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Examining Refeeding Protocols for Adolescents With Anorexia Nervosa (Again): Challenges to Current Practices

      See Related Articles pp. 573, 579, 585
      Effective treatment of adolescents with anorexia nervosa (AN) always starts with nutritional rehabilitation and weight restoration. Whereas weight restoration can be pursued for most adolescents in an outpatient setting, hospitalization is used to support medical monitoring and nutritional rehabilitation for those who are medically unstable owing to malnutrition or weight loss [
      • American Academy of Pediatrics
      Identifying and treating eating disorders.
      ]. Several nutritional treatment guidelines have been published, of which only two focused on children and adolescents; both were published 10 years ago [
      • American Academy of Pediatrics
      Identifying and treating eating disorders.
      ,
      • Golden N.H.
      • Katzman D.K.
      • Kreipe R.E.
      • et al.
      Eating disorders in adolescents: Position Paper of the Society for Adolescent Medicine.
      ]. However, neither of these provides a specific approach to refeeding children and adolescents. Given the risk of refeeding syndrome in these patients [
      • Katzman D.K.
      • Findlay S.M.
      Medical issues unique to children and adolescents.
      ], coupled with what is available from these practice guidelines, the standard modus operandi has been to advocate caution against too rapid nutritional replenishment. This clinical practice has recently been challenged, arguing that initiating nutrition at 1,200 kcal/day is too conservative [
      • Garber A.K.
      • Michihata N.
      • Hetnal K.
      • et al.
      A prospective examination of weight gain in hospitalized adolescents with anorexia nervosa on a recommended refeeding protocol.
      ], and that starting at 1,900 kcal/day can be more effective [
      • Whitelaw M.
      • Gilbertson H.
      • Lam P.Y.
      • et al.
      Does aggressive refeeding in hospitalized adolescents with anorexia nervosa result in increased hypophosphatemia?.
      ]. Commenting on this work in an editorial in the Journal of Adolescent Health, Katzman cautioned that a “start low, advance slow” approach can give cause to the “underfeeding syndrome,” and questioned whether this current nutritional practice is more of an urban legend as opposed to evidence-based information [
      • Katzman D.K.
      Refeeding hospitalized adolescents with anorexia nervosa: Is “start low, advance slow” urban legend or evidence based?.
      ]. That said, the safety of more aggressive refeeding protocols is not well established, and the editorial called for clinical trials to examine the most advantageous approaches to inpatient refeeding.
      In the current issue of the Journal of Adolescent Health, three studies examine nutrition rehabilitation protocols in hospitalized adolescents with AN. Broadly, all three studies were conducted in specialist inpatient eating disorder units and sought to examine the effect of higher caloric intake on weight gain, length of hospital stay, and incidence of the refeeding syndrome. In the first study, Golden et al. [
      • Golden N.H.
      • Keane-Miller C.
      • Sainani K.L.
      • Kapphahn C.
      Higher caloric intake in hospitalized adolescents with anorexia nervosa is associated with reduced length of stay and no increased rate of refeeding syndrome.
      ] conducted a retrospective chart review of 310 adolescents who presented at a mean age of 16.1 years and an average of 78.5% expected body weight (EBW). They found that refeeding commencing with a high caloric intake (1,400–2,000 kcal/day) as opposed to a low caloric intake (<1,400 kcal/day) is associated with reduced length of hospital stay (13 vs. 16.6 days respectively) and no increased risk of hypophosphatemia. No patients in their study developed full refeeding syndrome, and the authors concluded that hypophosphatemia is associated with admission weight as well as weight loss before admission, rather than inpatient energy intake.
      In a prospective observational study of 56 adolescents aged 16 years and presenting at 79% EBW, Garber et al. [
      • Garber A.K.
      • Mauldin K.
      • Michihata N.
      • et al.
      Higher calorie diets increase rate of weight gain and shorten hospital stay in hospitalized adolescents with anorexia nervosa.
      ] compared two patient groups: high baseline calorie intake (1,764 kcal/day) versus low baseline calorie intake (1,093 kcal/day). As might be expected, the higher calorie group gained weight faster than the comparison group, leading to hospital discharge nearly 6 days sooner. Using phosphate supplementation as needed, a relatively high 45% of patients developed hypophosphatemia during refeeding, although no cases of refeeding syndrome were seen. Hypophosphatemia was associated with the degree of malnutrition rather than with high or low calorie intake. The authors concluded that this study lends further support to more aggressive meal-based protocols for moderately malnourished adolescents with AN.
      In the third of these studies, another retrospective chart review, Leclerq et al [
      • Leclerq A.
      • Turrini T.
      • Sherwood K.
      • Katzman D.K.
      Evaluation of a nutrition rehabilitation protocol in hospitalized adolescents with restrictive eating disorders.
      ] evaluated an evidence-based nutrition rehabilitation protocol in 29 hospitalized adolescents with AN and eating disorder not otherwise specified–restricting type. The mean age of study patients was 14.7 years, with an average of 75.8% EBW. All patients were started at 1,500 kcal on the first day of full admission, with nutrition advanced at 250 kcal every day or every other day, to reach a total daily intake of 2,500 kcal at day 7. From that point forward, nutrition was advanced to maintain weight gain of at least 1.0 kg/week. With this nutrition rehabilitation protocol in place, sustained weight gain from day 2 through day 14 averaged 1.7 kg/week. Only one patient had hypophosphatemia that required supplementation. No cases of other electrolyte imbalance or refeeding syndrome were observed. This low incidence of hypophosphatemia may be attributed to the exclusion of patients who presented with EBW <70%. Also, and in contrast to the studies of Golden et al. [
      • Golden N.H.
      • Keane-Miller C.
      • Sainani K.L.
      • Kapphahn C.
      Higher caloric intake in hospitalized adolescents with anorexia nervosa is associated with reduced length of stay and no increased rate of refeeding syndrome.
      ] and Garber et al. [
      • Garber A.K.
      • Mauldin K.
      • Michihata N.
      • et al.
      Higher calorie diets increase rate of weight gain and shorten hospital stay in hospitalized adolescents with anorexia nervosa.
      ], patients in this study remained in hospital for about 5 weeks on average, although medical stability was achieved within about 2 weeks.
      Taking together the earlier work by Garber et al. [
      • Garber A.K.
      • Michihata N.
      • Hetnal K.
      • et al.
      A prospective examination of weight gain in hospitalized adolescents with anorexia nervosa on a recommended refeeding protocol.
      ] and Whitelaw et al. [
      • Whitelaw M.
      • Gilbertson H.
      • Lam P.Y.
      • et al.
      Does aggressive refeeding in hospitalized adolescents with anorexia nervosa result in increased hypophosphatemia?.
      ] on the one hand, and the three studies in this issue of the Journal of Adolescent Health [
      • Golden N.H.
      • Keane-Miller C.
      • Sainani K.L.
      • Kapphahn C.
      Higher caloric intake in hospitalized adolescents with anorexia nervosa is associated with reduced length of stay and no increased rate of refeeding syndrome.
      ,
      • Leclerq A.
      • Turrini T.
      • Sherwood K.
      • Katzman D.K.
      Evaluation of a nutrition rehabilitation protocol in hospitalized adolescents with restrictive eating disorders.
      ] on the other, consensus seems to be building in support of a more aggressive approach toward rapid nutritional rehabilitation for medically unstable adolescents with AN. These studies all underscore the notion that higher calorie meal-based approaches are feasible for moderately malnourished patients (75%–85% of EBW), whereas specific guidance for patients presenting as more severely malnourished or those who are chronically unwell still elude us. Although these studies have used different methodologies, some with limitations, and leaving room for future larger studies as well as randomized controlled approaches, several commonalities emerged: (1) most moderately malnourished patients with AN can safely commence refeeding at 1,500 kcal or even higher; (2) nutrition can be advanced at 250 kcal every day or every other day, approaching 2,500–3,000 kcal/day by day 14; (3) weekly weight gains of at least 1.5 kg is attainable within such a protocol; (4) none of the patients included in these three studies developed te refeeding syndrome (mild levels of hypophosphatemia can be corrected by phosphate supplementation); and (5) medical stability can commonly be achieved at about day 14 of hospitalization, which supports the adolescent's early return to the family by drastically reducing the length of hospital stay.
      Although it might be premature to confidently debunk the more conservative approaches to inpatient refeeding, because there are risks when the findings from these new studies are applied unthinkingly, nevertheless, it is time to consider a new edict that reads “Start high(er), advance fast(er).” However, much of inpatient refeeding done under expert dietetic guidance could be undone quickly if timely outpatient follow-up care is not available upon hospital discharge. This suggests another important area of research: the interface between inpatient and outpatient services. Another task, and one that is perhaps even more arduous than inpatient refeeding, is to ensure that the family is supported and guided in its efforts to build on the gains achieved by the inpatient team. The same new edict would also apply to the parents!

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