Parenteral Nutrition Formulation

Modern parenteral nutrition (PN) solutions are referred to as All-in-One (AIO) or multi-chamber bags (MCB) containing all the required nutritional components. Standardised fixed feeding regimens or individually compounded mixtures are available. Vitamins, trace elements, minerals and water may be added to both regimens but must only be done under controlled aseptic pharmaceutical conditions. Individually compounded solutions are manufactured under strictly controlled aseptic conditions in a suitable pharmacy manufacturing unit.  

In certain clinical conditions e.g. patients with chronic intestinal failure requiring long term home PN (HPN), the compounding of individualised parenteral nutrition is often required.  This gives the possibility of meeting the particular nutritional and fluid requirements of these patients, particularly where parenteral nutrition is a supplement to their oral intake.

Fluids and electrolytes in parenteral nutrition

Patients on PN require an appropriate amount of fluid and electrolytes. The volume will vary widely depending on oral intake, excess losses, and other medical conditions such as cardiac or renal failure. Inpatients may also have other intravenous drugs prescribed, containing significant amounts of electrolytes in variable volumes of fluid. Although the basal requirement for water is quoted as 25-35ml/kg/day, the above factors lead to wide variations in the total volume and electrolyte content of PN. 

Macronutrients in parenteral nutrition 


Carbohydrate in PN is provided by glucose, an energy source that is available in a range of concentrations (5-70%).  It is generally provided in amounts up to 60% of total energy provided per day.  While the inclusion of some carbohydrate is essential for central nervous system (CNS) function, the maximum glucose oxidation rate (4-7 mg/kg /min/day) should not be exceeded as this may result in hyperglycaemia, hepatic steatosis and impaired respiratory function with increased CO2 production.  Glucose tolerance may be impaired in patients with an inflammatory response and concurrent insulin treatment may be necessary to prevent hyperglycaemia. It is recommended that insulin be given as a separate infusion and not added to the PN solution.  Hyperglycaemia in hospitalised patients is associated with a higher risk of complications and should be avoided (Krinsley, 2003).


Nitrogen requirements are generally provided in a range of 0.17-0.3g/kg/day depending on degree of metabolic stress and catabolism present. Amino acid solutions are available with a range of nitrogen content (e.g. 6-20g). In addition, solutions enriched with certain amino acids have become available e.g. glutamine.  Glutamine, although not an essential amino acid, may become a conditionally essential amino acid during metabolic stress.  There are problems providing glutamine in PN solutions due to its instability and low solubility in aqueous solutions. 


Lipid in PN solutions provides a concentrated form of energy reducing the need for infusion of large amounts of glucose, minimise respiratory and metabolic stress, preventing essential fatty acid deficiency and allows peripheral infusion of nutrients.  It is available in 10%, 20% and 30% concentrations and generally used to provide 20-30% of daily energy requirements.  Lipid can accumulate in the reticuloendothelial system, impairing its ability to remove bacteria and endotoxins and increasing susceptibility to infection. It is therefore recommended that lipid content of PN should not exceed 1-1.5g/kg/day.  Cholestatic complications have also been noted to be associated with higher lipid content. Soybean emulsions, e.g. Intralipid®, are the oldest lipid emulsions available.  They provide essential fatty acids and fat soluble vitamins but contain a high proportion (>60%) of the polyunsaturated fatty acids (PUFA); linoleic acid (52-54%) and alpha linolenic acids (7-9%). These emulsions, rich in n-6 fatty acids, in conditions of stress may be pro-inflammatory and exert immunosuppressive effects.  Novel or so called third generation lipids have been developed with the intention of modulating inflammatory responses and improving outcomes. These include emulsions containing medium chain triglycerides (MCT), olive oil and fish oil in various combinations as a partial replacement for soybean oil.  Supplying n-3 fatty acids may have anti-inflammatory effects the opposite effect to fatty acids of the n6 series. Lipid preparations based on olive oil can also be used to decrease the intake of PUFA and may be less susceptible to lipid peroxidation than n6 and n3 PUFA.  Such novel lipids have been shown to be safe and may offer some advantages over the use of soybean oil alone but there is a lack of evidence on the differential effects of lipid emulsions on clinical endpoints.  More work is needed to evaluate these emulsions before recommendations can be made.

Micronutrients in Parenteral Nutrition 

An adequate supply of micronutrients is essential for patients on PN to prevent clinical and subclinical deficiency states. Commercially prepared mixtures are available that provide well-balanced amounts of all essential vitamins and trace elements. Requirements for parenteral vitamins, trace elements and minerals will vary among patients depending on clinical and metabolic status and the need to replace any losses or prevent toxicity e.g. in renal patients. Further supplements may be appropriate in certain circumstances.  For example, starved patients may require additional thiamine as reserves would be expected to be low. Electrolytes are added according to anticipated patient requirements. Excessive electrolyte losses from wounds, surgical drains, vomiting and diarrhoea need to be replaced in the PN formulation or other IV fluids.

PN can be administered via peripheral or central veins.  

1. Choice of nutrient solution for peripheral administration

Hyperosmotic solutions are poorly tolerated by peripheral veins, and could cause pain, thrombophlebitis and thrombosis. The inclusion of lipid and an increase in volume of solution may reduce osmolarity. Furthermore, lipid emulsion based admixtures may also have a pH better tolerated by small vessels. Electrolyte content is an important consideration, as additions of electrolytes will increase the tonicity and affect the pH. Solutions <1200mosm/l have been shown to be tolerated when infused into peripheral veins.

2. Choice of nutrient solution for central administration

The delivery of PN solutions into a large diameter high flow vein such as the superior or inferior vena cava enables highly concentrated nutrient solutions to be infused. Consequently, central PN will be required for patients with special nutrient requirements e.g. lipid free, high nutrient requirements or reduced fluid requirements or for patients who do not have suitable peripheral access.  


1. Krinsley 2003 Mayo Clinic Proceedings 78, (12), P 1471–1478

Association Between Hyperglycemia and Increased Hospital Mortality in a Heterogeneous Population of Critically Ill Patients

2. PJD Andrews, A. Avenell, D W Noble, M K Campbell, BL Croal, WG Simpson, LD Vale, CG Battison, D J Jenkinson, J A Cook, and the SIGNET (Scottish Intensive care Glutamine or seleNium Evaluative Trial) Trials Group. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients BMJ 2011; 342

3.  J. WERNERMAN, T. KIRKETEIG, B. ANDERSSON, H. BERTHELSON, A. ERSSON, H. FRIBERG, A. B. GUTTORMSEN, S. HENDRIKX, V. PETTILÄ, P. ROSSI, F. SJÖBERG, O. WINSÖ Scandinavian Critical Care Trials Group (2011).  Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients: Acta Anaesthesiol Scand. 2011 Aug;55(7):812-8