Background

• Anion gap (AG) = Na+ – (CI- + HC03 -): Difference between serum anions and cations. Based on the principle of electrical neutrality, the serum concentration of cations (positive ions) should = anions (negative ions). Normal anion gap: 12 mmol/L (10 – 14 mmol/L)
• N content: Nitrogen is a component in amino acids which make up proteins and is excreted mainly as urea in the urine. 1g N in each 6.25 g protein. N intake = grams of protein intake/6.25.
• Volume depletion can lead to acute renal failure (not enough for glomerular filtration) and death. Signs to watch: Sudden weight loss, hypotension, reflex tachycardia (heart pumps harder for the body to get the O2 and nutrients), acute decline in renal function, dry membranes, thirst.
• Dehydration: both blood urine nitrogen (BUN) and serum creatine (SCr) levels ↑. BUN: SCr ratio > 20:1 indicates dehydration. To rehydrate, use more diluted TPN so the water can flow into the direction of cells and hydrate them.
• Volume overload can lead to cardiac/pulmonary complications.  Signs to watch: Weight gain, increased blood pressure, lung sounds (rales, crackles), and peripheral edema.
• Fluid restriction: Chose the most concentrated TPN (70% dextrose, 20% lipids) and reconstitute with the least amount of fluid possible in IV. The high osmolarity of the concentrated TPN can draw fluids from cells, thus reducing edema.

 

Sodium (Na)

• Major extracellular Normal range: 135 – 145 mEq/L. Imbalance can lead to renal (Na reabsorption) or CV disease (Na can initiate action potential, thus important in conduction).
• Different sources of Na for PN: sodium chloride, sodium acetate, sodium phosphate or a combination of those.
• SIADH (syndrome of inappropriate antidiuretic hormone ADH): ADH maintains our blood volume, too much ADH can lead to hypervolemic, and water follows Na. Correcting low Na too rapidly can lead to osmotic demyelination syndrome.
• The pharmacist is going to need 70mEq of Na in the PN, half will be supplied by sodium acetate (2 mEq/mL), and half is going to be given as sodium chloride (4 mEq/mL). How many mL of sodium chloride will be needed?
  1. 70/2 = 35 mEq of Na needs to come from Na acetate.
  2. Remaining Na coming from NaCl = 70-35 = 35.
  3. 4mEq/ml = 35mEq/Xml, x = 8.75 ml
• A PN order calls for 85 mEq sodium and 45 mEq acetate. The available pharmacy stock solutions contain 4 mEq/mL Na as NaCl and 2 mEq/mL Na as Na acetate. The final volume of the PN will be 2.5 L to be infused at 100 mL/hr. How many ml of each stock solution should be added to the PN to meet the requirements?
  1. Na acetate: 2mEq/ml = 45 mEq/xml, x = 22.5ml
  2. mEq of Na from Na acetate: 22.5ml x 2 mEq/mL = 45 mEq Na
  3. mEq of Na left that should be provided by NaCl: 85 – 45 = 40 mEq
  4. 4 mEq/mL = 40mEq/xml, x = 10ml of NaCl

 

Potassium (K)

• Major intracellular Normal range: 3.5 – 5 mEq/L. The level may need to be reduced in renal or CV disease.
• Sources for PN: KCl or K phosphate (K3PO4), or K acetate.
• Mg is essential for K uptake, correct any low Mg before correcting K.

 

Calcium (Ca)

• Normal range: 5 - 10.2 mg/dL. An important role in bone homeostasis, muscle contraction, cardiac conduction.
• Half of Ca binds to albumin, a low level of albumin (<3.5) can lead to a falsely low level of Ca. Ca level must be adjusted in TPN.
• Ca and phosphate can precipitate, and we do not want that, so make sure total Ca + phosphate < 45 mEq/L. Chose Ca gluconate (lower dissolution) over Ca chloride (higher dissolution can bind phosphate ion better) for lower risk of precipitation; add phosphate first, and Ca in the end in the PN formulation.
• Ca _corrected  = [(calcium _{reported(serum)} + [(4.0 -  albumin) x 0.8] 

 

Phosphate (PO₄)

• Is involved in DNA (a component of nucleotide), cell membranes (phosphate lipid bilayer), ATP, buffer (anion), and is important in bone metabolism (inorganic component along with Ca). Basically, it is imperative, we must have the appropriate amount.
• Sources for PN: sodium phosphate (Na₃P04) or potassium phosphate (K Phos, K₃P04). The two forms do not provide equivalent amounts of phosphate. The order should be written in mmol of phosphate.
• Phosphate levels often need to be reduced in renal disease.

 

Albumin:

• Low level (<3.5) if the patient is elderly, ill or malnutrition.
• An important factor in TPN calculation.
• Can lead to intravascular fluid loss (due to osmolarity), and incorrect calcium concentration.

 

Acidotic Vs. alkalotic

• Normal ranges: Cl: 97- 106 mEq/L, Bicarb HCO3-: 22 - 28 mEq/L, CO2: 35 – 45 mmHg.
• Carbon dioxide acts as a buffer and an acid. When you exercise, your muscle produces a lot of waste including CO2, which partially dissolve in the blood: CO2 + H2O => HCO3- + H+
• Acidotic: pH < 7.35, ↓ HCO3-:, increased Cl, (instead of reabsorbing HCO3-, the kidney reabsorbs Cl-, loss of HCO3- is accompanied by an ↑ in the serum Cl-, think about acid HCL)
  • At least 50% of Na acetate should be used, rather than NaCl.
• Alkalotic: pH > 7.45, ↑HCO3-, ↓Cl.
• If someone has Cl level of 90? He is probably alkalotic.
• If someone has HCO₃^- level of 40? That means he is alkalotic!

 

Major TPN component a pharmacist is required to know:

 

Component	kcal/g
Dextrose (source for carbohydrates)	3.4
Amino Acids (source for protein)	4
Lipids	9
10% fat emulsion	1.1 kcal/ml
20% fat emulsion	2 kcal/ml
30% fat emulsion	3 kcal/ml

• Calorie = kcal, cal is a very small unit, so kcal is used instead.
• A PN order calls for 375 calories to be provided by lipids. The pharmacy has 10% lipid emulsion in stock. How many mL should be administered to the patient?
  • 1 kcal/ml = 375 kcal/ Xml, x = 340 ml

Protein requirement

• An ambulatory, non-stressed patient has a daily requirement of 0.8 - 1 g/kg.
• A hospitalized patient will require more protein intake, up to 2 g/kg.
• For simplicity, use 100g/day for most people (non-stressed, ambulatory).

 

Consider drug-nutrients interaction

• Warfarin: many enteral products bind warfarin (Would they more likely be lipo- or hydrophilic?), resulting in low INRs and the need for dose adjustments. Hold tube feeds 1- hour before and after warfarin administration. EN formulas contain varying amounts of vitamin K, which complicates warfarin dosing.
• Phenytoin (another famous drug with lipophilicity): levels are reduced when the drug binds to the feeding solution => less free drug available.
• TCN: chelate with metals (Ca, Mg, Fe), reduces drug availability; separate 1-2 hours from tube feeds.
• Ciprofloxacin: what can be the reason the oral suspension is not used with tube feeds? If it is oil-based suspension, then it can adhere to the tube and reduce the drug availability.

 

Filters

• Guidance on using in-line filters for parenteral nutrition (PN) to reduce the potential for patient harm.
• 22 micron filter for dextrose/amino acids (2-in-1) PN. Smaller filter for smaller molecules.
• 1.2 micron filter for total nutrient admixtures (3-in-1, all-in-one), IV fat emulsion (larger filter for larger particles). A larger filter for larger molecules makes sense.
• Place filter as close to the patient as possible on the administration system.
• Change the Filters (and administration sets) with each new PN container.

 

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