Incidence of ileus and associated factors in patients with acute pancreatitis: a nationwide analysis

Anmol Singh^a, Ritika Dhruve^b, Carol Singh^c, Vikash Kumar^d, Aalam Sohal^d, Divyesh Sejpal^d

Tristar Centennial Medical Center, Nashville, TN, USA; University of Southwestern Texas, Dallas, TX, USA; Dayanand Medical College, Ludhiana, PB, India; Creighton University, Phoenix, AZ, USA

^aDepartment of Internal Medicine, Tristar Centennial Medical Center, Nashville, TN, USA (Anmol Singh); ^bDepartment of Medicine, University of Southwestern Texas, Dallas, TX, USA (Ritika Dhruve); ^cDepartment of Internal Medicine, Dayanand Medical College, Ludhiana, PB, India (Carol Singh); ^dDivision of Gastroenterology, Creighton University, Phoenix, AZ, USA (Vikash Kumar, Aalam Sohal, Divyesh Sejpal)

Correspondence to: Aalam Sohal, MD, Creighton University School of Medicine, Phoenix, AZ, USA, e-mail: aalamsohal@gmail.com

Received 25 December; accepted 17 February; published online 17 April 2025

DOI: https://doi.org/10.20524/aog.2025.0957

Abstract

Background Ileus is a well-known complication of acute pancreatitis (AP). There are limited data on the factors associated with ileus, as well as its impact on AP patients. We aimed to investigate the incidence and clinical predictors of ileus in hospitalized AP patients.

Methods We queried the 2016-2019 National Inpatient Sample (NIS) database using the International Classification of Diseases (ICD)-10 codes. Adult patients diagnosed with AP (ICD-10 K85) were included, excluding those with chronic pancreatitis. Demographics, comorbidities, complications and interventions were stratified by the presence of ileus. Multivariate analysis identified factors associated with ileus, adjusting for patient and hospital characteristics, comorbidities, and pancreatitis complications.

Results Among 1,386,390 AP patients, 50,170 (3.6%) developed ileus. Female sex was associated with a lower risk (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.53-0.58; P<0.001). Hispanic patients had the lowest risk (aOR 0.82, 95%CI 0.76-0.88), while older age groups had a higher risk. Pseudocysts (P<0.001), sepsis (P<0.001) and portal vein thrombosis (P<0.001) were significant predictors. Pancreatic drainage was associated with ileus (P=0.007), but endoscopic retrograde cholangiopancreatography was not. Patients with ileus had greater mortality (P<0.001), longer hospital stays (+4.9 days, P<0.001), and higher costs ($67,855.91, P<0.001).

Conclusions This study highlights age, sex and racial disparities in the development of ileus in patients with AP. It also reveals a significant association of ileus with pseudocysts, portal vein thrombosis, and pancreatic drainage. Early recognition and timely enteral feeding are crucial to prevent disease progression and improve outcomes.

Keywords Ileus, pancreatitis, national inpatient sample, factors, incidence

Ann Gastroenterol 2025; 38 (3): 328-336

Materials and methods

Data source

The National Inpatient Sample (NIS) database, administered by the Agency for Healthcare Research and Quality, is the largest inpatient database in the US. It contains data from 20% of all hospitalizations in the US, representing approximately 8 million (unweighted) and 40 million (weighted) hospitalizations yearly [6]. The NIS database contains clinical and resource utilization data, while protecting the privacy of patients, physicians and hospitals. It includes 1 primary diagnosis, up to 40 secondary diagnoses, population baseline characteristics, patient comorbidities and total charges.

Study population

The NIS database from 2016-2019 was queried according to the International Classification of Diseases, Tenth Revision (ICD-10), Clinical Modification for patients with a discharge diagnosis of AP (ICD10-K85). Patients were divided into 2 groups based on the presence of ileus. ICD-10 codes K56.0, K56.3 and K56.7 were used to query patients with a concomitant diagnosis of ileus. Patients who were under 18 or had inadequate demographic information were excluded from the analysis. We also excluded patients with chronic pancreatitis and pancreatic cancer. A total of 1,386,389 patients were included in the analysis (Fig. 1).

Figure 1 Flowchart of case selection for patients with acute pancreatitis

Study variables

Data were collected on patient demographics (age, sex, race, primary insurance, income quartile), hospital characteristics (location, region, teaching status, size), and Elixhauser comorbidities [7]. We also studied common etiologies, such as biliary pancreatitis and alcohol-related pancreatitis, as well as the common conditions associated with pancreatitis, such as pancreatic pseudocyst, portal vein thrombosis, pneumonia and bacteremia. Information about common interventions, such as total parenteral nutrition (TPN) and endoscopic retrograde cholangiopancreatography (ERCP), was also included.

Outcomes

The primary study measure was the prevalence of ileus in patients with AP. Secondary outcomes were the factors associated with ileus in AP, and the effect of ileus on outcomes in patients with AP. The categorical outcome studied was mortality, while continuous outcomes studied were the length of stay and total hospitalization charges. Hospital charges are defined as the dollar amount the hospital charges for services prior to negotiating discounts with insurance companies.

Statistical analysis

The chi-square test was used to compare categorical variables, while the independent t-test was used to compare continuous variables. Data are presented as population-weighted mean ± standard error for continuous variables and as total number of patients with percentages for categorical factors. In order to study the factors associated with ileus in pancreatitis, we performed a univariate analysis to assess differences between patients with ileus and those without. This was followed by a multivariate analysis using variables found to be statistically significant in the univariate analysis (those with a P-value <0.1). The results were expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). To study the effect of ileus on continuous and categorical outcomes, a univariate and a multivariate regression analysis were performed to identify the relationship between ileus and outcomes. The categorical outcome studied was in-patient mortality, while continuous outcomes, such as length of stay, total hospitalization cost and charges, were also analyzed. The variables included in the univariate analysis were patient characteristics, hospital characteristics, Elixhauser comorbidity index, etiology of acute AP, complications of AP and common interventions. This was followed by a multivariate analysis that included those factors noted to be statistically significant.

Results

Patient demographics

A total of 1,386,389 patients were included in the analysis, of whom 50,170 (3.6%) developed ileus. Ileus was predominantly seen in males (65.03%), 35.3% of patients with ileus and AP were older than 65 years, while 91% were admitted to urban hospitals. Ileus was most commonly seen in Whites (69.52%), followed by African Americans (13.2%) and Hispanics (10.64%). Patients with ileus had a high comorbidity burden, with 73.28% having more than 3 Elixhauser comorbidities. Ileus was more common in patients with biliary pancreatitis (22.96%) as compared to alcohol-related pancreatitis (18.86%). A complete list of patient characteristics stratified by the presence of ileus is presented in Table 1.

Table 1 Patient characteristics and demographics, stratified by the presence of ileus

Comorbidities and complications

Patients with ileus had a higher incidence of cardiac arrhythmias (24.08% vs. 14.28%), congestive heart failure (12.2% vs. 9.27%), valvular diseases (3.64% vs. 2.93%), hypertension (59.87% vs. 56.53%), fluid and electrolyte disorders (64.09% vs. 43.74%), malnutrition (19.37% vs. 8.26%), chronic liver disease (24.1% vs. 20.63%), non-metastatic solid tumor (4.17% vs. 3%) and metastatic tumor (2.41% vs. 1.83% compared to controls).

Patients with ileus had a lower incidence of diabetes mellitus (25.47% vs. 28.45%), depression (11.8% vs. 13.89%), and drug abuse (6.34% vs. 7.39%). There were no significant differences noted in the incident rates between the 2 groups in terms of hypothyroidism (9.9% vs. 10.24%), alcohol use (24.55% vs. 25.38%), rheumatoid arthritis or collagen vascular diseases (2.3% vs. 2.61%).

There was a higher incidence of pneumonia (13.5% vs. 4.43%), acute kidney injury (AKI; 36.38% vs. 18.18%), and pancreatic pseudocyst (7.9% vs. 3.31%) in patients with ileus compared to those without. Patients with ileus also had a higher incidence of requiring total parenteral nutrition (8.69% vs. 1.02%) and pancreatic pseudocyst drainage (2.35% vs. 0.69%). The results of Elixhauser comorbidities, common conditions associated with pancreatitis, and interventions stratified by the presence of ileus are presented in Table 2.

Table 2 Comorbidities, complications and interventions in hospitalized patients with acute pancreatitis, stratified by the presence of ileus Q: Please check the highlighted numbers

Factors associated with ileus development

Older age (>65 years) was associated with a 14% higher risk of developing ileus compared to the younger age group, 18-44 years. Females had a lower risk of developing ileus compared to males after adjusting for other factors. Hispanic patients had the lowest risk of developing ileus, as low as 18%, compared to White patients. Patients with private insurance, as well as higher income quartiles (third or the highest), were at higher risk of developing ileus. There was no statistical difference based on the hospital’s location or teaching status on the risk of developing ileus. The results of the multivariate analysis of patient demographics and interventions are presented in Fig. 2, while the results for comorbidities and etiologies are presented in Table 3.

Figure 2 Forest plot depicting odds ratios of patient demographics and complications, after multivariate analysis. Adjustments were made for patient demographics, comorbidities and complications

AKI, acute kidney injury; ERCP, endoscopic retrograde cholangiopancreatography

Table 3 Odds ratios of patient comorbidities and etiologies, after multivariate analysis. Adjustments were made for patient demographics, comorbidities and complications

No statistically significant difference was noted in the risk of developing ileus in patients with biliary and alcohol-related pancreatitis. Patients with concomitant biliary and alcohol-related pancreatitis were at a 1.81 times higher risk of developing ileus as compared to patients with biliary pancreatitis alone. The risk of developing ileus was higher in patients with comorbidities than in those without comorbidities.

The presence of congestive heart failure was associated with a 26% higher probability of having ileus in patients with AP. The presence of fluid/electrolyte abnormalities was associated with a 59% higher probability of having ileus. Furthermore, alcohol or drug use was associated with a lower risk of having ileus in patients with AP. The presence of portal vein thrombosis and pancreatic pseudocysts in patients with AP was associated with a higher risk of developing ileus.

Patients with sepsis had higher odds of developing ileus. The presence of shock was also associated with 75% higher odds of having concomitant ileus. Acute kidney injury was associated with a 38% higher risk of developing ileus, while ERCP was not associated with higher odds of developing ileus. Pancreatic drainage and TPN use were associated with higher odds of having concomitant ileus.

Effect of ileus on outcomes in hospitalized patients with AP

Mortality

The incidence of mortality in patients with ileus and AP was 6.38% compared to 2.5% in patients without ileus. On multivariate analysis, ileus was noted to be an independent predictor of mortality (aOR 1.58, 95%CI 1.43-1.75; P<0.001).

Length of stay

The mean length of hospital stay in patients without ileus was 5.15±0.18 days. The mean length of stay in patients with ileus and AP was 12.67±0.15 days. On multivariate linear regression, the presence of ileus was associated with a statistically significantly longer hospital stay (+4.9 days, 95%CI 4.63-5.12 days; P<0.001).

Total hospitalization charges

The mean total hospitalization charges in patients without ileus were $57,963.3. The mean total hospitalization charges in patients with ileus and AP were $163,713.7. On multivariate analysis, the presence of ileus was associated with statistically significantly greater hospitalization charges (+67,855.91, 95%CI $62,373-$73,338; P<0.001).

Total hospitalization costs

The mean hospitalization cost in patients without ileus was $13,587.33, while the mean cost in patients with ileus was $38,941. On multivariate analysis, the presence of ileus was associated with a statistically greater hospitalization cost ($16,252.6, 95%CI $15,002-$17,502; P<0.001).

Discussion

Our study is the first to evaluate the prevalence of ileus in patients with AP in the US using a large database drawn from the inpatient population. Our analysis revealed the prevalence of ileus in AP to be 3.6%. The association with ileus differed by age group. The elderly population (age >65 years) was at higher risk of developing ileus compared to the younger population (age <45). This association may be due to the longer colonic transit time noted in the elderly [8]. Long-standing chronic medical conditions such as diabetes mellitus and hypothyroidism, which are more often seen in the elderly, may also decrease gastrointestinal motility [9,10]. In addition, many frequently used drugs in this patient population, such as anticholinergics, opioids and antidepressants, are associated with disordered gastrointestinal motility, which could also explain the higher risk of ileus.

Interestingly, females had a 44% lower risk of ileus compared to males, despite existing literature suggesting that females might be at higher risk due to slower colonic motility [11]. Racial differences were also noted in our study. Hispanics were noted to have a lower risk of ileus than Whites and African Americans. Differences were also noted based on the income quartile. Interestingly, the highest risk of developing ileus was noted in patients in the higher-income quartiles compared to the lower-income quartiles. Further research is needed to study the underlying factors responsible for age, sex, race, and income disparities.

Our study found that patients admitted to larger hospitals are at higher risk of developing ileus. Large hospitals often serve as transfer centers for patients with higher acuity from small and medium sized hospitals, which might contribute to the higher incidence of ileus. No differences were noted in the rates of ileus based on the teaching status or the location of the hospital. The risk of ileus also increased with the number of comorbidities. Patients with 3 or more comorbidities had a 54% higher risk than those without comorbidities.

We also found that electrolyte disorders were associated with a higher risk of ileus. Although not all electrolytes were studied separately, electrolyte abnormalities such as hypokalemia might contribute to this association. Electrolyte abnormalities have been studied in prolonged ileus, and it has been postulated that, although they may not be the primary etiology of ileus, they can delay recovery of gut motility [12]. Furthermore, patients with paralysis were at a higher risk of developing ileus. Immobilization is a known risk factor for ileus, which could explain this finding. Physicians should be aware of this association, and early physical therapy in patients with paralysis and AP may help decrease the risk of developing ileus.

Ileus was also associated with complications of pancreatitis, including pneumonia and AKI. The presence of pneumonia was associated with a 63% higher risk of developing ileus, while bacteremia was not associated with ileus. There is a possibility that acute infection can trigger the development of ileus via inflammatory pathways in pneumonia, although this needs to be further studied [13]. The presence of AKI was associated with a 38% higher risk of ileus. Patients with ileus may not receive enteral nutrition for days, leading to dehydration and AKI. Acute uremia in patients with AKI may also contribute to the development of ileus [14]. The development of AKI alone during AP is a poor prognostic factor with a high mortality rate [15].

On the contrary, patients with chronic kidney disease (CKD) had a lower risk of developing ileus. These patients may be resistant to small changes in waste products and, as a result, these have minimal effect on gut motility. Furthermore, patients with CKD stage 5 are on hemodialysis, which removes nitrogenous waste products and may help restore motility. We also found that patients with pseudocysts have a higher association with ileus. Ileus secondary to pseudocyst has previously been documented, and it has been suggested that it is due to the pressure effect of the pseudocyst on the bowel [16]. In addition, newly developed pseudocysts are associated with a severe course of AP, thus having a higher risk of complications such as ileus [17].

The incidence of sepsis, shock, and Intensive Care Unit admissions was higher in patients with ileus. Shock and sepsis are associated with increased intestinal permeability and decreased perfusion to the gut, possibly contributing to the development of ileus [18]. In animal models, severe AP has been associated with an increased proportion of nitric oxide synthase-immunoreactive neurons in the ileal myenteric ganglia, which may be involved with the development of ileus in these patients [19]. The incidence of death was also noted to be higher in patients with ileus. After adjusting for confounding variables, patients with ileus had 58% higher mortality than those without ileus. We also found that ileus was associated with a 4.9-day longer hospital stay, compared to patients without ileus, contributing to higher hospitalization charges ($62,373 vs. $16,252, respectively). The presence of ileus may delay enteral nutrition initiation and sometimes require total parenteral nutrition, contributing to higher costs and lengths of stay. Clinicians should recognize the development of ileus and its possible complications, which can lead to rapid decompensation.

This study had several limitations. First, the NIS lacks granular clinical data, limiting our ability to calculate the severity of illnesses, using metrics such as the APACHE or BISAP scores. Secondly, information about treatments, such as intravenous fluids or pain medications, is not included in the NIS, and these are important confounders that may affect patient outcomes. Additionally, the absence of patient identifiers precludes the tracking of readmissions or distinguishing primary admissions from readmissions. The study’s strength comes from its large population size and the exclusion of sample bias from data collected from a single region or hospital. These findings should be validated in a prospective cohort that captures more granular clinical data.

Our study revealed the prevalence of ileus in AP to be 3.6%. Older age, male sex and higher income were associated with a higher risk of ileus, while the risk was lower in the younger population, females, Hispanics, and patients with lower socioeconomic status. The concomitant presence of ileus in AP patients was associated with higher mortality, longer hospital stays and increased resource utilization. Early initiation of oral or enteral feeding (within 24-72 h) is a key strategy in preventing ileus. Clinicians should remain vigilant about the potential development of ileus in AP patients, especially those in the high-risk group.

Summary Box

What is already known:

Ileus is a recognized complication of acute pancreatitis (AP) and has been associated with disease severity
The exact mechanisms contributing to ileus in AP remain unclear, but are thought to involve inflammation-mediated gut dysmotility
Previous studies have suggested that ileus may prolong hospital stay and increase morbidity in AP patients
Limited nationwide data exist on the incidence, predictors, and clinical impact of ileus in patients with AP

What the new findings are:

The incidence of ileus in hospitalized patients with AP was 3.6%, with older age, male sex and higher income quartiles being significant risk factors
Ileus was associated with increased odds of mortality (adjusted odds ratio 1.58, 95% confidence interval 1.43-1.75), longer hospital stays (+4.9 days), and higher hospitalization costs
Specific pancreatitis complications, such as pseudocysts and portal vein thrombosis, were strongly associated with ileus development
Timely recognition and early enteral feeding could mitigate the negative impact of ileus in AP patients, improving clinical outcomes

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Notes

Conflict of Interest: None