October 2015 E-Journal Club

October 2015 traineesGreetings,

Our trainees in October hailed from Hampton, VA, and Hong Kong (2).  Our weather varied during the traineeship week from cold and rainy to “way too nice to be inside,” and our fall foliage had reached its peak colors.  Our journal club this month dealt with the potential associations between caloric deficit in the ICU and long term survival and quality of life.


October Citation:

Wei X, Day AG, Ouellette-Kuntz H, et al.  The Association Between Nutritional Adequacy and Long-Term Outcomes in Critically Ill Patients Requiring Prolonged Mechanical Ventilation: A Multicenter Cohort Study.  Crit Care Med. 2015;43(8):1569-1579.


This was a multicenter retrospective observational analysis of data from critically ill adult patients who were enrolled in a study of antioxidants and glutamine1. The study investigated relationships between nutritional adequacy in the ICU and long-term (6 month) survival as well as quality of life in mechanically ventilated patients who remained in the ICU more than 8 days.

Total calorie intake from EN, PN, and propofol was recorded for 28 days, but nutrition adequacy was defined as the percentage of calculated needs actually received for only the first 8 days of mechanical ventilation.  Nutrition adequacy was categorized as low (<50% calculated needs), moderate (≥50% <80%) and high (≥ 80%).  Patients were followed for a maximum of 6 months, and they or their families were contacted at 3 and 6 months to conduct a 36-item general health survey (SF-36v2). The Physical Functioning (PF) and Role Physical (RP) domains, as well as the summary Physical Component Scale (PCS), were reported as a measure of quality of life and physical function.

Inclusion and Exclusion Criteria:

Inclusion criteria:

Mechanically ventilated adult patients in the REDOXS study with 2 or more failed organs who remained in the ICU >8 days; within this group, those who survived to 6 months were eligible for the quality of life assessment.

Exclusion criteria:

From randomized study: No plan for full supportive care, contraindication to enteral nutrients, severe brain injury, seizure disorder requiring anticonvulsant medication, metastatic cancer with life expectancy <6 months, burns >30% body surface area, weight <50 kg. Additionally, patients who received ≥110% of prescribed energy were excluded from the retrospective analysis.

Major Results:

From a total of 1223 patients in the randomized study, there were 475 who were mechanically ventilated >8 days, 320 alive and participating at the 3 month follow up, and 302 alive and participating at 6 months.  Only 202 patients completed the SF-36 at 6 months, and 158 patients completed the SF-36 at both 3 and 6 months.

There were 182 patients in the low, 231 in the moderate, and only 62 in the high nutrition adequacy categories.  There were statistically significant differences in the baseline characteristics between the nutrition adequacy groups in male-female ratio, admission category (medical Vs surgical), and for primary ICU diagnosis.

Evaluation of unadjusted data demonstrated no significant difference in 6-month survival between the 3 groups. However, after adjusting for covariates (age, severity of illness, admission category, diagnosis) the difference between groups became significant (p =0.04). In the adjusted analyses, low nutritional adequacy was associated with a higher mortality rate compared with the high nutritional adequacy group (adjusted hazard ratio, 1.7; 95% CI, 1.1–2.6). Increasing age, greater comorbidity, and admission category were each independently associated with decreased survival. Subgroup analysis by admission category revealed that the association between nutritional adequacy and longer survival time was exclusive to medical patients.

When it came to quality of life, at 3-months follow-up the PF and RP scores were significantly increased for every 25% increase in nutritional adequacy (adjusted estimate for PF = 7.3, p = 0.02; for RP = 8.3, p = 0.004), but this effect was gone at 6 months.  After controlling for other relevant variables, greater nutritional intake was not significantly associated with PCS score; subgroup analysis by admission category did show significant associations between nutritional adequacy and each of the PF, RP, and PCS scores at 3 and 6 months in medical patients, but not in surgical patients.

Author’s Conclusions:

“This study has suggested an important relationship between receiving adequate caloric intake as early as the first week of ICU stay and longer survival time as well as faster physical recovery to 3 months but not 6 months post ICU discharge in critically ill patients with prolonged mechanical ventilation. Evidence from well-designed RCTs is required to provide stronger assessment of the causal impact of nutrition therapy on long-term outcomes. In the meantime, current recommendations advocating underfeeding in the ICU during the first week could be harming long-stay ICU patients.”


This was a retrospective observational study, which can only describe associations and should not be used to infer cause and effect, or to alter clinical practice until tested by randomized studies. It is simply not possible to know or statistically control for all of the factors that influence outcome in an observational study (which is why we do randomized studies).

Multiple observational studies have reported an association between decreased nutrition provision in the ICU and compromised outcome, but these associations have been disproven by randomized studies.2-3

Although both the article and the editorial mention the inherent limitation of observational studies, that does not seem to have prevented the article’s conclusions and the title of the editorial4 from making claims of causality.

Other aspects of this paper that we discussed were the small number of patients that received more than 80% of goal nutrition (62 patients), with a smaller number of these that survived for 3-6 months, and even fewer who completed the SF-36 survey.  Further, it is unclear how nutrition goals for this study were calculated or measured.  We also discussed the fact that an emphasis on calories does not consider the effect of other nutrient inadequacies.  The patients received an average of only 50 g of protein/day – a very low protein provision in a population with multiple organ failures who weighed more than 50 kg.  This suggests that patients who did not receive adequate volumes of feeding were severely protein underfed and likely did not meet basic micronutrient needs either.  Finally, it is unclear what mechanism would explain how fewer calories for 8 days would be a primary influence on long-term survival, especially in a study with no control for oral intake adequacy and rehabilitation efforts after extubation.

It is certainly feasible that cumulative nutrition deficits, especially in extended ICU admissions, could affect long-term patient outcomes and functionality – especially in older patients with sarcopenia and near-sarcopenia on admission. However, there is a need for randomized data on the optimum nutrition amounts and timing in the ICU, and it would be folly to assume that observational data provide good evidence to support early forced-goal nutrition programs in ICU patients.

Our Take Home Message(s)

  1. Observational studies describe associations that need to be tested in randomized studies and should not be used to infer cause and effect.
  2. There is a need for randomized studies on the optimum timing and amounts of nutrition for critically ill patients.
  3. The results of this study do not apply to hypocaloric feeding regimens that meet full protein and micronutrient needs.


  1. Heyland D, Muscedere J, Wischmeyer PE, et al.  A randomized trial of glutamine and antioxidants in critically ill patients.  N Engl J Med. 2013 Apr 18;368(16):1489-1497.
  2. Arabi YM, Aldawood AS, Haddad SH, et al. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults. N Engl J Med. 2015;372(25):2398-2408.
  3. 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.
  4. Wischmeyer PE.  Ensuring Optimal Survival and Post-ICU Quality of Life in High-Risk ICU Patients: Permissive Underfeeding Is Not Safe!  Crit Care Med. 2015;43(8):1769-1772.

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

  • 2016 Webinars to be announced shortly!
  • Latest Practical Gastroenterology article:   How to Buy, Store and Use Olive Oil by Bethany Blalock, October 2015

Joe Krenitsky MS, RDN

Bethany Blalock RDN

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