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David F Driscoll
Assistant Professor of Medicine
Harvard Medical School
The extemporaneous compounding of parenteral nutrition (PN) admixtures for patients is central to the role of the pharmacist on nutrition support teams.(1) Unlike other pharmaceutical compounding tasks, the “stakes” are far higher for PN admixtures. For one thing, sterility is absolutely essential in PN admixtures, especially for those formulations that may be of lower osmolality and/or contain lipid injectable emulsions, where nosocomial pathogens may thrive. Unfortunately, the clinical significance of this situation was poignantly demonstrated when two infants died as a result of a well-intentioned cost-containment effort to extend the use of plastic disposables in the compounding of infant PN admixtures.(2) Secondly, the composition of these formulations is very complex, with 50 or more individual chemical entities in a given PN admixture (eg, 15-20 crystalline amino acids, glucose, lipids, 10-12 electrolytes, 12-13 vitamins, 5-7 trace minerals and drugs). This vast array of components greatly increases the risk of incompatibility, as well as instability of certain additives, with the formation of potentially embolic matter and/or the deprivation of essential active nutrients.(3) In addition, PN dosage forms are administered intravenously (IV);therefore, significant errors in compounding practice involving the creation of untoward chemical reactions can also lead to fatal outcomes.(4) The purpose of this article is to review the essential tasks that all pharmacists must undertake in executing their professional responsibilities during the compounding and dispensing of PN admixtures to the patients they serve.
Completeness of the PN order
From the outset, once an order for PN therapy is received by the pharmacist it must be appropriately screened for its completeness. If the admixture is truly intended to provide all nutrients IV, then the essential macro- and micronutrients should be provided in sufficient quantities. Table 1 provides an example of the typical daily requirements for various adult weights with normal end-organ function. If a nutrient quantity is outside the typical ranges, the reasoning (eg, patient has fluid overload, renal disease) should be verified by closer evaluation of the medical record. If still unclear, the prescribing physician should be contacted. Similarly, the pharmacist should look for large-scale changes in PN admixture from one day to the next (eg, potassium was prescribed at 40mmol and now is 200mmol) and/or critical omissions of certain additives (eg, insulin was prescribed at 40 units and now is 0 units). Finally, the infusion rates are often given continuously, but the pharmacist should ensure that they are appropriately set so that no single PN infusion is administered for a period exceeding 24 hours.
PN compatibility and stability
Setting compounding standards
The pharmacist is in a key position to draft compounding standards for the final PN formulation based on published literature. Furthermore, the purchasing of drugs and injections is often carried out by the pharmacy department, and there are multiple manufacturers of the many ingredients used to compound PN admixtures, so certain demands can be reasonably placed upon them. Therefore, individual companies should offer financial benefits to the institution through aggressive contracts and at the same time provide pharmaceutical information that supports the compatibility, stability and, ultimately, the safety of the final formulations. Failure to participate in establishing minimum acceptance criteria that ensure the compatibility and stability of their products in your institution could result in contract forfeiture. Hence, nutrition support pharmacists and administrators need to foster these partnerships in order to optimise the delivery of safe and efficacious PN therapy to the patients they serve. Finally, the assignment of a “beyond-use date” by the pharmacist to the final PN admixture, which indicates the period of time in which it is safe to use, should also be verified accordingly.(5)
Setting clinical standards
The pharmacist has a responsibility to ensure the safety of PN formulations. To achieve this, each time a prescription is written, specific concentration limits of the various additives should be established within the institution, which is best accomplished via a multidisciplinary team. In the USA, the hospital committee responsible for medication and infusion safety is the pharmacy and therapeutics (P&T) committee, whose actions are reviewed and adopted by an overseeing medical executive committee. When devising such limits, a thorough review of the published literature, as well as documentation from the PN manufacturers, is essential. The best approach is to devise the widest range of nutrients which may be prescribed that represent clinically relevant and safe concentrations. For example, minimum and maximum concentrations (per litre) of macronutrients (ie, amino acids, glucose and fat) and micronutrients (electrolytes, vitamins, trace minerals and drugs) should be determined. As low-osmolality PN formulations given via the small veins of peripheral circulation have different compatibility and stability profiles compared with high osmolality admixtures intended for large veins of the central venous circulation, separate clinical limits should be established for each. Once such limits are devised, they should be sanctioned by the appropriate hospital committee(s), and then become the established guidelines for use whenever an order for PN is written within the hospital.
Medications in PN admixtures
The addition of medications to the PN admixture can be safely done within reasonable clinical limits. The main criteria for the addition of drugs to the PN admixture are listed in Box 1.(6) Clearly, there are a limited number of medications that can be safely and reasonably added, as they must pass rigorous compatibility, stability and efficacy criteria beforehand. Once the drugs meet these criteria, there are significant benefits associated with their addition such as minimising fluid intake in susceptible patients, improving pharmacokinetic dosing in some cases and even financial savings by the elimination of separate bags and administration sets normally required for IV infusion.
Supplementing additives during the infusion
The responsibility of the pharmacist in compounding PN admixtures has been established and clearly should not be performed by nonpharmacy personnel.(7) Many pharmacists view the dispensing of the admixture to the ward as the final act in PN therapy, but this viewpoint should be revised. �Pharmacists should ensure not only the timely delivery of the PN admixture to the ward, but that it is properly stored until its infusion. Moreover, what happens when lab results come back showing serum abnormalities of certain nutrients and the physician prescribes additives to be mixed with a running infusion? There are two options here:
In either case, the pharmacist should be informed to ensure the compatibility and/or stability of the coinfusion or the additive to the current infusion. In the latter case, the pharmacist should be the person to add the drug aseptically to a “stopped” infusion at bedside, after evaluating whether it is safe to do so. Common examples where such requests may occur at bedside include additional glucose (eg, a 50ml amp of 50% dextrose or D50) for a low blood sugar in a PN-containing insulin, additional supplementation with potassium or phosphorus for low blood levels, and so on.
In the provision of PN therapy to patients, pharmacists must assume full responsibility for the compatibility, stability and, ultimately, safety of the infusion. This responsibility extends from the time the PN prescription is received until the compounded infusion is completed.