Refeeding Syndrome

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Refeeding Syndrome

• Pam Roose RD, CNSD
• Marquette General Health System

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Study from Weinsier and colleagues

• 2 females 28 and 66 years old
• They were 40 and 70 of ideal body weight
• Parenteral nutrition was started D25W Amino Acids
  4 at 85ml/hr and 125ml/hr

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Study continued

• Both had low serum phosphorus, potassium and
  magnesium concentrations
• The first patient had a cardiovascular arrest and
  died within 24 hours
• The second patient had a respiratory arrest
  within 48 hours of parenteral nutrition and died
  within 3 weeks

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Defining Refeeding Syndrome

• Combination of metabolic and physiologic
  abnormalities that could occur during nutritional
  repletion
• Could potentially lead to death with aggressive
  repletion or over feeding

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Objectives

• To be able to define refeeding syndrome
• To identify patients at risk for refeeding
  syndrome
• To provide recommendations for prevention and
  treatment of refeeding syndrome

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The Hidden Syndrome

• Refeeding syndrome is generally under diagnosed
• Most clinicians do not look for it
• Therefore do not recognize it

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Nutritional Repletion

• Maintenance IV with Dextrose
• Enteral Nutrition
• Oral Diet
• Tube Feedings
• Parenteral Nutrition
• TPN (Central)
• PPN (Peripheral)

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Defining History

• Refeeding syndrome was first identified in
  prisoners after World War II
• After a long starvation, food was provided to the
  prisoners
• Cardiac failure seemed to occur

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With refeeding syndrome there can be changes in

• Phosphorus
• Potassium
• Magnesium
• Glucose Metabolism
• Vitamin Status
• Fluid Balance

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Most often reported life-threatening events
associated with refeeding

• Cardiac Arrhythmias
• Respiratory Arrest
• Congestive Heart Failure

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What happens during starvation?
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Starvation in a Non-Stressed Patient

• Decreased basal metabolic rate
• Decreased insulin levels
• Brain adapts to use fatty acids (fat is
  substituted and only small amounts of glucose is
  used as energy sources)
• Phosphorous requirements are decreased

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Starvation in a Stressed Patient(Trauma, Sepsis,
Surgery)

• Increased extra cellular fluid volume resulting
  in edema
• Total body stores of potassium, magnesium and
  phosphate are depleted as body cell mass is
  slowly lost

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Starvation in a Stressed Patient(Trauma, Sepsis,
Surgery) cont.

• Intracellular phosphate is lost in the urine from
  catabolism
• Decrease in the size and/or function of various
  organs (decrease in cardiac mass and output,
  respiratory function and intestinal function)

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InsulinThe driving factor of Refeeding Syndrome

• Feeding is initiated
• The body changes from fat as its major source to
  CHOs causing insulin secretion
• Anabolic synthesis begins causing an
  intracellular uptake of glucose, protein,
  phosphorus, magnesium and potassium

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• This intracellular influx could lead to severe
  electrolyte deficiencies in the blood serum
  levels causing life threatening complications.

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Phosphorus

• Phosphorylated intermediates are needed, such as
  ATP (i ATP weakens respiratory muscles)
• Phosphorus is needed for the making of 2,3
  diphosphoglyceride (2,3 DPG) decreased levels
  could alter the oxygen release from hemoglobin
• i phosphorus levels can reduce oxygen delivery
  to the cells (ischemia)
• 
  

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HYPOPHOSPHATEMIA
Altered mental status/seizures
Respiratory failure
Cardiac complications
Insulin resistance
Skeletal weakness
Leukocyte dysfunction
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Phosphorus Replacement

• Mild (2.3 3mg/dl) 0.16 mmol/kg over 4-6 hrs
• Moderate (1.5 2.2mg/dl) 0.32mmol/kg over 4-6
  hrs
• Severe (1.1mg/dl or less) 0.64mmol/kg over
  8-12hrs
• K lt4 mEq/L, KPO4 given
• K gt4 mEq/L, NaPO4 given
• Clark, Sacks, et al. Crit Care Med
  1995231504-11 (Refeeding Syndrome Conf. Gordon
  S Sacks, Pharm.D.,FCCP,BCNSP)

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Potassium

• Essential for normal cell and tissue function
• Important for the heart and nervous system
• Needed for the activity of pyruvate kinase (an
  important enzyme in carbohydrate metabolism)

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HYPOKALEMIA
Nausea, Vomiting, Constipation
Cardiac Complications
Respiratory Compromise
Paralysis
Muscle Weakness, Necrosis
Sudden Death
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Potassium Replacement

• Mild-moderate (2.5-3.4 mEq/L) 20 - 40 mEq IV/PO
  not to exceed 40 mEq/hr if IV
• Severe (lt2.5 mEq/L) 40 80 mEq IV, not to exceed
  40 mEq/hr
• Infusions via peripheral vein limited to 80mEq/L
  and for central vein limit to 120 mEq/L
• Usually infused at rates of 10 mEq/hr. Must have
  continuous cardiac monitoring for infusion rates
  gt 10mEq/hr
• Kruse JA et al. Arch Intern Med 1990150613-7.
  (Refeeding Syndrome Conf. Gordon S. Sacks,
  Pharm.D.,FCCP,BCNSP)
  

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Magnesium

• Adequate magnesium is essential for normalizing
  phosphorus and potassium levels
• Needed for many metabolic pathways including the
  making of ATP

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HYPOMAGNESIUM
Neuromuscular weakness/seizures
Cardiac depression, arrhythmias
Anemia
Diarrhea/constipation
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Magnesium Replacement

• 1 mEq/kg up to a maximum of 80 mEq/administration
• No faster then 8 mEq/hr
• Preferred if a large dose run over 24 hrs
• Magnesium concentrations may be elevated up to 2
  days following supplementation, because it takes
  around 36 to 48 hrs for it to disperse into the
  body tissues
• Roland N. Dickerson, PharmD, Hospital Pharmacy
  2001361201-1208

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Thiamine (Bl)

• Bl can be depleted in less than 28 days
• A glucose load will increase the metabolic need
  for Bl
• Wernickes Encephalopathy could precipitate with
  a Bl deficiency
• Bl helps in the conversion of pyruvate to acetyl
  CoA
• With a Bl deficiency the pyruvate can accumulate
  and it is then converted to lactate which could
  result in lactic acidosis (within 1-4 weeks) Also
  known as wet beriberi

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Thiamine Deficiency

• Dry Beriberi
• (Nervous System)
• Peripheral neuropathy
• Wernickes encephalopathy
• Korsakoffs syndrome

Wet Beriberi (Cardiovascular System)
Frequent headaches, irritability, unusual fatigue
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Thiamine Replacement

• RDA 0.5 mg per 1000 kcals
• Suspected deficiency 50 to 100 mg for 7 to 14
  days (IV or intramuscular routes) then oral dose
  of 10 mg per day until recovery is achieved
• Up-to-Date 1/15/2007

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Refeeding Syndrome Edema

• Adding too many CHOs can
• decrease sodium
• decrease water excretion
• increase total body water
• Increase extra cellular fluid volume

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Preventing Refeeding Syndrome
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First InterventionIDENTIFY PATIENTS AT RISK FOR
REFEEDING SYNDROME
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ANOREXIA NERVOSA
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(No Transcript)
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Other Patients at Risk For Refeeding Syndrome

• Chronic alcoholism
• Oncology patients
• Crohns disease
• Chronic renal failure
• Pregnancy with extended hyper emesis
• Uncontrolled diabetes mellitus (DKA)

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High stressed patient NPO or with very little
nutrition gt7 days
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Residents admitted from skilled nursing
facilities or Depression in the elderly
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Other Patients at Risk with Chronic Malnutrition

• Marasmus
• Kwashiorkor
• Morbid obesity with profound weight loss
• Prolonged fasting (including patients with
  non-nutritional IV fluids)
• Hunger strikers
• Significant weight loss over 2-3 weeks or longer

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No matter how hungry trapped miners are, too
much food too soon could be fatal!
Survivors face refeeding risk By David
Braithwaite May 1, 2006
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Victims of famine
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Second Intervention

• BEFORE STARTING NUTRITION CHECK BASELINE LABS

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Third Intervention

• REPLACE ABNORMAL ELECTROLYTE VALUES
• TREAT HIGH GLUCOSE LEVELS

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Fourth Intervention

• START NUTRITION SLOW!
• START AT 50 OR LESS OF THE PATIENT KILOCALORIE
  NEEDS

SLOW
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Fifth Intervention
Potassium

• CONTINUE TO MONITOR ELECTROLYTES AND GLUCOSE
  LEVELS

Phosphorus
Sodium
Magnesium
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Sixth Intervention

• Advance Nutrition Slowly As Tolerated
• IT COULD TAKE 7 DAYS OR LONGER ESPECIALLY IF THE
  PATIENT IS EXTREMELY EMACIATED

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Seventh Intervention

• Continue to Monitor
• VITAL SIGNS
• FINGER PULSE OXIMETRY
• ACID BALANCE
• EKG MONITORING
• LAB VALUES
• BLOOD SUGARS

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Other Suggestions when Initiating Nutrition
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PERMISSIVE UNDER FEEDING

• AVOID OVER FEEDING
• 20 25 KCALS/KG
• RE-EVALUATE KCAL AND PROTEIN NEEDS AS NEEDED FOR
  REPLETION

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BANANA BAGS

• Consider adding Multivitamins and Trace Elements
  to the patients maintenance IV if unable to
  start more nutrition for awhile

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What we do at MGH

• Consult the Dietitian for a nutritional
  evaluation
• Tube Feeding Protocol with guidelines
• Parenteral Nutrition Forms with guidelines
• Electrolyte Replacement Protocol

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Summary

• These are guidelines
• Individualize a plan for each patient
• And remember
• TO DO NO HARM!

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Looking back

• What can we do to prevent these life threatening
  events?
• Identify the patients at risk for refeeding
  syndrome
• Select appropriate nutritional support management
• Establish effective monitoring
• Order appropriate therapy for complications

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References

• Carol Rees Parrish et al. Practical
  Gastroenterology Jan 2005.
• Clark, Sacks, et al. Crit Care Med
  1995231504-11. (Refeeding Syndrome Conf. Gordon
  Sacks, Pharm.D.,FCCP,BCNSP)
• Kruse JA et al. Arch Intern Med 1990150613-7.
  (Refeeding Syndrome Conf. Gordon S. Sacks,
  Pharm.D.,FCCP,BCNSP)
• Roland N. Dickerson, Parm.D., Hospital Pharmacy
  2001361201-1208.
• Roland N. Dickerson, Parm.D., Hospital Pharmacy
  200237770-775.
• Up-to-Date (Thiamine) 1/15/2007
• David Braithwaite, Survivors face refeeding
  risk. May 1, 2006
• Intersociety Professional Nutrition Education
  Consortium. Refeeding Syndrome. (www.IPNEC.ORG)

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Case Study

• Reference
• Intersociety Professional Nutrition Education
  Consortium (www.IPNEC.ORG)

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History

• 55 year-old male
• On chronic ambulatory peritoneal dialysis (CAPD)
  for diabetic end-stage renal disease (ESRD)
• Admitted for peritonitis septic shock
• Wife reports he had gradually become weak and
  lethargic over the last few weeks
• Oral food intake had deteriorated
• He took no vitamin supplements
• Peritoneal fluid had become cloudy in the last
  week
• Intersociety Professional Nutrition Education
  Consortium (www.IPNEC.ORG)

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• Medications

• Subcutaneous insulin
• Ranitidine 150 mg qd
• Calcitriol 0.25 mg qd
• Calcium carbonate 675 mg tid
• FeSO4 325 mg tid
• ZnSO4 220 mg qd

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
56
Physical examination on admission

• Stuporous
• Height was 5 9" (175 cm) and his weight was 156
  lb (71 kg)
• Dry, flaky, hyper pigmented skin
• Dry but normally papillated tongue
• Dry lips
• Easily pluckable hair
• Sacral pressure sore
• Mild rales in both lung bases
• Normal heart examination
• Tender but soft abdomen

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
57
Vital signs

• Pulse 100
• BP 70/40
• Temperature 95 F

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
58
Laboratory values on admission

• Na 130
• K 4.0
• Cl 105
• bicarbonate 18
• BUN 25
• creatinine 4.3
• glucose 89

• Ca 6.7
• Mg 1.3
• phosphorus 4.0
• albumin 1.1
• Hct 32.2
• MCV 95
• WBC 5,500

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
59
Question 1. What kind of malnutrition does the
patient have, and what is the evidence for it?

• The patients history of metabolic stress
  (sepsis), physical exam (hair pluckability and
  pressure sore), and low albumin indicate that he
  has kwashiorkor. His dry, flaky, hyper pigmented
  skin also suggests chronic kwashiorkor zinc
  deficiency could also cause this, but his use of
  a zinc supplement makes it less likely.

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
60
Question 2. What is the nutritional impact of
CAPD?

• Protein, minerals (e.g., zinc), and
  water-soluble vitamins are lost with CAPD but
  glucose is absorbed, so that net protein is lost
  and calories are often gained. Therefore,
  patients on CAPD with poor dietary intake are at
  risk for deficiencies of protein, zinc, folic
  acid, and other water-soluble vitamins. While his
  anemia is likely due to chronic disease, a
  nutritional cause such as iron or folate
  deficiency should not be discounted.

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
61
Part 2 of The Case StudyClinical Course

• Admitted to the ICU
• Broad-spectrum antibiotics and hemodialysis
• Mental status improved somewhat
• 2200-kcal renal/diabetic diet was prescribed
• P.O. intake remained poor (lt 500 kcal/day)
• Developed a GI bleed and ileus

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
62
Clinical Course Continued

• TPN was started on the 9th hospital day
• providing 2200 kcal/day
• 19 of calories from protein
• 60 from carbohydrate
• 21 from fat
• 20 mEq potassium
• 10 mmol phosphorus were included
• No laboratory measurements were made on the day
  TPN was started

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Question 3. What complications may result from
the planned nutritional support?

• Even though the patient is not cachectic or
  marasmic, this regimen puts him at risk for
  refeeding syndrome in his semi-starved state. The
  rapid introduction of calories, particularly from
  glucose, without an opportunity to adapt to
  feeding, coupled with the low levels of
  phosphorus and potassium provided, may induce
  refeeding complications including hyperglycemia,
  cardiorespiratory failure, and multiple organ
  dysfunction from ATP deprivation.

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
64
Question 4. What laboratory values are most
important before starting TPN?

• It is especially important to measure phosphorus
  and potassium levels because intracellular shifts
  occur with feeding. It is also important to know
  the levels of glucose, sodium, and magnesium.

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
65
Part 3 Clinical course 12 hours later

• The patient was very short of breath
• Physical exam showed tachycardia and pronounced
  rales
• His blood pressure dropped (74/50)
• He required intubation
• CXR showed pulmonary edema

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
66
Part 3 Clinical course 12 hours later-- Lab
values

• creatinine 2.0
• glucose 445
• Ca 7.4
• phosphorus 0.9
• albumin 1.1

• Na 130
• K 2.9
• Cl 96
• bicarb 27
• BUN 13

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
67
Question 5. What has occurred and how should you
address the problems?

• Full-blown refeeding syndrome has occurred, with
  cardiorespiratory failure and marked
  hyperglycemia. The TPN should be discontinued
  while phosphorus (1 to 1.5 mmol/kg over 24 hours)
  and potassium are repleted.

Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
68
Question 5 answer cont.
Correction of the hyperglycemia is crucial, but
the patients blood glucose will not respond to
insulin until adequate phosphorus is available.
When these have been corrected the TPN can be
resumed at lower calorie levels, and gradually
increased. Enteral and oral feeding should be
used as soon as the ileus and mental status
improve.
Intersociety Professional Nutrition Education
Consortium (www.IPNEC.ORG)
69
Questions?