antoine cherfan, pharm.d., bcps, fccp, cacp … cherfan, pharm.d., bcps, fccp, cacp manager,...
TRANSCRIPT
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
79