University of Virginia Nutrition
This month our journal club was held in conjunction with our bi-annual Nutrition Support Forum. Our Forum is a ½ day affair where dietitians from the region bring interesting cases and we review articles in an informal setting. Our trainees this month hailed from Columbia Tennessee, Fresno California, and our own Virginia Beach. Here is a picture of the group that participated in our forum.
Fiaccadori E, Maggiore U, Rotelli C, et al. Effects of different energy intakes on nitrogen balance in patients with acute renal failure: a pilot study. Nephrol Dial Transplant. 2005;20(9):1976-80.
This was an open-label crossover trial in 10 consecutive patients with acute renal failure that were receiving both parenteral nutrition (PN) and dialysis in a specialized renal intensive care unit. Patients received 24 hours of protein-free PN (D20) and then either lower calorie PN (30 calories/kg) or higher calorie PN (40 calories/kg) for 3 days, and then were crossed over to the other regimen for 3 days without a washout period. The population had a mean age of 72 (range 60-83), mean APACHE II score of 27.1 (range 23-34) and 8/10 were mechanically ventilated. All patients received 1.56gm protein /kg.
Major Results reported by authors:
The authors reported that there was no significant difference between the two calorie levels in regards to nitrogen balance, protein catabolic rate, or rate of urea generation. However serum glucose level, insulin requirements (approx 20 units per day) and serum triglyceride level were all significantly increased in the higher calorie group. Two patients were excluded from the analysis because one patient expired, and one patient had significantly elevated serum triglyceride level (both patients from high-calorie group). Mean serum glucose and triglycerides were significantly elevated in the high-calorie group compared to the low-calorie group.
The authors reported that in critically ill patients, increasing calorie provision from 30 kcals/kg to 40 kcals/kg does not improve nitrogen balance, and may increase the risk of nutrition-related side effects.
This was a small study in terms of patient numbers (n = 10). Also, there is potential for bias to be introduced in a crossover study in an ICU where, time can influence the results in patients that are improving or new infections can develop quickly, changing nitrogen balance results. Our major observation was that both calorie levels likely exceeded actual calorie expenditure, and thus it is not surprising that they did not see a significant difference in nitrogen balance or urea generation rate. The mean age of the patients was 72.6 years, with a range of 60-82 years, therefore actual calorie expenditure may have been closer to 25 calories per kg. The difference in serum glucose between the groups was statistically significant (p,.05), but not clinically overwhelming (mean of 123mg/dl in low-cal, versus 143mg/dl in high-cal). However the high-calorie group did receive an average of 20 more units of insulin per 24 hours, and triglycerides were significantly elevated in the high-calorie group, suggesting that the high-calorie group was receiving more calories than they could utilize. It would be very interesting to see if there would have been a difference if one group was fed with permissive underfeeding (20-22 calories/kg) and the other group received 35 calories per kg. We encounter obese, critically ill patients with increasing frequency, and the dilemma of finding the optimum calorie level for these patients is compounded in the setting of acute renal failure. Unfortunately, it would be inappropriate to translate the results of this study to mean that adequate calories do not have a nitrogen-sparing effect compared to hypocaloric feeding. The group felt that this study only showed that there is no overwhelming advantage to overfeeding calories in terms of nitrogen balance or urea generation.
Take home message:
There is no advantage to overfeeding calories in terms of nitrogen balance or urea generation.
Singer P, Theilla M, Fisher H, et al. Benefit of an enteral diet enriched with eicosapentaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury. Crit Care Med 2006;34(4):1033-1038.
This was a non-blinded study of 100 patients with acute lung injury. Patients were randomized to receive enteral feedings with a formula containing gamma-linolenic acid (GLA) and eicosapentanoic acid (EPA) enriched with antioxidants (Oxepa); or an isocaloric and isonitrogenous control formula (Pulmocare). Primary outcomes were change in oxygenation and "breathing patterns" assessed at days 4, 7 and 14. Secondary outcomes were length of ventilation, length of ICU stay, length of hospital stay, and in-hospital mortality.
Major Results reported by authors:
The researchers reported that both groups reached 75% of goal feeding (REE X 1.2) in approx. 2 days, with no difference between groups. Oxygenation was significantly higher at days 4 and 7 in the EPA+GLA group compared to the control, but was not significantly different at day 14. Tidal volume and PEEP values were not significantly different between the groups. Static compliance improved in the GLA + EPA group from day 1 through day 7, but decreased in the control group. Day 7 static compliance was significantly higher in the EPA +GLA group. Median length of ventilation was decreased when analyzed as hours free from ventilation. Overall survival and length of stay was not significantly different between the groups.
The authors concluded that in patients with acute lung injury, a diet enriched with EPA + GLA may be beneficial for gas exchange, respiratory dynamics, and mechanical ventilation requirements.
We learned of an important correction to this article that needs to be discussed. A criticism of this article would have been that the older formulation of Pulmocare was used as the control formula for this study, based on the formula composition listed in Table 1. This was one of the primary criticisms of the Gadek study (1) - that the control formula was extremely rich in Omega-6 fatty acids. However, we have learned from our astute Ross representative that the control formula actually used in this study was, in fact, the current formulation of Pulmocare, which contains only 25% of the fat calories (14% of total calories) as Omega-6 polyunsaturated fat. Reportedly, a correction in Critical Care Medicine is forthcoming.
Our first observation is that this is not a blinded study. In any unblinded study there is potential for unintentional bias to enter into the study. The second observation is that this study was not analyzed on an intention-to-treat basis. The researchers simply discarded the results of 5 patients that were dropped from the study (2 patients placed on corticosteroids, and 3 due to severe diarrhea). This is especially concerning in an unblinded study in which 4 of the patients were dropped from the experimental group. It is important to analyze all patients randomized, especially if severe diarrhea occurred more in the experimental group, which might limit how many patients could be "helped" by the tested product. The length of ventilation was reported as significantly less in the GLA+EPA group on day 7, when it was reported as hours off vent. However, when viewed as days of ventilation it is 6.68 days in the experimental and 6.95 days in the control group - this is not a clinically significant difference in ventilator days.
There are significant improvements in oxygenation (PaO2/FiO2) and static compliance in the EPA+GLA group, however it does not appear that these changes resulted in a clinically meaningful improvement in overall outcome in terms of days on ventilator or survival. The authors also reported that a post-hoc analysis of the patients who survived showed a trend towards a reduction in the length of ventilation and time in the ICU.
Take home message:
Methodological limitations (unblinded, not intention to treat) of this study limit it's impact. In addition, there was no clinically significant outcome advantage of the experimental formula in terms of days on the ventilator or overall survival in patients with ALI.
1) Gadek JE, DeMichele SJ, Karlstad MD, et al. Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group. Crit Care Med. 1999;27(8):1409-20.
1) Check out the latest Practical Gastroenterology article at:
Scroll down to GI Nutrition on the far left column and click on
Scroll down to box with links within the nutrition site
Link to the Nutrition Articles in Practical Gastroenterology will be found in the right hand column:
Alnounou M, Munoz SJ. Nutrition concerns of the patient with primary biliary cirrhosis or primary sclerosing cholangitis. Practical Gastroenterology 2006; XXX(4):92.
Joe Krenitsky MS, RD
Carol Parrish RD, MS
PS - Please feel free to forward this on to friends and colleagues.