Is total parenteral nutrition (TPN) isotonic with plasma?

Is TPN Isotonic with Plasma?

No, standard TPN formulations are not isotonic with plasma—they are hypertonic and require central venous administration. 1

Osmolarity of TPN Solutions

Standard TPN solutions are inherently hypertonic due to their high concentrations of glucose and amino acids, making them unsuitable for peripheral venous administration without modification. 1 The hyperosmolar nature of these solutions (typically >900 mOsm/L) necessitates infusion through large-diameter central veins where rapid dilution occurs. 1

Central vs. Peripheral TPN Osmolarity

• Central TPN: Standard formulations contain 25% dextrose combined with 5% amino acid solutions, resulting in hyperosmolarity that prohibits peripheral vein use and mandates subclavian or central venous catheterization. 2, 3, 4

• Peripheral TPN: When peripheral administration is necessary, osmolarity must be kept below 900 mOsm/L to minimize the risk of thrombophlebitis and extravasation. 1 The ESPGHAN/ESPEN/ESPR/CSPEN 2018 guidelines provide a conditional recommendation (strong consensus) for this threshold. 1

• ASPEN adult guidelines similarly recommend maintaining peripheral PN solutions at less than 900 mOsm/L. 1

The Exception: Lipid Emulsions

Lipid emulsions are isotonic and therefore suitable for either peripheral or central venous administration. 1 This is the only component of TPN that approaches plasma isotonicity.

Clinical Implications

Route Selection Algorithm

1. Central venous access is the recommended delivery site for PN to provide complete nutritional requirements without osmolarity constraints. 1

2. Peripheral PN can be given for short periods only when:

   • Central access is unavailable or contraindicated 1
   • The solution osmolarity is maintained <900 mOsm/L 1
   • The patient requires supplemental rather than complete nutrition 1

3. If peripheral PN cannot meet the patient's full nutritional needs, switch to central administration. 1

Common Pitfalls

• Do not assume all PN formulations can be given peripherally—the standard hypertonic solutions will cause thrombophlebitis and vein damage when infused through small peripheral veins. 1

• Contradictory evidence exists regarding the safety threshold: Two retrospective pediatric studies showed conflicting results for osmolarity >900-1000 mOsm/L, with one reporting increased thrombophlebitis and the other finding similar adverse event rates. 1 Given this uncertainty, adhering to the <900 mOsm/L threshold is the safest approach.

• The osmolar load from electrolytes must be factored into formulation calculations, not just the glucose and amino acid content. 1