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Physicochemical stability of all-in-one mixtures inclinical setting
Clinical Nutrition (1998) 17 (Supplement 3): 3 © Harcourt Brace & Co. Ltd 1998
Physicochemical stability of all-in-one mixtures in the clinical setting D. E DRISCOLL Assistant Professor of Medicine, Harvard Medical School, Boston, USA
The use of intravenous lipid emulsions as a nutrient source in patients requiring nutrition support varies from a weekly or bi-weekly source of essential fatty acids, or more commonly, as a daily caloric supplement. In the latter case, lipids are used to substitute a portion of the glucose calories, thereby forming a mixed-fuel system that avoids an excess of either energy source when used alone (1). In fact, after a brief period of metabolic adaptation, glucose and fat have been shown to be equally nitrogen-sparing (2). Moreover, substituting a portion o f the glucose calories with lipids also affords clinical benefits. For example, the literature is replete with references associated with excessive administration of either glucose or fat in susceptible patients. These effects are accentuated during acute illness, in part, as a consequence of the metabolic response to injury (3). Some of the most notable adverse effects of excessive glucose administration include an increase in the rate of de novo lipogenesis and impairments in host defences affecting neutrophilic adhesion, chemotaxis, phagocytosis and glycosylation o f opsonins; whereas excessive lipid administration can alter pulmonary gas diffusion and interfere with immunity by impairments in the function o f the reticuloendothelial system. In each case, whether glucose or lipids are involved, these adverse effects are primarily the result errors in the rate and quantity of parenteral energy supplied to the patient. A proper balance between glucose and lipids will avert these problems, and provision as an all-in-one mixture is the most convenient way to provide complete and balanced parenteral nutrition support. All-in-one therapy represents the consummate dosage form in that it provides the entire nutritional needs of the patient in a single vehicle. However, the inclusion of lipid emulsion induces a physicochemical change in the dosage form that converts it from a solution to an emulsion. The importance of this physical transformation poses numerous challenges to the compounding pharmacist, as well as the prescribing physician (4). The clinical issues of providing adequate nutrients to the patient influences the final
composition of the formulation, and must be balanced against the pharmaceutical concerns associated with emulsion stability. This challenge is heightened further when the parenteral nutrition formulation is also used to treat underlying metabolic disorders in the acutely-ill patient, that, for example, frequently exceeds the usual electrolyte needs under more stable conditions. The practice of using a parenteral nutrition admixture as a vehicle to treat serious metabolic disorders generally occurs in the institutional setting, whereas more stable final formulations are often encountered in the outpatient or home TPN population. Clearly, there are overlapping concerns with respect to the physicochemical stability issues between patient-care settings, such as the final concentrations of cations, sources and types of intravenous lipid emulsion used and extemporaneous compounding order by the pharmacist. For example, recent evidence has shown that a mixture of medium chain and long chain triglycerides produces a more, stable all-in-one formulation than one entirely composed of long chain triglycerides (5). The pharmacist and physician must work together to provide safe and efficacious all-in-one therapy. The critical challenge before us is to be able to meet the clinical needs of the patient and simultaneously provide a safe final product. Appreciation of both perspectives results in a successful collaboration that ultimately benefits the patients we serve.
References 1. Wretlind A. Development of fat emulsions. JPEN 1981; 5:230 2. Jeejeebhoy K N, Anderson G H, Nakhooda A F, Greenberg G R, Sanderson I, Marliss E B. Metabolic studies in total parenteral nutrition with lipid in man. J Clin Invest 1976; 57:125 3. Driscoll D F. Clinical issues with total nutrient admixtures. Ann Pharmacother 1990; 24:296 4. Driscoll D F, Bhargava H N, Li L, Zaim, Babayan V K, Bistrian B R. The physicochemical stability of total nutrient admixtures. Am J Hosp Pharm 1995; 52:623 5. Driscoll D F, Bacon M N, Bistrian B R. Physicochemical stability of two different brands of lipid emulsion for total nutrient admixtures. JPEN 1998; 22:$6 (Abstract)
Physicochemical stability of all-in-one mixtures in the clinical setting D. E DRISCOLL Assistant Professor of Medicine, Harvard Medical School, Boston, USA
The use of intravenous lipid emulsions as a nutrient source in patients requiring nutrition support varies from a weekly or bi-weekly source of essential fatty acids, or more commonly, as a daily caloric supplement. In the latter case, lipids are used to substitute a portion of the glucose calories, thereby forming a mixed-fuel system that avoids an excess of either energy source when used alone (1). In fact, after a brief period of metabolic adaptation, glucose and fat have been shown to be equally nitrogen-sparing (2). Moreover, substituting a portion o f the glucose calories with lipids also affords clinical benefits. For example, the literature is replete with references associated with excessive administration of either glucose or fat in susceptible patients. These effects are accentuated during acute illness, in part, as a consequence of the metabolic response to injury (3). Some of the most notable adverse effects of excessive glucose administration include an increase in the rate of de novo lipogenesis and impairments in host defences affecting neutrophilic adhesion, chemotaxis, phagocytosis and glycosylation o f opsonins; whereas excessive lipid administration can alter pulmonary gas diffusion and interfere with immunity by impairments in the function o f the reticuloendothelial system. In each case, whether glucose or lipids are involved, these adverse effects are primarily the result errors in the rate and quantity of parenteral energy supplied to the patient. A proper balance between glucose and lipids will avert these problems, and provision as an all-in-one mixture is the most convenient way to provide complete and balanced parenteral nutrition support. All-in-one therapy represents the consummate dosage form in that it provides the entire nutritional needs of the patient in a single vehicle. However, the inclusion of lipid emulsion induces a physicochemical change in the dosage form that converts it from a solution to an emulsion. The importance of this physical transformation poses numerous challenges to the compounding pharmacist, as well as the prescribing physician (4). The clinical issues of providing adequate nutrients to the patient influences the final
composition of the formulation, and must be balanced against the pharmaceutical concerns associated with emulsion stability. This challenge is heightened further when the parenteral nutrition formulation is also used to treat underlying metabolic disorders in the acutely-ill patient, that, for example, frequently exceeds the usual electrolyte needs under more stable conditions. The practice of using a parenteral nutrition admixture as a vehicle to treat serious metabolic disorders generally occurs in the institutional setting, whereas more stable final formulations are often encountered in the outpatient or home TPN population. Clearly, there are overlapping concerns with respect to the physicochemical stability issues between patient-care settings, such as the final concentrations of cations, sources and types of intravenous lipid emulsion used and extemporaneous compounding order by the pharmacist. For example, recent evidence has shown that a mixture of medium chain and long chain triglycerides produces a more, stable all-in-one formulation than one entirely composed of long chain triglycerides (5). The pharmacist and physician must work together to provide safe and efficacious all-in-one therapy. The critical challenge before us is to be able to meet the clinical needs of the patient and simultaneously provide a safe final product. Appreciation of both perspectives results in a successful collaboration that ultimately benefits the patients we serve.
References 1. Wretlind A. Development of fat emulsions. JPEN 1981; 5:230 2. Jeejeebhoy K N, Anderson G H, Nakhooda A F, Greenberg G R, Sanderson I, Marliss E B. Metabolic studies in total parenteral nutrition with lipid in man. J Clin Invest 1976; 57:125 3. Driscoll D F. Clinical issues with total nutrient admixtures. Ann Pharmacother 1990; 24:296 4. Driscoll D F, Bhargava H N, Li L, Zaim, Babayan V K, Bistrian B R. The physicochemical stability of total nutrient admixtures. Am J Hosp Pharm 1995; 52:623 5. Driscoll D F, Bacon M N, Bistrian B R. Physicochemical stability of two different brands of lipid emulsion for total nutrient admixtures. JPEN 1998; 22:$6 (Abstract)