Refeeding syndrome in patients with anorexia nervosa - case reports


 
 Introduction: Refeeding syndrome RS is a life-threatening acute hormonal and metabolic disorder that occurs in patients with moderate or severe malnutrition as a result of improperly administered nutritional therapy.
 
 Material and method: The aim of this study is to describe the cases of two female patients suffering from anorexia nervosa, who developed a refeeding syndrome after starting nutritional therapy. Additionally, the available literature was reviewed in order to characterize the issue, including negative consequences and prevention of the refeeding syndrome.
 
 Results: In both cases, the development of the refeeding syndrome was found in the patients, resulting from the excessive supply of energy and nutritional substrates in a short time, preceded by a previous, months long period of starvation and exhaustion of the organism (both patients had a decrease in the body mass index - BMI - to the value of about 14 kg / m2). In patient 1, the symptoms concerned mainly the cardiovascular system: a significant increase in the concentration of N-terminal B-type natriuretic propeptide (NT-proBNP) and tachycardia, as well as a decrease in the concentration of inorganic phosphates and hypokalemia. On the other hand, in the case of patient 2, symptoms such as confusion or deep disturbances of consciousness, which led to hospitalization in the intensive care unit, dominated the clinical picture.
 
 Conclusions: Refeeding syndrome may develop during nutritional rehabilitation, especially in the case of a sudden, inadequately planned supply of nutrients. Particular care should be taken in patients with extremely low BMI when reintroducing nutrition.
 The presented case reports draw attention to the possibility of cardiological complications and mental disorders of the realimentation syndrome, and indicate the behavior of patients (eating excessive food) that may lead to the development of the refeeding syndrome.


Introduction
Anorexia nervosa (AN) is a severe eating disorder in which patient may experience strong fear of weight gain and disturbed body image, resulting in severe dietary restrictions or other behaviors leading to excessive weight loss. It is estimated that in highly developed countries it affects 1% of women and <0.5% of men [1] this percentage depends on the age of the studied group and the diagnostic criteria of AN [2,3]. Anorexia has the highest mortality rate among mental diseases [4]. It is estimated that among patients with anorexia nervosa, 81% manage to cure or reduce their symptoms, 21% have chronic eating disorders, and 5% die [2].
Treatment of AN is based on the implementation of appropriate psychotherapy and supplementing nutritional and energy deficiencies [1]. When treating people with moderate or severe malnutrition, there is a risk of developing refeeding syndrome (RS), also known as food shock syndrome or realimentation syndrome [5,6]. As a result of improperly conducted nutritional therapy (too fast and with too much food), complications may occur, such as: water and electrolyte disturbances (especially hypophosphatemia), vitamin deficiency, metabolic acidosis and even death [6,7]. The aim of the study is to describe the cases of two female patients suffering from anorexia nervosa, who developed refeeding syndrome.

Patient 1
A 15-year-old patient, she lives with her father and younger sister as well as her father's partner and her two daughters. The patient's mother has been dead for nine years (death due to cancer). Under the care of a psychological clinic for six months, under the care of a psychiatrist for five months. She has a difficult relationship with her stepmother.
The onset of eating disorders about a year earlier, the patient gradually introduced qualitative and quantitative restrictions on the food consumed, resulting in a loss of about 14 kg (highest body weight 50 kg with BMI = 20.00 kg / m 2 , lowest in the summer of the same year). The eating problems were accompanied by deterioration of the mental state in the form of intensified suicidal thoughts and auto-aggressive behavior.
In the eighth month from the onset of eating problems, the patient attempted suicide by ingesting an unknown amount of paracetamol and self-mutilating the skin of her forearms. She was taken to the Emergency Department of the University Children's Hospital (UCH), and then admitted to the Department of Paediatrics, Endocrinology and Diabetology. The girl was admitted three days later, for the first time to the Department of Psychiatry. During the first hospitalization, the patient was found to have a very low body weight -36 kg with a height of 158 cm (BMI = 14.42 kg / m 2 ). Four days after admission, increasing swelling of the lower limbs and rapid weight gain (6 kg in 4 days), and increasing fatigue were noticed. Tachycardia was also observed, which was absent on admission. Followup examinations were ordered. Compared to the tests on admission, they showed a significant increase in NT-proBNP -704 pg / ml (previously 62 pg / ml), decreasing potassium concentration -3.65 mmol / l (previously 4.24 mmol / l), increased concentration of aminotransferase alanine (ALT) -47.9 U / l (previously 17.0 U / l) and total cholesterol -260.5 mg / dl (previously 244.1 mg / dl) and a reduced level of inorganic phosphates -0.5 mmol / l (previously 0.73 mmol / l). The tests also showed abnormalities in the red blood cell system: erythrocytes -3.46 M / μl, hemoglobin -10.6 g / dl, hematocrit -32.5%. Due to the abnormal NT-proBNP result (at the norm for women up to 16 years of age <83 pg / ml -704 pg / ml) and the deteriorating general condition, the girl was referred to the Department of Paediatrics, Endocrinology and Diabetology in order to stabilize the somatic state, where the patient stayed for 9 days. Then she was readmitted to the Department of Psychiatry in order to continue the diagnostic and therapeutic process. At the time of re-admission, the above-mentioned abnormalities in the biochemical tests were not observed, with the exception of the persistently elevated concentration of alanine aminotransferase (ALT) -47.0 U / l. An electroencephalographic (EEG) examination one week after readmission showed no significant abnormalities. After 3 weeks, she was discharged from the ward at the request of her father, against medical recommendations, before completing the therapeutic process. After a few days, she was re-admitted to the ward as an emergency, due to self-mutilation in the left forearm and general deterioration of her mental state, where she stayed until her body weight normalized.

Patient 2
A 16-year-old patient, a young girl, 3rd grade student, lives with her parents and younger brother (15). The child's development was normal, she was reaching the milestones on time. In kindergarten and school, she did well and achieved high academic results. She had her last period about two years ago.
The onset of eating problems four years ago, when the patient began to restrict her food consumption and undertook excessive physical exercises. She constantly felt fear of weight gain. There was an approximately 10 kg (19% of body weight) weight loss. Therefore, the patient was hospitalized for the first time at the Neuropsychiatric Hospital, and then, six months later, at the Department of Psychiatry. In both cases, she was discharged by the family at their own request before the completion of the therapeutic process, against medical recommendations. Two years later, she was admitted to the Department of Endocrinology and Diabetology of the University Children's Hospital in Lublin due to general exhaustion of the organism. During her stay, the patient was aggressive towards other patients and showed a tendency to escape. Then she was transferred to the Department of Psychiatry for further treatment. BMI on admission: 13.3 kg / m 2 (height 167 cm, body weight: 36 kg). The results of the patient's laboratory tests showed low levels of total protein (5.84 g / dl at the norm of 6.4 -8.3 g / dl), leukocytes (3.15 K / µl at the norm of 4 -10 K / µl) , significant iron deficiency anemia (3.0 M / µl, hemoglobin 9.6 at the norm of 12-16 g / dl, hematocrit 27.8% at the norm of 37-47%), as well as a high level of ALT (alanine aminotransferase, 63 , 1 IU / l at the norm of 5-34 IU / l). The girl had low blood pressure (on admission 90/62 mm Hg). No significant changes were registered in the EEG test. In magnetic resonance imaging of the head, except for the expansion of extracerebral fluid spaces -no changes. Other results with no significant deviations.
During hospitalization, the patient began to eat a significant amount of food, stole sugar from the canteen, as well as other patients' food, while expressing fears that she would "die", "without food she would die". The patient became psychomotorically agitated, disorganized in contact and action, disturbances in consciousness, fresh memory, and sleep disturbances were observed.
The patient required constant supervision. She displayed aggressive behavior towards medical staff and other patients in the ward. It was necessary to use direct coercion in the form of immobilizing the patient. Due to a significant deterioration of the general conditionconfusion, disturbance of consciousness, uncontrolled physiological needs and the occurrence of symptoms of refeeding syndrome (behavioral disturbances and a reduced level of inorganic phosphates were observed -0.76 mmol / l at the norm of 0.84-1.45 mmol / l), the girl was transferred to the Intensive Care Unit of UCH in Lublin. After stabilization of the somatic state of the patient, she was re-admitted to the Department of Child and Adolescent Psychiatry, where she stayed until the normalization of her body weight -at discharge she weighed 52.42 kg (BMI = 18.8 kg / m 2 ).

Discussion
It is estimated that approximately 92% of people suffering from anorexia nervosa are women. There are two types of this disease: restrictive, characterized by limiting food intake to very small amounts, and bulimic type, in which the reduction of food intake is accompanied by periods of overeating or provoking vomiting and overuse of laxatives [8].
As a rule, anorexia coexists with other mental disorders. It is estimated that over 73% of adolescent women have comorbidities [10].
Refeeding syndrome was first diagnosed during the World War II, when long-term starving prisoners developed heart attacks and peripheral edema after reintroducing nutrition. Currently, it is found in people with anorexia nervosa, chronic malnutrition, patients with kwashiorkor or devastated by neoplastic disease, in whom an attempt is made to resume nutrition too abruptly [12].
There is no clear definition of RS. It is assumed that this is an acute hormonal and metabolic disturbance occurring in debilitated patients who refeed too quickly and / or intensely [6]. The most important marker of this pathology is hypophosphatemia. Apart from it, there are also hypokalemia, hypomagnesaemia, vitamin deficiency (mainly thiamine), hyperglycemia, increased fluid retention (edema) and micronutrient deficiencies [13]. These symptoms are observed when the exhausted organism is obtaining energy from alternative energy sources: amino acids and triglycerides. Suddenly, a violent process of glycolysis begins, requiring an increased supply of phosphate and thiamine. This process is accompanied by the secretion of insulin, which causes the movement of potassium, phosphorus and magnesium ions into the cells, leading to a disturbance of their concentration in blood [6]. Patients with severely lowered BMI are at particular risk of complications related to re-nutrition, including but not limited to: arrhythmias, exhaustion, respiratory failure, ataxia, and seizures. An increased risk of developing RS also occurs in the case of unintentional weight loss >15% during the last 3-6 months, low or no food intake in the last 10 days, and in people with decreased levels of potassium, phosphorus and magnesium before starting refeeding [14] . In practice, every patient hospitalized for AN is at risk of RS [6]. It was against this background that complications developed in the patients described above.
Unfortunately, currently there is no clear scientific position on the amount of calories a person at risk of RS should consume. It is indicated that electrolyte concentrations should be monitored and special caution should be exercised in the case of severely debilitated patients [6]. It is also important to gradually and slowly increase the caloric supply [15]. The guidelines of the American Society for Parenteral and Enteral Nutrition (ASPEN) suggest (for non-adult patients) starting refeeding at 40% -50% of the target value, usually around 4-6 mg / kg / min of glucose infused with a dose increment of 1-2 mg / kg / min daily [16]. The European guidelines recommend starting refeeding from 5-20 kcal / kg, and the American ones from 30-40 kcal / kg [15]. Recent studies suggest that starting the realimentation of AN patients with higher energy values (2000 kcal instead of 1400 kcal) does not contribute to an increase in the percentage of refeeding syndrome but allows for faster restoration of normal body weight [17].
Additionally, in Patient 1, re-alimentation was accompanied by cardiac complications. A significant increase in NT-proBNP concentration, increased fatigue and tachycardia may indicate heart failure [18]. Previously, cases of cardiogenic shock [19] and cardiac arrest [20,21] in the course of RS in patients with anorexia had been reported. This means that cardiac complications should be taken into account as one of the effects of the refeeding syndrome and special attention should be paid to the careful examination of debilitated patients to avoid cardiological abnormalities.
In the case of Patient 2, the refeeding syndrome also developed as a result of a sudden supply of a high energy diet in a very short time, which led to psychological symptoms such as confusion, lack of control of physiological needs or disturbed consciousness. A similar case, as described above, was presented by Soyam et al. [22], where a patient with AN increased her body weight by more than 13 kg in 9 days as a result of excessive consumption of food provided by the family, which resulted in the development of the refeeding syndrome. Both of the above cases show the importance of careful monitoring the behavior of patients with anorexia nervosa, not only in terms of avoiding meals, but also binge eating. Additionally, Tenconi et al. indicated that the high intensity of eating disorders symptoms (especially body dissatisfaction) and the early age of the first menstruation are factors that significantly influence the increased risk of compulsive overeating episodes in patients with AN [23].

Conclusions
Realimentation syndrome is a serious complication of refeeding the debilitated patients. Not only can it cause hormonal and metabolic disorders, but also, as the cases described above show, cardiovascular and mental disorders. The development of a unified definition of this complication will certainly be helpful in the diagnosis of RS. Clinicians should take great care while reintroducing nutrition of debilitated patients in order to better prevent complications of refeeding. It is also necessary to implement the education of physicians in the diagnosis and treatment of the refeeding syndrome.