The term “nutritional insufficiency” (NI) is used to encompass the medical and nutritional complications of eating disorders, including anorexia nervosa and bulimia nervosa. Eating disorders have the highest morbidity of any psychiatric illness, with as many as 2% to 10% of individuals dying of the medical complications of anorexia nervosa annually (1-3). The death rate for anorexia nervosa is up to 12 times higher than the mortality rate of all other causes of death for adolescent girls and young adult women (4-6). In addition, the medical complications caused by and/or exacerbated by disordered eating are myriad.
Hospitalists play a fundamental role in the initial identification and management of patients with NI. Acute malnutrition is a medical emergency that can occur at any given body weight, not just at an extremely low weight. Hospitalists should focus their efforts mostly on individuals with continued restrictive eating behaviors, laxative abuse, diet pill or diuretic abuse, and purging, for whom outpatient efforts to redirect harmful behaviors have failed.
Most important, hospitalists should recognize the life-threatening complications of refeeding syndrome and be aware of the current protocols for its treatment. Early recognition and timely intervention, based on a developmentally appropriate, evidence-based, multidisciplinary team approach (including medical, psychological and nutritional components), represent the ideal standard of care.
The research in this field is continuously evolving, as is the current knowledge of pathophysiology, clinical recognition and inpatient management of NI and eating disorders. This article will review epidemiology, medical pathology, and the role of an inpatient pathway to treat NI.
Currently in the United States, anorexia nervosa and bulimia nervosa are clinically present in approximately 0.5% and up to 5%, respectively, of adolescents and young adults. The female-to-male ratio is approximately 10 to 20 to 1 (1-6). Eating disorders have increasingly been described in younger populations and in boys (Peebles et al., Rome et al. Unpublished data) as well as in minority populations and the indigent, along with white upper-middle-class girls and young women.
There are multiple risk factors for both disorders (AN and BN), including family history of obesity or eating disorders; mood disorders and/or alcoholism in the immediate family; parental eating behavior; the practice of ballet, gymnastics, modeling or any “visual sport”; personality traits of perfectionism and rigidity; practice of compulsive exercise; history of excessive diets and missing meals; body image refusal; low self-esteem; and physical and sexual abuse (1).
Patients are generally admitted to the hospital with overt manifestations of malnutrition. The Table 1 outlines standard criteria for admission. These complications may be highly visible when an adolescent or adult loses weight from 110 pounds to 70 pounds over several months. However, the same medical complications can occur yet be “invisible” in the patient who goes from 200 pounds to 160 pounds in the same time period. In fact, the latter patient may be just as critically ill with respect to loss of heart muscle or abnormal rhythm but be cheered for his or her “obvious success” in addressing obesity.
A thorough history should be pursued, as Table 2, documenting the rate and amount of weight loss/change; current dietary intake and exercise practices; methods used for weight control, including compensatory behaviors (vomiting, dieting, exercise, insulin or growth hormone misuse, and/or use of diet pills, over-the-counter supplements, laxatives, ipecac, diuretics, etc.); menstrual history in females (including information on hormone replacement therapy, e.g., oral contraceptive pills); and a comprehensive history of growth and development, temperament and personality traits (1-4, 6). A complete physical examination may reveal the physical findings Table 3.
Patients with anorexia nervosa and NI will generally have two types of behaviors: restrictive and/or purging. Restrictive behavior is characterized by a marked caloric reduction (which may be as low as approximately 300 to 700 calories per day), with or without a component of compulsive exercise. Individuals with anorexia nervosa may also vomit, but the defining features remain restrictive behavior and body discontent.
The hallmark of bulimia nervosa, in contrast, is bingeing, with compensatory purging or non-purging behaviors. The binge may be large, with documented reports of intake exceeding 20,000 calories, or it may be a relatively normal meal accompanied by disproportionate guilt or negative feelings. The line between anorexia nervosa and bulimia nervosa may blur; as many as one in four individuals with anorexia nervosa go on to a binge-and-purge phase later.
Many studies classify patients at one point in time, so it may be more useful to conceptualize clinical manifestations as problems of restricting, problems of purging, and problems of bingeing (1-7). A classic phenotype that encompasses the endocrine manifestations of NI is the “female athlete triad,” which includes the presence of amenorrhea, disordered eating and osteopenia (8, 9).
Patients with chronic emesis and use of cathartics present with classic metabolic disturbance: hypokalemia, hypochloremia, and metabolic alkalosis. Dehydration and prerenal azotemia are not uncommon; in addition, other electrolyte abnormalities such as hypocalcemia and hypomagnesemia can be present. Parotitis may flare when the patient is trying to quit purging, similar to a smoker's cough worsening in the time period when he or she is quitting.
In patients with chronic emesis, the development of esophagogastric erosions (Mallory-Weiss tears), esophageal perforation (Boerhaave syndrome) and aspiration pneumonia has been described. The presence of gastric acid in the mouth can cause gingivitis, a characteristic pattern of dental erosions on the lingual and occlusal surfaces, parotid enlargement and oral ulcerations. The increased pressure associated with emesis can cause supraclavicular petechiae and subconjunctival hemorrhages. A careful examination of the hands can show Russell sign, or calluses over the knuckles due to the recurrent trauma of teeth on that area during self-inflicted emesis (10).
In patients who chronically use syrup of ipecac to purge, the emetine alkaloid toxicity may be irreversible, with subsequent development of potentially irreversible myositis and myocardial damage. All other medical complications of eating disorders should be fully reversible with proper treatment. Ipecac has been discontinued and is not available for purchase in the United States to prevent iatrogenic harm; however, this is not uniform across all countries (11, 12).
Patients with chronic laxative use can have colonic hyperpigmentation (melanosis coli). The abrupt discontinuation of laxatives has been associated with rapid weight gain (up to 5 kg in 24 hours) due to compensatory absorption of water by the colonic mucosa. Chronic laxative abuse alone may be sufficient reason to admit a patient with NI for medical stabilization, to manage fluid shifts after acute termination of laxatives and to prevent refeeding syndrome.
Patients with bulimia nervosa may appear healthy and have entirely normal laboratory results despite repeated purging behaviors, yet still be at risk of sudden cardiac death. Consider admission for persistent and recurrent emesis alone (10 to 20 times a day), especially in the face of bradycardia or orthostatic hypotension. All individuals with bulimia nervosa and cardiac arrhythmia should be admitted until their cardiac abnormalities correct. In addition, patients with NI may have multiple vitamin deficiencies, with accompanying Table 4 (12).
It is very important to acknowledge the substantial overlap of psychiatric comorbidity in individuals with eating disorders. Major depression or dysthymia occurs in up to 50% to 75%, anxiety disorders in up to 60%, obsessive-compulsive disorder (OCD) in up to 40%, and alcohol or drug abuse in up to 27% (7).
The differential diagnosis of the patient admitted with NI is very broad and includes diseases that predispose to severe body wasting and chronic inflammation, including malignancy, inflammatory bowel disease, celiac disease, malabsorption, diabetes mellitus, hyperthyroidism, hypopituitarism, adrenal insufficiency, chronic disease or infection, and superior mesenteric artery syndrome.
In addition to the possible overlap of psychiatric comorbidity, a starved brain and disordered eating can indicate a primary psychiatric disorder such as depression, mood disorder, substance abuse, anxiety disorder, and OCD. Schizophrenia is rarer; individuals with a starved brain may show evidence of thought disorder, but the mentation tends to clear as the eating disorder resolves (2, 13-15).
The outcome for individuals with eating disorders can be described by the rule of thirds. One-third of individuals improve, do well, and lead normal lives. Another third improve but manifest abnormal eating attitudes and behaviors when stressed. The remaining third follow a chronic and relapsing course, and a significant percentage die prematurely of medical complications or suicide. Patients in this last third have a relatively poor prognosis, which is determined by the severity of the malnutrition itself, psychiatric comorbidity, and a high recidivism rate (1, 2).
Patients with anorexia nervosa have a mortality rate of up to 5.6%, and 10% to 31% may never recover. It can take up to six years to recover completely (1, 6, 16-18). Patients can evolve throughout the spectrum of eating disorders—as many as 50% of patients with anorexia nervosa subsequently develop bulimia nervosa. Up to 45% of patients may never achieve marriage or stable relationships (1-7). The restricting subtype of anorexia nervosa has a worse prognosis than the compulsive subtype (1, 13-16). The restricting subtype of anorexia nervosa has a worse prognosis than the compulsive subtype (1, 14-17).
- Restricting type: The patient does not perform binge-eating or purging behavior (self-induced vomiting or misuse of laxatives, diuretics, or enemas).
- Compulsive (also known as “binge eating-purging type”): The patient regularly engages in compulsive (binge) eating or purging behavior (self-induced vomiting or the misuse of laxatives, diuretics, or enemas).
Patients with bulimia nervosa have a slightly better prognosis than those with anorexia nervosa, with 50% recovering within two years (1, 14-17). The mortality in the acute phase is the same, however, at 5.6% (1, 16-18), and the frequency of relapses is higher. As many as 46% of individuals with bulimia may still live with an eating disorder six years later (1, 16, 17). Psychiatric comorbidity is also prominent; 55% of patients have associated mood disorders and up to 42% have substance abuse problems (1, 16, 17).
Factors that predispose to poor prognosis for both AN and BN include prolonged disease duration, low initial weight, prerenal azotemia, premorbid obesity (in the case of bulimia), compulsive exercise, conflictive family relationships, obsessive-compulsive traits and neurotic personality (1, 5, 19, 20).
The criteria for inpatient admission are listed in the box on page 38 (1, 2). The objectives of inpatient management on a medical floor include acute medical stabilization and initiation of nutrition protocol and avoidance of refeeding syndrome. A multidisciplinary team approach has been associated with timely resolution of hemodynamic instability in children and adolescents (Rome et al. Unpublished data). Strict nursing routines help to ensure adherence to diet and no exercise. Psychological support does not hope to “fix” abnormal eating attitudes and distorted body image but can help with hospital stress/”toxicity,” relaxation strategies, and coping strategies such as distraction.
In settings with excellent coordination of care between the inpatient and outpatient environment, continued inpatient therapy may be feasible, but that is not necessarily normative in the United States. All hospitals should be able to acutely stabilize patients with NI but require motivated champions, including physicians, nurses, social workers, psychologists, psychiatrists, and nutritionists, to do so.
At the Cleveland Clinic, most patients with NI are admitted with bradycardia (heart rate <50 bpm while awake), and most have orthostatic hypotension. A smaller number require admission for prolonged QTc syndrome. Of those requiring inpatient admission, as many as 60% have orthostatic heart rate changes, which will resolve on average once they reach 80% of their ideal body weight. In one study, time to vital sign stability took approximately 21 ±11 days (21, 22). Preliminary data from our center documenting resolution of vital sign instability showed an initial response at two days for a majority of patients, but orthostatic hypotension might not be fully resolved at time of discharge. Discharge at our center occurs at day four, on average, when bradycardia or prolonged QTc resolve.
All patients should have continuous electrocardiography (ECG) monitoring while in the hospital, especially if they are not in an inpatient intensive care unit; loss of cardiac muscle, with a low-voltage ECG, is the exact setup in which electrolyte abnormalities, exercise, caffeine, or other stimulants can trigger sudden cardiac death. Of note, patients and family members should be reassured that the QTc will correct with nutritional rehabilitation (23, 24).
Simple refeeding and monitoring patients for evidence of refeeding syndrome should be the standard of care. Some centers use only oral feedings, while others may add nasogastric feedings initially (as in some centers in Australia) or as a nighttime supplement (24).
The Maudsley method refers to parent-based refeeding. The essence of family-based therapy consists of mobilizing/partnering with parents to teach them to refeed their child/adolescent, as well as exonerating them from potential guilt that they somehow “caused” their child's illness and having them take joint control of their child's eating until the child becomes able to maintain a safe, medically stable body weight (25). For patients younger than 18 years of age, the Maudsley method has the advantage of empowering parents to partner with the care team to improve the health of their child, with some evidence for earlier weight restoration and earlier resumption of normal growth, menses, and other aspects of health (25).
The Maudsley protocol follows the premise that patients with eating disorders lack the capacity to adequately select food to cover their nutritional requirements (25-28). This requires an active role for parents and caregivers in making decisions on behalf of the patient. It includes three phases:
- Phase 1, when the patient requires hospitalization, focuses on weight restoration. The family selects the food and encourages and monitors intake. It is fundamental to remember that the patient's brain energy stores are depleted, and he or she is generally unable to make decisions.
- Phase 2 focuses on outpatient management, when the patient recovers control over his or her food intake.
- Phase 3 is when the patient establishes a healthy identity.
Data are conflicting on the use of psychopharmacology during acute medical stabilization. In patients with anorexia nervosa, there is a paucity of clear evidence showing any predilection toward a specific antidepressant or antipsychotic (29-34). Low-dose antipsychotic medication may be useful in acute anorexia, especially in patients with high levels of anxiety, obsessive eating-related ruminations, and failure to engage in treatment (34).
On the other hand, in patients with bulimia nervosa, the use of cognitive behavioral therapy increases the remission rate by approximately 30% to 40%. In the acute stage, antidepressants—mainly selective serotonin reuptake inhibitors—may be effective for a brief period (26, 35, 36).
Patients with severe malnutrition are at very high risk of refeeding syndrome, the metabolic and clinical consequences of aggressive nutritional rehabilitation. Its pathophysiology is attributed to the insulin release that occurs in response to an abrupt glucose load; this increases the intracellular drive of phosphorus, potassium and magnesium. In addition, there is an increased need for metabolic ATP as well as 2,3-Diphosphoglycerate (DPG), which in turn increases the demand for phosphorus in addition to the intracellular shift conditions to phosphate depletion (37-39).
The subsequent decrease of ATP in end organs such as the heart and the kidneys predispose patients to acute heart failure, as well as azotemia. There is inefficient management of sodium and water load, with subsequent development of edema and increased blood volume; these shifts exacerbate the risk for congestive heart failure. In addition, similar to what happens in patients with alcoholism, malnourished patients with thiamine deficiency have depleted thiamine upon introduction of large glucose loads, which subsequently predisposes them to development of congestive heart failure.
Refeeding syndrome occurs in up to 6% of hospitalized adolescents. It is generally associated with very low weight (less than 70% of ideal body weight) and occurs with rapid introduction of high caloric content. Some centers, including the Cleveland Clinic, attempt to decrease the risk of refeeding syndrome by preemptively providing a phosphorus supplement (such as Neutra-Phos®, 250 to 500 mg orally twice a day for five days). The Cleveland Clinic has had no cases of refeeding syndrome despite a very high-risk population admitted for our NI protocol since its implementation in the early 2000.
The clinical spectrum of refeeding syndrome varies from simple peripheral edema to overt congestive heart failure and prolonged QTc. Hypophosphatemia can manifest as weakness, confusion, seizures and rhabdomyolysis; additional clinical features of refeeding syndrome are associated with different electrolyte abnormalities such as hypokalemia and hypomagnesemia (39).
The prevention of refeeding syndrome is based on slow introduction of calories and strict monitoring for the clinical manifestations of electrolyte deficiencies (i.e., monitoring of phosphorous, magnesium, potassium and renal function). Our center starts at 1,500 calories per day for women, increasing by 250 calories per day to achieve 0.2 kg of weight gain per day. In Australia, some centers start at 2,000 calories per day (40), while in Canada, some centers advocate for starting at 1,200 calories per day. More evidence-based data over time should help clarify recommendations for universal use.
Intravenous fluids can overload the system, causing rapid fluid shifts and peripheral edema. Immediate attention should be given to the patient who develops altered mental status, tachycardia, signs of congestive heart failure, QTc prolongation, atypical abdominal pain, severe hypokalemia or hypophosphatemia (37-39). In patients who develop refeeding syndrome, management is supportive and includes use of compression stockings and leg elevation for management of edema. Avoid using diuretics (7).
A standard protocol
Following is a standard protocol for stabilizing a patient with NI. First, upon admission, an exhaustive history and physical should be done to find any differential diagnosis that could be the culprit (e.g., inflammatory bowel disease, celiac disease, renal tubular acidosis, or malignancy).
Given the high likelihood of psychiatric comorbidity, all of the patient's personal effects should be sequestered to ensure that he or she has no objects that can inflict self-damage (e.g., knives). Our center does not allow patients to keep purses at the bedside, due to the risk of pocketing drugs, bringing drugs from home to use for surreptitious ingestion, inflicting self-harm, and other negative behaviors.
The patient should be monitored 24 hours a day by a sitter whose main priorities are to ensure adherence to medical treatment, to monitor the degree of food intake, and to notify clinicians of any deviation from the protocol. Surreptitious exercise, or sequestering of food up the sleeve or elsewhere, should also be monitored and corrected. If trained appropriately, the sitter may also be available to monitor vital signs, record observations, and provide immediate support. The sitter should not engage in any discussion or boundary-crossing relationship with the patient; his or her role is to ensure that the nursing staff is appropriately informed of any change in the patient's behavior, to monitor the patient's adherence to the protocol, and to ensure appropriate patient safety.
Communication between the primary team and the patient should be based on discussion of improvement in vital signs, as well as of the importance of providing nutritional rehabilitation and repairing end-organ damage. At our center we use blinded weights, as we have found that sharing weight numbers tends to lead patients to self-sabotage. We focus on restoration of the heart muscle, stabilization of vital signs, eventual restoration of menstrual periods (once an outpatient), and other tangible medical improvements.
Given the likelihood of cardiac dysrhythmias associated with malnutrition, all patients should have an ECG documented upon admission, and we recommend continuous monitoring with cardiac telemetry. Discharge criteria include a heart rate over 40 beats per minute while asleep and over 50 beats per minute by day, without orthostatic hypotension greater than a shift of 20 to 30 points in diastolic blood pressure.
Patients should minimize physical activity to limit caloric expenditure and maximize nutritional recovery quickly while in the hospital.
Patients younger than 18 years of age should be managed with the Maudsley protocol, meaning that their parents choose the menu. Menus should be reviewed and modified by dietitians to ensure that food selection will adequately cover a patient's caloric requirements. Our center's protocol mandates finishing a meal within 30 minutes. For patients unable to finish 100% of a meal, nutritional supplements can be used. We provide supplements as follows, based on percent of the meal completed:
- Breakfast: 0% to 50%, 2 supplements; 50% to 90%, 1 supplement;
- Lunch or dinner: 0% to 50%, 3 supplements; 50% to 99%, 2 supplements.
Supplements should be finished orally; if not consumed in 20 minutes, they may be administered by nasogastric tube (NGT).
Nursing care is the mainstay of inpatient management. A nursing routine for patients admitted with NI should include the following:
- ensuring bed rest to avoid caloric expenditure;
- avoiding showers until resolution of orthostasis to minimize peripheral vasodilatation that can exacerbate hypotensive episodes;
- ensuring completion of meals and application of NGTs according to the protocol;
- monitoring vital signs and adherence to a cardiorespiratory monitor;
- taking daily weight measurements in the morning, with the patient backward on a scale in a hospital gown without other clothes;
- ensuring patients wear a hospital gown at all times to avoid hiding food or tools for self-harm; and
- ensuring that the patient obtains, maintains or loses inpatient privileges based on adherence to the protocol.
In our center, we allow initial use of computers, the Internet, TV and books, as well as visits from family, but no “contraband,” including Internet or media resources that promote abnormal eating attitudes and behaviors. For example, watching the TV show “The Biggest Loser” would not be acceptable, nor would constant viewing of The Food Network, as both could trigger abnormal eating attitudes and behaviors. On the whole, we start from a permissive stance rather than a punitive stance; if adherence occurs, privileges remain. Patients who do not follow our protocol lose the use of their cell phones, their daily wheelchair ride with a sitter to a site off the floor, and other privileges.
Inpatient orders should include a regular diet, starting at 1,500 calories per day for women and 1,750 calories per day for men; this minimizes the sudden caloric overload that can predispose to refeeding syndrome. A daily increase of 250 calories per day should be pursued.
A nutrition consult should be obtained upon admission, which will ensure the patient gets the appropriate caloric intake and has appropriate changes to his or her meal plan. Communication between the primary care team and the dietitian is paramount to ensure seamless teaching for outpatient management, preparation of parents for their role in refeeding, and caloric adjustments while the patient is in the hospital. The Cleveland Clinic stresses multidisciplinary care, including representatives from the departments of nutrition, social work, adolescent medicine, child life, behavioral medicine and psychiatry.
The only routine medications should be phosphorus supplements. In our institution, we prefer Neutra-Phos® (potassium phosphate, 250 mg/packet), two packs orally, twice daily for five days. These are supplemented regardless of serum phosphorus levels, in an effort to prevent refeeding syndrome.
In patients with severe anticipatory anxiety prior to meals, it is useful to consider the addition of an anxiolytic agent such as lorazepam, 0.5 to 1 mg orally, 30 minutes before initiation of any meal. While no evidence supports the use of psychotropic agents, an antidepressant with anxiolytic and appetite-stimulating properties (e.g., sertraline or citalopram) may be considered in patients with bulimia and substantial anxiety.
The bloodwork that should be obtained upon admission includes complete blood count, chemistries (including electrolytes), liver function tests, creatinine, thyroid-stimulating hormone, erythrocyte sedimentation rate, and a urine pregnancy test (for girls deemed at risk). A daily urinalysis to monitor renal concentrating ability should be obtained as well.
A basal ECG is recommended in all patients to measure QTc.
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For purposes of documentation, medical rather than psychiatric diagnoses have traditionally been used. These diagnoses include but are not limited to:
- NI, for starvation or disordered eating (CPT code 269.9),
- bradycardia (CPT code 427.89),
- prolonged QTc syndrome (CPT code 794.31),
- specific electrolyte derangements, such as hypophosphatemia, hypokalemia, metabolic alkalosis, and their accompanying codes,
- refeeding syndrome (CPT code varies by coder),
- orthostatic hypotension (CPT code 458.0),
- amenorrhea (CPT code 626.0),
- irregular menses (CPT code 626.4), and
- osteopenia (CPT code 733.90).
Inpatient management of patients with eating disorders is very challenging and complex, and requires a multidisciplinary approach. The use of an inpatient protocol functions as a guide that must be individualized and tailored to individual requirements.