1. Anurag Goel ST5 Royal Preston Hospital.
Refeeding Syndrome
Anurag Goel
ST5
Royal Preston Hospital.

2. 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

3. 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

4. How common is RFS? True incidence is unknown
Study1 of 10,197 patients, incidence of hypophosphatemia = 43 %
Malnutrition one of strongest risk factors
Parenteral patients = 100% incidence of hypophosphatemia (if no PO4 in PN) ; 18% with PO4 containing PN2.
1. Mineral & Electrolyte Metabolism 1990;16:365-8
2. Nutr Hosp 2006;21:

5. 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

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

8. 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

9. 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

10. 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

11. 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

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

13. 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

14. 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

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

16. 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

18. 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)

19. 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)

20. 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

21. Managing refeeding syndrome
Identifying patients who are at risk.
Prevent Refeeding syndrome.
Once refeeding starts: Replace K, PO4, Mg even if normal (not if levels high)
Potassium: 2-4 mmol/kg/day
Phosphate: mmol/kg/day
Magnesium: Oral 0.4 mmol/kg/d OR i.v. 0.2mmol/kg/d
PS : Prefeeding replacement is not required even if electrolytes abnormal !!

22. Managing refeeding syndrome
Identifying patients who are at risk.
Prevent Refeeding syndrome.
Prefeeding replacement is not required if electrolytes abnormal
Replace K, PO4, Mg even if normal (not if levels high)
Potassium: 2-4 mmol/kg/day
Phosphate: mmol/kg/day
Magnesium: Oral 0.4 mmol/kg/d OR i.v. 0.2mmol/kg/d
MANTAINANCE

25. Managing refeeding syndrome
Feed cautiously – 10kcal/kg for first 2 days, 5kcal/kg in extreme cases Increase slowly (over 4 -7 days)
No more than 150 to 200 gm of glucose
gm of protein per kg actual bodyweight
20-30% of calories from fat
PS: Weight Gain is NOT the goal in first 2 weeks.
Thiamine (B1) is essential coenzyme in CHO metabolism. The symptoms of thiamine deficiency (Wernickes encephalopathy) can be precipitated by feeding with CHO in a vitamin B depleted patient

26. Hypo-phosphataemia verses initial feed rate
Feed-rate kcal / kg

27. 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.
Thiamine (B1) is essential coenzyme in CHO metabolism. The symptoms of thiamine deficiency (Wernickes encephalopathy) can be precipitated by feeding with CHO in a vitamin B depleted patient

28. Electrolytes in Refeeding: phosphate
Oral
One tablet = 16.1mmolPO4, 20.4mmol Na,
3.1mmol K)
i.v. (phosphate polyfuser) 500ml = 50mmol PO4,
81mmol Na,
9.5mmol K+)
Mild ↓ PO4 ( mmol/l)
Phosphate Sandoz (16mmol each) - 2 tds
15mmol PO4 Polyfusor (150ml) over 12hrs peripherally
Moderate
↓ PO4 ( mmol/l)
Preferred route - i.v.
25mmol PO4 Polyfusor (250ml) over 12hrs peripherally
Severe ↓ PO4 (<0.3 mmol/l)
Not recommended
50mmol PO4 Polyfusor (500ml) over 24hrs peripherally, measuringPO4 at 12hrs.

29. Precautions
Renal impairment – Half initial dose in significant renal impairment + monitor levels carefully
Low calcium levels - Phosphate administration can 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 PO4 and prevent its absorption

30. 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 (12mmol each) 1 tds OR
Kay-Cee L 10 mls TDS (1mmol/ml)
KCl 20mmol in 1000 mls normal saline or 5% dextrose over 8hrs.
Moderate
↓ K+
( 2.5 – 2.9 mmol / l)
Sando K (12mmol each) 2 – 3 tds
KCl 40mmol in 1000 mls normal saline or 5% dextrose over 8hrs.
Severe
( <2.5 mmol / l)
Sando K (12mmol each) 3 – 4 tds (However prefer i.v. replacement)
KCl 40mmol in 1000 mls normal saline or 5% dextrose over 4 hrs. Retest before repeating
Concentration must not exceed 40mmol/l peripherally.
Maximum infusion rate is 20mmol/hr unless via a central line with ECG monitoring.
CORRECT ↓ Mg+

31. Electrolytes in Refeeding: Magnesium
Maintenance requirement = 0.2 mmol/kg/day i.v. (or 0.4 mmol/kg/day orally )
Requirement
i.v.
oral
Mild to moderate hypomagnesaemia ( mmol/l)
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) MgSO4 in 100 mls N.S. Over 3 hrs.
(1 gm MgSO4 = 4 mmol Mg+)
-Magnesium Glycerophosphate 2 tds (4mmol/tab)
-Magnaspartate 1 (6.5gm) sachet bd (10mmol/sachet)
-Magnesium oxide (160mgs) 3.9 mmol per capsule 2 tds
Severe hypomagnesaemia (<0.5 mmol/l)
24 mmol over 6 hours i.v. then as for mild to moderate ↓ Mg.
3 grams MgSO4 (12 mmol) in 100 mls N.S. Over 3 hrs. (x2 infusions)
BMJ. Jun 28, 2008; 336(7659): 1495–1498

32. Electrolytes in Refeeding : Calcium
10-20 mmol calcium ( 40-80ml of Calcium Gluconate 10%) in 500ml of Normal Saline 0.9% over 6-8 hours

33. 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

34. 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

35. Monitoring K+ - check daily. Once or twice weekly once stable.
Mg2+ and Po43- daily monitoring.
Once weekly when stable.
BMs 4 times a day – beware hyperglycaemia.

36. 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

37. 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 MgSO4 and or Cal Gluconate??

38. 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)

39. Questions