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Section 3 - Management of TPN


The PN formulation is a complex mixture containing up to 40 different chemical components that may cause problems with stability and compatibility. Serious harm and death have resulted from improperly compounded parenteral feeding formulations.

TNA stability

Stability generally refers to the loss or degradation of the admixed nutrients over time. Compatibility relates to the physical and chemical interaction between nutrients. A small degradation of nutrients is expected with any compounded solution. However, incompatibilities between nutrients or other components may be harmful to the patient. Stability and compatibility issues are especially important for 3-in-1 or total nutrient admixtures (TNA). Destabilization of the lipid component of a TNA formulation can occur under certain conditions.

Stages of TNA destabilization

accumulation of triglyceride particles at the top of the emulsion.

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clumping of triglyceride particles within the emulsion.

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fusion of small triglyceride particles into larger particles.

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separation of the oil and water components of the emulsion.

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Use of a TNA with evidence of aggregation, coalescence or cracking may be harmful to the patient. Mild creaming may be reversible with gentle agitation. However, its reappearance after one or two hours indicates that the lipid particles may have become too large to be redispersed. In this case, the TNA may be unsafe to use, because large triglyceride particles can potentially cause lipid emboli or pulmonary capillary occlusion.

All TNAs should be closely inspected for signs of lipid destabilization prior to use and during infusion. Any TNA with signs of destabilization should not be used. If destabilization occurs during administration, it should be discontinued immediately. There are a number of factors which affect TNA destabilization, including:

  • Amino acid concentration
  • pH of the formulation
  • Dextrose concentration
  • Concentration of the electrolytes
  • Order of mixing

The risk of TNA destabilization may be reduced by:

  • Keeping the final amino acid concentration at 2.5% or greater.
  • Maintaining a final pH of 5.0 or above.
  • Keeping the final dextrose concentration at 3.3% or greater.
  • Avoiding trivalent cations (Iron dextran).
  • Avoiding mixing dextrose and lipid directly.
  • Add lipid last, after all other components (except vitamins) are mixed.

Calcium and phosphate stability

Calcium and phosphorus are common essential electrolytes in PN solutions. If mixed in too high a concentration, calcium and phosphorus may form an insoluble precipitate of calcium phosphate. Pulmonary emboli secondary to calcium phosphate precipitates have been the cause of at least two deaths. This is especially problematic in TNA's because (1) the lipid emulsion clouds the solution, making it nearly impossible to visually detect a precipitate and (2) 1.2 micron TNA filters do not remove calcium phosphate precipitates.

There are a number of factors which affect the formation of calcium phosphate, including:

  • Amino acid concentration
  • pH of the formulation
  • Temperature
  • Calcium salt used
  • Order of mixing
  • Concentration of the electrolytes

The risk of calcium phosphate precipitation may be reduced by:

  • Keeping the final amino acid concentration at 2.5% or greater.
  • Maintaining a final pH of 6.0 or lower.
  • Infusing the solution within 24 hours of preparation.
  • Using calcium gluconate instead of calcium chloride.
  • Avoiding mixing calcium and phosphorus in close sequence during preparation.
  • Keeping the calcium:phosphorus ratio greater than 1:2.
  • Keeping the total amount of calcium and phosphorus less than 45 mEq/L.
  • Keeping the calcium:phosphorus solubility product less than 150.
  • Adding cysteine to the amino acids.

Calcium and phosphate solubility differs substantially between the various amino acid brands (click for larger view).

Aminosyn II Aminosyn II
Novamine Novamine
TrophAmine Trophamine


Central PN

PN solutions are hypertonic to body fluids and, if administered inappropriately, may result in venous thrombosis, thrombophlebitis, and extravasation. To prevent damage to blood vessels, hypertonic PN solutions must be administered into a high flow venous system. Central venous administration entails placement of a catheter tip into the superior vena cava. Because of the high rate of blood flow, the PN solution is rapidly diluted and does not harm the vein.

Peripheral PN

Unlike the large central veins used for TPN therapy, where blood flow approaches 2500 mL/min, flow through the superficial veins is approximately 25 to 50 mL/min. To reduce the incidence of phlebitis from osmotic injury, PPN admixtures are formulated so that the final osmolarity is maintained at or below 900 mOsm/L. Concentrations above this level dramatically increase the risk of phlebitis. When the concentration exceeds 900mOsm/L, the ability of the peripheral veins to dilute parenteral infusions sufficiently is compromised, and chemical irritation of the vein intima occurs. Admixtures greater than 600 to 900 mOsm/L are associated with increased rates of phlebitis.

Estimating osmolarity

The osmolarity of the final PN formulation dictates the administration route. Osmolarity is primarily dependent on the dextrose, amino acid, and electrolyte content. The approximate osmolarity of commonly used PN components are:

Osmolarity of common PN components

mOsmol Factor
Amino acids 100 per % final conc
Glucose 50 per % final conc
Lipid 1.7 per g
Calcium 1.4 per mEq
Magnesium 1 per mEq
Potassium 2 per mEq
Sodium 2 per mEq

Calculating osmolarity


Use of a filter during the administration of PN solutions may prevent complications from particulate matter, microprecipitates or micro-organisms potentially present in the PN solution. Studies also show the benefits of in-line filtration in preventing peripheral vein phlebitis from PPN formulations.

A 0.2-micron filter should be used for 2-in-1 formulations and a 1.2-micron filter for 3-in-1 formulations. Routine replacement of filters will depend on the type of filter used and the infusion solution. The CDC recommends that sets and filters used for the infusion of lipid emulsion be changed every 24 hours.

Continuous vs Cyclic administration

Cyclic administration is the usual method for administering PN on a long term basis. The infusion is given overnight and the patient is free during the day from the PN solution and associated administration paraphernalia. Continuous administration is prefered in hospitalized patients as they often have fluid and electrolyte disturbances and hemodynamic instability which make cyclic administration difficult and potentially hazardous.


Once PN has been initiated for a patient, a variety of metabolic complications may develop. For this reason, diligent monitoring is necessary.

Suggested monitoring schedule

Baseline Acute patient Stable patient
Blood chemistry Yes 2 - 3 times/week Weekly
Lytes, BUN, creatinine Yes Daily 1 - 2 times/week
Triglycerides Yes Weekly Weekly
CBC w/diff Yes Weekly Weekly
PT, PTT Yes Weekly Weekly
Glucose 3 times/day 3 times/day
until <200 consistently
3 times/day
until <200 consistently
Weight Yes Daily 2 - 3 times/week
I & O Daily Daily Daily
Nitrogen balance PRN PRN PRN

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Section 3 - Management of TPN