Inflammatory Status Upon Hospital Admission Tied to Nutritional Support Response

By Marilynn Larkin

March 25, 2020

NEW YORK (Reuters Health) - A patient's inflammatory status at admission to the hospital was associated with their response to nutritional support in a secondary analysis of a randomized clinical trial.

"In patients with high inflammation, a less aggressive nutritional approach may be better, with a slow increase in caloric and protein targets, Dr. Philipp Schuetz of the University of Basel in Switzerland told Reuters Health by email. "Patients with lower inflammation levels (may) benefit from early, individualized nutritional support to reach higher caloric and protein targets."

Dr. Schuetz and colleagues conducted a secondary analysis of the EFFORT trial, a randomized study testing the effect of early nutritional support on frailty, functional outcomes, and recovery of malnourished hospital patients.

As reported in JAMA Network Open, 1,950 patients (median age, 75; 52.6% men) at eight Swiss hospitals were included. Inflammation (as reflected by C-reactive protein levels) was low in 27.3% (CRP <10 mg/L); moderate in 45.9% (10 to 100 mg/L); and high in 26.8% (>100 mg/L).

All patients were at nutritional risk. The most common diagnoses were infectious disease (30.4%), cancer (18.5%), and cardiovascular disease (10.1%), with significant differences among inflammation groups.

For example, the high inflammation group included more patients with infectious diseases than the moderate or low inflammation groups (60% vs. 26.3% vs. 8.1%), and the low inflammation group had more patients with cardiovascular disease (13.5% vs. 12.8% vs. 2.1%).

Compared with the control group, the 978 patients who received nutritional support showed a significant reduction in 30-day mortality, regardless of CRP level (adjusted odds ratio, 0.61). In the subgroup with high inflammation, no beneficial effect of nutritional support was seen (aOR, 1.32).

Dr. Schuetz said, "The results may explain why nutritional trials have been heterogeneous in the past, particularly in the critical care setting, with some trials showing benefit from nutrition and other showing harm. In the future, maybe we need to better select patients before trial inclusion."

"The results may also help (us) to understand some basic biological concepts - namely, that during severe disease, the body aims to focus on cell detoxication - i.e., autophagy - and nutrition may (compete) with this mechanism," he suggested. "Inflammation may be the missing link here, as it reduces appetite and food intake, (and) patients with inflammation also have (few) benefits from nutrition."

More research is needed, he added, "to understand how to best adapt the quality and quantity of nutrition for... patients with high inflammation to improve mortality and morbidity."

Dr. Deirdre Tobias, an epidemiologist at Brigham and Women's Hospital in Boston, commented in an email to Reuters Health, "This is an exploratory analysis of a previously conducted trial, not the primary objective of the trial. Exploratory analyses should be interpreted with caution."

"The authors hypothesize that inflammation itself is preventing these patients with high CRP levels from benefiting from the nutritional therapy intervention," she said. "There is compelling biology to support this hypothesis. However, these data are not able to show this conclusively."

"There could certainly be other reasons why the patients in this high CRP category are not deriving benefit, including other characteristics related to their illnesses and higher severity of disease," she noted. "CRP could just be a marker correlated with these other unmeasured factors."

"Replication of this in other populations and in patients with various other conditions is warranted," she added. "It would also be necessary to understand the 'why' and the 'who' for patients not being responsive to the benefits of nutritional therapy before strategies are implemented."

"Withholding this effective treatment for a patient who would benefit would be a misstep," she said. "On the other hand, if there are patients for whom the treatment is not effective or even potentially harmful, then further research will bring this to light."

SOURCE: JAMA Network Open, online March 11, 2020.


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