Anurag Goel
ST5
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
 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;21:657-60.
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, PO4, 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. 0.2mmol/kg/d
PS : Prefeeding replacement is not required even if electrolytes abnormal !!
Managing refeeding syndrome



 Replace K, PO4, Mg even if normal (not if levels high)
 Potassium: 2-4 mmol/kg/day
 Phosphate: 0.3-0.6 mmol/kg/day
MANTAINANCE
 Magnesium: Oral 0.4 mmol/kg/d OR i.v. 0.2mmol/kg/d
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
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 1st day feed rate
(kcal / kg).
100
90
80
% Patients
70
whose
phosphate 60
dropped 50
below 0.65 40
mmo/l
30
20
10
0
P = 0.008
Feed-rate kcal / kg
≤ 10. N = 14
> 10, ≤ 20. N = 26
> 20. N = 8
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 =
16.1mmolPO4,
20.4mmol Na,
3.1mmol K)
i.v. (phosphate
polyfuser) 500ml =
50mmol PO4,
81mmol Na,
9.5mmol K+)
Mild ↓ PO4 (0.6-0.85
mmol/l)
Phosphate Sandoz
(16mmol each) - 2 tds
15mmol PO4 Polyfusor
(150ml) over 12hrs
peripherally
Moderate
↓ PO4 (0.3-0.6 mmol/l)
Phosphate Sandoz
(16mmol each) - 2 tds
25mmol PO4 Polyfusor
(250ml) over 12hrs
peripherally
Preferred route - i.v.
Severe ↓ PO4 (<0.3
mmol/l)
Not recommended
50mmol PO4 Polyfusor
(500ml) over 24hrs
peripherally,
measuringPO4 at 12hrs.
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
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
+
↓K
( <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+
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)
MgSO4 in 100 mls
N.S. Over 3 hrs.
-Magnesium
Glycerophosphate 2
tds (4mmol/tab)
-Magnaspartate 1
(6.5gm) sachet bd
(10mmol/sachet)
-Magnesium oxide
(160mgs) 3.9 mmol
per capsule 2 tds
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)
(1 gm MgSO4 = 4
mmol Mg+)
BMJ. Jun 28, 2008; 336(7659): 1495–1498
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
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.
 Mg2+ and Po43- 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 MgSO4 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)
Questions