Complications Associated with Enteral Nutrition: CAFANE Study

Objectives: To determine the association between home enteral nutrition (HEN) administration modality and its complications in patients. Methods: This is a prospective multicenter longitudinal study including 15 Spanish hospitals, from April 2015 to March 2017. A 4-month follow-up period was conducted for each patient by home visit. The study subjects were adult patients who began their nutrient intake by tube feeding, known as HEN, during the recruitment period. The variables studied included the type and modality of HEN administration and its related complications, such as vomiting, regurgitation, constipation, diarrhea, and abdominal distention. Mechanical complications and bronchoaspiration were also evaluated. Descriptive variables were used for fitting. Results: The study consisted of 306 patients; 4 were lost due to death. Specific HEN modalities protected against constipation (odds ratio (OR) = 0.4) and regurgitation (OR = 0.4). The use of a nasogastric tube (NGT) resulted in a lower risk of diarrhea compared to percutaneous endoscopic gastrostomy (PEG) (OR = 0.4) but resulted in a higher risk of tube obstruction (OR = 7.4). The use of intermittent gravity versus bolus feeding was a protection factor against vomiting (OR = 0.4), regurgitation (OR = 0.3), constipation (OR = 0.3), diarrhea (OR = 0.4) and abdominal distension (OR = 0.4). The increase in the number of doses was a risk factor for the incidence of regurgitation (OR = 1.3). Conclusions: Gastrointestinal complications were the most frequent problems, but an adequate choice of the formula, route, feeding modality, number of doses, administration time, and dose volume can reduce the risk of these complications.


Introduction
Keeping a patient hospitalized for the sole purpose of administering nutritional support has become an inappropriate decision from a bio-psycho-social perspective, and wasteful for health institutions and for society from an economic perspective. The introduction of home enteral nutrition (HEN) involves the concerns of correctly selecting candidates, applying a good training programme to the patient and the caregiver, ensuring the supply of formula and necessary materials, providing adequate follow-up and monitoring the quality of patient care [1].
Interestingly, Parsons et al. [2] concluded that for patients admitted to nursing homes, oral nutritional support could improve the quality of life and nutrient intake more effectively than dietary advice.
The participating researchers were granted personalized access (username and password). The questionnaire variables are listed below.
Variables related to the type and modality of HEN administration. Type of formula administered: standard, specific and others (hypercaloric, hyperproteic, hypercaloric-hyperproteic); HEN with fiber: yes or no; Route of administration: percutaneous endoscopic gastrostomy (PEG), nasogastric tube (NGT) and other ostomies (including jejunostomy); Feeding modality: bolus feeding, intermittent gravity, other modalities (including continuous gravity or pump feeding); Administration time of each intake in minutes; Number of intake periods per day; Dose volume (mL); Total daily volume (mL); Washing of the probe: yes or no; Position during intake (≥45 • or <45 • ) and after intake (at least 1 h) [11].

Descriptive and Fitting Variables
Gender: man or woman; Age: in years; Weight: in kilograms (kg) (if the weight could not be obtained by direct measurement, it was estimated according to gender, age, arm circumference and knee height using the "Malnutrition Universal Screening Tool" [12]); Height: in meters (m) (if the height could not be obtained, it was estimated by the length of the forearm [12]); Body mass index (BMI): weight (kg) divided by the height squared (m); Place of residence: family home or social-health institution; Caregiver: family member, paid family member, employee, volunteer or without caregiver; Diagnostic groups: neurological, oncological, and with other diagnoses.

Statistical Analysis
For the qualitative variables, the absolute and relative frequencies (percentages) were calculated. For the quantitative variables, the mean and its standard deviation, the median (Me), the interquartile range (IQR) and the standard deviation were calculated.
The association between the qualitative variables was analyzeanalyzed by the chi-squared test, while Student's t-test was used for the quantitative variables to verify the significance of the difference in means for the independent samples. To compare the means between more than 2 groups for a quantitative variable, analysis of variance (ANOVA) was performed using the Tukey method.
The incidence rate (IR) was calculated to find the number of complications involved in the study period (4 months).
A logistic regression model was applied using each of the different complications as a dependent variable (0 = no complication, 1 = one or more complications). The independent variables were route of administration (1 = PEG, 2 = NGT; 3 = other ostomies); feeding modality (1 = intermittent gravity, 2 = bolus feeding, 3 = other modalities); fiber (1 = yes; 2 = no); administration time; number of intake periods; volume of intake; and total volume. All models included the following variables: gender, age, BMI, place of residence, caregiver, and diagnostic group. The probability was measured by the odds ratio (OR).
The level of significance used in all hypotheses was p ≤ 0.05. Quality control of the data was carried out through double tables, and the potential errors were corrected by consulting the originals. The statistical software IBM SPSS Statistics for Windows, version 23.0 (IBM Corp, Armonk, NY, USA) was used to analyze the data.

Results
The data from 306 patients were included; 4 patients were lost due to death. The descriptive data of the population is presented in Table 1. The results show that the place of residence was primarily the family home (224 patients, 73.2%). With the exception of 16 patients (5.2%), most had some type of caregiver, generally a relative (226 patients, 73.9%), and this person was usually a woman (246 cases, 80.4%). The base pathology did not influence the relationship of the complications associated with the HEN modality.
No intergroup associations were found between the BMI and the mean of the majority of the complications: vomiting (p = 0.054), regurgitation (p = 0.415), constipation (p = 0.401), diarrhea (p = 0.113) and probe obstruction (0.204). However, there were significant differences in abdominal distension between the normal weight and obese groups (p = 0.040) and for aspiration pneumonia among the overweight and obese groups (p = 0.031).
Regarding the HEN-related variables, all of the patients were tube-fed, with 254 (83.0%) patients being exclusively tube-fed, while 52 (17.0%) took in some food orally. The HEN-related descriptive results and the HEN administration modalities are presented in Table 2.   The most frequent complications recorded in the 4 months of follow-up were digestive, predominantly abdominal distension, with an IR of 2.4, while regurgitation had an IR of 2.2. Aspiration pneumonia presented the lowest IR of 0.1. Some significant differences were found, with higher values in men for abdominal distension (3.5 versus 1.1, p-value 0.001) and constipation (3.5 versus 1.1, p-value 0.001). The number of episodes (n) and the IRs of HEN-related complications are shown in Table 3.

Complications Related to the HEN Type and Modality
When analyzing the pre-and post-fitting results regarding the relation between complications and the type of formula used (see Table 4), it was found that the use of a specific HEN formula protected against regurgitation episodes (OR = 0. The increase in the number of doses represented a risk for the appearance of regurgitation (OR = 1.3 in pre-fitting and post-fitting) and for the obstruction of the catheter (OR = 1.9 in pre-fitting; OR = 1.7 in post-fitting). Likewise, the intake position was associated with probe obstruction (OR = 0.1 in pre-fitting and post-fitting).
The post-fitting results showed association with an increased risk of diarrhea when the administration time (OR = 4.5) and the dose volume (OR = 1.4) increased.
The results of the complications related to the type and modality of HEN administration are shown in Table 4.

Discussion
This study enabled us to determine the complications associated with enteral nutrition administration in a considerable number of patients over a period of several months, which is a strength of this study.
In terms of their pathology, the studied patients presented similar characteristics as those of previous studies-they were older adults with neurological or oncological disease, with a dependence on and a need for a caregiver [13,14].
There was no clear significant association between the BMI and the complications resulting from HEN, although a greater number of complication episodes in relation to obesity was observed, a situation already highlighted by Wiggins et al. [15].
Given the median age of the studied population, it is normal in the Spanish socio-cultural context that the place of residence was primarily the family home, a nucleus with sufficient roots and a caretaker tradition. Likewise, the fact that the main caregiver is typically a woman has been widely noted in the scientific literature [16,17] and must be considered when implementing an artificial nutrition regimen, since it can be a great burden for the caregiver [18].
The greater use of PEG compared to NGT, common in the participating health centers, contrasts with previous research that observed a greater tendency to use NGT in older adults [1,14,19]. In any case, gastrostomy is associated with greater efficacy and safety compared to NGT [20].
Bolus feeding continued to be used with a greater frequency, though it could be inferred that the infusion speed is not easy to regulate, and there could be alterations in the administration that would lead to some complications. On the other hand, the formula type, the volume administered and the number of doses were all within normal ranges, and it was not surprising that a formula with fiber was administered to patients with long-term HEN, a recommended practice in the absence of contraindicateons [21].
The IR of HEN-related complications demonstrated the intimate relationship with the route and administration modality. The correct management of HEN reduces these complications and minimizes laryngopharyngeal reflux [22].
The differences in the observed complications between men and women show an important gender background. Women typically take better responsibility for their own healthcare, especially regarding communication between the patient and the doctor, the understanding of the disease, and their attitudes at the end of life [23,24].

Complications Related to the Type and Modality of HEN Administration
It is important to know that specific formulas are associated with fewer episodes of regurgitation and constipation. However, in many patients, these complications are already present before the initiation of HEN therapy. Therefore, the addition of prokinetic drugs would be useful to prevent regurgitation. In addition, constipation is more frequent than diarrhea in patients fed exclusively by HEN [25].
The current evidence does not allow us to determine the causes of the increased risk of aspiration pneumonia in nonspecific HEN; the evidence could possibly indicate a recommendation for using a post-pyloric probe, but it is not certain [26].
Regarding the administration modality, PEG has become the method of choice for enteral feeding in the medium and long term. Most of the complications related to PEG are minor; however, rare major complications can be more serious. The increased risk of diarrhea, vomiting and regurgitation that was observed in this study in relation to PEG was mainly associated with abdominal distension and could show a stronger relation with the administration modality and the volume of the shot. Some complications occur shortly after tube placement; others develop later when the gastrostomy tract has matured. Senior patients with comorbidities and infections appear to be at greater risk of developing complications [27]. Gomes et al. [20] demonstrated the nonexistence of significant differences in mortality rates or adverse events, including aspiration pneumonia, between comparison groups (PEG versus NGT). However, they pointed out that factors such as the demographics of the participants, the underlying diseases, age, gender and the gastrostomy technique should be considered. In this sense, Gomez-Candela et al. [19] indicated that to achieve a low incidence of complications, it was essential to establish an adequate educational programme.
Bolus feeding has been associated with virtually all gastrointestinal complications, and this feeding modality may explain the increased infusion rate, with an abrupt change in the gastrointestinal walls or rapid temperature change. Contrary to these findings, a previous study by Kadamani et al. [28] did not find differences in the incidence of complications between both administration modalities. However, according to scientific evidence, continuous nutrition should always be chosen for infants with birth weights below 1250 g or infants with haemodynamic deterioration [29].
Likewise, the present study has shown that an enteral diet containing fiber is a protective factor against intestinal motility disorders [25,30].
It has also become clear that an increase in the number of doses and the volume of the intake cause greater gastrointestinal problems and that the patient's position upon intake is related to the possibility of probe obstruction.

Conclusions
It can be concluded that there was a higher incidence of gastrointestinal complications. However, an adequate choice of the formula type, the route and feeding modality, the number of doses, administration time and volume of intake can greatly reduce the IR. Therefore, to reduce these complications, the existence of multidisciplinary teams focused on the follow-up of patients is essential to optimize the results. However, all health care providers should have knowledge regarding the most frequent HEN-related complications and the skills to manage these problems.