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Original Investigation
October 19, 2020

Short-term Outcomes of the Study of Refeeding to Optimize Inpatient Gains for Patients With Anorexia Nervosa: A Multicenter Randomized Clinical Trial

Author Affiliations
  • 1Division of Adolescent and Young Adult Medicine, Department of Pediatrics, University of California, San Francisco
  • 2Department of Preventive and Restorative Dental Sciences, University of California, San Francisco
  • 3Department of Psychiatry and Behavioral Medicine, University of California, San Francisco
  • 4Division of Adolescent Medicine, Department of Pediatrics, Stanford University, Stanford, California
  • 5Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, Illinois (emeritus)
  • 6Division of Adolescent and Young Adult Medicine, Department of Pediatrics, University of California, Los Angeles
  • 7Department of Clinical Pharmacy, University of California, San Francisco
JAMA Pediatr. 2021;175(1):19-27. doi:10.1001/jamapediatrics.2020.3359
Key Points

Question  How does higher-calorie refeeding compare with the standard of care, lower-calorie refeeding, for malnourished patients with anorexia nervosa?

Findings  In this randomized clinical trial enrolling 120 adolescents and young adults with anorexia nervosa and atypical anorexia nervosa and 60% or more of median body mass index for age and sex, higher-calorie refeeding restored medical stability faster, with no increase in electrolyte abnormalities and marked cost savings.

Meaning  Higher-calorie refeeding is more efficacious and less costly than lower-calorie refeeding, with no increase in safety events among hospitalized patients with malnutrition due to restrictive eating disorders.

Abstract

Importance  The standard of care for refeeding inpatients with anorexia nervosa, starting with low calories and advancing cautiously, is associated with slow weight gain and protracted hospital stay. Limited data suggest that higher-calorie refeeding improves these outcomes with no increased risk of refeeding syndrome.

Objective  To compare the short-term efficacy, safety, and cost of lower-calorie vs higher-calorie refeeding for malnourished adolescents and young adults with anorexia nervosa.

Design, Setting, and Participants  In this multicenter randomized clinical trial with prospective follow-up conducted at 2 inpatient eating disorder programs at large tertiary care hospitals, 120 adolescents and young adults aged 12 to 24 years hospitalized with anorexia nervosa or atypical anorexia nervosa and 60% or more of median body mass index were enrolled from February 8, 2016, to March 7, 2019. The primary analysis was a modified intent-to-treat approach.

Interventions  Higher-calorie refeeding, beginning at 2000 kcal/d and increasing by 200 kcal/d vs lower-calorie refeeding, beginning at 1400 k/cal and increasing by 200 kcal every other day.

Main Outcomes and Measures  Main outcomes were end-of-treatment outcomes; the primary end point of this trial will be clinical remission over 12 months. Short-term efficacy was defined a priori as time to restore medical stability in the hospital, measured by the following 6 indices: 24-hour heart rate of 45 beats/min or more, systolic blood pressure of 90 mm Hg or more, temperature of 35.6 °C or more, orthostatic increase in heart rate of 35 beats/min or less, orthostatic decrease in systolic blood pressure of 20 mm Hg or less, and 75% or more of median body mass index for age and sex. The prespecified safety outcome was incidence of electrolyte abnormalities; cost efficacy was defined as savings associated with length of stay.

Results  Because 9 participants withdrew prior to treatment, the modified intention-to-treat analyses included 111 participants (93%; 101 females [91%]; mean [SD] age, 16.4 [2.5] years). Higher-calorie refeeding restored medical stability significantly earlier than lower-calorie refeeding (hazard ratio, 1.67 [95% CI, 1.10-2.53]; P = .01). Electrolyte abnormalities and other adverse events did not differ by group. Hospital stay was 4.0 days shorter (95% CI, −6.1 to −1.9 days) among the group receiving higher-calorie refeeding, which was associated with a savings of $19 056 (95% CI, −$28 819 to −$9293) in hospital charges per participant.

Conclusions and Relevance  In the first randomized clinical trial in the US to compare refeeding approaches in patients with anorexia nervosa and atypical anorexia nervosa, higher-calorie refeeding demonstrated short-term efficacy with no increase in safety events during hospitalization.

Trial Registration  ClinicalTrials.gov Identifier: NCT02488109

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    1 Comment for this article
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    Short-term efficacy and safety among patients with anorexia nervosa with special reference to higher-calorie refeeding
    Tomoyuki Kawada, MD | Nippon Medical School
    Garber et al. conducted a randomized clinical trial to compare the short-term efficacy, safety, and cost of lower-calorie vs higher-calorie refeeding for 120 adolescents and young adults aged 12 to 24 years hospitalized with anorexia nervosa (1). The content of interventions included higher-calorie refeeding, beginning at 2000 kcal/d and increasing by 200 kcal/d vs lower-calorie refeeding, beginning at 1400 k/cal and increasing by 200 kcal every other day. Short-term efficacy was judged by six body indices. The adjusted hazard ratio (95% CI) of higher-calorie refeeding against lower-calorie refeeding for medical stability with short-term efficacy was 1.67 (1.10-2.53). Hospital stay was 4.0 days shorter among the group receiving higher-calorie refeeding, and hospital charge of this group was significantly lower. In addition, there was no electrolyte abnormalities between two groups. I have a comment about their study.

    The same author previously reviewed the past methods of refeeding in adolescents and adults (2). In the past decade, twelve studies examined approaches starting with higher calories than currently recommended (≥1400 kcal/d), and higher calorie refeeding has not been associated with increased risk for the refeeding syndrome, although they were no randomized clinical trial. In addition, there is insufficient evidence to change the current standard of care in severely malnourished inpatients. Furthermore, the long-term impact of higher-calorie refeeding has not been evaluated.

    The authors clarified that higher calorie approaches of refeeding in mildly and moderately malnourished patients was effective and safe in short-term evaluation (1). I deeply desire the findings of long-term outcomes, and also wants to see clinical outcomes in severely malnourished patients.


    References
    1. Garber AK, Cheng J, Accurso EC, et al. Short-term outcomes of the study of refeeding to optimize inpatient gains for patients with anorexia nervosa: A multicenter randomized clinical trial. JAMA Pediatr 2021;175(1):19-27.
    2. Garber AK, Sawyer SM, Golden NH, et al. A systematic review of approaches to refeeding in patients with anorexia nervosa. Int J Eat Disord 2016;49(3):293-310.
    CONFLICT OF INTEREST: None Reported
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