October 2016 E-Journal Club

Greetings,

We hosted 3 wonderful trainees in October who hailed from Albany, GA; Fort Myers, FL and Springfield, MO (see above).  Our journal club article for October was a study that investigated if permissive reduction in calories in critically ill adults had detrimental effects in patients that were at increased nutritional risk.

October Citation:

Arabi YM, Aldawood AS, Al-Dorzi HM, et al. Permissive Underfeeding or Standard Enteral Feeding in High and Low Nutritional Risk Critically Ill Adults: Post-hoc Analysis of the PermiT trial. Am J Respir Crit Care Med. 2016 Sep 2. [Epub ahead of print]

Summary: 

This was a post-hoc analysis of a randomized, unblinded study of 894 adult ICU patients comparing hypocaloric EN with standard feeding (see our June 2015 e-journal club for a full synopsis).¹ The goal of the post-hoc analysis was to see if permissive calorie underfeeding had a more detrimental effect on 90-day mortality and other outcomes, in patients that were determined to be at nutritional risk. “Nutritional risk” for this study was determined by BMI, lab values (including serum proteins) urinary urea nitrogen and the modified NUTRIC score.

The NUTRIC score (Nutritional Risk in Critically Ill) is calculated from age, APACHE II, SOFA score, number of comorbidities, days from admission to ICU admit and IL-6, while the modified score omits IL-6.² The NUTRIC score has been described as a “nutritional risk score” because observational data suggested an association between mortality and nutritional provision in patients with a high NUTRIC score who stayed in the ICU for more than 3 days.

The primary outcome was 90-day mortality and secondary outcomes investigated were more than 21 other mortality (28-day, 180-day) and morbidity outcomes.

Inclusion and Exclusion Criteria:

Inclusion criteria:

ICU patients aged ≥ 18 years, receiving enteral feeding within 48 hours of admission and expected to stay 72 hours or more in the ICU.

Exclusion criteria:

Lack of commitment to ongoing life support (terminal illness, DNR order in the first 48 hours and brain death within 48 hours of admission), preexisting condition with expected 6 month mortality, > 50% EN cannot be started within 48 hours of admission, receiving PN or oral feeding, previously enrolled in the study within the same admission, pregnancy, post-liver transplant, cardiac arrest, burn patients, prisoners, age >80 years, patients on “significant” inotropic support.

Major Results:

Among the 894 patients, 378 (42.3%) were categorized as “high

nutritional risk” (NUTRIC Score 5-9) and 516 (57.7%) patients as “low nutritional risk” (NUTRIC Score 0-4). Baseline characteristics were similar between those patients randomized to the permissive underfeeding and standard feeding groups.

The was no significant association between permissive underfeeding versus standard feeding with mortality in either the high-NUTRIC (aOR 0.84, 95% CI 0.56-1.27) or low-NUTRIC score (aOR 1.01, 95% CI 0.64-1.61) (interaction p=0.53) There were also no significant differences in ICU, hospital, 28-day or 180-day mortality, or in survival estimates between the two groups.

In patients with a high NUTRIC score, there was a statistically increased requirement for renal replacement therapy in the standard feeding group (35/148, 23.7%) compared to the permissive underfeeding group (22/153, 14.4%) (aOR 0.45, 95% CI 0.23-0.89, p=0.02). However, in patients with a low NUTRIC score there was no significant difference in need for renal replacement therapy between the standard and hypocaloric group.

Serial SOFA scores, prealbumin, nitrogen balance, phosphate, creatinine, bilirubin, PaCO2, hemoglobin, body weight, potassium, transferrin, and UUN were not statistically different between the high and low NUTRIC groups.

There were no differences in any other variables, including mechanical ventilation duration and ICU LOS, between the high and low NUTRIC groups.

Patients with a prealbumin < .10 g/L had a trend for decreased 90-day mortality with hypocaloric compared to standard feeding.  There was no significant difference in 90-day mortality in patients with a prealbumin between .10 and .15 g/L or patients with a prealbumin > .15 g/L. (prealbumin ≤ 0.10 g/L aOR 0.57, 95% CI 0.31-1.05, p=0.07).  Patients with a baseline prealbumin < .10 g/L had significantly decreased hospital mortality in the hypocaloric group, compared with standard feeding, but no differences in hospital mortality with a prealbumin between .10 and .15 g/L or patients with a prealbumin > .15 g/L (hospital mortality prealbumin <.10 g/L aOR 0.33, 95% CI 0.17-0.65, p=0.001).

Author’s Conclusions:

“…in patients with high and low nutritional risk alike, enteral feeding to

deliver moderate calories with full protein intake was associated with similar mortality compared with standard caloric feeding with full protein requirements. Available nutritional assessment measures do not appear to differentiate the risk association of moderate versus full caloric doses on mortality.”

Evaluation:

We normally don’t think highly of post-hoc analysis studies, but this particular study was an exception because of the limitations of previous data regarding the NUTRIC score.  The modified NUTRIC score is composed on 2 validated indicators of severity of illness (APACHE II and SOFA), age, number of comorbidities and the number of days from admission to ICU admit.²  Noticeably absent from the calculation of the NUTRIC score is any indicator of nutrition status. In the initial development of the NUTRIC score, there was no information available regarding the weight history or recent oral intake in over 2/3 of the patients enrolled and only about 5% of the population had a BMI < 20. ²  There was no attempt to investigate changes in functional status or muscle mass. It is no surprise then, that nutrition indicators did not affect the ability of NUTRIC to predict patient outcome.  NUTRIC score is associated with patient outcome, but there is no good data that NUTRIC has anything at all to do with nutrition status. NUTRIC has been validated in an observational manner, because previous studies did not assign patients to a different amount of nutrition – so naturally there is an association between decreased nutrition and poor outcome, because patients that are doing worse (need more lines, CT scans, have slower motility, etc), receive less nutrition.^2-3  Association is not cause and effect, and there is no way to statistically control for all factors that affect outcome: this is why we need to do randomized studies in the first place.

The current study did randomize patients to 2 different amounts of nutrition.  Although protein provision in both groups was inadequate, and there was not a vast difference in actual calories received by the 2 groups (see our June 2015 e-journal), there did not appear to be a negative effect of hypocaloric feeding in patients with an increased NUTRIC score.  In fact, there was actually a suggestion of harm with increased calories as evidenced by the sicker patients (increased NUTRIC score) who received more calories with a greater requirement for renal replacement.

It is difficult to interpret the information regarding prealbumin, since we know that prealbumin is not a valid indicator of nutrition status.  However, if the group with a decreased baseline prealbumin represents the more critically ill patients, the data suggest that increased calories may have a greater harm in sicker patients (or decreased calories has greater benefit).

Our Take Home Message(s)

1. The best available evidence does not support the aggressive provision of full energy expenditure in the initial days of critical illness.
2. NUTRIC score does not appear to be a valid indicator of nutrition risk or an indicator of need for full calories.
3. Observational data is inadequate to suggest cause and effect conclusions or to incorporate into clinical guidelines.

References:

1. Arabi YM, Aldawood AS, Haddad SH, et al. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults. N Engl J Med 2015; 372: 2398-2408.
2. Heyland DK, Dhaliwal R, Jiang X, Day AG. Identifying critically ill patients who benefit the most from nutrition therapy: the development and initial validation of a novel risk assessment tool. Crit Care 2011; 15: R268.
3. Rahman A, Hasan RM, Agarwala R, et al. Identifying critically-ill patients who will benefit most from nutritional therapy: Further validation of the “modified NUTRIC” nutritional risk assessment tool. Clin Nutr 2016; 35:158-162.

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

Upcoming Webinars 2016:

December 13:  ICU Fluid Management and Implications for Nutrition Support.

Latest Practical Gastroenterology article:  Achalasia and Nutrition:  Simple Physics or Biology?

Weekend Warrior Mini-Traineeship: March 11-12, 2017 in Charlottesville, VA

Spring Week-Long Traineeship Dates now posted

 

Joe Krenitsky MS, RDN

 

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