Refeeding Syndrome Anurag Goel ST 5 Royal Preston

Refeeding Syndrome Anurag Goel ST 5 Royal Preston Hospital.

What is It? � Potentially fatal shifts in fluids and electrolytes that may occur in malnourished patients receiving artificial refeeding (whether enterally or parenterally) �The hallmark biochemical feature of re feeding syndrome is hypophosphataemia JPEN J Parenter Enteral Nutr 1990; 14: 90 -7

Discovery of RFS �Observed & described after WWII �Victims of starvation experienced cardiac and/or neurologic dysfunction �After being reintroduced to food �Neurologic signs & symptoms developed later

How common is RFS? �True incidence is unknown �Study 1 of 10, 197 patients, incidence of hypophosphatemia = 43 % �Malnutrition one of strongest risk factors �Parenteral patients = 100% incidence of hypophosphatemia (if no PO 4 in PN) ; 18% with PO 4 containing PN 2. 1. Mineral & Electrolyte Metabolism 1990; 16: 365 -8 2. Nutr Hosp 2006; 21: 657 -60.

Understanding Starvation �Glucose is normally the main fuel. �Starvation - Shifts to protein & fat �Insulin ↓ (due to ↓ availability of glucose) �Catabolism of protein → loss of cellular & muscle mass → atrophy of vital organs & internal organs �Respiratory & cardiac function ↓ due to muscular wasting & fluid/electrolyte imbalances �Body is now surviving by slowly consuming itself

Starvation �The serum concentrations of electrolytes may appear normal in the starved state!! (Due to alterations in renal excretion rates of electroytes. )

Effects of Refeeding on the Cardiovascular System �Increases in heart rate, blood pressure, oxygen consumption, cardiac output �expansion of plasma volume �Response is dependent on amount of calories, protein and sodium given �The malnourished heart can easily be given a metabolic demand that is too high for it to supply

Effects of Refeeding on the Cardiovascular System �Congestive Heart Failure is a common complication of refeeding �Cardiac output can’t increase enough to meet the needs from the increased plasma volume, increased oxygen consumption and increases in blood pressure and heart rate

Effects of Refeeding on the Respiratory System �Excess carbon dioxide production and increased oxygen consumption from giving too much glucose and overfeeding �A person with malnutrition-induced respiratory muscle wasting can get short of breath �Can’t sustain an increased ventilatory drive �Pulmonary edema due to increased water load

Effects of Refeeding on the Gastrointestinal System �Activity of the brush border enzymes and pancreatic enzyme secretion return to normal with refeeding �Requires a period of readaptation to food to minimize GI complaints �Diarrhea, nausea and vomiting

Main Pathophysiologic Features �Disturbances of body-fluid distribution �Abnormal glucose & lipid metabolisms �Thiamine deficiency �Hypophosphatemia �Hypomagnesemia �Hypokalemia

Hypophosphatemia �Phosphorus is predominantly intracellular �Impaired cellular-energy pathways �Adenosine triphosphate (ATP) � 2, 3 -diphosphoglycerate (2, 3 DPG) �Impaired skeletal-muscle function �Including weakness & myopathy �Seizures & perturbed mental state �Impaired blood clotting processes & hemolysis also can occur

Hypomagnesemia �cofactor in most enzyme systems, including oxidative phosphorylation and ATP production. �also necessary for the structural integrity of DNA, RNA, and ribosomes. �Mild cases: often asymptomatic �Severe cases: �Cardiac arrhythmias �Abdominal discomfort �Anorexia �Tremors, seizures, & confusion �Weakness

Hypokalemia �major intracellular cation. Serum levels may remain normal in starvation! �Features: �Cardiac arrhythmias �Hypotension �Cardiac arrest �Weakness �Paralysis �Confusion �Respiratory Depression

Thiamin Deficiency �Functions as a cofactor in intermediary carbohydrate metabolism (TCA cycle) �Amount needed depends on carbohydrate ingested. �Mental confusion, ataxia, muscle weakness, edema, muscle wasting, tachycardia and cardiomegaly �Wernicke’s encephalopathy can be precipitated by carbohydrate feeding in thiamine-deficient patients

Who is at risk? Some risk: �People who have eaten little or nothing for more than 5 days �REMEMBER: Even an overweight or obese patient can be malnourished & a victim for RFS NICE guidelines (2006)

Who is at risk? High Risk �Either patient has 1 or more: � BMI <16 � Unintentional weight loss >15% in past 3 -6 mo � Little/no nutritional intake for 10 days � Low levels of potassium, phosphate, or magnesium before feeding �Or patient has 2 or more: � BMI <18. 5 � Unintentional weight loss >10% in past 3 -6 mo � Little/no nutritional intake for >5 days � History of alcohol misuse or drugs NICE guidelines (2006)

Patients at high risk: �Anorexia nervosa �Chronic alcoholism �Oncology patients �Postoperative patients �Elderly �Uncontrolled diabetes mellitus �GI fistulas �Chronic malnutrition: �Marasmus �Prolonged fasting or low energy diet �Morbid obesity with weight loss �Long term antacid users �Long term diuretic users

Managing refeeding syndrome �Identifying patients who are at risk. �Prevent Refeeding syndrome. �Once refeeding starts: Replace K, PO 4, Mg even if normal (not if levels high) � Potassium: 2 -4 mmol/kg/day � Phosphate: 0. 3 -0. 6 mmol/kg/day � Magnesium: Oral 0. 4 mmol/kg/d OR i. v. 0. 2 mmol/kg/d PS : Prefeeding replacement is not required even if electrolytes abnormal !!

Managing refeeding syndrome �Identifying patients who are at risk. �Prevent Refeeding syndrome. �Prefeeding replacement is not required if electrolytes abnormal �Replace K, PO 4, Mg even if normal (not if levels high) �Potassium: 2 -4 mmol/kg/day MANTAINANCE �Phosphate: 0. 3 -0. 6 mmol/kg/day �Magnesium: Oral 0. 4 mmol/kg/d OR i. v. 0. 2 mmol/kg/d

Managing refeeding syndrome �Feed cautiously – 10 kcal/kg for first 2 days, 5 kcal/kg in extreme cases Increase slowly (over 4 7 days) � No more than 150 to 200 gm of glucose � 1. 2 -1. 5 gm of protein per kg actual bodyweight � 20 -30% of calories from fat �PS: Weight Gain is NOT the goal in first 2 weeks.

Hypo-phosphataemia verses initial feed rate Phosphate levels as a function of 1 st day feed rate (kcal / kg). P = 0. 008 100 90 80 70 60 % Patients whose phosphate dropped below 0. 65 mmo/l 50 40 30 20 10 0 Feed-rate kcal / kg ≤ 10. > > 20. N = 10, ≤ N = 14 20. 8 N= 26

Managing refeeding syndrome � Pabrinex (high dose thiamine) and balanced multivitamin/mineral supplement �ORAL: Thiamine 200 – 300 mgs + Vit B Co Strong 1 -2 tabs TDS X 10 days �IV: Pabrinex OD X 10 Days. �first dose being administered at least 30 minutes before starting feeding.

Electrolytes in Refeeding: phosphate Oral One tablet = 16. 1 mmol. PO 4, 20. 4 mmol Na, 3. 1 mmol K) i. v. (phosphate polyfuser) 500 ml = 50 mmol PO 4, 81 mmol Na, 9. 5 mmol K+) Mild ↓ PO 4 (0. 6 -0. 85 mmol/l) Phosphate Sandoz (16 mmol each) - 2 tds 15 mmol PO 4 Polyfusor (150 ml) over 12 hrs peripherally Moderate ↓ PO 4 (0. 3 -0. 6 mmol/l) Phosphate Sandoz (16 mmol each) - 2 tds 25 mmol PO 4 Polyfusor (250 ml) over 12 hrs peripherally Preferred route - i. v. Severe ↓ PO 4 (<0. 3 mmol/l) Not recommended 50 mmol PO 4 Polyfusor (500 ml) over 24 hrs peripherally, measuring. PO 4 at 12 hrs.

Precautions � Renal impairment – Half initial dose in significant renal impairment + monitor levels carefully �Low calcium levels - Phosphate administration cause hypocalcaemia �Rapid IV infusion may cause metastatic soft tissue calcification �CCF, hypertension : High sodium content of Phosphate-Sandoz® and Phosphates Polyfusor® �Oral Mg, Ca or Al containing products – binds oral PO 4 and prevent its absorption

Electrolytes in Refeeding: Potassium Mantainance requirement 2 -4 mmol/Kg/Day ORAL (not preferred) I. V. Mild ↓ K+ (3. 0 – 3. 5 mmol/l) Sando K (12 mmol each) KCl 20 mmol in 1000 mls 1 tds OR normal saline or 5% Kay-Cee L 10 mls TDS dextrose over 8 hrs. (1 mmol/ml) Moderate ↓ K+ ( 2. 5 – 2. 9 mmol / l) Sando K (12 mmol each) KCl 40 mmol in 1000 mls 2 – 3 tds normal saline or 5% dextrose over 8 hrs. Severe ↓ K+ ( <2. 5 mmol / l) Sando K (12 mmol each) KCl 40 mmol in 1000 mls 3 – 4 tds (However normal saline or 5% prefer i. v. replacement) dextrose over 4 hrs. Retest before repeating Concentration must not exceed 40 mmol/l peripherally. Maximum infusion rate is 20 mmol/hr unless via a central line with ECG monitoring. CORRECT ↓ Mg+

Electrolytes in Refeeding: Magnesium Maintenance requirement = 0. 2 mmol/kg/day i. v. (or 0. 4 mmol/kg/day orally ) Mild to moderate hypomagnesaemia (0. 5 -0. 7 mmol/l) Severe hypomagnesaemia (<0. 5 mmol/l) Requirement i. v. oral Initially 0. 5 mmol/kg/day over 24 hours iv, then 0. 25 mmol/kg/day for 5 days i. v. 2 gms (8 mmol) Mg. SO 4 in 100 mls N. S. Over 3 hrs. -Magnesium Glycerophosphate 2 tds (4 mmol/tab) -Magnaspartate 1 (6. 5 gm) sachet bd (10 mmol/sachet) -Magnesium oxide (160 mgs) 3. 9 mmol per capsule 2 tds 24 mmol over 6 hours i. v. then as for mild to moderate ↓ Mg. 3 grams Mg. SO 4 (12 mmol) in 100 mls N. S. Over 3 hrs. (x 2 infusions) (1 gm Mg. SO 4 = 4 mmol Mg+) BMJ. Jun 28, 2008; 336(7659): 1495– 1498

Electrolytes in Refeeding : Calcium � 10 -20 mmol calcium ( 40 -80 ml of Calcium Gluconate 10%) in 500 ml of Normal Saline 0. 9% over 6 -8 hours

Electrolytes in Refeeding : Sodium �Sodium must be given carefully to prevent overexpansion of the extracellular fluid �Upon refeeding, renal sodium losses stop �Hence Sodium and water retention �Restrict Sodium <1 mmol/Kg/day

Fluid in Refeeding �Refeeding results in expansion of the extracellular space and fluid must be given carefully �Aim for fluid replacement 20 – 30 mls/Kg/Day �Weight gain greater than 1 kg the first week is due to fluid retention �Fluid may need to be restricted to 800 to 1000 mls/day �Increases in blood pressure, heart rate and respiratory rate may be early signs of fluid excess

Monitoring �K+ - check daily. �Once or twice weekly once stable. �Mg 2+ and Po 43 - daily monitoring. �Once weekly when stable. �BMs 4 times a day – beware hyperglycaemia.

Priorities – Only one cannula!! �Aim to correct potassium �Then bring magnesium and calcium to safe levels, not necessarily in the normal range �Then bring phosphate levels up to a safe, not necessarily normal value �This may need to be done in stages to allow for further calcium or magnesium infusions

Priorities – Only one cannula!! �Aim to correct potassium �Then bring magnesium and calcium to safe levels, not necessarily in the normal range �Then bring phosphate levels up to a safe, not necessarily normal value �This may need to be done in stages to allow for further calcium or magnesium infusions. � Can we mix the KCl with Mg. SO 4 and or Cal Gluconate? ?

Summary Points �Characterized by hypophosphatemia �Patients at high risk: undernourished, little or no energy intake for > 10 days �Start refeeding at low levels �Correction of electrolyte & fluid imbalances before feeding is not necessary (do not delay feeding)

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