Refeeding Syndrome

Incidence and Management

Ismail Sagap

Chairman NST UKMMC

Malnutrition

N=502 consecutive admission Malnutrition was present in ~24% of hospitalized patients. The prevalence of malnutrition was significantly higher in

malignant diseases (50.9 vs. 21.0%, p < 0.0001). High prevalence rates >30% were observed in subgroups of

inflammatory bowel diseases, chronic heart failure and benign lung diseases Patients with gastrointestinal diseases, were not more frequently

malnourished than other medical patients (28.8 vs. 22.0%). Malnourished patients were significantly

older 40% longer hospital stay than well-nourished patients

Pirlich M et al: Prevalence of malnutrition in hospitalized medical patients: impact of underlying disease. Dig Dis.

2003;21(3):245-51

Refeeding Syndrome (RFS)

First described in starved Far East prisoners of war after World War II

when starved occupants of Leningrad and prisoners of war were re-fed and developed edema, dyspnea, and cardiac failure, which resulted in death

Refers to metabolic complications that can occur when nutrition is reintroduced for patients who are severely malnourished.

Incidence

Unknown No universal definition Wide variety of clinical manifestation

Using a proxy marker to show patients at risk of refeeding syndrome severe hypophosphataemia

incidence = 0.43% in hospital patients, with malnutrition being one of the strongest risk factors

prospective study of intensive care unit ICU patients, 34% of patients experienced hypophosphataemia soon after feeding was started

Camp MA, Allon M. Severe hypophosphatemia in hospitalised patients. Mineral & Electrolyte

Metabolism. 365368. Marik PE, Bedigan MK. Refeeding Hypophosphataemia in an Intensive Care Unit: A Prospective

Study. Arch Surg. 131:10431047

How?

Administration of a glucose load by any route (but classically with intravenous glucose solutions or TPN) leads to intracellular electrolyte shifts and sodium retention which are responsible for most of the clinical manifestations of RFS

Crook MA, Hally V, Panteli JV: The importance of the refeeding syndrome. Nutrition 2001;17:6327

Mallet M: Refeeding syndrome. Age Ageing 2002;31:656

Syndrome

Acute electrolyte abnormalities

Fluid retention

Dysfunction of various organ systems

potentially fatal

occur with any form of nutrition (oral,enteral, or parenteral) in patients who are malnourished from any cause.

Pathophysiology

During a period of suboptimal oral intake there will be loss of : lean tissue mass water minerals

Results in total body depletion of phosphorus. When a malnourished patient is administered nutrition,

(typically in the form of CHO) Insulin release leads to transcellular shifts of phosphorus,

potassium and magnesium hypophosphatemia hypokalemia hypomagnesemia

Pathophysiology

In addition, increased tissue anabolism leads to increased cellular demand for phosphorus, glucose, potassium and water.

Synthesis of adenosine triphosphate, 2,3-diphosphoglycerate, and creatine phosphokinase may also contribute to phosphorus depletion.

Carbohydrate loading also leads to sodium and water retention, which results in volume expansion and edema, which can lead to circulatory overload and heart failure.

Hyperglycemia is common and can lead to osmotic diuresis, acidosis, and increased susceptibility to bacterial infection

Marinella MA: Refeeding syndrome, in Frequently Overlooked Diagnoses in Acute Care. 2003

Soloman DM, Kirby DF: The refeeding syndrome: A review. JPEN J Parenter Enteral Nutr 1990;14:907 Marik PE, Bedigian MK: Refeeding hypophosphatemia in critically ill patients in an intensive care unit. Arch Surg 1996;

131:10437

Pathophysiology

Also, hypophosphatemia may lead to decreased erythrocyte adenosine triphosphate levels

resulting in increased cell membrane rigidity hemolytic anemia Thrombocytopenia

Diminished red cell levels of 2,3diphosphoglycerate impair oxygen release from hemoglobin to the tissues local tissue hypoxia

Dwyer K, Barone JE, Rogers JF: Severe hypophosphatemia in postoperative patients. Nutr Clin Pract 1992;7:27983

Fisher M, Simpser E, Schneider M: Hypophosphatemia secondary to oral refeeding in anorexia nervosa. Int J Eat Disord 2000;28:1817

Clinical menifestations

Cardiac* Arrhythmias Congestive heart failure

Pulmonary Dyspnea Respiratory failure

Neurologic Seizures Weakness Paraesthesias Delirium Guillain-Barre

Musculoskeletal Rhabdomyolysis Myalgia

Hematologic Hemolytic anemia Thrombocytopenia

Immunologic Infection

Metabolic Metabolic acidosis Hyperglycemia/insulin resistance

Renal Acute tubular necrosis Myoglobinuria Hemoglobinuria

*major cause of mortality

Patients at risk

Prolonged starvation/poor intake

Dysphagia Vomiting Diarrhea Surgery Nasogastric suction Alcoholism Cancer chemotherapy Homelessness Anorexia nervosa Depression

Diagnosis

Recognition of the syndrome and having a high index of suspicion in at-risk patients especially those with little or no oral intake for several days

Eg. a patient transferred to our ward from a medical or surgical floor may have a recent history of vomiting, diarrhea, or nil orally status and on reinstitution of oral or enteral feeding, may develop RFS.

Eg. Recent poor oral intake for several days develop symptoms of confusion, weakness, dyspnea, tachycardia, paresthesias

Laboratory evidence of hypophosphatemia hypokalemia, hypomagnesemia hyperglycemia

Treatment

Recognizing patients at risk Reinstituting nutrition slowly*

orally, enterally or parenterally

Supplement (Oral or parenteral) K+, Mg2+ and PO4

In patients with established RFS Slow the rate of caloric intake Decrease Na+ and intravenous fluid Treat hyperglycemia with insulin Supplement electrolytes

NOT discontinue nutritional support altogether!

*Melchior JC: From malnutrition to refeeding during anorexia nervosa. Curr Opin Clin Nutr Metab Care 1998;1:4815

Guidelines for management. * if severely malnourished, e.g. BMI less than 14 kg/m or negligible intake for 2 weeks or more, start feeding at maximum of 5 kcal/kg/day. From NICE and British Association of Parenteral and Enteral Nutrition guidelines

Treatment

severe hypoK+ (2.5 mEq/liter) IV KCL via a central vein.

If hypoPO4 is also present IV potassium phosphate in doses of 15 mmol or

0.08 mmol/kg Rosen GH, Boullata JI, ORangers EA, et al: Intravenous phosphate repletion regimen for critically ill patients with moderate hypophosphatemia. Crit Car

Me1995;23:120410

Significant hypoMg2+ 24 g of intravenous magnesium sulfate

Conclusions

RFS is an underappreciated common cause of life-threatening electrolyte derangements in hospitalized patients. It can be fatal.

Risks for developing RFS include (malnourished)

poor oral intake

vomiting and/or diarrhea

recent surgery

Dysphagia

Given nutritional support

Conclusions

At risk patients (malnourished) should be regularly monitor serum phosphorus, potassium, magnesium,

glucose and clinical volume status.

Supplemental magnesium, phosphorus, and potassium should be considered in at-risk patients and for patients with established electrolyte deficiencies

Glycaemic control is also important