January seemed to fly-by this year – between Clinical Nutrition Week, deadlines for articles, and rolling out some new Traineeship programs we suddenly find ourselves in mid-February! Although Charlottesville has been light on winter weather this year, we cannot say the same about the flurry of new research in the last several months. Our February journal club is the companion to our December article, because the studies were completed simultaneously in a 2X2 factorial design. This month’s article promises to be a controversial one since the results question the need to calculate calorie expenditure or provide full feedings to some ICU patients.
February Citation:
The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial Trophic vs. Full Enteral Feeding in Patients with Acute Lung Injury: The EDEN Randomized Trial. 2012;307(8):795-803.
Summary:
This study was part of the very large National Heart, Lung, and Blood Institute (NHLBI) ARDS Clinical Trial Network study – the EDEN-OMEGA trial. EDEN-OMEGA was a multi-center study that was designed to answer 2 questions by randomizing patients with acute lung injury (ALI)/ARDS to receive:
· trophic compared to full feeding and also,
· omega-3/gamma-linolenic fatty acids with antioxidants vs. placebo in a 2X2 factorial design.
Patients randomized to receive trophic feedings received 10 mL/hr of feeding until day 6, then were advanced to full feedings. After the first 272 patients had been enrolled and the Omega arm of the study was stopped for futility, those in the trophic arm were increased to 20 kcals/hr to approximate the calories from the Omega-3 or placebo supplement. Patients randomized to full feedings had a feeding goal of 25-30 kcals/kg and 1.2-1.6 gm protein/kg. There were 1000 total patients enrolled, with 508 in the trophic and 492 in the full-feeding group. The trophic versus full feeding portion of the study was open label (not blinded).
The primary outcome of this study was ventilator-free days (VFD = number of days alive and breathing without assistance from randomization until day 28). Secondary end points included the daily percentage of goal enteral feeding, frequency of gastrointestinal intolerance, 60-day mortality before hospital discharge with unassisted breathing, ICU- and organ failure– free days, and new infections.
Inclusion and Exclusion Criteria were:
Inclusion criteria:
Patients with ALI (PaO2/FiO2 < 300) who required mechanical ventilation and whose physicians intended to start enteral nutrition.
Exclusion criteria:
There were more than 30 exclusion criteria (too many to list in full), but the most common reasons patients were excluded were previous severe chronic lung disease, > 48 hrs since ALI diagnosis or 72 hours since intubation, inability to obtain consent, likely fatal underlying disease, recent intracranial hemorrhage, severe liver disease, moribund, refractory shock, coagulopathy or refused consent. There were 144 patients excluded due to severe malnutrition (out of the 7968 patients screened).
Major Results reported by authors:
There was no significant differences between the groups in the primary endpoint of VFDs to day 28 (14.9 VFDs trophic compared with 15.0 in the full feeding group; difference, −0.1 [95% CI, −1.4 to 1.2]; P=.89). There were also no significant differences between the groups in any of the secondary endpoints of 60-day mortality, organ failure-free days, ICU-free days, incidence of infection between groups, VFDs or survival when analyzed by body mass index category, or when subsets of patients with shock or more severe lung injury (acute respiratory distress syndrome) were analyzed. The investigators also reported that there was no interaction between the OMEGA assignment and feeding group on VFDs (P= 0.47).
“Gastrointestinal intolerance” occurred less often in the trophic feeding group, with significantly fewer episodes of intolerance on study days 2 and 3. The trophic-feeding group experienced fewer episodes of regurgitation (0.4% vs 0.7%; P=.003), vomiting (1.7% vs 2.2%; P=.05), elevated GRVs (defined as >400mL) (2.2% vs 4.9%; P<.001), and constipation (2.1% vs 3.1%; P=.003) compared with the full-feeding group. There was no difference in aspiration or ventilator-associated pneumonia between the groups. Patients in the trophic feeding group received antidiarrheal and prokinetic medications on significantly less days than the full-fed group. Postpyloric tubes were used in less than 20% of patients. In the full-feeding group, 444 patients (90%) reached goal feeding rates in a mean time of 1.3 (SD, 1.2) days.
Author’s Conclusions:
In patients with ALI, initial trophic enteral feeding for up to 6 days did not increase the number of VFDs or reduce mortality compared with full enteral feeding.
Evaluation:
This is a landmark study because it is the first study with adequate numbers of patients that has randomized adult critically ill patients to different calorie levels. The investigators successfully fed most of the patients, primarily by the gastric route (>80%), most of their calorie needs in the full feeding group – with 90% (444 patients) reaching goal feeding in an average of 1.3 days. The full fed group received approximately 1300 calories/day which was a mean of 80% of calculated needs. The trophic group received an average of 400 calories/day, which was approximately 25% of calculated needs.
Although it is clear that the “full fed” group did not meet 100% of their calorie needs, it is evident that there was a substantial difference (900 calories/day) in nutrition provision between the two groups. Considering that a 900 calorie/day difference (about 56% of needs) did not affect outcome in any meaningful way, I suspect that in the future it will be hard to argue with a straight face (or retained credibility) that a particular method of estimating calorie needs is superior to another because it predicted calorie expenditure 5-10% more accurately.
The authors and the editorial1 made a point to outline what this study does not tell us. The fact that the patients had an average BMI of 30, and patients with severe malnutrition were not included in the study suggests that the results may not apply to patients that are malnourished on admission. Additionally, more than half of the patients were extubated in 6 days, suggesting that many of these patients may not have required nutrition support at all, and the results may not apply to those patients that have an extended ICU stay.
The phase-2 study with similar design and 200 patients2 (see our May 2011 e-journal club) found that significantly more survivors in full feed group were able to be discharged to home rather than to a rehabilitation facility. However, this study did not collect data of post-hospital disposition so it is unclear if some patients had longer term functional consequences from underfeeding.
The trophic group generally received inadequate amounts of all nutrients – proteins and micronutrients as well as calories, so this study does not address the concept of “metabolic nutrition support” where full protein and micronutrients are provided with decreased calories during the early part of the admission3.
Although there were a number of statistically significant differences in measures of “GI intolerance” such as regurgitation or gastric residual volumes, these differences did not appear to have any clinical ramifications. As pointed out in the editorial, this study suggests that gastric feeding is safe and effective, and the use of a 400 mL residual cut-off allows delivery of full feeding to most patients with a low incidence of aspiration and pneumonia.
After 30 years (more or less) of “modern” nutrition support we still do not have quality randomized data about when (or even IF) to begin nutrition support in critically ill patients, or how much nutrition will result in the best clinical outcome. Hopefully this study will be only the first of many that will begin to answer these “meat and potato” questions about the nutrition needs of our critically ill patients.
Our Take Home Message
· Modest differences in calorie provision for well-nourished patients during the first week of ALI/ARDS does not appear to affect patient outcome in the ICU.
· Reduced-calorie feedings may reduce perceived GI intolerance and decrease administration of prokinetic and anti-diarrheal medications.
· If you are still checking gastric residuals and have not adopted a higher threshold for cut-off, it is time.
· Most patients should be gastrically fed initially, and changed to post-pyloric if a problem arises.
References:
1. Griffiths RD. Nutrition for critically ill patients: how much is enough? JAMA. 2012 Feb 22;307(8):845-6.
2. Rice TW, Mogan S, Hays MA, et al. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med. 2011;39(6):1-8.
3. Burke PA, Young LS, Bistrian BR. Metabolic vs nutrition support: a hypothesis. JPEN 2010 Sep-Oct;34(5):546-8.
Other News on the UVAHS GI Nutrition Website: (www.ginutrition.virginia.edu):
Upcoming Webinars for Spring 2012:
· Wednesday, March 21–Liver Disease, Part I: Hepatic Encephalopathy–Neeral Shah, MD
· Tuesday, April 17—Liver Disease, Part II: Nutrition Support in Liver Disease—Joe Krenitsky, MS, RD
· 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:
· “ Resources for the Nutrition Support Clinician”
Latest Practical Gastroenterology article:
· Chan L-N. To Hold (Enteral Feeding) or Not to Hold: That IS the question; A Commentary and Tutorial. Practical Gastroenterology 2012;XXXVI(1):13.
· Thompson T. Celiac Disease: What Gluten-Free Means Today. Practical Gastroenterology 2012;XXXVI(2):19.
Joe Krenitsky MS, RD
Carol Rees Parrish MS, RD
PS – Please feel free to forward on to friends and colleagues.