Refeeding syndrome (RS) describes a group of metabolic derangements that occurs after the reintroduction or increased delivery of calories following a period of inadequate or absent caloric intake. First documented during World War II, RS caused a rise in mortality rates as nutrition was reinstituted in prisoners of war, concentration camp survivors, and famine victims. These extreme cases prompted research on how to prevent RS resulting in the 1944 Minnesota Starvation Experiment, a randomized control trial that studied the physiologic effects of prolonged inadequate nutrition. The study focused on both the effects of starvation and the results of different refeeding programs and included volunteer subjects who participated for a year in lieu of being drafted into the military. Observation of the subjects revealed physical, psychological, behavioral, and social changes. Specific impacts included significant weight loss, edema, hair loss, cold intolerance, and alterations in basal metabolic rate.1, 2
Today, much of the literature on this topic still comprises case reports describing extreme incidents of RS that resulted in organ failure and death. There is a need for further investigation into identifying who is at risk for RS, and how to safely reintroduce or increase delivery of calories after periods of extreme deficiency. In 2017, the American Society for Parenteral and Enteral Nutrition (ASPEN) Parenteral Nutrition Safety Committee and the Clinical Practice Committee formed a task force to meet this need by developing consensus recommendations for screening and managing RS based on specific criteria. Together, this interprofessional committee has redefined the benchmarks for who is at risk for RS and provides recommendations for safe introduction of nutritional support.
When treating patients at risk for RS, it is vital to understand the pathophysiology occurring from the reintroduction of carbohydrates. Once patients undergo long periods of inadequate nutrition, their bodies resort to the use of fat and protein stores to produce energy to survive. As the period of starvation continues, there is further depletion of energy stores, as well as vitamins and electrolytes. When carbohydrates are reinstituted into the body, insulin secretion occurs to assist with the metabolism of glucose. However, the increase in insulin secretion can cause an intracellular shift of potassium and phosphorus due to the demand for and stimulation of sodium-potassium adenosine triphosphatase (Na-K-ATPase). When this stimulation of Na-K-ATPase occurs, it can also reduce cellular transport of potassium because this enzyme is magnesium dependent. As glucose is reintroduced, a thiamine deficiency secondary to increased utilization may also occur, potentially causing encephalopathy and confusion.1
Identifying At-Risk Patients
Even when the pathophysiology is understood, the lack of a unifying definition for RS has caused challenges in identifying the risk for RS. Consistent characteristics of patients at risk include prolonged undernourishment and electrolyte abnormalities (eg, hypokalemia, hypomagnesemia, hypophosphatemia).1 Additionally, patients being treated for the following conditions are often candidates for RS:1,3
In 2017, the ASPEN Parenteral Nutrition Safety Committee and the Clinical Practice Committee task force was formed. The task force was composed of dieticians, nurses, pharmacists, and physicians with expertise in providing specialized nutrition. Together, the committee developed an outline of criteria for identifying adult patients at moderate to severe risk for RS (see TABLE 1). A standard benchmark was created for pediatric patients as well (see TABLE 2).
Treatment of Refeeding Syndrome
There is a shortage of information on exact formulas for initiating nutrition support in patients at risk of RS. Most recommendations are based on clinical experience and anecdotal evidence rather than statistically significant data. To address this gap in the literature, the ASPEN committee also developed consensus recommendations for the treatment of RS in at-risk adults. The recommendations begin with providing 10-20 kcal/kg, via parenteral nutrition (PN) if necessary, to the patient for the first day, with a 33% increase toward goal caloric intake every one to two days provided that electrolyte levels are within normal limits or able to be corrected in tandem.1 After initiating this nutrition support, it is vital to institute a protocol for monitoring patient status changes as RS is likely to occur within 70 hours of nutrition support initiation.4
Nutrition support treatment should also include both reactive and preemptive supplementation, dependent on the severity of RS. Draw labs specifically for serum magnesium, phosphorus, and potassium before the initiation of nutrition to establish a baseline for each patient.1
Recommended values for each electrolyte include:
Following the initiation of nutrition support, these electrolytes should be monitored a minimum of every 12 hours for the first 3 days in patients determined as high-risk, or more often as clinically necessary, then routinely thereafter.1 Electrolyte replacement may be needed according to the electrolyte serum levels and RS severity and should be individualized to each patient.3,5-7 Furthermore, it is recommended to supplement thiamine 100 mg before feeding or before initiating dextrose-containing IV fluids in patients determined as high-risk. However, drawing routine thiamine levels is not recommended due to little clinical value. Multivitamin (MVI) should be added to PN daily as long as PN is continued.1 Due to the risk of fluid overload, be cautious when providing sodium and hydration until the patient is metabolically stable.2 Monitor vital signs every 4 hours for the first day after initiating nutritional support treatment. Finally, note that daily weights with monitored intake and output should be performed routinely.1
Refeeding Syndrome is a complex disorder that can lead to serious harm and death in at-risk patients. Despite a historical shortage of clinical information on RS, approaching identification and parenteral nutrition treatment in a data-driven manner is vital to ensure appropriate patient care. Implementing a cohesive protocol for monitoring patient recovery and adjusting as individually necessary is essential.
Phil Ayers, PharmD, BCNSP, FMSHP, FASHP, is chief, clinical pharmacy services at Baptist Medical Center, and associate clinical professor at the University of Mississippi School of Pharmacy. He received his BS in pharmacy and his PharmD from the University of Mississippi. Phil serves as secretary-treasurer for the board of directors of ASPEN, is the past chair of the ASPEN Parenteral Nutrition Committee and is the chair of the USP Parenteral Nutrition Expert Panel.
Andrew Mays, PharmD, BCNSP, CNSC, is a clinical pharmacy specialist in nutrition support at the University of Mississippi Medical Center in Jackson. He is a clinical assistant professor at the University of Mississippi School of Pharmacy. Andrew serves as president-elect for the Mississippi Society of Health-System Pharmacists and president of the Mississippi Society for Parenteral and Enteral Nutrition. He received his PharmD from the University of Mississippi.
Caroline Bobinger, PharmD, BCPS, is a clinical pharmacy specialist at Baptist Medical Center in Jackson, Mississippi. She received her BS in pharmacy and her PharmD from the University of Mississippi.
Sarah Erwin, RDN, LD, is a registered dietitian nutritionist who received her bachelor of science from Mississippi State University and completed her dietetic internship through North Oaks Medical Center in Hammond, Louisiana. She has worked in both inpatient and outpatient settings and is currently employed by Baptist Medical Center in Jackson, Mississippi. Sarah presently serves in the roles of Nutrition Support, Adult Critical Care, and Critical Illness Recovery.