Pharmaceutical evaluation of parenteral nutrition prescription

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SILVA, Alex Sander Lopes da [1], COMARELLA, Larissa [2]

SILVA, Alex Sander Lopes da. COMARELLA, Larissa. Pharmaceutical evaluation of parenteral nutrition prescription. Revista Científica Multidisciplinar Núcleo do Conhecimento. Year. 06, Ed. 09, Vol. 01, pp. 26-40. September 2021. ISSN: 2448-0959, Access link:


Parenteral Nutrition Therapy (PNT) is the nutritional intake method used for clinically stable patients, unable to use the gastrointestinal tract. It is accompanied by a Multiprofessional Nutritional Therapy Team (EMTN), which must be composed of at least one doctor, a nutritionist, a pharmacist and a nurse. Among the various responsibilities of the emtn pharmaceutical professional is the pharmaceutical evaluation of the prescription of parenteral nutrition (PN) regarding its adequacy, concentration, physical-chemical compatibility and administration dosage. However, what criteria, clinical protocols and standards for concentration of PN components, physical-chemical interactions and incompatibilities should be part of the pharmacist’s list of technical knowledge for the production of a safe PN? In order to assist in this challenge, the present study aimed to report the stages of pharmaceutical evaluation of PN prescription, its main parameters and critical points, through a literature review, based on journals, books and access to databases of academic publications existing on the Internet. The evaluation of osmolarity, type of access, macronutrients, electrolytes, vitamins, trace elements, calcium versus phosphorus interaction, calcium versus magnesium interaction and critical aggregation number (CAN) were the challenges that require particular attention when performing the pharmaceutical evaluation of the prescription of PN.

Keywords: parenteral nutrition, evaluation, prescription, pharmaceutical.


Among the numerous activities of pharmaceutical care is the analysis of the medical prescription, an indispensable activity for the pharmacist and the good performance in the health care of patients. This is a detailed analysis of the prescription, observing the parameters of therapeutic indication, dosage of prescribed items, drug interactions, food/drug interactions, route of administration, and when formula scans, analysis of pharmacotechnical, physical-chemical and compatibility and stability parameters (BRASIL, 1973; BRASIL, 1998).

The analysis of the prescription maintains its importance and takes its own nuances in parenteral nutrition therapy (PNT), in which pharmaceutical care is expressed through the steps pertinent to pharmaceutical evaluation, manipulation, quality control, conservation and transportation (BRASIL, 1998).

The Ministry of Health defines Parenteral Nutrition (PN), through Ordinance 272/1998, as a solution or emulsion, composed basically of carbohydrates, amino acids, lipids, vitamins and minerals, sterile and pyrogenic, packed in a glass or plastic container, intended for intravenous administration in malnourished patients or not, in hospital, outpatient or household, aiming at the synthesis or maintenance of tissues, organs or systems (BRASIL, 1998).

In this context, the pharmaceutical evaluation of parenteral nutrition is the analysis of the prescription/formulation, regarding its concentration, physical-chemical compatibility of its components and dosage. It is an exclusive activity of the pharmaceutical professional, extremely important for PNT and for the good progress of care offered by the Multidisciplinary Team to patients undergoing Parenteral Nutritional Therapy (PNT) (BRASIL, 1998).

The pharmaceutical evaluation of parenteral nutrition is a very important stage of PNT, because it can be verified and corrected any irregularity in the prescription, preventing the manipulation of inadequate PN. The pharmaceutical professional should be aware of the parameters to be analyzed and, mainly, of the potential physical-chemical incompatibilities that make it impossible to produce a safe PN.

However, what criteria, clinical protocols and standards for concentration of PN components, physical-chemical interactions and incompatibilities should be part of the pharmacist’s list of technical knowledge for the production of a safe PN? In order to assist in this challenge, the present study aimed to report the stages of pharmaceutical evaluation of the prescription of PN, its main parameters and critical points.



The present work was constructed from a comprehensive review of the literature, through specialized books, sites with academic and scientific production databases, such as Scielo, in addition to an extensive consultation of all legislation pertinent to the subject, such as Ordinances of the Ministry of Health, Federal Laws and recommendations of ANVISA and the Federal Council of Pharmacy (CFF).



PNT is the set of therapeutic procedures for maintaining or recovering the nutritional status of patients through PN and can only occur through the follow-up of a Multiprofessional Nutritional Therapy Team (EMTN), consisting of at least one medical professional, a pharmacist, a nurse and a nutritionist, qualified and with specific training for the practice of Nutritional Therapy (BRASIL, 1998).

The importance of EMTN is globally accepted and there are recommendations, both technical and legal, that Nutrition Therapy, especially TNP, should not occur without the constant monitoring of all professionals involved in it. The standardization of clinical protocols by EMTN, in units that provide TNP and the constant monitoring of patients by EMTN are essential for the success of therapy, especially with regard to its safety and there should be specific protocols for neonatal, pediatric, adult and patient patients in specific situations, such as hepatopathies and nephropathies, considering the peculiarities of the organisms in the different stages of life and the clinical complications that may be present (LEITE et al., 2005; GULIN; LOPEZ GARCIA, 2010; GUIMARÃES, 2011; BERMUDEZ; SANABRIA; VEIGA, 2013; PINTO; CASTRO; REIS, 2015; SCHOENENBERGER; RODRIGUEZ, 2015).

The attributions of the pharmaceutical professional at EMTN include, from the selection, procurement, storage and distribution of all the products necessary for the preparation of PN, to supervision in the operational routines of preparation (BRASIL, 1998).

To this do so, it is also part of their responsibilities, the qualification of suppliers; monitoring of manufacturers’ certificates and analysis reports; the evaluation of the formulation of the medical prescription; the use of pre-established techniques of PN preparation that ensure physical-chemical compatibility, sterility, pyrogenicity and absence of particles; the determination of the shelf life of each standardized PN, based on strict quality control criteria; the correct sampling for microbiological analysis; the correct labelling of the finished product; the analysis of adverse reactions and drug-nutrient and nutrient-nutrient interactions, from the registered pharmacotherapeutic profile; the training, continuing education and attentive supervision of employees in the handling / pharmacy sector, in addition to the maintenance of mandatory legal records, such as date and time of preparation of PN, full name of the patient, identification (name and registration) of the physician and handler (BRASIL, 1998).


The Pharmaceutical Evaluation of the prescription of PN is a mandatory activity, according to Brazilian legislation and specified in Ordinance 272/1998 of the Ministry of Health:

The pharmaceutical evaluation of the prescription of PN regarding its adequacy, concentration and physical-chemical compatibility of its components and dosage of administration, should be performed by the pharmacist before the beginning of the manipulation. Any change in the prescription, which is necessary, depending on the pharmaceutical evaluation, should be discussed with the physician of the team responsible for its formal alteration (BRASIL, 1998).

In this context, it is up to the pharmaceutical professional to evaluate the prescription item by item, in addition to the physical-chemical stability of the resulting mixture, to discuss with the medical professional the appropriate adjustments and, if any, from the resulting agreement, request a new prescription with the changes made (BRASIL, 1998).

It is very important that this step be performed with total care and interaction between the EMTN. It is empirical knowledge and also demonstrated by studies (GUIMARÃES, 2011) that there are nonconformities in the vast majority of PN prescriptions and it is in the Pharmaceutical Prescription Assessment that these non-conformities can be observed and corrected before the manipulation of PN.

The first step in the prescription of PN is the assessment of the nutritional status of the patient and his/her vital clinical functions, since PN should only be initiated in patients with stable vital functions and with minimum treatment forecast for three days for malnourished patients and five days for eutrophic patients, gastrointestinal tract to justify the risk/benefit of treatment (FERRERIA, 2007). In addition, it is important that PN is initiated with 30% to 50% of the estimated nutritional needs, gradually progressing to 100% between 48 and 72 hours of the beginning of therapy, in order to reduce the risks of metabolic disorders, especially of feedback syndrome, especially in hypermetabolic individuals with severe starion (CALIXTO-LIMA et al., 2011, p.35). This step should be performed by the nutritionist and the nurse nutrologist of the EMTN and reviewed by the pharmacist in the evaluation of the prescription.


Osmolarity is the concentration of active particles in the solution, that is, particles capable of exerting osmotic pressure, per liter of solution (BAXTER; WAITZBERG; RODRIGUES, 2000, p. 659). There are several formulas to calculate the final osmolarity of PN, however, the most precise method is to verify the information provided by each manufacturer for each of the components to be inserted in the formulation and then add the individual contribution of each of them, because the osmolarity varies depending on the differences, even if minimal, components of the insums (CALIXTO-LIMA et al., 2011, p.58).

There is no consensus on what is the maximum optimal osmolarity for infusion of PN via peripheral access (small-caliber veins, usually in the arm). Some authors suggest 600 mOsmol/L (SOUZA, 2008, p.278-89), while others consider it acceptable up to 900mOsmol/L for infusion of PN in peripheral access (COSTA, 2014, p.38).

In clinical practice, the Multidisciplinary Team defines the standard for the institution they represent, within the scientifically established limits. After the cutoff point is defined, between 600 and 900mOsmol/L, this becomes the institutional standard for defining the type of acceptable access for PN. It is up to the pharmaceutical professional to accurately calculate the final osmolarity of the PN solution and, if the osmolarity is superior to that defined for peripheral access, discuss with the EMTN the exchange of access from the patient to the central type (catheter inserted in a large vein, usually the superior vena cava) or, if it is not feasible, ask the prescribing physician to adapt the prescription so that the osmolarity fits for peripheral access, suggesting minimal adjustments that allow it, such as a small decrease in glucose and amino acid intake, for example.


Amino acids, glucose and lipid emulsion are considered macronutrients in PN when present. These are the elements that will contribute to the patient’s energy contribution (CALIXTO-LIMA et al., 2011, p.58). The calculation of the Total Energy Value (VET) is made by the nutritionist or the nutritionist of the EMTN nutrologist and this caloric contribution is divided into the prescription through the supply of macronutrients. If the patient needs weight gain / body mass, the prescribing physician will determine a caloric intake in PN  higher than VET, making the caloric supply greater than the energy expenditure.

Chart 1 demonstrates the recommendation of macronutrient prescription for adult patients in PNT. It is important to emphasize that the values depend on the individual tolerance of each patient and lower or higher values do not represent a prescription error, provided that they occur through plausible clinical justification.

Table 1: Recommended Prescription for Adult Patients in Parenteral Nutrition

PROTEINS 1.2 To 1.5 g/kg/day 0.8 to 1g/Kg/day
CARBOHYDRATES ≤ 3mg/kg/min ≤ 5mg/kg/min
LIPIDS 1g/Kg/day 1 to 2 g/kg/day

Source: Calixto-Lima et al., 2011, p.36

There are special amino acid solutions on the market for nephropathic patients, only with essential amino acids and histidine, special solutions for hepatopathic patients, with a decrease in the percentage of aromatic amino acids and special amino acid solutions for neonatal and pediatric patients, with a breast milk profile. It is important that the amino acid solution in PN corresponds to the patient’s clinical need and that specialized solutions for nephropaths, hepatopaths and pediatric solutions are used when this is the patient’s profile, to ensure greater safety and efficacy in therapy (CALIXTO-LIMA et al., 2011, p.6).

Glutamine, the most abundant amino acid in plasma and the main substrate of immune cells and enterocytes, is an amino acid considered conditionally essential in catabolic processes and can be administered in physical-chemically stable dipeptide solutions (FERREIRA, 2007; CALIXTO-LIMA, 2011). There is insufficient scientific evidence for the routine use of glutamine in PN, however, patients with burns and traumas are widely benefited from its use, with a lower rate of infectious complications and a significant reduction in hospitalization time in these cases (FERREIRA, 2007).


Electrolytes are essential for maintaining osmotic balance, acid-base balance, as well as various cellular functions and should be present, in therapeutic doses, daily in PN, in order to maintain homeotase.

The needs of each patient for each of the available electrolytes should be carefully evaluated using their clinical history. Comorbidities, the state of liver and kidney functions, the interference of the medications used by the patient in the plasma concentration of electrolytes (hydrochlorothiazide causes greater potassium depletion, for example), cardiac and respiratory conditions, as well as extrarenal losses such as diarrhea and emesis (CALIXTO-LIMA et al., 2011, p.22).

There are standards for determining the prescription of individualized electrolytes for adult, pediatric and neonatal patients, each with their respective limits of daily recommendation. The electrolyte pattern for adult patients, without associated organic dysfunction and without considerable loss of electrolytes by extrarenal pathways is presented in Chart 2.

Table 2: Daily Electrolyte Recommendations

Calcium 10 to 15 mEq
Magnesium 8 to 20 mEq
Phosphate 20 to 40 mMol
Sodium 1 to 2 mEq/Kg + replacement
Potassium 1 to 2 mEq/Kg
Acetate as needed to maintain basic acid balance
Chloride as needed to maintain basic acid balance

Source: Calixto-Lima et al., 2011, p.23

It is important to emphasize that the dosing limits of prescription patterns can and should be exceeded, if there is clinical need signaled by the prescribing physician, such as severe hypokalemia, among others. It is up to the pharmacist to evaluate whether the dosing recommendations are being followed, or, if they are not, to verify with the prescribing physician the real presence of clinical need for non-standardized doses in order to ensure the safety of patients using PNT (BRASIL, 1998).

Iron is not added to PN and should be administered separately intravenously, due to its high chemical reactivity with the other components of the formulation, which can provide the formation of quelates, besides causing instability in lipid emulsion (FERREIRA, 2007).


Trace elements or trace elements are minerals that act as enzymatic co-factors. Without being associated with these micronutrients, many enzymes lose their role as a catalyst for biochemical processes and the entire functioning of the body is compromised. These minerals should be added to PN in doses and presentations that do not alter the physical-chemical stability of the solution (CALIXTO-LIMA, 2011, p.26). They should also be monitored constantly, mainly with regard to phosphorus, magnesium and zinc, in order, if necessary, to adjust the supply in order to maintain normal serum levels (FERREIRA, 2007). The daily recommendation of the intake of trace elements in PN for adult patients is presented in Chart 3.

Table 3: Recommendation of Trace Elements for Adult Patients in Parenteral Nutrition

Zinc 2.5 to 5mg/day
Copper 0.3 to 0.5mg/day
Chromium 10 to 15μg/day
Manganes 60 to 100μg/day

Source: American Society for Parenteral and Enteral Nutrition, 1998, by Calixto-Lima et al., 2011, p.26

Vitamins are essential substances for metabolism and the body cannot synthesize, and should therefore obtain them from the diet. Vitamin needs in critically ill patients are not well established (FERREIRA, 2007), but there are daily recommendations for adult patients (MARCHINI, 1998) can be seen in Chart 4.

Table 4: Recommended Doses of Vitamins in Adult Patients

Vitamin A 1,000μg
Vitamin B1 3mg
Vitamin B12 5μg
Vitamin B2 3.6mg
Vitamin B6 4mg
Vitamin C 100mg
Vitamin D 5 to 10μg
Vitamin E 10 to 15mg
Vitamin k 200μg

Source: Adapted from Marchini, 1998.

It is important to highlight that Vitamin K is not present in the multivitamins we have in the market for use in PN, as it can cause serious changes in patients using anticoagulants. In addition, Vitamin K usually inactivates Vitamin C, as does Vitamin B12 (SPOLIDORO, 2000). If necessary, Vitamin K must be provided by another means (FERREIRA, 2007).

If it is standard of the manipulative institution to produce PN in two bags, separating the bag from the lipid emulsion from the other components, it is also suggested to separate the trace elements of the vitamins, because copper and zinc can degrade Vitamin C. This reaction can be visually perceived, if it occurs, by a bluish color ation in PN (SPOLIDORO, 2000).

Due to vitamin B12 inactivity in PN in patients on prolonged PNT, it is advisable to administer Vitamin B12 intramuscularly 100mg/month or 300mg every 3 months (SPOLIDORO, 2000).


It is known that calcium ions and phosphate ions, from a certain critical concentration in solution, tend to cluster forming calcium phosphate, an insoluble precipitate. This happens mainly when phosphorus is supplied as potassium phosphate, which leaves phosphate free for the occurrence of the chemical reaction of precipitation. An ideal ratio of 1.7mg of calcium for each milligram of potassium is considered maximum, with the sum of calcium and phosphorus concentrations at 40mEq/L or a Calcium x Phosphorus ratio equal to 250mEq/L. Higher values are highly indicative of the occurrence of physical-chemical instability by the formation of calcium phosphate precipitate, making it impossible to manipulate the prescription by physical-chemical instability of the resulting solution. The supply of potassium in the form of potassium glycerophosphate does not leave phosphate ions free for the precipitation reaction to calcium to occur and dispenses with the calculations of physical-chemical stability in relation to this parameter (SPOLIDORO, 2000).


The relationship between Calcium ions and Magnesium ions is also a factor to be monitored to ensure the stability of the PN solution. It is known that a Calcium + Magnesium ratio greater than 16 mEq/L tends to destabilize the lipid emulsion by ionic pressure or neutralization of lipid emulsifier loads, forcing the opening and aggregation of micelles, with consequent separation of the oily phase of the aqueous phase of the solution (Souza, 2008; SPOLIDORO 2000).


The Critical Aggregation Number, also known as CAN (Critical Number Aggregation), is one of the parameters that evaluate the possibility of phase separation or rupture of the PN solution. It is calculated by the Shultz-Hard formula:

CAN = (A + 64 x B + 729 x C) x 1000 / Total volume of PN, where: A = concentration of monovalent cations in mMol/L

B = bivalent cation concentration in mMol/L C = trivalent cation concentration in mMol/L

In this calculation, all ions that can neutralize the emulsifier sloads present in the lipid emulsion, promoting an increase in the size of micelles, or even total separation of the aqueous and oily phases are considered, according to their chemical valence for this, being recommended a value between 400 to 700 mMol/L (GASTALDI, 2009). CAN values higher than 700 are preventing manipulation, and the prescribing physician should be informed of the fact and the prescription to be adequate to the parameter with ion reduction, especially the dilates, such as calcium and magnesium, in order to promote a safe PN production (GASTALDI, 2009).


The Pharmaceutical Evaluation of parenteral Nutrition Prescription is a critical stage of PNT, is mandatory according to Brazilian legislation and recommended by all major global institutions related to health.

It is up to the pharmaceutical professional, as an active member of the EMTN to make a rigorous evaluation of the medical prescription, preventing the manipulation of inadequate PN’s, with respect to the concentration, physical-chemical compatibility of its components and dosage of administration, signaling and discussing with the prescribing physician the necessary changes for the production of a safe and effective PN for the patient in PNT, obtaining an appropriate prescription for therapy before starting manipulation.

The creation and standardization of protocols in the units that provide PNT service, following the known scientific recommendations, a good interaction between EMTN professionals, constant training and improvement, are the main means to increase the efficacy and, mainly, the safety of Nutritional Therapy as a whole, including the Pharmaceutical Assessment of the Prescription of NP.


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[1] Master’s degree in Pharmaceutical Sciences (PPGFARMA, UNEB); specialist in Hospital Pharmacy (Uninter); specialist in Quality Management and Environmental Management (Uninassau); bachelor’s degree in Pharmacy with qualification in Industry (UFVJM).

[2] Guidance counselor.

Submitted: March, 2021.

Approved: September, 2021.

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