March 2012 E-Journal Club


Things have been buzzing with activity here this spring. We have hosted a Weekend Warrior, webinars, dietetic intern rotations, back to back 5-day traineeship programs and Spring Break in just several weeks.  The result of this staccato nutrition support pace is that we have already had our April Journal club before we could write up the one from March!  This month we return to the topic of GLA/EPA/antioxidant enteral formulas in sepsis.

March Citation:

Pontes-Arruda A, Martins LF, de Lima SM, et al; Investigating Nutritional Therapy with EPA, GLA and Antioxidants Role in Sepsis Treatment (INTERSEPT) Study Group.  Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT study.  Crit Care. 2011 Jun 9;15(3):R144.


This study was a multicenter, randomized, double-blinded, controlled trial of the effect of an enteral feeding formula with EPA/GLA/antioxidants (Oxepa™) compared with an isonitrogenous, isocaloric feeding with standard amounts of fat (Ensure Plus HN™) in patients with early sepsis.  Goal feeding was based on Harris Benedict X 1.3.  Patients were enrolled and randomized within 36 hours of admission, and feedings were started within 12 hours after randomization. Patients were scheduled to receive 50% of estimated needs within 24 hours and 75% of nutrition goal in 72 hours. The feedings were continued for 7 days or until stopped by MD or patients started oral intake.  The primary outcome studied was development of severe sepsis (defined as organ failure) and septic shock (defined as refractory hypotension) in 28 days after randomization.  Secondary outcomes studied included ICU and hospital length of stay, need for mechanical ventilation, development of individual organ failure and 28-day all-cause mortality.  The authors reported that the protocol was approved at 12 centers, but the patients were recruited from only five of the centers during the 21-month study.

Inclusion and Exclusion Criteria were:

Inclusion criteria:

Age >18 years, admitted to an ICU with a diagnosis of early sepsis and requiring enteral nutrition.

Exclusion criteria:

Severe sepsis (at least one organ failure) or septic shock (hypotension despite fluid resuscitation) at baseline, clinical diagnosis of sepsis for more than 36 hours, pregnancy or breastfeeding,< 18 years old, limited survival prognosis, chronic renal insufficiency, need for dialysis, body mass index (BMI) ≥ 29, acute pancreatitis without established origin, participation in other clinical trials less than 6 months previously, head trauma with a Glasgow Coma Scale score ≤ 5, recent stroke or subarachnoid hemorrhage (less than 3 months), severe immunologic suppression (defined as a leukocyte count below 5,000 cells/mm3), HIV infection, no indication for enteral feeding or imminent need for parenteral nutrition, partial parenteral nutrition to achieve caloric goals, presence of uncontrolled diarrhea, recent gastrointestinal bleeding, physician’s decision to exclude patients on the basis of the study protocol, or the presence of respiratory failure (defined as evidence of acute pulmonary dysfunction with a ratio of partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) < 300).

Major Results reported by authors:

A total of 115 patients were randomized, but 9 were excluded due to protocol violations. The intention-to-treat (ITT) analysis demonstrated that compared to the control diet, significantly fewer patients fed the EPA/GLA diet developed severe sepsis and/or septic shock (50% versus 26.3 respectively; P = 0.0259), cardiovascular failure (36.2% versus 21%, respectively; P = 0.0381) and respiratory failure (39.6% versus 24.6%, respectively; P = 0.0362).  Patients that received the EPA/GLA diet remained in the ICU significantly fewer days than the control population (ITT patients: 21.1 ICU-free days versus 14.7 ICU-free days, respectively; P < 0.0001) and had significantly fewer days at the hospital (ITT patients: 19.5 hospital-free days versus 10.3 hospital-free days, respectively; P < 0.0001.

The percentage of patients fed the EPA/GLA diet requiring invasive mechanical ventilation was less than controls, but this difference was not statistically significant (ITT patients: 18.9% versus 33.9%, respectively; P = 0.394).  There were no significant differences in 28-day all-cause mortality between groups.

Author’s Conclusions:

“… EPA/GLA may play a beneficial role in the treatment of enterally fed patients in the early stages of sepsis without associated organ dysfunction by contributing to slowing the progression of sepsis-related organ dysfunction, especially with regard to cardiovascular and respiratory dysfunction.”


This study has a number of strong points including the multi-center design, use of control feeding that was not high in fat content, and a double-blind design.  It does appear that the study was not as “multi-center” as was originally intended as evidenced by only 5 hospitals enrolling patients out of the 12 centers that initially intended to participate. What is not revealed in the initial publication that was discussed when this paper was presented at clinical nutrition week was that the majority of participants were enrolled from only 1 hospital.  The presenter explained that the difficulty in enrolling patients resulted from the need to find patients with early sepsis without respiratory failure who still required enteral nutrition support.

The narrow study population and difficulty in finding eligible patients defines the major limitations of this study.  The relatively modest number of participants increases the likelihood of reporting a significant difference between groups, and is too small to adequately examine mortality.  A limitation in terms of implementing the study results in practice is that most facilities do not provide tube feeding in the early part of the admission to patients with early sepsis.  We also determined that nearly 17% of the patients studied presumably had feeding tubes on admission (gastrostomy or jejunostomy) and may not be representative of all patients with early sepsis.  Additionally, we noted the fact that this study excluded patients with a BMI > 29 which is also not representative of our patient population (it is interesting to note that the EDEN study population discussed in our February 2012 post had a mean BMI of 30)

Of course, the idea that early provision of inflammatory modulating nutrients in sepsis may help reduce progression of organ failure is an appealing theory, and if larger trials with patients representative of the mild sepsis (and normal BMI of the population found here) repeat these results, we might find ourselves starting enteral feeding in this population.

Our Take Home Message

Early provision of EPA/GLA/antioxidant enriched enteral feeding formulas in early sepsis may decrease organ dysfunction in patients that require enteral feeding.  Larger multi-center trials with a wider variety of patients are required before embarking upon clinical application of these results.

Other News on the UVAHS GI Nutrition Website: (

Upcoming Webinars for Spring 2012:

  • Tuesday, May 15:  Enteral Nutrition–Carol Rees Parrish, MS, RD
  • Tuesday, June 12–Effectively Communicating with Physicians–Kate Willcutts, MS, RD, CNSC

Check out What’s New:

Latest Practical Gastroenterology Article:

Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD


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