Antoine Cherfan, Pharm.D., BCPS, FCCP, CACPManager, Pharmacotherapy ServicesCleveland Clinic Abu Dhabi

Disclosure Information:

Parenteral Nutrition in Critical Care Antoine Cherfan, Pharm.D., BCPS, FCCP, CACPName of Presenter

I have no financial relationship to disclose.

AND

I will not discuss off label use and/or investigational use in my presentation.

Learning Objectives• At the completion of this activity, you will be able to:

• Understand the history and safety aspects of parenteral nutrition

• Describe differences between central and peripheral parenteral nutrition

• Validate patient caloric requirements based on patient specific factors

• Identify the complications of parenteral nutrition

• Review electrolyte replacement principles in the critical care setting

• Describe and present the controversies of :• Heparin In parenteral nutrition

• Vitamin K Supplementation

• Insulin in parenteral nutrition

• Permissive underfeeding Vs. target feeding in critical illness

The Highest Alert formula in Pharmacy

The most complex prescription in Pharmacy

Contains more than 50 active ingredients

Parenteral Nutrition

What is Safe PN Solution?

• Balanced Formula

• Iso-Osmolar

• Physiological pH

• Sterile / Pyrogen-free

• Particulate-free

• Accurately compounded

Poorly Ordered/Compounded/Administered IV/PN Solution

• Metabolic Complications

• Mechanical Complications

• Infectious Complications

• Quality of life related complications

• Cost

• Harm/Death

PN Errors

• 6-week-old infant died with PN containing 60 times the dose of prescribed Sodium

• ISMP, Sept 21, 2011

• Preterm infant received 1000-fold dose of Zinc; error missed by 6 hospital staff. Patient died.

• ISMP; Sept 21, 2011

Reported Sentinel Events with PN

• 10 patients on PN were exposed to PN contamination with Serratia Marcescens resulting in 9 deaths

• ISMP Sept 21, 2011

• 1000 units of Insulin instead 1000units of Heparin• Cohen MR, Hospital Pharmacy 1991;26;998-999

Reported Sentinel Events with PN

50% of all patients on PN were prescribed inappropriate therapy

• DeLegge MH. et al., Nutr Clin Pract. 2007;22:246-249

32% of PN inappropriately prescribed at 4 tertiary care hospitals (cost $125,000)

• Martin K. et al, JPEN. 2010; 20(10)

PN: What is Wrong

& What is Right?

Bladder irrigation of Ampho B has been confused with PN and given IV

Breast Milk had been confused with IV Fat and given IV

PN given through Foley Cath as irrigation instead of Ampho B

Enteral Nutrition given IV!!

Administration Errors

Total Poisonous Nutrition

Marik P.A. et al., Intensive Care Medicine 29:867-869, 2003

Ordering TPN by Incompetent Clinicians:

Compher C. JPEN, 31(2), 127-134, 2007

Bobby Thomas lived 29 years on

PN

PN is Safe in Good Hand Clinicians

PN Indications

Non-functioning GI tract• Small bowel obstruction

• Short bowel syndrome

• Prolonged ileus

• Malabsorption

Inability to achieve or maintain enteral access • Total obstruction

Patients who cannot be adequately nourished by oral diets or enteral nutrition Intractable vomiting and diarrhea

Hyperemesis Gravidarum

Parenteral Nutrition Indications

Central or Peripheral PN?

Venous Sites for Access to the Superior Vena Cava

• SVC = 2000 ml/min

• SCV= 800ml/min

• Cephalic/Basilic: 40-95ml/min

PPN vs CPNPeripheral Parenteral Nutrition (PPN)

Central line not required

Short term nutrition (≤ 2wks)

Max osmolarity: 900-1000 mOsm/L

o 100 mOsm per x% of amino acids (limit to 7.5- 10%)

o 50 mOsm per x% of dextrose (limit to 2.5%)

Max K+: 40-80 mmol/L

Rate is usually 88-125mL/hr

Should NOT be used for patients with poor peripheral access or who require fluid restriction

Central Parenteral Nutrition (CPN)

Requires a central line

Long term nutrition (> 2wks)

Range from 1500 – 2800 mOsm/L

Rate is usually 60- 80mL/hr

Fluid restriction: 40 ml/hour

PN is part of TFI

• Partial support

• Phlebitis

• No surgery

• Low risk Sepsis

• Max Dextrose

• Adult: 7.5-10%

• Max protein: 2.5%

• Max osmolarity: 900/L

Peripheral

• Full support

• No phlebitis

• Surgery

• Sepsis

• No Max for Dextrose

• No max for protein

• No max osmolarity

Central

Peripheral Vs. Central Parenteral Nutrition

Peripheral or Central TPN?

• Degree of malnutrition

• Duration of PN

• Quality of veins

• PICC lines

Preventing Peripheral PN Complications

• Maximum dextrose = 7.5-10%

• Maximum Protein = 2.5%

• Calculate final osmolarity (< 1000 mOsm/L)

• Minimize Na, K, Ca

• Add Heparin and Hydrocortisone

• Re-site the veins q 24-48 hours

• Maximize IV LIPID

Heparin and Hydrocortisone for All??Does IV lipids Increase Tolerance in PPN??

Hydrocortisone in PN

Heparin In PN : Back to 1977

26

Early 80’s Literature

Early 80’s Literature

28

90’s Literature

Osmolarity, Heparin and Intralipids: Impact on Phlebitis In PPN

Heparin In Parenteral Nutrition: ASPEN 2015 Recommendation

• Should heparin be included in the PN admixture to reduce the risk of central vein thrombosis?

• We suggest that heparin not be included in PN admixtures for reducing the risk of central vein thrombosis.

• Strength of the Evidence :WEAK

Parenteral Nutrition Types

Continuous PNo Infused continuously over 24 hrso Start time is 21:00

Cyclic PNo Infused over 12-16 hrs instead of 24 hrs (preferred for home

infusions) o Max K+: 10 mmol/hro Ex: 1000mL TPN

• 50 mL/hr x 1 hr• 100 mL/hr x 10 hrs• 50 mL/hr x 1 hr

Intradialytic PNo Only infused during dialysiso Oral or enteral nutrition may not meet protein needs required for

dialysis patientso 500 ml concentrated to the max.

How Much Calories?

Caloric Requirement: Adult

Maintenance: 30-45 kcal/kg/day

Stressed/multi-trauma: 25-30 kcal/kg/day

Underweight (BMI < 18.5): 30-35 kcal/kg/day

Burns: 35-50 kcal/kg/day

Obese (BMI >30): 15-25 kcal/IBW/day

Mechanical Ventilation:o IJEE equation: 1784 – 11(age) + 5(weight in kg) + 244(for males) + 239(for

trauma)o Multiply IJEE x 1.1 (activity factor) for desired range

Renal Disease

Higher calorie requirements in HD, PD, or CRRT: 30-35 kcal/kg/day

All PN run at stable rate

Protein, potassium, phosphorus, magnesium, and ranitidine must be adjusted

Protein requirements:o Non-dialysis: 0.6-1 gm/kg/day

o HD: 1.2-1.4 g/kg/day (up to 2 g/kg/day). Check prealbumin

o CRRT: 1.5-2 g/kg/day

Liver Disease

Cirrhosiso Protein: 0.8-1.2 gm/kg/day

Cholestasiso Total bilirubin >26 mmol/L (1.5 mg/dL): Decrease trace elements to

0.5mL o Total bilirubin >34 mmol/L (2.0 mg/dL): Omit trace elements, add zinc

5mg, selenium 60mcg, and chromium 10mcg

Hepatic Encephalopathyo Protein: 0.6-0.8 gm/kg/day; may increase up to 1.5gm/kg/day as

tolerated

Protein, potassium, phosphorus, magnesium, manganese, Copper and ranitidine must be adjusted

ACCP Recommendation

“ A total caloric intake of 25 Kcal/kg usual body weight per day appears to be adequate for ALL patients”

Cerra FB, et al. “Applied nutrition in ICU patients: A consensus

Statement of ACCP”. Chest 1997 111:769-777

How much calories for obese ICU pts (BMI > 30)?

• 11-14 Kcal/kg actual BW or 22-25 Kcal/kg IBW/d

• Protein at 2-2.5 g/kg IBW/d

SCCM & ASPEN Guidelines, Crit Care Med, 37(5), 2009

Mortality and Outcomes of Caloric Intake in Critical Illness

• Higher caloric intake is helpful and can reduce mortality

VS.

• Studies linking caloric restriction to lower morbidity, as long as protein intake is adequate

• Prospective Randomized Trial

• 994 critically ill adults with a medical, surgical, or trauma admission category to:

• Permissive underfeeding (40 to 60% of calculated caloric requirements) or

• standard enteral feeding (70 to 100%) for up to 14 days while maintaining a similar protein intake in the two groups

• Permissive-underfeeding group received fewer mean (±SD) calories than did the standard-feeding group:

• 835±297 kcal per day vs. 1299±467 kcal per day, P<0.001

• 46±14% vs. 71±22% of caloric requirements, P<0.001)

• Protein intake was similar in the two groups (57±24 g per day and 59±25 g per day, respectively; P=0.29)

• The 90-day mortality : 27.2% in the permissive-underfeeding group and 28.9% in the standard-feeding group died (RR with permissive underfeeding, 0.94; 95% confidence interval [CI], 0.76 to 1.16; P=0.58)

• No significant between-group differences with respect to feeding intolerance, diarrhea, infections acquired in the

PERMIT Study Results

No Mortality Difference at 90 Days as the Primary Endpoint

Proteins

Calories: 4 kcal/gm

Generally provided in amounts of 10-20% of total kcal/day

Aminosyn 10-15% is commonly used

We dose based on Actual body weight. Adjusted body weight for Obese patients.

Start with 0.7 g /kg/d up to 2 g/kg/d

Carbohydrates

Calories: 3.4kcal/gm

Generally provided in amounts of 50-60% of total kcal/day

Dextrose 50-70% is commonly used

Max infusion rate is 4-6mg/kg/mino 3 mg/kg/min in ICUo Up to 7mg/kg/min in burn/trauma patients

IV Lipids• Adult: Max 0.1g/kg/hr• Start same time with PN

• Infusion time: • less than 12 hours• Over 20 hours with PPN

• Accurate TG result: hold for 4 hours• Send always in bottle.

• Don’t transfer Lipid (20-30cc overfill)

• Absolute contraindication:• TG more than 4 mmol/L• TG-induced by Acute Pancreatitis

•Check TG

•? Severe respiratory distress

•Eating or on Enteral Formula?

•Low platelets?

•Can we give lipid alone?

Can we accept PN without lipids?

How Much Fluid?

Assess patient’s fluid statuso Renal function

o I/O balance

Standard volume = 1500- 2000mL = 60 -80mL/day

Max volume = 3 Liters = 125mL/day

All PNs are overfilled with 100ml

Several strategies used:o 30-40mL/kg/day

o 1mL/kcal/day

o Use same rate as IV fluids ordered

Fluid Requirements

May result from several days of excessive volume

Signs of volume overload:o Input >> Output over several days

o Decreasing serum sodium levels

o Orders for diuretics (ex: furosemide)

o Edema documented in progress note

IV fluid rate should be reduced or discontinued when PN initiated

Assess fluid status: BUN/SCr ratio, UOP, I/O, BNP

Post-op patients require a high rate of IV fluids initially, however rate should decrease as the patient recovers

Complications: Volume Overload

Other Complications

Hyperlipidemiao Hold IVFE if TG > 4.5 mmol/L (400 mg/dL)

Essential Fatty Acid Deficiencyo If no lipids for 1 -3 weeks

Hepatobiliary Complicationso Typically seen as mild liver enzyme elevations within 2 weeks of starting TPNo Severe liver complications, including steatosis and PN-associated cholestasis, may

occur with long term use

Infectiono Catheter-related, especially Staph aureus and Candida albicans

Electrolyte Abnormalitieso IV boluses may be needed if electrolytes too lowo PN may need to be stopped if electrolytes to high

Defined as blood glucose > 10mmol/L (180mg/dL)

Causes include diabetes, sepsis, medications

Diabetics with glucose > 10mmol/Lo Give no more than 150 g dextrose in initial bag

o Add 0.1 unit regular insulin per gram of dextrose

Diabetics with glucose < 10mmol/L (or non-diabetic hyperglycemic patients)o Give no more than 150 g dextrose in initial bag

Complications: Hyperglycemia

Insulin in Parenteral Nutrition

Insulin Availability in Parenteral Nutrition

Further Evidence on Availability of Insulin from Parenteral Nutrition Solutions

Electrolyte Management

Lab values fall outside normal range

Lab trends up or down over several days

Substantial increase from previous day’s lab values

Changes in renal function

Changes in IV fluids or medications

Electrolytes Management Principles

Hypernatremia

• 10% of all cases: High intake of Na• Cause: NS, ABx, Albumin, etc.

• Rx: D5W + Furosemide

• 90% of all cases: Volume depletion• Cause: Fever, Hyperventilation, Sweating,

GI losses

• Symptoms: Thirst , Weight loss,

• Signs: High BUN, Albumin, Hct

• Rx: NS or D5 NS

Causes: gastric output or fistula, volume overload (CHF), hypotonic fluids, SIADH, cirrhosis, hyperglycemia

Max sodium: 154 mmol/L

Patient may need fluid restriction and/or a diuretic

If suspect SIADH, max concentrate TPN (remove all sterile water)o Check urine osmolality, urine sodium, and serum osmolality

Hyponatremia (Na+ < 136 mmol/L)

Hypokalemia (K+ < 3.5 mmol/L)

Causes: diuretics, nasogastric suction, nausea/vomiting, diarrhea, low magnesium

Replace using KCl 10-40mmol IV bolus depending on K+ level and renal function

Approximately 10mmol of KCl will increase K+ level 0.1mmol/L

Maximum potassium: 240mmol/day

o CPN: 120mmol/L

o PPN: 40mmol/L

Hyperkalemia (K+ > 5.1 mmol/L)

Causes: medications (spironolactone, KCl boluses, diuretic changes), metabolic acidosis, decreased renal function

Consider lab error or lab drawn from line infusing TPN

If K+ < 5.3, cut TPN rate in half and make adjustments to the next bag

If K+ ≥ 5.3, stop TPN and hang D10W at same rate (unless diabetic); decrease or omit K+ in the next bag

Other Meds (C A BIG K Drop)o Calcium gluconateo Albuterolo Sodium bicarbonateo Insulino Dextroseo Kayexalateo Diuretics, dialysis

Causes: GI fluid losses, diarrhea, diuretics

Replace using magnesium sulfate 2-4gm IV bolus depending on lab value

Infusion rate: 1 gm/hr

Hypomagnesemia (Mg2+ < 0.6 mmol/L)

Causes: refeeding syndrome, alcoholism, respiratory distress

Replace using sodium phosphate or potassium phosphate IV boluso Sodium phosphate: 3mmol/mL Phos = 4 mmol/mL Na+o Potassium phosphate: 3mmol/mL Phos = 4.4 mmol/mL K+

Replacement is based on weight o Mild (or renal impairment) (Phos 0.55-0.69): 0.08mmol/kg over 4 hrso Moderate (Phos 0.4-0.54): 0.16-0.24mmol/kg over 4-6 hrso Severe (Phos <0.4): 0.32mmol/kg over 6 hrs

Adjust TPN in 9-18 mmol increments (minimum 20% change)

Max: 40 mmol/bag

Also consider Ca2+/Phos ratio to avoid precipitation

Hypophosphatemia (Phos < 0.7 mmol/L)

Hypocalcemia (Ca2+ < 2.05 mmol/L)

Causes: hypoparathyroidism, excess blood transfusions or CRRT (citrate), hypomagnesemia, foscarnet

Ionized calcium should be used to determine replacement needs

If ionized calcium is not available, use adjusted calcium:

o Adjusted Ca2+= 0.8(4-albumin) + Ca2+

Replace using calcium gluconate IV bolus 1 to 2 gm

Infusion rate: 1 gm/hr

Adjust TPN in 5-10 mEq/bag (min 50% change)

Max: 24mEq/bag

Also consider Ca2+/Phos ratio to avoid precipitation

Risk increases with increasing concentrations of Ca2+ and phos

Higher risk with calcium chloride compared to calcium gluconate

Phos should be added first, mix well, then add Ca2+

Use sodium glycerophosphate if high doses of phosphorus needed

Final amino acid concentration should be at least 2.5%o Forms soluble complexes with Ca2+ and phos

o Buffer to maintain a lower pH to prevent precipitation

Filters decrease the risk of embolization

Calcium-Phosphorus Precipitation

• Human eyes can see subjects bigger than 50 microns only

• Ca++ H+ PO4--- crystal size is 5-100 microns

Is Physical Checking of the Final Admixture Sufficient?

1. Refrigerate

2. Use in-line filters

How to avoid Calcium-Phosphates Precipitation

Calcium-Phosphate Solubility Curves

After 24 Hours at Room Temperature

0

5

10

15

20

25

30

0 5 10 15 20 25 30 35 40 45 50

Phosphates (mmols/liter)(Based on mixed mono and dibasic phosphates pH=6.6)

Ca

lciu

m G

luc

on

ate

(m

mo

ls/lit

er)

A. Primene 1% + Glucose 5%*B. Primene 2% + Glucose 5%*C. Primene 3.5% + Glucose 10%** Based on the inclusion of 4 mmol/liter Magnesium

A B C

Other Electrolytes Adjustments

Hypernatremia (> 145 mmol/L)

o Causes: dehydration or excess sodium

o Treatment: decrease or remove in TPN; increase free water via D5W or ½ NS IV fluids or free water tube flushes

Hypermagnesemia (> 1.1 mmol/L)

o Causes: excessive intake or renal insufficiency

o Treatment: decrease or remove in TPN

Hyperphosphatemia (> 1.5 mmol/L)

o Causes: excessive intake or renal insufficiency

o Treatment: decrease or remove in TPN; may need phosphate binders

Alkalosis: If CO2 is elevated, use chloride salt forms

o Sodium chloride

o Potassium chloride

Acidosis: If Cl is elevated, use acetate salt forms

o Sodium acetate

o Potassium acetate

Acid-Base Considerations

Vitamin K in Parenteral nutrition

Vitamin K Serves in Activating many Dependent Proteins

Study of coagulopathy due to vitamin K deficiency in 42 critically ill, hospitalized patients, most of whom had been misdiagnosed as having disseminated intravascular coagulation.

• 26 patients (62%) reported reduced dietary intake for periods of 1–7 weeks before hospitalization.

• Coagulopathies occurred between days 12 and 22 of hospitalization

• 21 patients (50%) had undergone major surgery 3–12 days before vitamin K deficiency was diagnosed

Vitamin K Deficiency Common in Critical Care

• The natural source of vitamin K in parenteral feeds is phylloquinone contained in the lipid emulsion.

• The natural phylloquinone content of commercial PN products varies widely depending on the oil source:

• In soybean oil (150–300 mcg per 100 g) • Relatively low levels in safflower oil (6–12

mcg per 100 g)

Vitamin K content of Intralipid Products

Nutrition support teams be aware of the vitamin K content of the lipid emulsion and the multivitamin preparations in their institutions

March 2015

Vitamin K Dietary Reference Intakes (DRIs) by Food and Nutrition Board (FNB)

Cernevit ® multivitamin: No Vitamin K

Occurs within the first few days after refeeding of starved patients

Combination of fluid, micronutrient, electrolyte, and vitamin imbalances

o Hypokalemia

o Hypomagnesemia

o Hypophosphatemia

Risk factorso Alcoholism

o Anorexia nervosa

o NPO X 7-10 days prior to admission

o Rapid refeeding

o Excessive dextrose infusion

Preventiono Add thiamine and folic acid to TPN

o Keep dextrose between 100-150gm/day until electrolytes are stable

o Increases dextrose by 50gm/day until goal calorie level is achieved

Complications: Refeeding Syndrome

Premixed Parenteral Nutrition

PROS CONS

• Not for ICU

• Not or unique needs i.e. Renal failure, CHF

• Limit in optimizing calories and protein

• No fine tuning of electrolytes

• Does not eliminate need for compounders

• Clinician acceptance

• Reduce compounding workload

• USP compliance

• Free time to hang and initiate PN

• Less contamination

• Less compounding errors

• Less cost

• Less complexity in ordering

Thank you

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