EN in trauma patients.
  2. Be wary of sources that would quote this study as evidence that omega-6 fatty acid rich feeding poses no risks in trauma or other critically ill populations.

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

Upcoming Webinars 2015:

–On hold due to technical issues—stay tuned for updates

Check out What’s New:

–“Nutrition Support Blog”

–“ Resources for the Nutrition Support Clinician

Latest Practical Gastroenterology article:

–Neander-Chan L, DiBaise J, Parrish CR. Part IV-A: A Guide to Front Line Drugs Used in the Treatment of Short Bowel Syndrome. Practical Gastroenterology 2015;XXXIX(3):28.

–Neander-Chan L, DiBaise J, Parrish CR. Part IV-B: A Guide to Front Line Drugs Used in the Treatment of Short Bowel Syndrome. Practical Gastroenterology 2015;XXXIX(4):24.


Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD


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