Total parenteral nutrition: hospital pharmacy vs pharma industry bags – a case study

Massimiliano Donato Petrelli

Debora Busni

Marina Taus

Alessandra Tucci

Mietta Giambenedetti

Elena Lamura
Pharmacy

Albano Nicolai

Dietetic and Clinical Nutrition
Ospedali Riuniti
Ancona, Italy

Total parenteral nutrition (TPN) can be proposed for every patient if oral or enteral nutrition is insufficient, ineffective, impossible or contraindicated (when the rest of the digestive tract is required). Its widespread use has led to several therapeutic modalities. The different nutrients required for parenteral nutrition can be administered either with separate bottles or with specially prepared admixtures. Several types of admixtures are marketed by the pharmaceutical industry or prepared by hospital pharmacies.(1)

Hospital formulations are prepared as sterile solutions for injection under the joint responsibility of the Dietetic and Clinical Nutrition Unit and the hospital pharmacist. In Italy, the production process must comply with strict quality standards defined by Good Practices for Manufacturing Solutions for Injection promulgated by the Italian Ministry of Health.(2) These quality and safety standards require production in a protected unit, in accordance with well-defined and detailed techniques, by motivated and specially trained personnel.(3,4) In recent years the pharmaceutical industry has proposed several new bags and initiatives to reduce the costs.

Case study
For correct formulation and preparation of a nutritional admixture a parenteral nutrition team is required. This team comprises a nutrition physician, a pharmacist and at least three technicians (all of them with experience in parenteral nutrition). In our study, the pharmacy nutrient formulations, done by the nutritionist, were prepared aseptically under a class A horizontal laminar flow hood situated in a class B controlled atmosphere. Formulations were prepared every day for inpatients (according to the daily clinical and laboratory situation of each patient; therefore we are able to provide a specific bag to every patient) and once a week for outpatients. Ethylvinylacetate bags (a double-compartment bag for outpatients) were filled with the different solutions using a sterile pressure pump. The bags were labelled, checked and packaged individually in a thermo-sealed bag and covered with a black sack to protect the vitamins from light. The bags were immediately sent to the hospital units or held for 24 hours at 4°C before distribution to the patient’s home. The bags were transported in refrigerated boxes.(5)

Samples for bacteriology quality control were taken weekly from each production lot of the nutrient formulation.(6) The method used at our hospital is based on routine culture sampling plus a membrane filtration method.

To compare therapeutic alternatives of equivalent nutritional value, the study was performed for the most frequently employed formulation and similar commercial preparations. The most widely prescribed formulation for patients was the C1L, a ternary formulation (57% of the prescriptions). The commercial admixtures with a ternary formulation the closest to our C1L formulation were Clinomel N7-1000 (Baxter; Italy) and Kabiven 2053 (Fresenius Kabi; Italy) (see Table 1).

[[HHE07_table1_P25]]

Current market prices were used for product and equipment costs. Personnel costs were based on the mean salary for each category of hospital personnel.

Different parameters were taken into account to determine the cost of producing a hospital formulation. Variable costs depended on the type of formulation and included the cost of the raw material and the container. Fixed costs included consumable items, bacteriology controls, depreciation of equipment/facilities and personnel costs.(7–10)

As the commercial admixtures available for parenteral nutrition do not contain vitamins and trace elements, their cost was calculated after supplementation. The supplementation process requires strict aseptic conditions, preferably under laminar flow, under the control of an expert.(11) The commercial bags were supplemented in accordance with the manufacturer’s recommendations: one bottle of Addamel on even days alternate with one bottle of Cernevit on odd days for both Clinomel N7-1000 and for Kabiven 2053. The times required for supplementation under the laminar flow hood, labelling and packaging were recorded.

The cost of the C1L bag is summarised in Table 2, while costs and comparison of commercial bags are summarised in Table 3.

[[HHE07_table2_P25]]

[[HHE07_table3_P25]]

Discussion
Cost analysis is one of many approaches useful for determining an optimal strategy for nutritional support, which must be chosen on the basis of medical and economic effectiveness.(12) The overall cost of parenteral nutrition depends on the type of product administered, the administration modalities, monitoring protocols and treatment of potential complications.(13)

Surely separate bottles are the most economical means for administering parenteral nutrition, especially in those hospitals that do not have a dietetic and clinical nutrition unit and the laboratory for parenteral nutrition. This method offers greater latitude for the prescriber, who can use different combinations to rapidly adapt nutritional support to the patient’s individual needs. The sequential nature of the infusions can, however, have unfavourable metabolic consequences. In addition, daily administration requires more time for preparation and surveillance and a greater number of manipulations, which increases the risk of bacterial contamination despite a correctly applied aseptic protocol.(14-16)

Therefore administration of a complete nutritional admixture in a ready-to-use bag reduces the risk of infection since a single infusion line is used. The time required for nurse surveillance is also shorter.

Admixtures prepared in the hospital pharmacy allow prescribers to establish a precise formulation specifically designed for the nutritional needs of the individual patient, both in terms of quantity and quality. This type of organisation has prerequisites, namely appropriate pharmaceutical logistics and good collaboration between all the hospital units and the unit of dietetic and clinical nutrition, and especially between this unit and the pharmacy.

Nutritional products manufactured by pharmaceutical firms offer the advantage of meeting well-established standard requirements and, because of their longer shelf-life, of more convenient stock management and distribution to the different units.(17) The need for supplementation does, however, limit this advantage, because after supplementation the stability of these products can be guaranteed for only two or three days at 4°C. Supplementation also has to be organised and requires manipulations. The cost of these admixtures is largely dependent on the purchase price, which can vary greatly depending upon local supply.

Our cost assessments are nevertheless quite similar to those reported by others using similar methodologies. The personnel cost depends on whether bag preparation is an exclusive activity or whether the personnel also participate in other activities. The time required to prepare the bags reported in other studies has ranged from 15 to 25 minutes depending on the level of activity of the unit.(8,11,18) For hospital bags prepared under laminar flow, reported costs have been €38.72, €44.06 and €44.82.(7,8,11) These costs (measured in France) are slightly higher than the cost we report here, probably because they refer to years 1994-1999. In that period also our bags were more expensive, probably due to lower-number production. Some of the comparative studies have demonstrated a higher cost for the use of commercial bags supplemented by the caregiver in comparison with hospital-prepared bags.(10-11;19-20) On the contrary, there is a study reported by Pichard et al, comparing separate bottles, hospital bags and supplemented commercial bags, in which there was a net money saving with the use of supplemented commercial bags compared with hospital bags; the high cost of the raw materials required to produce the nutritional admixtures explained the higher cost of the hospital preparations.(21)

Conclusion
In the last 10 years the pharmaceutical industry has given us a wide range of different nutritional bags. The range is so wide that it is easy to find the right commercial bromathologic formulation for almost all patients’ metabolic needs.(22-24) We can presume that in the near future most patients’ parenteral nutritional needs will be satisfied by the pharma industry products. Increasing the annual production of bags, all the pharma firms could further reduce unit costs (already decreased in the last four years). Assuming all this, we can expect in the next few years a reduction in hospital-made nutritional bags, those particular bags being reserved for patients with complicated pathologies and/or metabolic-electrolytic deterioration. Final considerations:

• Nowadays total cost for supplemented commercial preparations is almost equal to that of hospital preparations, with equivalent nutritional value and safety.
• In the near future the cost of hospital-made bags is estimated to increase (raw products, personnel, new machinery); meanwhile, the unit cost of commercial bags will fall by 8–10% if their consumption increases.
• Consumption of commercial bags should increase especially in those hospitals that do not have a laboratory for parenteral preparation as commercial bags represent a complete and safe product. In fact, both hospital laboratories and the pharmaceutical industry give legal guarantees as to safety and nutritional balance.2 Bottled admixtures at the patients’ bedside do not guarantee the same safety.

But it must be underlined that we have to increase the correct use of parenteral bags (ie, for nutritional purposes) and not increase their improper use (ie, for hydration of agonic patients). Considering all these data reported, we could probably presume that personalised preparation of nutritional bags will be necessary in about 20% of patients requiring TPN.

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