Gastrointestinal (GI) events in Enteral Nutrition Therapy (ENT) may be a result of the nutritional formula that is infused, the drug therapy being taken by these patients, or the background illness justifying its use.1 Adverse events occurring from medications can vary depending on the drug prescribed, as well as on the clinical condition of the patient. Medications to be administered should be carefully evaluated in order to prevent such problems, primarily in the hospital setting where patients are undergoing multiple drug therapies.2 Few studies have attempted to investigate this association between medication use and patients in such a scenario.

The aims of this study were to verify the frequency of GI complications (diarrhea, abdominal distension, nausea/vomiting, and constipation) associated with the use of ENT in adult inpatients at the Hospital de Clínicas de Porto Alegre (HCPA), and to identify the possible association with medications simultaneously administered during treatment.

The study involved 95 patients with no loss of follow-up.

Demographic data and population characteristics are presented in Table 1.

The medical prescription for the body positioning of the patient in bed was not related to the occurrence of clinically relevant pulmonary aspiration, with only one patient presenting this condition. Patients with diarrhea used enteral diet for a longer period of time than those who did not present with this complication (median: 32 days) (p=0.001).

Observed GI events that occurred in this population are shown in Table 2. All prescribed medications presented in the medical records were considered for the purpose of this study.

The weighted Kappa values, which analyzed the concurrence between gastroenterologists in relation to the evaluated variables, showed a variation of 0.45-0.62, an interval considered moderate to good.6,7 The frequency of adverse events in relation to the negativity and positivity of association with medications used by patients during their stay at the HCPA is shown in Table 3.

Table 4 shows the medications frequently associated with adverse gastroenterological events in this sample.

We believe that this is the first study attempting to evaluate the relationship between GI events and simultaneously administered pharmacologic agents in hospitalized patients being treated with ENT.

Our results confirm a high incidence of digestive symptoms in this population, with constipation and diarrhea being the most important manifestations.

The occurrence of diarrhea was higher in the group of patients that received ENT for a longer period of time. This fact can be explained by the multifactorial causes of diarrhea. The aggravation of diarrhea can occur in patients with longer periods of hospitalization, extensive use of medications (laxatives, medications that contain sorbitol, antibiotics, and oncologic agents), or as a result of underlying illnesses or medical conditions (such as diabetes mellitus or contamination with the Human Immunodeficiency Virus-HIV).1,8 It is worth noting that in our sample, patients who were using antibiotic therapy presented higher frequencies of diarrhea, which agrees with findings from other studies.8,9

When comparing our results to a study conducted by Luft et al.10 involving 302 patients receiving or not receiving ENT and that represented a population with similar characteristics to ours in terms of patient age, number of days of hospitalization, applied definition of diarrhea, and type of diet used, the prevalence of diarrhea was found to be 18.20% as opposed to the 38.90% obtained in our study. Methodological data collection differences were probably responsible for this discrepancy.

The medications most frequently associated with diarrhea involved stimulants or osmotic laxatives for the treatment of constipation, such as mineral oil, lactulose, bisacodyl, and also the use of antibiotics.11,12

Approximately two-thirds of our sample (70.50%) presented with constipation. This result represented a higher percentage than that found in studies conducted by Montejo13 (15.70%) and Pancorbo-Hidalgo et al.14 (29.80%). However, it was comparable to the findings of Nassar5 (69.90%), whose study design was similar to ours. This result can be explained by our sample characteristic in which 50.50% of patients suffered from neurological diseases which can predispose to constipation in a hospital setting. These patients often spend longer periods of time in bed, as well as being subject to certain constipating medications (levodopa and carbidopa, for example) that inhibit both colonic motility and perception of evacuative impulses.15,16 A lack of fiber in the ENT formula does not appear to be related to this symptom, as the average daily fiber infusion was 20.7g, an amount within the recommended daily consumption.17,18

Few clinical studies have evaluated the risk associated with medication use and the occurrence of constipation in patients receiving ENT; this association presented a positive relationship in 63.70% of our patients.1 The occurrence of this clinical problem can be caused by many medications regularly used in the hospital setting, such as opioid analgesics (morphine, codeine) and nonsteroidal anti-inflammatory drugs (naproxen, ibuprofen).12,16,19,20

The underlying disease itself that necessitates the use of ENT is also an important factor in the occurrence of GI complications.21,22 This should be taken into consideration when modifications to infused medications and/or changes in the enteral feeding formula are contemplated, with the aim of improving newly arising symptoms in the clinical setting.

Caution should be exercised when making any generalization of the results of this study, given that our sample was obtained from a university hospital context and we had a team of experienced health professionals with well-established routines for the care of patients requiring ENT; the HCPA is a regional reference center for health services in Southern Brazil.

A limitation of this study with respect to the quality of information could involve the method of data collection (patient medical records), as both under-reporting and over-reporting of signs and symptoms may occur. A further drawback to consider is the lack of a validated tool for evaluating the relationship between medication use and GI complications developed by patients. It was necessary to create such an instrument based on the content of the National Agency for Sanitary Vigilance (ANVISA),23 as well as the tool of Naranjo and Busto24 that is widely used in clinical trials. This latter instrument could not be used in clinical practice due to methodological issues, because it attempts to study one variable (pharmacologic intervention) at a time and uses information related to placebo intervention in order to define the level of association. For the purposes of our study, we used only the terminology and operational definitions of Naranjo and Busto, without using the other characteristics they applied in their clinical research.8,10,13,14

Although the instrument used had not previously been validated, the Kappa test applied to evaluate the agreement relationship between the gastroenterologists considered it to be moderate to good,6,7 which suggests that it may be used in a larger sample in order to evaluate sensitivity, specificity, and predictive values.

The strength of this research lies in the fact that it is an observational study set in the real-life context of the operational realities of enteral nutrition application within a tertiary reference hospital in Southern Brazil. Care was taken to avoid the Hawthorne effect whereby behavior or performance can be modified simply because a person is aware that they are being evaluated.4 To this end, medical, nursing, and nutrition teams were never aware that a researcher was collecting study data from patient medical records. It was equally important for the data to be collected in a randomized manner, thus enabling a representative sample of the hospital as a whole to be obtained. Additionally, all data collection was conducted by the same researcher and no sample loss occurred, resulting in the matching of the sample calculation with the number of patients studied.

GI symptoms are frequent in patients using ENT. However, the causes associated with them should be carefully examined in the clinical context of each patient, as they are often connected to the prescribed medications that are jointly administered with ENT. Consequently, enteral nutrition per se should not be seen as a principal cause of GI complications. Healthcare teams should consider all risk factors present for each patient when evaluating the occurrence of these adverse effects, paying particular attention to the prescribed medications in use before modifying, reducing, or suspending ENT administration.

The authors declare that there is no conflict of interest.

No financial support was received in relation to this article.