Preventive Strategies for Feeding Intolerance in Patients with Severe Traumatic Brain Injury in China: An Online Cross-Sectional Survey


 Background

The application of preventive strategies for feeding intolerance in severe traumatic brain injury (STBI) patients is discrepant among different hospitals. We aim to investigate the application status of preventive measures of feeding intolerance in China.
Method

 A cross-sectional study was carried out among 996 clinicians and nurses working in intensive care units of 89 hospitals in China (response rate of 89.81%). Data were collected by means of an online survey. Descriptive statistics were used to analyze respondents’ characteristics and questionnaire responses.
Results

Clinicians and nurses usually applied several methods simultaneously to assess gastrointestinal functions and risk of feeding intolerance among STBI patients, including assessment scales, gastrointestinal symptoms, etc. Furthermore, initiating enteral nutrition (EN) within 24-48 hours (61.45%), < 500 ml initial volume of EN solution (50.00%), using non-nutritional preparations as initial EN formula (65.56%), nasogastric tube EN (91.16%), continuous feeding by pump (72.89%), 30°-45° of head-of-bed elevation during EN (89.46%), monitoring gastric residual volume by syringe (93.67%), assessing gastric residual volume every 4 hours (51.51%), EN solution temperature of 38℃-40℃ (65.46%), prokinetic agents (73.29%), enema (73.59%), probiotics (79.01%), and antacid agents (84.13%), were mostly applied strategies in clinical practice for preventing feeding intolerance among STBI patients.
Conclusions

The data from the survey showed that medical staffs in China are closely concerned with the gastrointestinal functions of STBI patients and EN delivery protocol, and have a positive attitude towards preventive strategies for feeding intolerance. Meanwhile, there are still many points need to be paid attention to and solved, and researchers, clinicians, nurses and dietitians should strengthen the cooperation to explore more valuable preventive strategies for feeding intolerance in STBI patients.


Introduction
Severe traumatic brain injury (STBI) patients are susceptible to negative nitrogen balance, weight loss and malnutrition, which leads to poor prognosis [1]. It has been reported that early enteral nutrition (EN) could reduce the in ammatory responses, prevent bacterial translocation, improve nutritional status, and promote gastrointestinal functions [2][3][4][5]. However, due to the damage to the central nervous system (CNS), gut-brain axis dysfunction and secondary damage to gastrointestinal tract, it is di cult to deliver early EN in STBI patients, which is usually interrupted by feeding intolerance [6]. Moreover, the application of some conventional therapeutic measures such as analgesia and sedation might also aggravate the occurrence of feeding intolerance [7]. Studies have shown that the incidence of feeding intolerance can reach 60%-75% during EN among STBI patients [6,8], which is a huge challenge for medical staff.
In the past two decades, with increasing understanding of the therapeutic role and signi cance of EN for critically ill patients, experts and researchers have conducted a series of explorations on how to improve gastrointestinal dysfunctions and reduce the incidence of feeding intolerance in STBI patients [9][10][11]. A variety of preventive and curative strategies for feeding intolerance have now been applied in clinical practice. However, the application of preventive strategies for feeding intolerance is discrepant among different hospitals, and even different departments in the same hospital.
To better apply the preventive strategies for feeding intolerance among STBI patients, the application status of these strategies needs to be known rstly. Thus, in this study we aimed to further understand the current application status of preventive measures for feeding intolerance in China by a crosssectional survey, in order to provide a basis for medical staff to make more rational treatment decisions for STBI patients and reveal the research directions that need further exploration.

Survey development
We conducted a cross-sectional study by a self-completed questionnaire among clinicians and nurses working in intensive care units (ICU) of grade II level A to grade III level A hospitals in China. The survey tool was developed via a multi-step co-design process in collaboration with medical staff and experts.
First, a literature review was conducted to identify initial questionnaire themes and items, including basic characteristics of participants (sex, age, educational background, department, job type, job title, work experience, hospital classi cation), and clinical treatments for preventing the occurrence of feeding intolerance among STBI patients (methods for assessment of gastrointestinal functions, methods for EN delivery, and preventive strategies of feeding intolerance in STBI patients). Twenty-ve medical staff in ICU from 2 grade III level A hospitals were chosen to give advice of the prototype questionnaire. The questionnaire was re ned according to the feedback and suggestions. Then, 7 experts in intensive care were invited to test the validity of the questionnaire. The questionnaire was further revised based on feedback and advice from experts. The nal version of questionnaire was put into the Wenjuanxing website, an online crowdsourcing platform (https://www.wjx.cn/), for further large-scale investigation.

Participants and setting
The cross-sectional survey was performed among clinicians and nurses in general ICU or neurological ICU (NICU) beginning December 25th 2019 over a 2-week period in 89 hospitals of China. Inclusion criteria: registered clinicians and nurses; have worked in ICU or NICU at least for 1 year; willing and able to give informed consent.

Data collection
The survey distribution and data collection were completed between December 25th 2019 and January 7th 2020 by Wenjuanxing in 89 hospitals in China. The questionnaire took about 5 min to complete. Nonprobability sampling methods (convenience sampling and snowball sampling) were used to select participants. According to the 7 geographic regions of China (including East China, South China, North China, Central China, Southwest China, Northwest China, Northeast China), 1 grade III level A hospital was selected in each region for survey. After obtaining consent and support from the surveyed hospitals, the link of questionnaire was sent to participants by WeChat. Meanwhile, we also distributed the questionnaire to the neighboring hospitals and through academic groups in a snowballing manner. A total of 1109 eligible participants were identi ed, and 996 returned a completed survey (response rate of 89.81%).

Statistical analysis
All the data collected in this study were analyzed using SPSSAU platform. Descriptive statistics were used to report respondents' characteristics and questionnaire responses. Percent of responses and percent of cases are displayed. Percent of response is the percentage of each response out of total responses from the given data-set (sum total of percent of response is 100). Percent of cases is the percent of cases or respondents saying "yes" for the particular means of communication.

Participants
A complete overview of the basic characteristics of respondents was shown in Table 1. The majority of the respondents were female (84.84%), 18-35 years old (81.83%), and with Bachelor degree (68.47) ( Table   1). Besides, 89.06% of the respondents were nurses and 72.49% of the respondents were from grade III level A hospitals in China (Table 1).

Preventive strategies for feeding intolerance in STBI patients
There were 81.22% of the respondents applied preventive strategies to promote gastrointestinal motility among STBI patients (

Combined use of several methods were conducted to assess gastrointestinal functions and risk of feeding intolerance in STBI patients
The results of the survey showed that more than a half of respondents chose at least 3 options to assess patients' gastrointestinal functions as well as predicting the risk of feeding intolerance, which indicated that most of the medical staff use multiple methods to evaluate gastrointestinal functions and tolerability of EN in patients with STBI. Further analysis of the collected data suggested that the current assessment methods of gastrointestinal functions are mainly based on clinical symptoms related to gastrointestinal dysfunction (85.04%), GRV (82.23%) and bowel sounds (78.31%). There were only 28.81% and 15.66% of the respondents took AGI grade and medical imaging methods (motility of gastric antrum), respectively, which showed that these 2 measures were not yet widely applied in clinical practice. In 2012, European Society of Intensive Care Medicine (ESICM) proposed AGI grade to assess the degree of acute gastrointestinal impairment in critically ill patients [12]. The low prevalence of AGI grade in evaluating gastrointestinal functions might due to 2 reasons: AGI grade lacks of objective evaluation indexes and is hard to quantify the severity; on the other hand, as most respondents involved in the survey were nurses (89.06%), we supposed that the use of AGI grade might have not been included in the scope of nurses' responsibility. Using imaging measure to evaluate gastrointestinal functions is an emerging technique in the eld of intensive care in recent years, and it can visually re ect the gastric antrum movement [13]. The low prevalence of this imaging measure may be due to that it's a novel technique and has not yet been widely conducted among STBI patients. We suggest that timely comparative studies of emerging methods with traditional methods are urgently needed to con rm their effectiveness and feasibility in assessing gastrointestinal functions, in order to make these newest techniques timely applied in critically ill patients.
The present study found that 71.39% of respondents predict the risk of feeding intolerance in STBI patients based on injury severity (GCS, APACHE II, etc.), 60.84% of the respondents based on assessment scales, and 60.64% of the respondents based on the patients' basic characteristics (age, sex, etc.). It is well known that disease severity is closely related to the occurrence of feeding intolerance [14]. GCS and APACHE II scores are applied in STBI patients within 24 hours after admission to assess the injury severity [15]. The risk of gastrointestinal dysfunctions is predicted on the basis of these assessments. As these 2 scores are the classic assessment methods for STBI patients, they have long been used in clinical practice and are therefore more widely applied. Studies have shown that basic characteristics of patients such as age and sex are risk factors for disease severity [16,17]. For example, atrophy of intestinal mucosa can occur in the elderly, affecting the absorption and transportation of water and electrolytes [18]. Therefore, clinicians and nurses should pay attention to the basic characteristics of patients such as age and sex when considering EN delivery. Recent years, researchers in China have developed risk assessment scales to facilitate the assessment and prediction of the feeding intolerance in critically ill patients [19,20]. These results of present survey showed that the assessment scales for feeding intolerance are used widely among STBI patients, indicating that clinical staff prone to use methods which are based on objective indexes and clear grading. However, considering the heavy workload and various assessment scales needed to complete in ICU, we suggest that it is necessary to further optimize the assessment scales and procedure, in order to improve the effectiveness in evaluation of feeding intolerance and reduce the workload of medical staff.

Evidence-based strategies for EN delivery have been widely used
We found the following feeding strategies were mostly applied in China: using nasogastric tube (91.16%), 30°-45° of head-of-bed elevation during EN (89.46%), continuous infusion method (72.89%), 38-40℃ of EN solution, and initiating EN within 24-48 hours after admission (61.45%) with <500ml EN solution (50%). Some of these strategies were in accordance with several guidelines and expert consensus on nutritional support for critically ill patients [21,22], which indicating that most clinicians and nurses are able to apply evidence-based strategies during EN delivery. In recent years, it has been reported that administration of low-temperature EN solutions (22°C-25°C) [23] and intermittent infusion semi-solid solutions [24,25] can reduce the risks of gastric ulcer and aspiration, while these 2 strategies were only used among 13.65% and 38.35% of the respondents, respectively. The low utility rates might due to the related researches were limited, causing insu cient popularization and application. Thus, for these effective methods found in clinical practice, we should summarize and spread them timely, and carry out multicenter and multidisciplinary studies to con rm their effectiveness.
The amount of GRV is positively correlated with the incidence of re ux and aspiration [26,27]. Therefore, monitoring GRV is an important part during EN. The collected data in our survey presented that retraction of gastric content by syringe is still the main method for monitoring GRV (93.67%). However, it has been reported that the accuracy of use of syringe withdrawal would be in uenced by various factors, such as patient's position and gastric tube diameter [28]. Recent years, more accurate and feasible methods for monitoring GRV have been explored, including ultrasound. Some studies have shown that GRV could be calculated accurately using 3-dimensional morphology by ultrasound, which would not be affected by other factors [29,30]. However, only 9.74% of the respondents chose to apply ultrasound to monitor GRV.
The reason for this result may be related to the fact that use of ultrasound for EN is still in its early phase, and the ultrasound instrument is a highly specialized technique, which requires systematic learning and training. We suggest that we should focus on the timely training of new methods or techniques to make them applied in clinical practice better and faster.
The results also showed that gastric retention in China is mainly de ned by GRV > 200 ml/time within 24 hours (57.73%). However, GRV > 500 ml every 6 hours was recommended by ESICM in 2017 [31] and has been only used in 36.95% respondents. The de nition of gastric retention can directly in uence the EN delivery, as well as preventive and curative measures. If the de nition is too conservative, it may lead to more feeding interruptions and clinical interventions during EN; if the threshold of the de nition is too strict, it might increase the risk of feeding intolerance. Therefore, how to de ne the threshold of gastric retention still needs more further scienti cally explorations.

The prevention of feeding intolerance has been paid more attention in clinical practice
Strategies for promoting gastrointestinal motility (81.22%) and defection (84.14%), protecting the mucosa (93.67%), and modulating gut microbiota (80.92%) have been widely used before the occurrence of feeding intolerance. We found that antacid agents (84.13%) are still important treatments for preventing stress-related gastrointestinal bleeding among STBI patients. The antacid is a double-edged sword. It can protect the gastrointestinal mucosa, while it will also increase the gastric pH and aggravate the risk of feeding intolerance. Expert consensus has stated that we should discontinue the application of proton pump inhibitors as soon as possible when TBI patients could take adequate energy by oral feeding [32]. Thus, how to use the antacid properly still needs further exploration.
The current survey also found that clinicians have paid attention to the effects of gut microbiota for STBI patients, and probiotics were mainly used in clinical practice (79.01%). With the increasing understanding of the interaction of gut microbiota-brain axis, it has been found that regulating the gut microbiota after TBI can not only improve gut dysbiosis, but also promote the recovery of neurological functions [33,34]. The results of survey indicated that enema is a commonly used strategy to assist defection in STBI patients. While enema can only alleviate the symptoms, but not treat primary cause of constipation.
Studies suggested that nursing strategies such as rectal stimulation [38] and acupoint massage [39] are effective in stimulating gut motility and promoting defecation re exes in patients. There were only 28.41% of the respondents chose nursing strategies, which might due to that these methods are mild and takes a longer time and shows slower progress. Moreover, it may also relate with the limited manpower of ICU nurses who are unable to perform tasks other than those prescribed by clinicians.
Most of the respondents gave STBI patients non-nutritional preparations (glucose, warm water, etc.) at the initiation of EN. Critically ill patients are commonly accompanied by gastrointestinal dysfunctions.
Solutions such as glucose and water that can be easily digested and absorbed are given rstly in clinical practice, which will make the gastrointestinal tract to adapt the following EN solution. A research reported that giving non-nutritional preparations 1 day before giving EN solution could reduce the incidence of diarrhea in critically ill patients [40]. We also found that rice broth, milk or other solution were also used as the initial type of EN formula. This result suggests that there is a need to further explore and standardize what, how much and how long to give at the beginning of EN in STBI patients, so that EN can be delivered smoothly at the early stage.

Preventive measures for feeding intolerance need to be further explored
We provided an analysis of the reasons for not taking preventive measures. The survey found that the main reason why preventive measures are not used is "unclear preventive effects". The results suggest that comparative studies of various measures for preventing feeding intolerance are urgently needed, which are important to con rm the effectiveness of these treatments and provide basis for clinical practice. Furthermore, medical staff should make an effort to learn the knowledge relevant to EN and the latest techniques, methods and theories, in order to reduce the risk of feeding intolerance as effective as possible.
As a nationwide survey, this survey is expected to provide a more realistic picture of the clinical conditions regarding feeding intolerance in STBI patients. In view of the diversity and complexity of clinical measures in practice, the survey was designed with the option "others" as the nal option, in order to discover the points that the survey did not cover. We found that some nurses lled in "relying on dietitians' assessment or suggestion" or "no medical advice". This indicates that some nurses only act as a "implementer" during EN delivery period and lack initiative. A study has con rmed that nurse-led EN delivery protocols can help reduce feeding interruptions and improve the nutritional status of critically ill patients [41]. We suggest that it is important for nurses in ICU to improve their role awareness and skills in EN support for critically ill patients, which might signi cantly contribute to reducing the risk of feeding intolerance.

Limitations
This cross-sectional survey study provides a snapshot of medical staff's views on preventive strategies for feeding intolerance in STBI patients. The demographic of the participants and the fact that participants were mostly recruited from grade II level A or above hospitals which may limit the generalizability. The non-probability sampling methods (convenience sampling and snowball sampling) used to approach hospitals or participants for inclusion in this study signi es that the ndings are likely to not be generalizable to the wider medical staff in China.

Conclusions
Through the cross-sectional survey of medical staff of ICU in 89 grade II level A or above hospitals in China, we have gained the current application status of the preventive measures for feeding intolerance in patients with STBI. The results showed that clinicians and nurses in China are closely concerned with the gastrointestinal functions of STBI patients and EN delivery procedure, and have a positive attitude towards preventive strategies for feeding intolerance among STBI. Meanwhile, there are still some points need to be paid attention and solved. For example, the effectiveness of many clinical measures still needs to be further clari ed, and some effective new technologies and methods are required to be timely applied in clinical practice. We suggest that researchers, clinicians, nurses and dietitians could strengthen cooperation to explore more valuable preventive strategies for feeding intolerance in STBI patients.

Declarations
Con icts of interest: The authors declare that they have no con ict of interests.