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Stheneur, C.; Proulx-Cabana, S.; , . Management of Adolescents Admitted with Severe Anorexia Nervosa. Encyclopedia. Available online: (accessed on 23 June 2024).
Stheneur C, Proulx-Cabana S,  . Management of Adolescents Admitted with Severe Anorexia Nervosa. Encyclopedia. Available at: Accessed June 23, 2024.
Stheneur, Chantal, Stephanie Proulx-Cabana,  . "Management of Adolescents Admitted with Severe Anorexia Nervosa" Encyclopedia, (accessed June 23, 2024).
Stheneur, C., Proulx-Cabana, S., & , . (2022, April 01). Management of Adolescents Admitted with Severe Anorexia Nervosa. In Encyclopedia.
Stheneur, Chantal, et al. "Management of Adolescents Admitted with Severe Anorexia Nervosa." Encyclopedia. Web. 01 April, 2022.
Management of Adolescents Admitted with Severe Anorexia Nervosa

Anorexia Nervosa (AN) affects up to 0.5% of adolescents. It is considered the third most common chronic disease in adolescence and also the psychiatric illness with the highest mortality rate, ranging from 2–8%. Part of this high mortality is explained by the multi-systemic stress caused by prolonged fasting, especially on the cardio-vascular system. Although there is a general agreement regarding admission criteria, the initial management of admitted patients with severe malnutrition due to AN is still highly variable with no international consensus on the optimal nutritional rehabilitation for this specific population.

Anorexia Nervosa adolescent inpatient medical stabilization refeeding syndrome

1. Introduction

Anorexia Nervosa (AN) affects up to 0.5% of adolescents [1][2]. It is considered the third most common chronic disease in adolescence and also the psychiatric illness with the highest mortality rate, ranging from 2–8% [1][2]. Part of this high mortality is explained by the multi-systemic stress caused by prolonged fasting, especially on the cardio-vascular system. The risk of death due to medical complications is proportional to the severity of malnutrition at presentation [3]. Hence, providing safe inpatient nutritional rehabilitation to patients presenting with severe AN and medical instability is essential.
Several clinical guidelines have established criteria for hospitalization of adolescents with AN including the Society for Adolescent Health and Medicine (SAHM) [4]. These criteria recommend admission for patients with significant underweight, defined as median BMI ≤ 75% for age and sex, acute medical or psychiatric complications and medical instability of which bradycardia is the most frequent in practice [4].
Although there is a general agreement regarding admission criteria, the initial management of admitted patients with severe malnutrition due to AN is still highly variable with no international consensus on the optimal nutritional rehabilitation for this specific population. In a North American survey, only a minority (37%) of physicians reported using standardized protocols for the initial nutritional rehabilitation phase and large variations were reported for both initial caloric intake and use of nasogastric tube [5]. Even with a same goal of high-calory nutritional rehabilitation, different inpatients protocols from Australia, United States of America and Germany showed major differences, reflecting different practices worldwide [6]. In 2010 and 2011, the Royal College of Psychiatry published the MARSIPAN (Management of Really Sick Patients with Anorexia Nervosa) and Junior MARSIPAN practice guidelines targeting respectively adults and children and adolescent severely ill due to AN, in order to standardize care in the United Kingdom [7][8]. Both constituted the first guidelines designed for the inpatient management of this population, but they were mainly relying on experts’ opinions due to limited evidence. In 2015, the ESCAP (European Society for Child and Adolescent Psychiatry) reviewed the clinical guidelines of four European countries and concluded that research is needed to provide evidence-based recommendations for the management of adolescents with AN [9].

2. Nutritional Rehabilitation Protocol

Weight restoration has been associated with better short and long-term outcomes for adolescents with AN, including improvement in cognitive impairment facilitating psychotherapy treatment and reversal of medical complications such as decreased bone density and growth retardation [10]. When dealing with severe malnutrition associated with AN, treatment should be focused on rapid nutritional rehabilitation and weight gain. Benefits of these should however be considered in parallel to the risk of refeeding syndrome (RS), a potentially lethal multi-systemic metabolic reaction triggered by increase in caloric intake in severely malnourished patients [11].
Until recently, conservative initial caloric intake, usually starting at 800 to 1000 kcal/day [10], was recommended by experts as a mean to prevent the development of RS. This approach has been associated with persistent weight loss in the first week of hospitalization [12], without providing evidence of effective reduction of the risk of RS. Articles in the last decade demonstrated that, in patients mildly to moderately malnourished due to AN, risk of RS is similar with higher initial caloric intake [12][13][14][15][16][17]. Furthermore, these studies also showed additional benefits in terms of weight recovery and length of hospital stay [12][13][14][15][16][17], quicker recovery of medical stability [17] and no difference in clinical remission and rehospitalization when compared to lower-caloric nutritional rehabilitation at 1-year [18]. A systematic review by Garber et al. concluded that evidence supported higher initial caloric intake (>1400 kcal/day) for mildly to moderately malnourished patient with AN, but highlighted the lack of evidence regarding those with severe malnutrition due to AN [19]. Due to this lack of evidence, the Junior MARSIPAN still recommend initial caloric intake limited to 5–20 kcal/kg/day [8]. A study in an adult population of 103 patients with severe AN, reported no RS with an initial caloric nutritional rehabilitation plan of 2000 kcal/day with systematic supplementation with phosphate and thiamine [20]. Peebles and al. reported hypophosphatemia requiring supplementation in only 14% of a population of children and adolescents admitted with eating disorders (including AN) refed with mean initial caloric intake of 1466 kcal/day, 84% of which were considered as severely malnourished [21]. None of these patients met the diagnostic criteria for RS [21]. Maginot et al. (2017), reported for 26 severely malnourished adolescents, defined as expected body weight (EBW) of less than 75%, no increased risk of hypophosphatemia, hypomagnesemia or hypokalemia when starting nutritional rehabilitation at higher calory (>1500 kcal/day) [22]. Although there seems to be clear benefits of opting for a higher-calory nutritional rehabilitation, concerns about the impact of the rapid weight restoration on lipid metabolism [23] and the psychological health [24] have been expressed, further highlighting a gap in research needing to be addressed.

3. Route for Nutritional Rehabilitation

The two main routes for nutritional rehabilitation are meal-based plan and nasogastric tube feeding. There is no current evidence to recommend one over the other [19]. The oral route, constituted of meals and snacks under supervision of specialized ED professionals, is the most common approach in North America. If the patient cannot complete the food, calories can be replaced with nutritional supplements containing 1 to 1.5 kcal/mL [8]. If collaboration to oral feeding is impossible, nasogastric tube feeding should be considered.
Some centers have opted for systematic nasogastric tube feeding in all admitted adolescents mildly to moderately malnourished, limiting the stigmatizing or punitive connotation associated with installing a nasogastric tube after a failure of oral feeding [15]. Their protocol consists of 24-h continuous nasogastric feeding with 1 kcal/mL enteric solution started at 1500–1800 kcal/day. This protocol was associated with better weight gain in the first 2 weeks and reduced length of stay [15]. No patient developed electrolyte disturbances suggestive of RS, provided that 90.3% of patients received prophylactic phosphate supplementation [15]. When nasogastric tube feeding is used, a progressive increase of 200 kcal/day is suggested by the Junior MARSIPAN [8], unless there is a drop in blood phosphate levels. Caloric intake progression should be stopped until phosphate normalizes [8]. The use of nasogastric tube feeding as an adjunct to a meal plan has also been associated with better weight gain during hospitalization in both an adult population and a pediatric population with AN [25][26].
Another potential benefit of 24-h gastric enteral feeding in patients at high risk of RS is that it could limit postprandial insulin peaks related to carbohydrate load [27] and, subsequently, reduce the risk of post-prandial hypoglycemia [28]. Other recommendations to limit the post-prandial insulin surge associated with RS include a diet with less than 40% carbohydrate and with a high phosphate content [28]. Accordingly, the use of 1 kcal/mL enteral formula is preferred in several protocols [15][29], considering that 2 kcal/mL formulas with a greater amount of carbohydrates could increase the risk of RS [8]. Study by Parker et al. (2021) demonstrated that using an enteral formula containing low carbohydrates (28%)/high fat (56%) has been associated with reduced incidence of hypophosphatemia at 1 week of nutritional rehabilitation in adolescents and young adults with AN, although these results should be taken with caution due to the very small sample size (N = 24) and a majority of patient presenting with only mild to moderate malnutrition [30].

4. Blood Tests

Starvation in AN is associated with depleted total body potassium and phosphate, although serum values are usually initially preserved through metabolic compensation [31]. Refeeding syndrome is a potentially fatal complication caused by intracellular electrolytes shifts due to insulin surges with reintroduction of carbohydrates in a malnourished patient, revealing the absolute electrolytic deficit previously compensated [11]. Although hypomagnesemia and hypokalemia can be observed, hypophosphatemia is the most common and precocious manifestation of RS [32][33][34]. The clinical manifestations of RS are multisystemic, including congestive heart failure, arrhythmias, seizures and coma [35]. The risk of refeeding syndrome is the highest in the first 3 to 7 days of nutritional rehabilitation [36]. In patients hospitalized for AN, the mean incidence of RS in a systematic review was 14% and was more strongly correlated with a % mBMI below 70% than with the initial caloric intake [37][28]. Predisposing risk factors for RS include % mBMI less than 70%, absolute BMI less than 0.4th centile, very low daily caloric intake (<500 kcal/day) for ≥3–4 days, 15% of total weight loss in the last 3 months and electrolyte abnormalities before starting nutritional rehabilitation [8][37][38].
To monitor for RS in newly admitted patients with AN, blood tests are considered part of best practices, but recommendations on frequency are variable. In high-risk patients and those with enteral tube feeding, daily blood samples including electrolytes, phosphorus, calcium and magnesium are recommended for the first 2–5 days of nutritional rehabilitation for early refeeding syndrome surveillance and between days 7 and 10 for late refeeding syndrome [8].
On the other hand, in adolescents with non-severe AN, a study of 3960 blood tests done daily for the first 5 days of nutritional rehabilitation and every other day thereafter in a population of 196 adolescents revealed that only 1.9% were below normal, 0.28% resulted in supplementation and none were associated in a change on nutritional rehabilitation plan [39]. The estimated cost was $1373.73 per patient [39]. Ghaddar et al. also demonstrated in a pediatric population of 99 adolescents with AN, that only 1.61% of performed blood tests revealed abnormal values and 0.85% led to supplementation. There was no difference between the subgroup of patient with a percent median BMI of less than 70% [40]. Once again, average cost was of $1504 per patient, representing an important financial burden [40].

5. Phosphate Supplementation

During nutritional rehabilitation of an AN patient, a serum phosphate level dropping to 0.9–1 mmol/L or lower can represent the first sign of RS and supplementation should be considered [12][37][35]. In moderate hypophosphatemia (0.35–1 mmol/L), oral route is recommended at a dose of 30–60 mg/kg/day divided into 3–4 doses per day [35]. In severe hypophosphatemia (<0.35 mmol/L), intravenous route under cardiac monitoring is recommended [35].
There is no consensus in the pediatric literature whether systematic phosphate supplementation during the initial nutritional rehabilitation of all patients admitted for AN with severe undernutrition is better than supplementing if serum phosphate decreases to supplementation threshold. In a survey of physicians practicing in the United States and Canada, only 15% prescribed systematic phosphate supplementation for patients with AN as part of inpatient nutritional rehabilitation [5]. An observational study in a pediatric population refed with an initial caloric intake of 1900 kcal/day, only observed mild hypophosphatemia, defined as 0.8–1.1 mmol/L, in 38% of patients, with a median nadir of 4 days. This suggested that, with regular bloods tests, two-thirds of patients would not need phosphate supplements [41]. In an adult population with extreme AN, as defined by ideal body weight (IBW) less than 65%, where systematic prophylactic phosphate supplementation was not used by concerns of diarrhea, only 35% developed hypophosphatemia, with no correlation to initial caloric intake that ranged from 900 kcal/day to 1400 kcal/day [42].
On the other hand, retrospective chart review study conducted by Leitner et al., examined the effects of systematic phosphate supplementation with 1 mmol/kg/day (31 mg/kg/day) for 7 days in admitted adolescents with AN with mild to moderate malnutrition refed at 1800 kcal/day [32]. No patient developed hypophosphatemia while 14.7% had at least one episode of hyperphosphatemia as defined as serum phosphate >1.8 mmol/L within 7 days of starting nutritional rehabilitation. All patients with hyperphosphatemia remained asymptomatic, supporting the opinion of some experts that the benefits of prophylactic phosphate supplementation as a preventive measure of RS probably outweighs the risk of potential side effects [32].

6. Sodium and Fluids

Clinical hydration status in patients with AN should be evaluated clinically to establish appropriate fluid requirements [8]. If a patient presents with signs of hypovolemic shock, 0.9% NaCl bolus of 10 mL/kg should be used to avoid precipitating an acute cardiac failure in the context of malnutrition and risk of RS [8]. No specific daily water intake is recommended for the pediatric population. In the adult MARSIPAN and ESPEN guidelines, total daily fluid intake ranging from 20–30 mL/kg/day in the first 72 h of nutritional rehabilitation to 30–35 mL/kg/day is considered appropriate [7][43].
In addition, daily sodium restriction at 1 mmol/kg is recommended in adults to limit the risk of edema [43]. In pediatrics, there is no evidence to support this recommendation.

7. Hypoglycemia

Hypoglycemia is a rare complication of AN as glucose homeostasis is maintained by compensatory phenomena including increased secretion of GH and cortisol as well as decreased gluconeogenesis due to reduced insulin [44]. In contrast, during nutritional rehabilitation, increased glucose load provokes postprandial insulin surges which can provoke post-prandial hypoglycemia in a pathophysiology similar to the dumping syndrome [45]. Additionally, there is a glycogen depletion in very malnourished patients, leading to dysfunction of the secreted glucagon to counter-regulate this insulin peak [46]. In an adult study of patients with severe AN, with a mean BMI of 13.1 kg/m2, 44% presented mild hypoglycemia (<3.3 mmol/L) and 27% severe hypoglycemia (<2.2 mmol/L). These hypoglycemic episodes lasted for a median period of 8 days and 64% of them were either in the morning or in the post-prandial period [47]. In an adult population with extreme AN, as defined by IBW less than 65%, 38% of adult patients experienced hypoglycemia. This was most likely in those with transaminase levels higher than 3 times the normal and with a greater severity of malnutrition [42].
Literature focusing on hypoglycemia in pediatric patient with AN is sparse. There is no clear frequency for blood glucose monitoring and no clear value for defining significant hypoglycemia. Some authors propose a threshold of <2.5 mmol/L to define hypoglycemia [48] and suggest to check blood glucose in the morning and 2 h after the meals for the first 72h of admission or more frequently if the patient presents symptoms compatible with hypoglycemia [46]. If there is hypoglycemia, continuous enteral feeding could be considered to improve glycemic control [46]. As far as possible, correction of hypoglycemia should be done enterally [8]. However, intravenous correction with a 10% dextrose solution at 2 mL/kg should be used for severe hypoglycemia with impaired consciousness or convulsion. An infusion containing NaCl 0.45% 10% glucose at 5 mL/kg/h has been recommended thereafter to avoid rebound hypoglycemia [8]. In the context that this is not a standard pre-prepared bag of fluids in researchers' institution, and in order to avoid potential errors, researchers instead use a D10% NaCl 0.9% but at a rate of 3 mL/kg to avoid excessive sodium intake. Glucagon should not be used as it has not been shown to be effective due to low glycogen reserve in malnourished patients with AN [8].


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