This study enrolled critically ill patients admitted to the Intensive Care Unit (ICU) of Jining First People’s Hospital between November 2024 and February 2025, based on the following eligibility criteria.

A total of 144 ICU patients were enrolled in this study, including 87 patients with feeding tolerance (FT) and 57 patients who developed ENFI, yielding an overall ENFI incidence of 39.6%. Among patients in the ENFI group, males were more prevalent, the majority had chronic comorbidities, and nearly two-thirds had undergone mechanical ventilation and presented with serum albumin levels below 35 g/L. A detailed comparison of baseline demographic and clinical characteristics between the ENFI and non-ENFI groups is provided in Table 1.

The results of this study indicate that critically ill patients with an APACHE II score > 20 are significantly more likely to develop enteral nutrition feeding intolerance (ENFI), with an odds ratio of 2.128 compared to those with a score ≤ 20. This finding is consistent with previous research by Wang et al. (16), who also identified a high APACHE II score as an independent predictor of ENFI. Additionally, our study shows that the risk of ENFI in patients with an APACHE II score > 20 is 2.128 times higher than in those with an APACHE II score ≤ 20.

The APACHE II score is a widely used clinical tool to assess the severity of illness in ICU patients; higher scores are associated with greater physiological derangement, increased stress response, and poorer outcomes (17). Elevated APACHE II scores reflect a heightened systemic inflammatory and metabolic response, which may negatively impact gastrointestinal function. Under such stress conditions, patients often exhibit reduced gastrointestinal perfusion, impaired peristalsis, and compromised mucosal barrier integrity. These pathophysiological changes lead to delayed gastric emptying, increased intestinal permeability, and ultimately reduced tolerance to enteral nutrition (15, 18). Several studies support the relationship between high APACHE II scores and ENFI risk. For example, Bolayir et al. (18) found that an APACHE II score greater than 20 was significantly associated with gastrointestinal intolerance in critically ill stroke patients.

Given this evidence, ICU clinicians, particularly nurses and dietitians, should pay close attention to such patients. In addition to actively treating the underlying disease and stabilizing the condition, prokinetic agents can be used to prevent the occurrence of FI, ensuring the smooth implementation of enteral nutrition.

In this study, the majority of patients in the ENFI group had hypoalbuminemia (ALB ≤ 35 g/L), and multivariate analysis confirmed that low albumin was an independent risk factor for ENFI, with an odds ratio (OR) of 2.450 (p = 0.009). Albumin is a key biomarker reflecting both nutritional status and systemic inflammation. Adequate albumin levels contribute to enhanced gastrointestinal tolerance through several physiological mechanisms. McClave et al. (4) reported that ICU patients with albumin levels ≥30 g/L exhibited significantly lower gastric residual volumes and achieved target enteral feeding rates more rapidly compared to those with lower albumin levels. Albumin helps maintain plasma colloid osmotic pressure, which can effectively reduce intestinal wall edema and support the recovery of gastrointestinal mucosal integrity (19, 20). Moreover, albumin has anti-inflammatory and detoxifying functions—it can bind and neutralize circulating endotoxins, thereby mitigating intestinal inflammation and reducing the risk of feeding-related complications (21). These protective mechanisms highlight the multifaceted role of albumin in supporting enteral nutrition tolerance.

Given these findings, close monitoring of serum albumin levels is essential in ICU patients receiving EN. For those with ALB ≤ 35 g/L, timely nutritional interventions, including protein supplementation and inflammation management, may improve EN tolerance and reduce the incidence of ENFI.

In this study, nearly half of the patients in the ENFI group exhibited IAP ≥ 12 mmHg, identifying elevated IAP as an independent risk factor for ENFI. IAP refers to the pressure within the abdominal cavity, and the gastrointestinal tract is among the most sensitive organs to elevated IAP (22). Increased IAP can reduce mesenteric perfusion, compress the thin-walled mesenteric veins, and obstruct intestinal venous return, which leads to intestinal edema, impaired mucosal barrier function, and delayed gastrointestinal motility and emptying (23).

Moreover, a bidirectional relationship may exist: while elevated IAP can impair gastrointestinal function, compromised intestinal digestion and delayed gastric emptying can in turn exacerbate IAP, forming a vicious cycle (24, 25). Thus, IAP functions as both a cause and consequence of ENFI, forming a self-perpetuating pathophysiological loop. Bejarano et al. (26) demonstrated that IAP is negatively correlated with enteral nutrition tolerance, and elevated IAP values can be used as a predictive marker for ENFI in critically ill patients.

Measurement of IAP via bladder pressure is widely recognized as the gold standard due to its simplicity, non-invasiveness, reliability, and minimal interference from external variables (27). In this study, IAP was regularly monitored using bladder pressure measurements as part of routine ICU care. When elevated IAP was detected, clinical staff proactively investigated potential causes—such as constipation, abdominal distension, fluid overload, or mechanical ventilation settings—and implemented timely interventions to mitigate further gastrointestinal compromise.

The results of this study indicate that the timing of EN initiation is an independent risk factor for ENFI, with a later start of EN associated with a reduced risk of developing feeding intolerance. This finding challenges the traditional emphasis on initiating EN as early as possible in all critically ill patients (3, 15, 28).

According to the 2019 ESPEN clinical nutrition guidelines for intensive care units, early initiation of EN—typically within 24 to 48 h—is recommended primarily to preserve gut integrity and reduce infection complications in patients without contraindications (3). However, the same guidelines also emphasize that full-dose EN should not be started too early in critically ill patients to avoid the risk of overfeeding and associated complications. The guidelines suggest that a gradual advancement of caloric and protein targets over the first 3 to 7 days may be safer and more physiologically appropriate. Furthermore, Singer et al. (3) reported that while early EN may reduce infection-related complications in non-ICU patients, this benefit is not as clearly observed in ICU populations. As such, overly aggressive early EN in hemodynamically unstable or severely ill ICU patients may increase the risk of ENFI due to impaired gastrointestinal tolerance. In this context, delaying the initiation of EN beyond 48 h, until the patient’s condition stabilizes, may improve tolerance and reduce gastrointestinal complications.

These findings highlight the need for individualized EN strategies based on patient condition, rather than strict adherence to early EN protocols. Clinical staff should evaluate factors such as gastrointestinal function, hemodynamic status, and nutritional risk when determining the optimal time to initiate EN.

In this study, the incidence of ENFI among patients receiving MV was 73.7%, and MV was identified as an independent risk factor for ENFI. Patients who underwent MV were 2.892 times more likely to develop ENFI compared to those who did not, consistent with the findings of Li et al. (29). This highlights a strong association between MV and the development of feeding intolerance in critically ill patients.

MV is a common supportive therapy in the ICU, but it may adversely affect gastrointestinal function through multiple mechanisms. Positive-pressure ventilation can cause air to enter the digestive tract, resulting in gastric distension and impaired gastrointestinal motility (22). Furthermore, factors such as positive end-expiratory pressure (PEEP) can compromise splanchnic perfusion, leading to reduced gastrointestinal blood flow and elevated IAP (30). As noted previously, elevated IAP is itself an independent risk factor for ENFI.

In addition, patients receiving MV frequently require sedatives, analgesics, and vasoactive agents. Sedative and analgesic drugs, such as benzodiazepines and opioids, are known to suppress gastrointestinal motility, thereby increasing the risk of delayed gastric emptying and FI (31). Meanwhile, vasoactive medications may induce gastrointestinal ischemia and hypoperfusion, further exacerbating mucosal damage and dysfunction.

In conclusion, MV not only independently contributes to the risk of ENFI but also acts through multiple synergistic pathways that impair gastrointestinal function and tolerance to enteral feeding. In clinical practice, special attention should be paid to patients undergoing MV. It is essential to maintain appropriate endotracheal cuff pressures, monitor gastrointestinal symptoms closely, assess abdominal and respiratory parameters dynamically, and aim to wean patients from ventilatory support as early as clinically feasible to reduce the risk of ENFI.

In this study, no statistically significant differences were observed between the ENFI and non-ENFI groups in terms of the following variables: age, gender, BMI, combined chronic diseases, antibiotics, NRS 2002, sedative analgesics, potassium preparations, and EN feeding methods. The lack of significant differences may indicate that the development of ENFI is more strongly influenced by acute pathophysiological factors (e.g., disease severity, intra-abdominal pressure, mechanical ventilation status) rather than baseline demographic or general clinical characteristics. However, further multicenter studies with larger sample sizes are warranted to confirm these findings and explore potential interactions. The specific analysis is as follows:

Aging is known to be associated with a decline in gastrointestinal function, including slower gastric emptying and reduced motility. Horowitz et al. (32) demonstrated that advancing age is correlated with delayed gastric emptying. Additionally, gender-based physiological differences have been observed, with studies showing that healthy women have slower gastric motility compared to men (33).

However, in the present study, no statistically significant differences in age or gender were observed between the ENFI and non-ENFI groups. One possible explanation is that all study participants were critically ill, and the acute severity of illness may have outweighed the influence of baseline demographic factors. In such patients, pathophysiological disturbances such as systemic inflammation, organ failure, and hemodynamic instability may play a more dominant role in gastrointestinal dysfunction than age-related decline.

While several previous studies have identified advanced age as an independent risk factor for ENFI (7, 34, 35), other studies have failed to find a significant association (36, 37). These inconsistencies suggest that the relationship between age and ENFI may be context-dependent and influenced by factors such as study population, illness severity, and comorbidities. Therefore, further research is warranted to clarify the role of age as an independent predictive factor, particularly in heterogeneous populations of critically ill patients in the ICU.

Antibiotics not only eradicate pathogenic bacteria but also disrupt the balance of beneficial gut microbiota, leading to gastrointestinal dysbiosis and contributing to the development of FI (38). In this study, the use of potassium supplements was also recorded. Potassium preparations are known to directly irritate the gastrointestinal mucosa and may induce symptoms such as nausea, vomiting, abdominal pain, and diarrhea, thereby diminishing patients’ appetite and tolerance to enteral nutrition (39). Although a large proportion of patients in this study had chronic underlying diseases, the specific types of comorbidities were not stratified or analyzed in detail, which represents a limitation. Previous research has shown that the incidence of FI can vary significantly across different disease populations. Research (40) reported that patients with burns, gastrointestinal disorders, sepsis, and cardiovascular diseases exhibit higher rates of FI compared to those with respiratory diseases. These findings underscore the importance of considering disease-specific factors in FI risk assessments and highlight the need for future studies to include more detailed clinical classifications of comorbid conditions.

In this study, the NRS 2002 score was not found to be a statistically significant factor associated with FI. However, a large-scale, multicenter, longitudinal database study conducted by Heyland et al. (41) reported significant differences in severe nutritional risk scores between patients with and without FI, suggesting a potential association. Despite its widespread use in nutritional screening, there is currently limited research specifically examining the predictive value of the NRS 2002 score for FI. This tool was primarily developed to assess overall nutritional risk rather than gastrointestinal tolerance. Therefore, its utility in predicting FI in critically ill patients remains uncertain. Further prospective studies are needed to determine whether the NRS 2002 score can reliably identify patients at higher risk of developing FI and whether it should be integrated into FI risk prediction models.

In clinical practice, nasogastric and nasojejunal tubes are commonly used for short-term enteral nutrition (EN) in patients requiring nutritional treatment for less than 6 weeks. A study (42) showed that nasojejunal feeding is associated with a lower incidence of gastric residuals, reduced risk of reflux, aspiration, and diarrhea, and improved nutrient absorption, compared to nasogastric feeding. These findings suggest that the choice of feeding route may influence the risk of enteral nutrition feeding intolerance (ENFI). In the present study, nasogastric tubes were the predominant feeding route, which may have influenced the observed outcomes. However, no statistically significant difference in ENFI incidence was found between different feeding routes (p > 0.05). This may be attributed to the relatively small sample size or limited use of nasojejunal tubes, which may have reduced the power to detect a difference. Future studies with a more balanced distribution of feeding routes and larger sample sizes are needed to further explore the impact of tube placement on feeding intolerance in critically ill patients.

In this study, the incidence of enteral nutrition feeding intolerance (ENFI) was 39.6%, which is consistent with the rates reported in clinical guidelines (43). Generally, the area under the ROC curve (AUC) is used to evaluate the diagnostic or predictive performance of a model: an AUC between 0.5 and 0.7 indicates low accuracy, 0.7 to 0.9 suggests moderate accuracy, and an AUC greater than 0.9 reflects high accuracy. The AUC of the predictive model developed in this study was 0.800, indicating moderate discriminatory ability and suggesting that the model has practical clinical value. Based on the optimal Youden index, a cutoff probability of 30.6% was identified to classify a positive prediction of ENFI, which balanced the sensitivity (82.5%) and specificity (72.4%) of the model. Overall, the risk prediction model constructed for ICU patients demonstrates good predictive performance and can effectively assist clinicians in early identification and intervention for patients at high risk of developing ENFI.

This study offers a simple and visual prediction model in the form of a nomogram that enables early risk stratification for ENFI in ICU patients. By assessing five routinely available clinical variables, clinicians can estimate the likelihood of feeding intolerance and adjust nutritional strategies accordingly. For high-risk patients, measures such as slower feeding advancement, alternative feeding routes, prophylactic prokinetic agents, or closer gastrointestinal monitoring may be considered to enhance EN tolerance and avoid complications. The model may also support communication with multidisciplinary teams and facilitate decision-making during ICU rounds.