Abstract
Inflammation is a key driver of malnutrition during illness and is often accompanied by metabolic effects, including insulin resistance and reduction of appetite. However, it still remains unclear if inflammation influences the response to nutritional support among patients with disease-related malnutrition. To examine whether patients' baseline inflammatory status is associated with the effect of nutritional support on 30-day mortality. This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized clinical trial conducted in 8 Swiss hospitals from April 2014 to February 2018. A total of 1950 participants who had C-reactive protein measurements at the time of admission were included in this secondary analysis. Data analysis was conducted between June and July 2019. Hospitalized patients at risk for malnutrition were randomly assigned to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or standard hospital food (control group). The primary end point was 30-day mortality. Based on C-reactive protein levels at admission, patients were stratified into groups with low, moderate, or high inflammation (<10 mg/L, 10-100 mg/L, and >100 mg/L, respectively). A total of 1950 patients (median [interquartile range] age, 75 [65-83] years; 1025 [52.6%] men) were included; 533 (27.3%) had low levels of inflammation, 894 (45.9%) had moderate levels of inflammation, and 523 (26.8%) had high levels of inflammation. Compared with the control group, patients receiving nutritional support showed a significant reduction in 30-day mortality, regardless of C-reactive protein level (adjusted odds ratio, 0.61; 95% CI, 0.43-0.86; P = .005). In the subgroup of patients with high inflammation, there was no beneficial effect of nutritional support (adjusted odds ratio, 1.32; 95% CI, 0.70-2.50; P = .39), providing evidence that inflammation has a significant modifying association (P for interaction = .005). Based on this secondary analysis of a multicenter randomized trial, a patient's admission inflammatory status was associated with their response to nutritional support. If validated in future clinical trials, nutritional support may need to be individualized based on a patient's initial presentation and markers of inflammation. These results may also help to explain some of the heterogeneity in treatment effects of nutrition seen in previous critical care trials. ClinicalTrials.gov Identifier: NCT02517476.
Highlights
Disease-related malnutrition is a frequent condition among hospitalized medical inpatients, with a prevalence of 20% to 50%.1-3 The 2019 Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT)[4] demonstrated that starting individualized nutritional support early reduces complications and mortality among medical inpatients at risk for malnutrition
Compared with the control group, patients receiving nutritional support showed a significant reduction in 30-day mortality, regardless of C-reactive protein level
In the subgroup of patients with high inflammation, there was no beneficial effect of nutritional support, providing evidence that inflammation has a significant modifying association (P for interaction = .005)
Summary
Disease-related malnutrition is a frequent condition among hospitalized medical inpatients, with a prevalence of 20% to 50%.1-3 The 2019 Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT)[4] demonstrated that starting individualized nutritional support early reduces complications and mortality among medical inpatients at risk for malnutrition. Inflammation has several metabolic effects, including an increase in insulin resistance and reduction of appetite, leading to an inhibition of nutrition entering cells.[5,6] independent of underlying disease, inflammation is thought to be a key driver for disease-related anorexia, reduced food intake, and muscle catabolism. This may partly explain the inferior patient outcomes associated with inflammation, which include longer hospital stays and increased mortality.[7,8] The relevance of inflammation in the pathogenesis of malnutrition is reflected in its classification by the European Society of Clinical Nutrition and Metabolism (ESPEN). Several mainly preclinical studies have evaluated the relevance of inflammation on malnutrition, there is a lack of clinical data investigating whether the inflammatory status of a patient influences treatment response to nutritional support
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