Psychosomatics 49:249-251, May-June
doi: 10.1176/appi.psy.49.3.249
© 2008 Academy of Psychosomatic Medicine
Too Much Too Soon? Refeeding Syndrome as an Iatrogenic Cause of Delirium
Jason P. Caplan, M.D.
Received March 13, 2007; revised June 7, 2007; accepted June 18, 2007. From Massachusetts General Hospital, Warren 605, 55 Fruit St., Boston, MA 02114. Send correspondence and reprint requests to Dr. Caplan. e-mail: jpcaplan{at}gmail.com
© 2008 The Academy of Psychosomatic Medicine
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ABSTRACT
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BACKGROUND: Delirium is a significant and costly complication of medical hospitalization, and it has been shown to be a significant predictor of morbidity and mortality. It is often noted as a symptom in reported cases of refeeding syndrome, which is a potentially fatal complication in the treatment of patients suffering from malnutrition. OBJECTIVE: A case of delirium due to refeeding syndrome in a 61-year-old man is presented to help clinicians recognize this entity. The pathophysiology of refeeding syndrome and its possible role as an as-yet poorly-identified iatrogenic cause of delirium are discussed. METHOD: A diagnosis of delirium due to refeeding syndrome was made, and a nutrition consult was requested. Per nutrition recommendations, the patient was placed on a restricted calorie regimen, with aggressive supplementation of magnesium and phosphate. RESULTS: With his new dietary regimen, his mental status gradually improved, with complete resolution of his delirium by the 8th hospital day. He suffered no further episodes of confusion or disorientation. CONCLUSION: The relationship between refeeding syndrome and delirium may be of particular significance in the elderly, since malnutrition, medical hospitalization, and delirium are prevalent phenomena in this population.
Key Words: Eating Disorders • Anorexia • Refeeding
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INTRODUCTION
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"Mr. B" was a 61-year-old white man with a previous history of bipolar disorder, panic disorder, and cerebral aneurysm clipping, who was admitted to a major tertiary-care hospital with worsening gait disturbance and a weight loss of 80 pounds over the preceding 4 months. The patient noted that his progressive gait disturbance and frequent falls had limited his ability to leave his apartment to get food, reporting "after a few weeks of not eating as much, I just lost my appetite." Psychiatric consultation was sought on admission to assist with management of his complex psychotropic regimen, which included sertraline, olanzapine, gabapentin, diazepam, and buprenorphine (prescribed for mood stabilization), which had served to control his mood and anxiety symptoms for many years. He noted that he had been able to maintain his medication regimen via home delivery of his prescriptions.
On admission, Mr. B experienced a marked improvement in his appetite. He was noted to be eating throughout his initial psychiatric consultation, and multiple progress notes from other disciplines remarked on the volume of food he was consuming. His initial psychiatric examination revealed no active signs or symptoms of depression, mania, anxiety, or psychosis. Furthermore, no deficits were observed on thorough cognitive testing. On the evening of his 4th hospital day, nursing staff remarked that Mr. B seemed confused and disoriented. Repeat psychiatric examination on the morning of his 5th hospital day revealed that he was oriented only to himself, with marked deficits in attention and memory—a stark contrast to results of the mental status exam that had been conducted on admission. Laboratory studies performed that morning revealed no indicators of infection, with a white blood count of 7.0, a negative urinalysis, and a chest x-ray without evidence of infiltrate or effusion. Physical exam provided no indication for a cause of his confusion, and a CT scan of his head showed no changes from previous studies. It was noted, however, that his serum phosphate and magnesium levels had fallen precipitously from their recorded values on admission (from 3.1 mg/dL to 1.2 mg/dL, and from 1.8 meq/L to 1.0 meq/L, respectively).
A diagnosis of delirium due to refeeding syndrome was made, and a nutrition consult was requested. Per nutrition recommendations, Mr. B was placed on a restricted calorie regimen, with aggressive supplementation of magnesium and phosphate. Despite his confusion and intermittent somnolence, Mr. B continued to eat voraciously from his meal trays, raising concern for aspiration in the context of his clouded mental status. On his 6th hospital day, he was noted to suffer dyspnea and wheezing, with chest x-ray revealing new changes in the lower lobe of his right lung, consistent with aspiration pneumonia. Nonetheless, with his new dietary regimen, his mental status gradually improved, with complete resolution of his delirium by the 8th hospital day (without changes to his psychotropic regimen), despite his lingering aspiration pneumonia.
Mr. B remained in the hospital for a total of 28 days, undergoing an extensive work-up for his gait disturbance. He suffered no further episodes of confusion or disorientation. At the time of discharge, no clear etiology of his gait disturbance had been identified, although spinocerebellar degeneration and the cerebellar variant of Shy-Drager syndrome remained in the differential diagnosis.
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Discussion
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First described in Japanese prisoners of war in the aftermath of World War II by Schnitker and colleagues,5 refeeding syndrome is a potentially fatal complication of the reinitiation of carbohydrate and protein metabolism in malnourished persons.6
During periods of starvation, the total body stores of potassium, magnesium, and phosphate (along with other important factors) are depleted, although serum levels are maintained at the expense of the intracellular environment. In the absence of carbohydrate metabolism, energy is instead produced from lipolysis, resulting in a decrease in insulin secretion. In the setting of refeeding, the sudden excesses of carbohydrate and protein produce an anabolic environment, creating an intracellular demand for glucose, phosphate, and potassium. The simultaneous increase in insulin secretion similarly enhances the transport of potassium, phosphate, and magnesium into the cells. These factors combine to cause severe and abrupt hypokalemia, hypomagnesemia, and (most prominently) hypophosphatemia within 3–4 days of refeeding.
Deficits of phosphate interfere with the production of ATP and 2,3-diphosphoglycerate (2,3-DPG), which are vital intermediaries in multiple ubiquitous cellular processes. Potassium and magnesium are similarly vital in the maintenance of membrane potentials and cellular metabolism.7 Thus, refeeding syndrome presents clinically with a spectrum of symptoms, including weakness, muscle pain, ataxia, paresthesia, paralysis, confusion, respiratory depression, seizures, cardiac arrhythmia, and sudden death. It can be avoided by gradual caloric repletion, usually starting at 20 kcal/kg/day, with a gentle titration upward as the body is able to replete its stores.6 Close monitoring and supplementation of potassium, magnesium, phosphate, thiamine, and other vitamins and trace elements can aid in the avoidance of critical deficiencies.
In the psychiatric literature, refeeding syndrome has most often been associated with patients suffering from anorexia nervosa. Multiple published case reports of refeeding syndrome in the settings of anorexia nervosa, chronic alcohol dependence, or malnutrition due to other causes all list confusion or delirium as a primary symptom.8–11 Despite the reported frequency of cognitive impairment presenting as a symptom of refeeding syndrome, a literature search did not reveal any published data regarding how frequently the diagnosis of delirium in hospitalized patients is attributed to an underlying refeeding syndrome such as that seen in the case report above. Because patients in the general hospital frequently have multiple other potential causes for delirium, refeeding syndrome may be overlooked, given the frequent presence of infection, deliriogenic medications, or neuropathology. Indeed, in this case, the diagnosis of refeeding syndrome was made only after careful investigation of other potential etiologies of delirium. Stable neuroimaging and no previous history of confusion seemed to indicate that fluctuating cognitive changes were not a part of his presenting complaint. Although Mr. B was prescribed several potentially deliriogenic medications (most notably diazepam), he had been stable on this medication regimen for many years without acute confusion. Although he did eventually develop an aspiration pneumonia, this did not occur until after the onset of his confusion, and it was thought to be a result of his delirium (due to inability to protect his airway), rather than a cause. The relationship between refeeding syndrome and delirium may be of particular significance in elderly patients, since malnutrition, medical hospitalization, and delirium are prevalent phenomena in this population. One study found 91% of elderly patients in subacute-care settings to be malnourished or at risk for malnutrition,12 with another recent study finding that 14.1% of elderly patients suffered from hypophosphatemia congruent with a diagnosis of refeeding syndrome in the general-hospital setting.13 Another prospective study of intensive-care unit patients of all ages found that 34% of patients experienced refeeding syndrome.14
The detection of hypokalemia and hypomagnesemia are of particular importance in patients suffering from delirium that may require treatment with haloperidol or other neuroleptics, since these particular deficiencies are known to increase the risk of QTc prolongation and the possible development of torsades de pointes (a potentially fatal polymorphic ventricular tachycardia), a risk also associated with neuroleptic administration.15 It is well known that hospitalized elderly and critically ill patients are at increased risk for the development of delirium, a risk that is magnified by concurrent malnutrition or electrolyte disturbance. Given the remarkably high indications of malnutrition reported in nonhospitalized elderly persons, refeeding syndrome may be precipitated on admission to the general hospital, where they are often provided with complete nutrition and prompting from hospital staff to "clean their plates." The potential role of refeeding syndrome as an iatrogenic cause of delirium in the general hospital requires further investigation.
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ABSTRACT
INTRODUCTION
