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Pharmaceutical interventions in medications prescribed for administration via enteral tubes in a teaching hospital

Abstract Objective: to analyze the impact of guidelines regarding errors in medications prescribed for administration through enteral tubes. Method: quantitative study, in three phases, undertaken in internal medicine, neurology and an intensive care unit in a general teaching hospital. In Phase 1, the following was undertaken: a protocol for dilution and unit-dose repackaging and administration for 294 medications via enteral tubes; a decision flowchart; operational-standard procedures for dilution and unit-dose repackaging of oral pharmaceutical forms and for administration of medications through enteral tubes. In phase 2, errors in 872 medications prescribed through enteral tubes, in 293 prescriptions for patients receiving inpatient treatment between March and June, were investigated. This was followed by training of the teams in relation to the guidelines established. In Phase 3, pharmaceutical errors and interventions in 945 medications prescribed through enteral tubes, in 292 prescriptions of patients receiving inpatient treatment between August and September, were investigated prospectively. The data collected, in a structured questionnaire, were compiled in the Microsoft Office Excel(r) program, and frequencies were calculated. Results: 786 errors were observed, 63.9% (502) in Phase 2, and 36.1% (284) in Phase 3. In Phase 3, a reduction was ascertained in the frequency of prescription of medications delivered via enteral tubes, medications which were contraindicated, and those for which information was not available. Conclusion: guidelines and pharmaceutical interventions were determined in the prevention of errors involving medications delivered through enteral tubes.


Introduction
Routinely, in hospital practice, when patients are fed via Enteral Nutrition (EN) and do not present efficacious swallowing, or are at risk of pulmonary aspiration, enteral tubes are also used for the administration of medications (1) .
As health establishments have the duty to promote safe practices in the use of medications, in compliance with the Protocol for Safety in Prescription, Use and Administration of Medications, an integral part of the National Patient Safety Program* , **, it is the responsibility of the health team to appropriately prescribe, handle and administer medications through enteral tubes, avoiding complications and failures in the nutritional and drug therapies (2)(3) .
As a result, it is important to investigate the principal aspects which restrict or contra-indicate the administration of medications through enteral tubes. Thus, it is possible to select the drug and/ or pharmaceutical form with the least probability of provoking complications, to undertake dilutions or transformations of medications, when necessary, and use an appropriate administration technique (3)(4) .
The principal aspects which restrict or contra- Obstructions of enteral tubes, besides entailing reduction in the absorption of the drug and/or of nutrients, can lead to the substitution of the tube, exposing the patient to the risks of a new procedure and additional costs, involving radiological materials and examinations for confirming its positioning (5) . Although more comfortable for the patient, the tubes which are most prone to obstructing are those with smaller calibers -5 to 12 French -1.65 to 3.96 millimeters in diameter (6) . The following may be cited as causes of obstructions: high viscosity and insufficient flow of the EN, drug/EN incompatibility, adherence of the drug to the enteral tube and specific characteristics of the drug or of the pharmaceutical form.
Interactions can occur between the drug and the nutrients (7) and between two or more drugs, if administered concomitantly. In order to avoid interactions between drugs, when it is necessary to administer more than one medication at the same time, and these should be administered separately, the enteral tubes should be flushed with water between each drug (2) .
Alterations in the pharmacokinetics can occur because it was not planned for the medications to be administered through enteral tubes and because administration through this route entails modifications in the absorption of the drug.
Gastrointestinal effects can be caused principally by oral liquid formulations (8) . The osmolarity is one of the physical characteristics which determine the organism's tolerance to a formulation. The closer the osmolarity of the formulation administered is to that of the gastrointestinal secretions -approximately from 100 to 400mOsm/kg, the greater the tolerance will be. Any liquid formulation, whose osmolarity is higher than 1000mOsm/ kg, such as the syrups, can cause abdominal distention, nausea, intestinal spasms and diarrhea, principally when administered directly into the small intestine (4) .
Many sweeteners, including mannitol, lactose, sorbitol, saccharin and sucrose, can cause or worsen situations of diarrhea. Among these, the excipient which is most prone to adverse gastrointestinal reactions is sorbitol, which is an inactive component, used as a sweetening agent in order to improve flavor and stability. Doses superior to 10 g per day can cause abdominal distention and flatulence, while 20 g per day can cause an osmotic laxative effect, resulting in diarrhea and abdominal spasms (2,9) .
When possible, oral liquid pharmaceutical forms are the formulations of first choice for administration via enteral tubes. However, when a liquid oral pharmaceutical form is inappropriate, or is not available, solid oral pharmaceutical forms can be used for administration through enteral tubes (6,10) . This process, called transformation or derivation, occurs when one pharmaceutical form is elaborated based on the manipulation of another, so long as that the drug's*** stability is preserved and safety is guaranteed.

Analysis of the data
The data were compiled using a Microsoft Office Excel ® spreadsheet and, based on these, the absolute and relative frequencies were calculated.

Results
The 294 medications, in the standardized solid and liquid oral pharmaceutical forms, were analyzed in relation to the possibility of administration via enteral tubes, for the elaboration of the institutional protocol.
Of these, the majority was classified as PR and Prespectively, 27.6% (81) and 30.6% (90), while for 24.1% (71), a lack of information available was observed, as shown in Table 1.  In Table 3 Table 3.  In Figure 2 and in Table 3, in Phase 3, it was possible to observe a ratio of 2.0 pharmaceutical interventions undertaken per medication prescribed for administration via enteral tubes with errors (574/284).

Discussion
The administration of medications via enteral tubes is an off-label use, that is, the manufacturers do not evaluate the same and few references bring information on the issue. In one prospective study, undertaken by a drugs information center of a private hospital (9) , there were divergences between the information from manufacturers and bibliographic sources consulted, in relation to the recommendations for the use of medications via enteral tubes, in 39.5% of the consultations made.
In the present study, information was found in the references consulted for 75.9% of the standardized medications analyzed. This value is higher than the 58% found by other authors (1) . The lack of information available for 24.1% of the medications could be a limiting factor for this study; however, in Phase 3, there was a drop in the frequency of prescription of medications without information available of 5.4% in Internal Medicine and 9.4% in ICU.
In one review involving 234 standardized solid oral medications in the hospital, regarding the possibility of administration via enteral tubes, 57 alternatives in the liquid pharmaceutical form were found and suggested (5) .
In another study (8) , for 48% of the medications prescribed for administration via enteral tubes, there was an alternative standardized pharmaceutical form in the institution. In the same way, in one work undertaken in a teaching hospital, 38.2% (26/68) of the solid oral medications had substitutes in the liquid pharmaceutical form (4) .
In this research, after the analysis undertaken in the as occurs in other studies (5,(11)(12) .
In the study undertaken in an intensive care unit in a teaching hospital, where there was no institutional protocol available, 30 pharmaceutical interventions were undertaken, and, of these, 10.0% were requests to change the medication (11) . These results differ from those found in this study, as when it was not possible to establish pharmaceutical alternatives, the pharmaceutical interventions of request for changing the medication and request for alteration of route of administration were not made frequently.
It is important to take into account that 17.7% (52/294) of the medications were considered as administration contraindicated via enteral tube and that this, although inferior to the 40.8% found in another study (2) , is a significant number. However, in Phase  (13)(14) . It was observed that the transformation was undertaken without knowledge of the restrictions and contraindications which involve this process and, if more than one medication was prescribed for the same time, the same were administered at the same time and using the same syringe. In another, retrospective, study, undertaken in a teaching hospital, following the implantation of pharmacotherapeutic treatment of patients using enteral tubes, of the 267 pharmaceutical interventions undertaken, 53.18% (142) were guidance regarding crushing and reconstitution, given to the Nursing team (12) . In one study undertaken in an intensive care unit, where nursing technicians prepared the medications for administration via enteral tubes, the authors found error rates in the procedures of over 40% (10) .