September 2011 E-Journal Club


Cooler days have finally arrived in Charlottesville, along with a new school year, and our new class of dietetic interns.  In addition to our existing activities, we have also been working to develop a new curriculum for a specialized Weekend Warrior program dedicated to GI nutrition topics, as well as expanding our website with a nutrition support blog.

September Citation:

Grau-Carmona T, Morán-García V, García-de-Lorenzo A, et al.  Effect of an enteral diet enriched with eicosapentaenoic acid, gamma-linolenic acid and anti-oxidants on the outcome of mechanically ventilated, critically ill, septic patients.  Clin Nutr. 2011 Apr 5. [epub ahead of print].


This was a multicenter, prospective, open-label study of 160 patients admitted with sepsis that were randomized to receive an enteral feeding formula supplemented with eicosapentaenoic acid, gamma-linolenic acid and anti-oxidants (Oxepa) or a control diet that had standard fat calories (30% — Ensure Plus HN).  Patients were followed until ICU discharge or day 28.

The primary outcome was new organ dysfunction determined by total daily SOFA score and delta SOFA changes (SOFA admit – worst SOFA score on day of measurement), measured at days 1, 3, 7, 14 and 21 after randomization.

The secondary end-points were the incidence of nosocomial infections throughout the ICU stay, ICU and hospital length of stay, number of days on mechanical ventilation, and overall all-cause mortality in the first 28 days after ICU admission.

Inclusion and Exclusion Criteria were:

Inclusion criteria:

18 years or older, a diagnosis of sepsis on admission, receiving mechanical ventilation, and could be fed by enteral nutrition (EN).

Exclusion criteria:

Pregnancy, recently received artificial nutrition (15 days prior), food allergy to study diet components; severe hyperlipidemia, gastrointestinal diseases precluding EN, inability to position the feeding tube, immune suppression states, systemic chemotherapy in the past 3 months, autologous hematopoietic precursor cell transplantation in the previous year, allogeneic hematopoietic precursor cell transplantation in the past 2 years, graft-versus-host disease, advanced chronic liver disease (Child-Pugh stage C), grade IV heart failure (NYHA), functional grade IV chronic respiratory failure, end-stage degenerative neurological processes, neoplasm, short life-expectancy processes including end-stage kidney failure, acute processes implicating short patient survival, shock of any etiology with multiple organ failure refractory to therapy in the first 48 h, or post-cardiopulmonary resuscitation with serious neurological damage 72 h after arrest, or current or recent (one month) inclusion in other trials of experimental treatments.

Major Results reported by authors:

EN was started in the first three days (range: 1.5–3) after hospital admission, and in the first 2 days (range: 1–3) after ICU admission, with both groups achieving more than 80% of planned caloric intake across the 28-day study period.

There was no statistically significant difference in the primary outcome of new organ dysfunction between the groups.

The authors reported a non-significant trend for a lower SOFA score, delta SOFA, PaO2/FiO2 rate and number of days on mechanical ventilation in the group of patients treated with EPA-GLA diet. However, this trend was so modest that the study was stopped earlier than planned because it was determined that the number of patients needed to treat in order to find statistically significant differences was > 3200 patients.

Mortality was 16% in the study group and 18% in the control group. The incidence of nosocomial infections was similar in both groups. The EPA-GLA diet group had a significantly shorter ICU stay with a median of 16 days (IQ range: 11–25), whereas the control group had a median ICU stay of 18 days (IQ range: 10–30) (p = 0.02).

Author’s Conclusions:

“A diet enriched with EPA, GLA, and anti-oxidants does not improve gas exchange or decrease the incidence of novel organ failures in critically ill septic patients with acute lung injury or ARDS. Patients treated with the EPA-GLA diet stayed in the ICU for less time, but we did not find any differences in infectious complications.”


This is a potentially important study because previous investigations with EPA/DHA formulas in sepsis and ARDS used a high-fat control formula.  Due to evidence that high-fat formulas might increase production of inflammatory cytokines in sepsis or ARDS, it was unclear if the specialty formula had a benefit compared to a standard-fat formula.

Unfortunately there are several limitations of this study that limit the strength of any conclusions.  Although this study has the strength of being randomized with blinded allocation into a treatment group, it was not conducted in a double-blind fashion.  The fact that the researchers were not blinded to the treatment group is especially relevant when you consider the study dropouts and the way that the study was analyzed.

Studies should be analyzed according to intention to treat, which means that all patients that are randomized are included in the analysis in order to preserve the randomization.  The current study analyzed only 132 of the 160 patients that were randomized and (importantly) there was an uneven level of dropouts after randomization between the two groups.  More than 2X as many patients were dropped from the group assigned to study diet (n=19) compared to those dropped from the control feeding (n=9) after randomization.  It is notable in this non-blinded study that a large number of dropouts in the study group were those patients where the treating doctor decided to exclude the patient (7 in study group compared to 1 in control).

Additionally, patients in the study could be fed either by NG or NJ tube at the discretion of the primary team, but no details were provided on any potential feeding site differences between groups.

Other limitations that we noted were that there was no details provided of how soon it took patients to receive the goal volume of formula and no mention of how feeding adequacy was recorded and monitored.  The authors state that feedings were started within 2 days, and provide information only about average feeding adequacy over 28 days.  The time to meet goal feeding is important because the single study that did report significantly improved outcomes in mortality in sepsis/ARDS1 with a EPA/GLA formula is remarkable for providing feedings very soon (approx 3 hours) after admission and the average time for patients to receive 75% of estimated needs was only 26 hours.

Overall mortality and the incidence of ARDS suggest that the population of the current study may be different than that of the study where EPA/GLA improved outcomes.1  The current study had a mortality of 16% in the study group, while in the previous study,1 the study group (same formula) was 33%.  Also, in the current study only 66% of control and 77% of study patients had ARDS on admission.  It is worthy to note that by the time any of the patients received the study formula (day 1) the average PaO2/FiO2 ratio of both groups no longer met criteria for ARDS (200 or greater).

Our Take Home Message

–An enteral formula enriched with EPA/GLA and antioxidants fed within 2 days of admission did not appear to have significant benefits when compared to a standard fat (30% of calories) enteral formula in a population with sepsis.

–There is a need for larger blinded multi-center trials comparing EPA/GLA formulas to standard high-nitrogen formulas.


1)   Pontes-Arruda A, Aragao AM, Albuquerque JD.   Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock.  Crit Care Med. 2006;34(9):2325-33.


Other News on the UVAHS GI Nutrition Website ( :

Upcoming Webinars for Fall 2011:

·         October 13: The Basics of Gastrointestinal Anatomy & Physiology–Cynthia Yoshida, MD

·         November 15: Vitamin and Mineral Issues in Gastric Bypass–Kelly O’Donnell, MS, RD, CNSD

·         December 6: The Basics of GI Anatomy & Physiology, Part II: The Malabsorption Workup–Carol Parrish, MS, RD

Check out our new:

·         “Nutrition Support Blog”

·         “ Resources for the Nutrition Support Clinician

Latest Practical Gastroenterology article:

·         Parrish CR, McCray S.  Gastroparesis & Nutrition: The Art . Practical Gastroenterology 2011;XXXV(9):26.


Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD


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