The impact of enteral feeding intolerance on the prognosis of patients with septic shock in South Korea

Hyun-Jun Park; Yoon Hae Ahn; Hong Yeul Lee; Sang-Min Lee; Jinwoo Lee

doi:10.4266/acc.000700

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Original Article Nutrition The impact of enteral feeding intolerance on the prognosis of patients with septic shock in South Korea: Acute and Critical Care 2025;40(2):304-312.
DOI: https://doi.org/10.4266/acc.000700
Published online: May 30, 2025

Hyun-Jun Park¹

, Yoon Hae Ahn¹

, Hong Yeul Lee¹

, Sang-Min Lee^1,2

, Jinwoo Lee²

¹Department of Critical Care Medicine, Seoul National University Hospital, Seoul, Korea

²Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

Corresponding author: Jinwoo Lee Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-2228 Fax: +82-2-762-9662 Email: realrain7@gmail.com

• Received: February 11, 2025 • Revised: April 2, 2025 • Accepted: April 3, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
KEY MESSAGES
NOTES
REFERENCES

Abstract

Background
While enteral feeding intolerance (EFI) is associated with worse clinical outcomes in critically ill patients, the relationship between the number of days of EFI and mortality outcomes remains unclear.
Methods
We retrospectively analyzed adult patients admitted to the medical intensive care unit (ICU) with septic shock at a tertiary referral center. EFI was defined as the presence of vomiting, abdominal distension, pain, diarrhea, or radiographic evidence of ileus. EFI status was assessed daily, and we evaluated the prognostic impact of total number of EFI days during the first 3 days of enteral feeding on clinical outcomes.
Results
A total of 94 patients were included in the analysis, with 77 (81.9%) experiencing EFI. During the first 3 days of enteral feeding, 25 patients (26.6%) experienced EFI for 1 day, 22 patients (23.4%) experienced EFI for 2 days, and 30 patients (31.9%) experienced EFI for all 3 days. The total number of EFI days was identified as an independent risk factor of 90-day mortality (adjusted hazard ratio, 1.400; 95% CI, 1.021–1.919). Higher total EFI days was significantly associated with increased ICU mortality (P for trend=0.036), in-hospital mortality (P for trend=0.007), 30-day mortality (P for trend=0.004), and 90-day mortality (P for trend=0.006).
Conclusions
An increase in the total number of EFI days was significantly associated with mortality outcomes in patients with septic shock, suggesting that EFI may serve as a useful indicator for predicting outcomes in this population.
Key Words: enteral nutrition; intensive care units; mortality; septic shock

INTRODUCTION

Enteral nutrition (EN) helps preserve mucosal structure and the immune system within the gastrointestinal (GI) tract, thereby reducing the risk of bacterial translocation, systemic infection, and the development of multiple organ dysfunction syndrome in critically ill patients [1-3]. Therefore, it is recommended to initiate enteral feeding (EF) within 24–48 hours of intensive care unit (ICU) admission for critically ill patients [4,5]. However, the initiation of EF is often hindered by various GI symptoms and signs, such as gastric retention, abdominal distension, diarrhea, nausea, and vomiting. Clinicians use the term enteral feeding intolerance (EFI) to describe this phenomenon [6]. Although broad and inconsistent definitions of EFI lead to variability in incidence across studies, it appears to be common, with reported rates ranging from 2% to 75% [7,8].

Previous studies have shown that EFI is closely associated with worse clinical outcomes, such as inadequate nutrition, fewer ventilator-free days, longer ICU and hospital stays, and higher mortality, emphasizing the importance of carefully monitoring EFI during EN feeding in critically ill patients [9-11]. Patients with septic shock are particularly vulnerable due to the need for high-dose vasopressor support, the risk of low GI tract perfusion, and the potential for complications such as mesenteric ischemia or, in severe cases, non-occlusive bowel necrosis upon initiation of EF [3,12]. Consequently, current guidelines have not established a consensus on the optimal timing for initiating EN in patients with septic shock [13].

This study aimed to determine quantify the number of days with EFI events in patients with septic shock and examine the association between frequency and clinical outcomes. We hypothesized that EFI would be highly prevalent among septic shock patients and that a higher frequency of EFI events would be associated with worse clinical outcomes.

MATERIALS AND METHODS

Ethics Statement

This study was conducted in compliance with the amended Declaration of Helsinki and was approved by the Institutional Review Board of Seoul National University Hospital (No. H-2202-049-1298). The requirement for written informed consent was waived due to the retrospective nature of the study.

Study Population

We included adult patients aged 18 years and older admitted to the medical ICU for septic shock at a tertiary referral center in South Korea from January 1, 2023 to November 30, 2023. Septic shock was defined in patients with a Sequential Organ Failure Assessment (SOFA) score of 2 or above who required vasopressor support to maintain a mean arterial pressure of 65 mm Hg or higher despite receiving adequate fluid resuscitation with 30 ml/kg of crystalloid within 3 hours of diagnosis [14]. The exclusion criteria were as follows: patients who were not receiving vasopressors at the time of EF initiation, those in moribund status, those readmitted to the ICU during the same hospitalization period, patients who did not receive EF during their ICU stay, and those with GI conditions contraindicating EF, such as GI obstruction, GI bleeding, ischemic colitis, esophageal rupture, peritonitis, or acute pancreatitis.

EF Protocol

Our institution implements a structured, multidisciplinary approach to EN, managed collaboratively by a dedicated Nutrition Support Team and ICU staff. Twice-weekly multidisciplinary rounds are conducted to optimize nutrition strategies. In hemodynamically stable patients without contraindications, EN is typically initiated at 300–600 kcal/day and advanced by 200–300 kcal/day based on clinical tolerance. However, for hemodynamically unstable patients, an individualized feeding protocol is established for each patient, with decisions on initiation of nutrition, caloric advancement, and formula selection made based on the risks and benefits.

Definitions and Assessment of EFI Events

We defined an EFI event as the presence of any of the following GI complications: vomiting, abdominal distension, abdominal pain, diarrhea, or ileus on abdominal x-ray. Diarrhea was defined by a stool volume of 250 ml or more per day or the occurrence of three or more stools per day [15]. Vomiting referred to any visible regurgitation of gastric contents. Abdominal distension was identified either through clinical suspicion or an increase in abdominal girth measured by the clinician [11]. Abdominal pain was defined as subjective discomfort in the abdominal area or the presence of tenderness or rebound tenderness observed during a physical examination. Ileus was diagnosed based on the radiologist’s report of the abdominal x-ray. The presence of EFI was assessed daily, and a day was considered an EFI day if any of these GI complications were observed. We then calculated the total number of EFI days during the first 72 hours of EF for analysis.

Clinical Variables

Demographic, laboratory, and clinical data at baseline and through the study period was collected through retrospective review of medical records. For norepinephrine equivalent (NEE) dose, we assessed the dose at the time of EF initiation and the maximum dose administered during each 24-hour period within the first 72 hours following EF initiation. To measure the NEE dose, we standardized all vasopressor and inotropic medications administered to patients into a single equivalent dose expressed as micrograms per kilogram per minute of norepinephrine. The NEE dose was calculated using the formula outlined in a previously published study [16]. To ensure consistency and relevance, doses that were administered continuously for more than 2 hours were included in the calculations.

Outcomes

The primary outcomes of this study were 30-day and 90-day mortality. Secondary outcomes were length of stay (LOS) in the ICU, LOS in the hospital after ICU admission, mechanical ventilation (MV)-free days within 28 days from the day of intubation, and number of EFI-related GI complications.

Statistical Analysis

For continuous variables, data were summarized using either the mean and standard deviation or the median and interquartile range. Categorical variables were summarized using frequencies and proportions. To assess the trend in the association between increasing total days of EFI and clinical characteristics/outcomes, the P-value for the trend was calculated using regression models. Linear regression was applied for continuous outcomes, while logistic regression was used for binary outcomes. Total days of EFI was treated as an ordinal variable, and the P-value for the trend was derived from the regression coefficient. Variables with P-values below 0.05 were considered to demonstrate significant trends.

Cox proportional hazards analysis was utilized to assess the impact of EFI on mortality outcomes, with hazard ratios (HRs) and 95% CIs calculated. Multivariable analysis was adjusted for variables associated with mortality including relevant clinical confounders. All statistical analyses were conducted using the R statistical software version 4.2.0 (R Foundation for Statistical Computing).

RESULTS

Study Population and Clinical Characteristics

Among a total of 451 patients with septic shock, aged 18 years or older, 357 were excluded based on the exclusion criteria. Figure 1 presents a flowchart outlining the patient selection process. A total of 94 patients were included in analysis. While 17 patients did not experience EFI during the first 3 days of EF, most patients (77 patients, 81.9%) had at least one episode of EFI. Among the patients who experienced EFI, 25 patients (26.6%) experienced EFI for 1 day, 22 patients (23.4%) experienced EFI for 2 days, and 30 patients (31.9%) experienced EFI for all 3 days.

Age, sex, body mass index (BMI), clinical frailty scale, high risk of refeeding syndrome, immunocompromised status, and comorbidities did vary significantly by number of EFI days. In contrast, blood urea nitrogen and creatinine levels increased significantly with higher total EFI days. The proportion of patients receiving renal replacement therapy (RRT) also rose progressively with increasing EFI days. Severity scores, including the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the SOFA score, increased in parallel with total EFI days. mNUTRIC score was also significantly associated with longer duration of EFI. The most common site of infection was pulmonary (n=66), followed by abdominal (n=18), unknown origin (n=8), catheter-related (n=4), urinary tract (n=3), and skin/soft tissue (n=3) (Table 1).

Association between EFI Days and Mortality

In the analysis of mortality variables, an increase in total EFI days was significantly associated with increased ICU mortality (P=0.036), in-hospital mortality (P=0.007), 30-day mortality (P=0.004), and 90-day mortality (P=0.006) (Table 1). Multivariable Cox proportional hazards regression analysis demonstrated that number of EFI days was independently associated with 90-day mortality (adjusted HR [aHR], 1.400; 95% CI, 1.021–1.919; P=0.037) but not 30-day mortality (aHR, 1.496; 95% CI, 0.992–2.258, P=0.055) (Table 2).

Secondary Outcomes

LOS in both ICU and hospital showed a decreasing trend as the number of EFI days increased (P for trend=0.027 and 0.013, respectively). However, MV-free days within 28 days from the day of intubation did not exhibit a significant increase or decrease with an increasing number of EFI days. Similarly, no significant differences across groups or according to total EFI days were observed for the time from ICU admission to EF initiation, the time from septic shock to EF initiation, the amount of EF intake, the percentage ratio of delivered to target kcal in EF, average protein intake, or the concomitant administration of parenteral nutrition. There were no significant differences in NEE dose at the time of EF initiation or in the maximum dose on day 1 following EF initiation across groups. However, on days 2 and 3 following EF initiation, patients with a greater number of EFI days demonstrated a tendency toward higher maximum NEE doses (Table 3).

The most frequently observed GI complication was diarrhea, reported in 41 patients (43.6%) with a total of 102 occurrences. This was followed by abdominal distension, observed in 35 patients (37.2%) with 79 occurrences; ileus detected on abdominal x-ray, noted in 7 patients (7.4%) with 13 occurrences; vomiting, seen in 6 patients (6.4%) with 6 occurrences; and abdominal pain, reported in 2 patients (2.1%) with 3 occurrences (Figure 2).

DISCUSSION

This study demonstrated a relatively high prevalence of EFI (81.9%) among septic shock patients admitted to the ICU compared to the previously reported range of 2% to 75% in critically ill patients [6]. This discrepancy may be attributable to the study’s specific focus on patients with septic shock. EN increases splanchnic metabolic demands, which can result in oxygen and/or energy mismatch in the hypo-perfused GI tract during septic shock. This mismatch may cause the absorptive processes of the GI tract to exceed the limits of cellular metabolism, leading to cellular ischemia [17]. For these reasons, current guidelines provide conservative and vague recommendations regarding early EN support in patients with septic shock [18]. However, initiating EN as early as possible, even in the context of septic shock, can help preserve the mechanical and immunological functions of the gut barrier, stimulate intestinal trophism, reduce bacterial translocation, and lower the incidence of sepsis and multiple organ failure [19,20]. A meta-analysis of five randomized controlled trials and 10 non-randomized studies suggested that early EN in septic shock patients may reduce the duration of MV and SOFA scores in critically ill septic patients, albeit with an apparent increase in the frequency of non-serious adverse events such as diarrhea [21].

In our study, an increase in the total number of EFI days was significantly associated with higher 90-day mortality even after adjusting for relevant clinical confounders. As the total number of EFI days increased, there was a significant increase in both ICU mortality and in-hospital mortality. EFI is conceptually and clinically aligned with acute intestinal failure (AIF), a state of insufficient gut function to maintain health and homeostasis [22,23]. AIF reflects a continuum of GI dysfunction, which encompasses the features of EFI, especially in critically ill patients. AIF has increasingly been recognized as a central contributor to poor outcomes in the ICU due to its impact on nutrient absorption, inflammation, and systemic deterioration [24]. Incorporating the concept of AIF provides a stronger physiological rationale for our findings and highlights the importance of recognizing persistent EFI in septic shock. While SOFA score is widely used to evaluate organ dysfunction and predict outcomes in sepsis [25], it does not account for GI function. Given the growing evidence that GI dysfunction, including EFI, contributes to poor outcomes, complementing existing severity scores with direct GI assessment may offer a more comprehensive measure of organ failure in this population.

Unfortunately, a standardized definition of EFI has not yet been established, and the definitions employed in previous studies vary widely. These definitions are largely categorized into delayed gastric emptying, GI symptoms, and inadequate EN delivery [8]. Concerns have been raised regarding the reliability of gastric residual volume (GRV) monitoring as an indicator of delayed gastric emptying due to the lack of standardized measurement techniques, its poor predictive value for regurgitation or aspiration, the absence of established normal values, and the lack of a validated single cutoff value to define "large" GRV [26,27]. Furthermore, a systematic review concluded that GRV thresholds are not significantly associated with the prevalence of EFI, given the weak correlation between GRV and gastric emptying [28]. Inadequate EN delivery may be influenced by factors unrelated to GI function, such as interruptions for procedures, delayed initiation of EN, or clinician decisions to withhold EN. Also, there is no universally accepted threshold for adequate EN delivery.

Regarding mortality outcomes, total EFI days was identified as an independent risk factor for 90-day mortality, but not 30-day mortality after adjusting for confounding factors. This is likely because 30-day mortality is primarily determined by acute factors such as initial hemodynamic instability and multi-organ failure [29], whereas 90-day mortality is influenced by cumulative effects of EFI over time, particularly through its impact on nutritional status. Reduced volumes of EN delivered due to EFI can lead to malnutrition [30]. Malnutrition, in turn, can result in a wide range of adverse outcomes, including increased risk of pressure ulcers and impaired wound healing, immune suppression and higher infection rate, muscle wasting and functional loss increasing the risk of falls, and longer length of hospital stay [31]. These factors are likely linked to increased 90-day mortality.

Despite significant differences in clinical outcomes, total caloric intake across groups remained comparable. The presence and persistence of EFI may reflect more than just reduced energy delivery. It may be associated with impaired gut motility, increased mucosal permeability, and compromised nutrient absorption, all of which can promote systemic inflammation and contribute to multiple organ failure [32]. Through these mechanisms, EFI appears to influence clinical outcomes independently of the total volume of nutrition delivered. To accurately determine the isolated effect of enteral caloric intake on mortality outcomes, a fully standardized EF protocol is essential. However, such standardization was not feasible in our cohort due to the clinical characteristics of the population. Many patients were hemodynamically unstable, requiring individualized nutrition decisions based on ongoing clinical changes, with feeding initiation, rate of advancement, and formula selection determined through multidisciplinary discussion in real-world ICU practice.

This study has several limitations. First, it was conducted in a tertiary medical ICU with a high prevalence of complex comorbidities and immunocompromised patients, limiting generalizability. Second, the retrospective design introduced potential confounding and information bias. Third, GRV was not included in the definition of EFI due to growing evidence that GRV is a poor surrogate marker of gastric emptying and not consistently associated with feeding intolerance or clinical outcomes. This study focused on GI symptoms as the definition of EFI, as they are more easily measurable and applicable in routine clinical practice. This approach was chosen to enhance the practicality and consistency of EFI assessment in real-world settings. Fourth, the relatively small sample size limited this study’s statistical power and the ability to conduct robust subgroup analyses. Finally, as an observational study, patients were not managed under a uniform EN protocol, resulting in potential variation in formula composition, feeding methods and approach to advancing EN volume. Future large, prospective, multicenter studies with standardized EN protocols are warranted to validate these findings and further explore the impact of EFI on clinical outcomes.

In conclusion, 81.9% of septic shock patients admitted to the medical ICU experienced EFI. An increase in the total number of EFI days was significantly associated with higher 90-day mortality, even after adjusting for relevant clinical confounders. These findings highlight the critical role of GI dysfunction in septic shock and suggest that EFI may serve as a valuable prognostic marker. Further studies are needed to explore the role of EFI monitoring and to investigate its link to clinical outcomes among critically ill patients.

KEY MESSAGES

▪ A relatively high prevalence of enteral feeding intolerance (EFI) can be occurred among patients with septic shock admitted to the intensive care unit, compared to the other critically ill patients.

▪ An increase in the total number of EFI days was significantly associated with higher 90-day mortality, even after adjusting for relevant clinical confounders.

▪ These findings highlight the critical role of gastrointestinal dysfunction in septic shock and suggest that EFI may serve as a valuable prognostic marker.

NOTES

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

FUNDING

This study was supported by grant no.04-2022-3090 from the Seoul National University Hospital Research Fund.

ACKNOWLEDGMENTS

None.

AUTHOR CONTRIBUTIONS

Conceptualization: HJP, JL. Methodology: JL. Formal analysis: HJP, JL. Data curation: HJP, YHA, HYL, JL. Visualization: HJP, JL. Writing - original draft: HJP,. Writing - review & editing: YHA, HYL, SML, JL. All authors read and agreed to the published version of the manuscript.

Figure 1.

Flow diagram of patient enrollment in the study. ICU: intensive care unit; EFI: enteral feeding intolerance.

Figure 2.

Frequency of gastrointestinal (GI) complications associated with enteral feeding intolerance diagnosis during the first 3 days of enteral feeding.

Table 1.

Clinical characteristics of the patients according to the presence of EFI and total EFI days

Variable	Non-EFI group (n=17)	EFI group			P for trend
Variable	Non-EFI group (n=17)	EFI for 1 day (n=25)	EFI for 2 days (n=22)	EFI for 3 days (n=30)	P for trend
Age (yr)	71 (60–76)	69 (62–81)	71 (61–80)	68 (59–74)	0.865
Male	11 (64.7)	14 (56.0)	12 (54.5)	18 (60.0)	0.846
Body mass index (kg/m²)	21.5 (19.4–23.6)	21.7 (19.4–24.2)	21.8 (19.9–23.0)	23.4 (20.6–26.3)	0.119
Clinical frailty scale	4.0 (4.0–6.0)	4.0 (3.0–5.0)	4.5 (4.0–6.0)	4.5 (3.0–6.0)	0.460
High risk of refeeding syndrome^a)	9 (52.9)	16 (64.0)	9 (40.9)	22 (73.3)	0.319
Immunocompromised state^b)	8 (47.1)	8 (32.0)	10 (45.5)	19 (63.3)	0.100
Comorbidity
Heart failure	0	11 (44.0)	4 (18.2)	6 (20.0)	0.743
Chronic kidney disease	3 (17.6)	4 (16.0)	11 (50.0)	10 (33.3)	0.078
Diabetes mellitus	8 (47.1)	10 (40.0)	8 (36.4)	11 (36.7)	0.497
Laboratory test
Albumin (mg/dl)	2.9±0.5	3.2±0.6	2.9±0.5	2.9±0.5	0.338
BUN (mg/dl)	20.0 (15.0–26.0)	22.0 (15.0–31.0)	33.5 (20.0–51.0)	40.5 (21.0–55.0)	0.001
Creatinine (mg/dl)	0.8 (0.6–0.9)	1.0 (0.7–1.8)	1.4 (0.8–4.4)	1.8 (1.1–3.5)	0.025
Lactate (mmol/L)	1.7 (1.2–2.4)	2.3 (1.3–4.6)	2.3 (1.5–3.1)	2.4 (1.6–3.4)	0.109
MV use on ICU admission day	11 (64.7)	15 (60.0)	12 (54.5)	15 (50.0)	0.291
RRT use on ICU admission day	1 (5.9)	2 (20.0)	7 (31.8)	15 (50.0)	<0.001
APACHE II score	18.4±5.7	17.4±6.2	19.5±7.4	23.2±6.7	0.003
SOFA score	8.6±4.2	8.6±3.4	9.8±3.5	11.5±3.9	0.003
mNUTRIC score	5 (4–6)	5 (4–6)	6 (4–7)	6 (5–7)	0.004
The site of infection^c)
Pulmonary	12 (70.6)	22 (88.0)	19 (86.4)	13 (43.3)	0.009
Abdominal	3 (17.6)	2 (8)	1 (4.5)	12 (40.0)	0.023
Urinary	1 (5.9)	0	0	2 (6.6)	0.626
Skin/soft tissue	1 (5.9)	0	1 (4.5)	1 (3.3)	0.969
Catheter-related	1 (5.9)	0	0	3 (10.0)	0.305
Unknown	2 (11.8)	3 (12)	0	3 (10.0)	0.612
Mortality variable
ICU mortality	1 (5.9)	4 (16.0)	6 (27.3)	9 (30.0)	0.036
In-hospital mortality	4 (23.5)	9 (36.0)	12 (54.5)	18 (60.0)	0.007
30-Day mortality	2 (11.8)	5 (20.0)	8 (36.4)	14 (46.7)	0.004
90-Day mortality	4 (23.5)	9 (36.0)	13 (59.1)	18 (60.0)	0.006

Values are presented as median (interquartile range), number (%), or mean±standard deviation.

EFI: enteral feeding intolerance; BUN: blood urea nitrogen; MV: mechanical ventilation; ICU: intensive care unit; RRT: renal replacement therapy; APACHE: Acute Physiologic and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; NUTRIC: nutrition risk in the critically ill.

^a)Patients at high risk of refeeding are defined as those who either have one or more of the following: a body mass index (BMI) <16 kg/m², unintentional weight loss >15% in the past three to 6 months, little or no nutritional intake for >10 days, or low levels of potassium, phosphate, or magnesium before feeding; or those who meet two or more of the following criteria: a BMI <18.5 kg/m², unintentional weight loss >10% in the past three to 6 months, little or no nutritional intake for >5 days, or a history of alcohol misuse or drug use, including insulin, chemotherapy, antacids, or diuretics;

^b)Immunocompromised status was defined as the presence of conditions or therapies that suppress the patient's resistance to infection, including immunosuppressive therapy, chemotherapy, radiation therapy, long-term or high-dose corticosteroid use, or advanced conditions such as leukemia, lymphoma, or AIDS;

^c)Patients could have more than one site of infection; therefore, infection sites are not mutually exclusive and may exceed the total number of patients.

Table 2.

Association between EFI days and mortality

Variable	Unadjusted HR (95% CI)	P-value	Adjusted HR (95% CI)	P-value
30-Day mortality
Age	2.739 (1.246–6.022)	0.012	3.238 (1.379–7.600)	0.007
Male sex	1.179 (0.567–2.451)	0.660	0.856 (0.393–1.863)	0.695
BMI	1.016 (0.923–1.118)	0.748	1.002 (0.899–1.117)	0.974
SOFA score	1.171 (1.063–1.291)	0.001	1.139 (1.014–1.280)	0.028
MV use on ICU admission day	1.376 (0.650–2.915)	0.404	1.500 (0.695–3.239)	0.301
RRT use on ICU admission day	2.789 (1.345–5.785)	0.006	1.026 (0.406–2.592)	0.956
Total EFI days	1.685 (1.161–2.444)	0.006	1.496 (0.992–2.258)	0.055
90–Day mortality
Age	2.396 (1.294–4.438)	0.005	2.761 (1.408–5.418)	0.003
Male sex	1.348 (0.746–2.437)	0.322	1.129 (0.605–2.108)	0.703
BMI	0.957 (0.881–1.040)	0.300	0.943 (0.859–1.035)	0.218
SOFA score	1.137 (1.049–1.131)	0.002	1.107 (1.004–1.220)	0.041
MV use on ICU admission day	1.086 (0.598–1.973)	0.786	1.182 (0.635–2.200)	0.598
RRT use on ICU admission day	2.803 (1.543–5.090)	0.001	1.377 (0.664–2.855)	0.390
Total EFI days	1.511 (1.137, 2.007)	0.004	1.400 (1.021–1.919)	0.037

Multivariable analyses adjusted for age, sex, BMI, SOFA score, MV use on ICU admission day, RRT use on ICU admission day.

EFI: enteral feeding intolerance; HR: hazard ratio; BMI: body mass index; SOFA: Sequential Organ Failure Assessment; MV: mechanical ventilation; ICU: intensive care unit; RRT: renal replacement therapy.

Table 3.

Comparison of clinical outcomes according to the presence of EFI and total EFI days

Variable	Non-EFI group (n=17)	EFI group			P for trend
Variable	Non-EFI group (n=17)	EFI for 1 day (n=25)	EFI for 2 days (n=22)	EFI for 3 days (n=30)	P for trend
Treatment duration
Length of stay in ICU (day)	12.0 (9.0–26.0)	9.0 (6.0–17.0)	7.5 (6.0–14.0)	11.0 (6.0–13.0)	0.027
Length of stay in hospital (day)	53.0 (26.0–66.0)	23.0 (14.0–41.0)	24.0 (13.0–35.0)	20.5 (12.0–42.0)	0.013
MV free days within 28 days from the day of intubation	7 (0–23)	1 (0–23)	0 (0–25)	3 (0–22)	0.978
Time to EF initiation
Time from ICU admission to EF initiation (day)	1.4 (1.1–2.0)	1.5 (1.0–2.2)	1.3 (0.9–2.0)	1.8 (1.0–2.7)	0.348
Time from septic shock to EF initiation (day)	1.3 (0.6–1.6)	1.6 (1.2–2.0)	1.3 (0.7–2.1)	2.0 (1.0–3.0)	0.154
Nutritional variable
Amount of EF intake (kcal/day)	533.3 (433.3–633.3)	500.0 (366.7–700.0)	550.0 (433.3–900.0)	566.7 (400.0–700.0)	0.736
Percentage ratio of delivered to target kcal in EF	38.2 (32.7–48.1)	37.3 (27.0–55.7)	43.1 (33.3–58.4)	41.1 (27.7–49.7)	0.563
Average protein intake (g/day)	36.4 (30.0–47.8)	34.0 (27.4–42.3)	34.6 (26.3–44.2)	40.4 (25.3–47.4)	0.644
Concomitant administration of parenteral nutrition-	2 (11.8)	3 (12.0)	3 (13.6)	4 (13.3)	0.846
Norepinephrine equivalent dose
Dose at the time of EF Initiation (μg/kg/min)	0.075 (0.050–0.091)	0.106 (0.031–0.157)	0.071 (0.031–0.153)	0.096 (0.053–0.134)	0.568
Maximum dose on day 1 (μg/kg/min)	0.075 (0.050–0.115)	0.138 (0.062–0.206)	0.114 (0.060–0.162)	0.117 (0.075–0.167)	0.513
Maximum dose on day 2 (μg/kg/min)	0.034 (0.015–0.083)	0.086 (0.016–0.156)	0.085 (0.036–0.195)	0.113 (0.017–0.192)	0.015
Maximum dose on day 3 (μg/kg/min)	0.007 (0.000–0.066)	0.024 (0.000–0.127)	0.061 (0.008–0.118)	0.087 (0.017–0.176)	0.016

Values are presented as median (interquartile range) or number (%).

EFI: enteral feeding intolerance; ICU: intensive care unit; MV: mechanical ventilation; EF: enteral feeding.

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The impact of enteral feeding intolerance on the prognosis of patients with septic shock in South Korea

Acute Crit Care. 2025;40(2):304-312. Published online May 30, 2025

DOI: https://doi.org/10.4266/acc.000700

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The impact of enteral feeding intolerance on the prognosis of patients with septic shock in South Korea

Figure 1. Flow diagram of patient enrollment in the study. ICU: intensive care unit; EFI: enteral feeding intolerance.

Figure 2. Frequency of gastrointestinal (GI) complications associated with enteral feeding intolerance diagnosis during the first 3 days of enteral feeding.

Figure 1.

Figure 2.

The impact of enteral feeding intolerance on the prognosis of patients with septic shock in South Korea

Variable	Non-EFI group (n=17)	EFI group			P for trend
Variable	Non-EFI group (n=17)	EFI for 1 day (n=25)	EFI for 2 days (n=22)	EFI for 3 days (n=30)	P for trend
Age (yr)	71 (60–76)	69 (62–81)	71 (61–80)	68 (59–74)	0.865
Male	11 (64.7)	14 (56.0)	12 (54.5)	18 (60.0)	0.846
Body mass index (kg/m²)	21.5 (19.4–23.6)	21.7 (19.4–24.2)	21.8 (19.9–23.0)	23.4 (20.6–26.3)	0.119
Clinical frailty scale	4.0 (4.0–6.0)	4.0 (3.0–5.0)	4.5 (4.0–6.0)	4.5 (3.0–6.0)	0.460
High risk of refeeding syndrome^a)	9 (52.9)	16 (64.0)	9 (40.9)	22 (73.3)	0.319
Immunocompromised state^b)	8 (47.1)	8 (32.0)	10 (45.5)	19 (63.3)	0.100
Comorbidity
Heart failure	0	11 (44.0)	4 (18.2)	6 (20.0)	0.743
Chronic kidney disease	3 (17.6)	4 (16.0)	11 (50.0)	10 (33.3)	0.078
Diabetes mellitus	8 (47.1)	10 (40.0)	8 (36.4)	11 (36.7)	0.497
Laboratory test
Albumin (mg/dl)	2.9±0.5	3.2±0.6	2.9±0.5	2.9±0.5	0.338
BUN (mg/dl)	20.0 (15.0–26.0)	22.0 (15.0–31.0)	33.5 (20.0–51.0)	40.5 (21.0–55.0)	0.001
Creatinine (mg/dl)	0.8 (0.6–0.9)	1.0 (0.7–1.8)	1.4 (0.8–4.4)	1.8 (1.1–3.5)	0.025
Lactate (mmol/L)	1.7 (1.2–2.4)	2.3 (1.3–4.6)	2.3 (1.5–3.1)	2.4 (1.6–3.4)	0.109
MV use on ICU admission day	11 (64.7)	15 (60.0)	12 (54.5)	15 (50.0)	0.291
RRT use on ICU admission day	1 (5.9)	2 (20.0)	7 (31.8)	15 (50.0)	<0.001
APACHE II score	18.4±5.7	17.4±6.2	19.5±7.4	23.2±6.7	0.003
SOFA score	8.6±4.2	8.6±3.4	9.8±3.5	11.5±3.9	0.003
mNUTRIC score	5 (4–6)	5 (4–6)	6 (4–7)	6 (5–7)	0.004
The site of infection^c)
Pulmonary	12 (70.6)	22 (88.0)	19 (86.4)	13 (43.3)	0.009
Abdominal	3 (17.6)	2 (8)	1 (4.5)	12 (40.0)	0.023
Urinary	1 (5.9)	0	0	2 (6.6)	0.626
Skin/soft tissue	1 (5.9)	0	1 (4.5)	1 (3.3)	0.969
Catheter-related	1 (5.9)	0	0	3 (10.0)	0.305
Unknown	2 (11.8)	3 (12)	0	3 (10.0)	0.612
Mortality variable
ICU mortality	1 (5.9)	4 (16.0)	6 (27.3)	9 (30.0)	0.036
In-hospital mortality	4 (23.5)	9 (36.0)	12 (54.5)	18 (60.0)	0.007
30-Day mortality	2 (11.8)	5 (20.0)	8 (36.4)	14 (46.7)	0.004
90-Day mortality	4 (23.5)	9 (36.0)	13 (59.1)	18 (60.0)	0.006

Variable	Unadjusted HR (95% CI)	P-value	Adjusted HR (95% CI)	P-value
30-Day mortality
Age	2.739 (1.246–6.022)	0.012	3.238 (1.379–7.600)	0.007
Male sex	1.179 (0.567–2.451)	0.660	0.856 (0.393–1.863)	0.695
BMI	1.016 (0.923–1.118)	0.748	1.002 (0.899–1.117)	0.974
SOFA score	1.171 (1.063–1.291)	0.001	1.139 (1.014–1.280)	0.028
MV use on ICU admission day	1.376 (0.650–2.915)	0.404	1.500 (0.695–3.239)	0.301
RRT use on ICU admission day	2.789 (1.345–5.785)	0.006	1.026 (0.406–2.592)	0.956
Total EFI days	1.685 (1.161–2.444)	0.006	1.496 (0.992–2.258)	0.055
90–Day mortality
Age	2.396 (1.294–4.438)	0.005	2.761 (1.408–5.418)	0.003
Male sex	1.348 (0.746–2.437)	0.322	1.129 (0.605–2.108)	0.703
BMI	0.957 (0.881–1.040)	0.300	0.943 (0.859–1.035)	0.218
SOFA score	1.137 (1.049–1.131)	0.002	1.107 (1.004–1.220)	0.041
MV use on ICU admission day	1.086 (0.598–1.973)	0.786	1.182 (0.635–2.200)	0.598
RRT use on ICU admission day	2.803 (1.543–5.090)	0.001	1.377 (0.664–2.855)	0.390
Total EFI days	1.511 (1.137, 2.007)	0.004	1.400 (1.021–1.919)	0.037

Variable	Non-EFI group (n=17)	EFI group			P for trend
Variable	Non-EFI group (n=17)	EFI for 1 day (n=25)	EFI for 2 days (n=22)	EFI for 3 days (n=30)	P for trend
Treatment duration
Length of stay in ICU (day)	12.0 (9.0–26.0)	9.0 (6.0–17.0)	7.5 (6.0–14.0)	11.0 (6.0–13.0)	0.027
Length of stay in hospital (day)	53.0 (26.0–66.0)	23.0 (14.0–41.0)	24.0 (13.0–35.0)	20.5 (12.0–42.0)	0.013
MV free days within 28 days from the day of intubation	7 (0–23)	1 (0–23)	0 (0–25)	3 (0–22)	0.978
Time to EF initiation
Time from ICU admission to EF initiation (day)	1.4 (1.1–2.0)	1.5 (1.0–2.2)	1.3 (0.9–2.0)	1.8 (1.0–2.7)	0.348
Time from septic shock to EF initiation (day)	1.3 (0.6–1.6)	1.6 (1.2–2.0)	1.3 (0.7–2.1)	2.0 (1.0–3.0)	0.154
Nutritional variable
Amount of EF intake (kcal/day)	533.3 (433.3–633.3)	500.0 (366.7–700.0)	550.0 (433.3–900.0)	566.7 (400.0–700.0)	0.736
Percentage ratio of delivered to target kcal in EF	38.2 (32.7–48.1)	37.3 (27.0–55.7)	43.1 (33.3–58.4)	41.1 (27.7–49.7)	0.563
Average protein intake (g/day)	36.4 (30.0–47.8)	34.0 (27.4–42.3)	34.6 (26.3–44.2)	40.4 (25.3–47.4)	0.644
Concomitant administration of parenteral nutrition-	2 (11.8)	3 (12.0)	3 (13.6)	4 (13.3)	0.846
Norepinephrine equivalent dose
Dose at the time of EF Initiation (μg/kg/min)	0.075 (0.050–0.091)	0.106 (0.031–0.157)	0.071 (0.031–0.153)	0.096 (0.053–0.134)	0.568
Maximum dose on day 1 (μg/kg/min)	0.075 (0.050–0.115)	0.138 (0.062–0.206)	0.114 (0.060–0.162)	0.117 (0.075–0.167)	0.513
Maximum dose on day 2 (μg/kg/min)	0.034 (0.015–0.083)	0.086 (0.016–0.156)	0.085 (0.036–0.195)	0.113 (0.017–0.192)	0.015
Maximum dose on day 3 (μg/kg/min)	0.007 (0.000–0.066)	0.024 (0.000–0.127)	0.061 (0.008–0.118)	0.087 (0.017–0.176)	0.016

Table 1. Clinical characteristics of the patients according to the presence of EFI and total EFI days

Values are presented as median (interquartile range), number (%), or mean±standard deviation.

Patients at high risk of refeeding are defined as those who either have one or more of the following: a body mass index (BMI) <16 kg/m², unintentional weight loss >15% in the past three to 6 months, little or no nutritional intake for >10 days, or low levels of potassium, phosphate, or magnesium before feeding; or those who meet two or more of the following criteria: a BMI <18.5 kg/m², unintentional weight loss >10% in the past three to 6 months, little or no nutritional intake for >5 days, or a history of alcohol misuse or drug use, including insulin, chemotherapy, antacids, or diuretics;

Immunocompromised status was defined as the presence of conditions or therapies that suppress the patient's resistance to infection, including immunosuppressive therapy, chemotherapy, radiation therapy, long-term or high-dose corticosteroid use, or advanced conditions such as leukemia, lymphoma, or AIDS;

Patients could have more than one site of infection; therefore, infection sites are not mutually exclusive and may exceed the total number of patients.

Table 2. Association between EFI days and mortality

Multivariable analyses adjusted for age, sex, BMI, SOFA score, MV use on ICU admission day, RRT use on ICU admission day.

Table 3. Comparison of clinical outcomes according to the presence of EFI and total EFI days

Values are presented as median (interquartile range) or number (%).

EFI: enteral feeding intolerance; ICU: intensive care unit; MV: mechanical ventilation; EF: enteral feeding.