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 lifethreatening 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