To the Editor:

The refeeding syndrome (RFS) is a severe hydroelectrolytic diorder, which is generated following dietary supplementation in patients with major basic nutritional deprivation. In this syndrome, multiple electrolyte disorders, vitamin deficiencies and severe cardiovascular effects appear.1

We report the case of a 70-year-old female with high blood pressure and endometrial adenocarcinoma diagnosed in 2010, who was treated with hysterectomy, chemotherapy and pelvic radiation therapy. About a month after completing chemotherapy, she was admitted with febrile neutropenia, ileal enteritis and E. coli bacteraemia. Tests highlighted severe leukopenia (0.22x109/l, 0 neutrophils), creatinine 70.2mmol/l sodium 139mmol/l, potassium 3.74mmol/l, serum calcium 2.45mmol/l, serum phosphate 1.2mmol/l, metabolic acidosis (pH 7.27, pCO2 45mmHg, bicarbonates 20.7mmol/l) and hypoalbuminaemia (32mg/l).

Bowel rest, intravenous fluid therapy, empirical antibiotic therapy and granulocyte colony-stimulating factor are introduced. After slow abdominal evolution, she started on parenteral nutrition (PN) on the third day with intake of 1500kcal/day. After 24 hours, she presented neurological symptoms with generalised tremors, hyperreflexia, Chvostek and Trousseau signs, peripheral oedema and QTc prolongation on electrocardiogram. Tests highlighted hypocalcaemia (1.6mmol/l-1.76 albumin-corrected), hypomagnesaemia (0.45mmol/l), hypophosphataemia (0.68mmol/l), hypokalaemia (2.59mmol/l), normal renal function and acid-base balance with pH 7.41, pCO2 31mmHg, pO2 48mmHg and bicarbonate 19.6mmol/l. Given the temporal relationship with the start of PN, RFS was suggested as the clinical profile.

DISCUSSION

RFS is a series of hydroelectrolytic disorders (hypophosphataemia, hypomagnesaemia, hypokalaemia) that may occur after initiation of enteral or parenteral nutrition with high caloric intake, and that may have life-threatening consequences. The condition of chronic malnutrition (marasmus, malabsorption syndrome, chronic alcoholism, multiple comorbidities in elderly patients and morbidly obese patients after bariatric surgery), anorexia nervosa, poorly controlled diabetes mellitus, chronic use of antacids, high metabolic stress lasting more than 7 days, recent surgery and cancer are predisposing factors for developing RFS.2 In these circumstances, the decrease of baseline metabolism and insulin levels produce a number of adaptive mechanisms that lead to increased protein catabolism and fat metabolism with ketone body generation and enhancement of gluconeogenesis as an energy generation source (Figure 1).3

After refeeding, nutrient availability generated increased levels of insulin with the subsequent introduction of phosphorus, potassium, magnesium and thiamine intracellularly, used to reactivate the glycolysis process. These components decreased rapidly in plasma, which added to metabolic and water overload in a depressed baseline myocardium, produces serious clinical consequences (Table 1).2

RFS treatment focuses on prevention. The most important steps are to identify the patients at risk, start nutrition with a low energy intake (20kcal/kg/day or 1000kcal/day) and gradually introduce the requirements for a period of one week. If ionic disturbances are present, they should be corrected before starting refeeding. NICE4 also recommends thiamine intake. When signs and symptoms of RFS appear, nutrition should be discontinued, and early correction of electrolyte abnormalities as well as additional supportive measures must be carried out according to the profile (vasopressors, oxygen, diuretics, etc...).4

Our case dealt with a patient with multiple comorbidities, cancer, with a high risk of suffering RFS, who started PN with standard caloric intake, which resulted in hypophosphataemia, hypokalaemia, hypomagnesaemia (secondary hypocalcaemia) and hypervolaemia, with neurological consequences and electrocardiography repercussions. Caloric intake decreased to 1000kcal per day (but did not stop) as well as the volume of intravenous fluid therapy. Corrective treatment of the electrolyte imbalances was started and thiamine supplements were administered, with improvement of neurological symptoms, peripheral oedema and correction of electrolyte imbalances.

RFS is a severe disorder and is avoidable, and as such, it should be considered in all patients at high risk of early nutritional support.

Conflicts of interest

The authors declare that they have no conflicts of interest related to the contents of this article.

Figure 1. Refeeding syndrome physiopathology

Table 1. Disorders and symptoms associated with refeeding syndrome