Implementation of an Enteral Nutrition Protocol in the Cardiac Care Unit　― A Retrospective Study of Critically Ill Cardiovascular Patients ―

Abstract

Background: Enteral nutrition (EN) is often delayed in critically ill cardiovascular patients due to concerns about bowel ischemia, especially when under vasopressor or mechanical support. We evaluated the impact of a structured EN protocol designed to promote timely and safe nutrition delivery in the Cardiac Care Unit (CCU).

Methods and Results: This single-center retrospective study compared mechanically ventilated CCU patients before (April 2019–March 2020) and after (April 2022–March 2023) protocol implementation. The protocol specified hemodynamic safety thresholds and used a peptide-based formula. Outcomes included EN-related complications, time to EN initiation, and nutritional adequacy within the first week. A total of 116 patients (58 per group) were analyzed. No significant differences were observed in vomiting (P=0.717), diarrhea (P=0.219), or bowel ischemia (P=0.364). The post-protocol group showed a significantly shorter time to EN initiation (median 39.5 vs. 76.0 h; P<0.001). By Day 5, enteral energy adequacy improved (40.8% vs. 12.3%; P<0.001), and protein adequacy increased (62.2% vs. 31.0%; P<0.001). Exploratory analyses showed no significant differences in CCU stay, ventilator-free days, or in-hospital deaths.

Conclusions: The EN protocol enabled earlier initiation and improved EN delivery in high-risk CCU patients without increasing complications, offering a safe and practical approach to narrowing the gap between guidelines and practice.

Central Figure

In cardiovascular intensive care, nutritional management is often overlooked despite its established importance in general critical care. Evidence specific to cardiovascular patients is limited, and current recommendations are largely based on guidelines from the Japanese Society of Intensive Care Medicine, European Society for Clinical Nutrition and Metabolism (ESPEN), and American Society for Parenteral and Enteral Nutrition (ASPEN), which advocate early nutritional intervention within 48 h of intensive care unit (ICU) admission for patients unable to eat orally.^1–4 Compared with parenteral nutrition (PN), enteral nutrition (EN) offers advantages such as intestinal mucosal protection and cost-effectiveness,⁵ and early EN has been associated with reduced mortality rates, shorter mechanical ventilation, and decreased ICU/hospital stay.^6,7

However, a subgroup analysis of the 2011 International Nutrition Survey revealed delayed EN initiation in Japanese ICUs, particularly for cardiovascular patients, beyond the 48-h guideline and showed markedly lower nutritional adequacy (21% of target calories vs. 52% in non-cardiovascular patients; global average: 52–64%).⁸ This conservative practice likely reflects concerns about non-occlusive mesenteric ischemia, which carries 70–100% mortality and is linked to cardiogenic shock, cardiovascular disease, and use of vasopressors.^9,10 Nevertheless, recent studies have shown that early EN, even in patients receiving vasopressors or veno-arterial extracorporeal membrane oxygenation (VA-ECMO), can reduce the 28-day mortality rate,^11,12 challenging the notion that EN should be routinely delayed in this population. Recent Japanese studies have also demonstrated that malnutrition is strongly associated with adverse outcomes in cardiovascular patients, including increased bleeding events in peripheral artery disease,¹³ and higher mortality rates in acute coronary syndrome.¹⁴

Given the gap between evidence and practice, protocol-based standardization of nutrition care is essential. In Japan, ICU nutrition protocols are implemented in only 22.2% of facilities, compared with 82.4% elsewhere,⁸ and protocol use has been shown to promote earlier feeding and greater nutritional adequacy.^15,16 As cardiovascular specialists may have less expertise in nutritional therapy than general intensivists, we developed an EN protocol for the Cardiac Care Unit (CCU) that adjusts blood pressure thresholds and administration rates to patient vulnerability. The aim of this study was to evaluate the safety and efficacy of the protocol in CCU patient care.

Methods

Study Population

This retrospective comparative study evaluated nutritional management before and after EN protocol implementation. Patients admitted to the CCU at Osaka Keisatsu Hospital between April 2019 and March 2020 (pre-protocol) and April 2022–March 2023 (post-protocol) were screened. Inclusion criteria were admission after cardiovascular surgery, admission for intrinsic cardiovascular disease, or requirement for mechanical ventilation (invasive or non-invasive). Exclusion criteria were patients with oral intake within 7 days, who died within 7 days, or had missing height data required to calculate target energy provision.

As shown in Figure 1, 277 pre-protocol patients were screened, with 219 excluded, leaving 58 for analysis; of 356 post-protocol patients, 298 were excluded, also leaving 58. In the post-protocol group, adherence was defined as initiation and progression of EN per protocol without deviation in timing or route; others were classified as non-adherent. The study was approved by the Osaka Keisatsu Hospital Ethical Committee (No. 1646), which waived written informed consent per institutional and national guidelines.

Figure 1.

Flowchart of patient selection. CCU, Cardiac Care Unit.

Nutrition Protocol

The nutrition protocol in the CCU is presented in Figure 2. It targeted mechanically ventilated patients expected to require non-oral nutrition for >2 days. EN was initiated when all protocol criteria were met: (1) intact gastrointestinal tract, (2) hemodynamic stability (including patients on mechanical circulatory support (MCS); systolic blood pressure ≥90 mmHg or mean arterial pressure (MAP) ≥65 mmHg; noradrenaline ≤0.1 μg/kg/min, dopamine ≤5 μg/kg/min, or dobutamine ≤3 μg/kg/min), and (3) gastric residual volume (GRV) <200 mL. If criteria were not met, the aspirated GRV was discarded, prokinetics or opioid reduction considered, and the patient was reassessed after 4 h (next day if unresolved). When criteria were met, EN was started at 10 mL/h with Peptamen AF (high-protein [6.3 g/100kcal], high-energy [1.5kcal/mL] formula; Nestlé Health Science, Bridgewater, NJ, USA), targeting 25 kcal/ideal body weight (IBW)/day. GRV was monitored every 8 h; if <200 mL, the EN rate was increased by 5 mL/h until the target was achieved. If ≥200 mL, prokinetics were considered and the rate was reduced by 10 mL/h (minimum 5 mL/h); persistent elevation prompted physician review.

Figure 2.

Enteral nutrition (EN) protocol in the Cardiac Care Unit. IBW, ideal body weight; MAP, mean arterial pressure.

PN was considered if target intake was unlikely within 7 days. Vomiting was managed by stepwise rate reduction and discontinuation if repeated; diarrhea by probiotics, Clostridioides difficile testing/treatment if on antibiotics, and other supportive measures. Bowel ischemia was ruled out in all cases.

Collection of Clinical Data

We collected baseline characteristics including age, sex, admission diagnosis, body weight, body mass index (BMI), creatinine, and estimated glomerular filtration rate (eGFR) for renal function, and hemoglobin A1c (HbA1c) for glucose tolerance. Severity at admission was assessed by the Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, use of MCS (i.e., intra-aortic balloon pump (IABP), VA-ECMO, Impella, and left ventricular assist device (LVAD)), and vasopressor administration (dopamine, dobutamine, noradrenaline). Nutritional risk at admission was evaluated using the modified Nutrition Risk in the Critically Ill (mNUTRIC) score.

Endpoints

Safety endpoints were the incidence of EN-related complications (vomiting, diarrhea, bowel ischemia). Efficacy endpoints were time from CCU admission to EN initiation, and adequacy of energy and protein intake within the first week. Data on vomiting, diarrhea, and bowel ischemia were extracted from medical records; vomiting and diarrhea frequency were recorded for 7 days after admission. Diarrhea was defined as ≥3 watery (Bristol 7) or loose (Bristol 6) stools per day. Bowel ischemia was identified during hospitalization from physician documentation and CT reports. “Time to initiate EN” was defined as hours from CCU admission to EN initiation. Cases in which EN was not initiated during the CCU stay were considered missing for this variable. Daily EN and PN energy/protein intakes were recorded for 7 days. Target energy was 25 kcal/IBW/day; adequacy was calculated as actual intake/target. Target protein was 1.2 g/IBW/day, with adequacy defined similarly. Exploratory analyses included CCU length of stay, ventilator-free days, and in-hospital death. Ventilator-free days were defined as the number of days from successful liberation from invasive mechanical ventilation to Day 28 after CCU admission, with patients who died before Day 28 or who required ventilation for >28 days assigned a value of zero.¹⁷ Hemodynamic changes around EN initiation were also assessed: MAP and heart rate (HR) were collected daily from 3 days before to 3 days after EN initiation.

Statistical Analysis

All analyses were performed using R software (version 4.1.1; R Foundation for Statistical Computing, Vienna, Austria), with P<0.05 considered statistically significant. Continuous variables are presented as median [interquartile range (IQR)] and compared using the Mann-Whitney U-test, and categorical variables as counts (%) and compared using Fisher’s exact test. Admission diagnoses were classified into 7 categories (heart failure, ischemic heart disease, valve disease, aortic disease, arrhythmia, pulmonary hypertension/embolism, others) and compared using Fisher’s exact test. The mortality rate was assessed by logistic regression, with odds ratios (ORs) and 95% confidence intervals (CIs), and confirmed using Fisher’s exact test. A post hoc subgroup analysis was performed in patients receiving MCS (IABP, VA-ECMO, Impella, LVAD), comparing the same endpoints between groups using these methods. A sensitivity analysis was also conducted in the post-protocol group, comparing protocol-adherent patients with the pre-protocol cohort.

Results

Baseline Clinical Characteristics

Table 1 summarizes the patients’ baseline characteristics at CCU admission and clinical status at EN initiation. The median age was 77.5 years [IQR, 71.0–81.0] in the pre-protocol group and 74.0 years [IQR, 61.2–80.0] in the post-protocol group (P=0.144). Sex distribution, BMI, renal function, HbA1c, and mNUTRIC scores were similar between groups. SOFA scores did not differ significantly, but APACHE II scores were higher in the post-protocol group (P=0.044). The distribution of admission diagnoses was comparable (P=0.108). At EN initiation, the post-protocol group had a higher MAP (P=0.009) and higher noradrenaline dosage (P<0.001), while HR, use of MCS, and other catecholamine use or dosage were similar between groups. Baseline characteristics by protocol adherence within the post-protocol group are shown in Supplementary Table 1.

Table 1.

Baseline Characteristics at CCU Admission and Clinical Status at EN Initiation

Variable	Pre-protocol (N=58)	Post-protocol (N=58)	P value
Clinical profile at CCU admission
Age (years)	77.5 [71.0–81.0]	74.0 [61.2–80.0]	0.144
Sex: male (n)	38 (65.5)	39 (67.2)	1.000
Body weight (kg)	55.5 [48.8–64.7]	61.2 [49.7–71.0]	0.185
BMI (kg/m2)	21.9 [18.9–25.8]	23.9 [20.8–26.5]	0.076
Creatinine (mg/dL)	1.1 [0.9–1.7]	1.0 [0.9–1.4]	0.836
eGFR (mL/min/1.73 m2)	46.6 [28.3–59.8]	45.9 [35.6–61.4]	0.853
HbA1c (%)	5.9 [5.6–6.6]	6.2 [5.8–7.0]	0.215
SOFA	7.0 [4.0–8.8]	6.0 [5.0–8.0]	0.960
APACHE II	14.0 [10.0–21.0]	17.0 [13.0–22.0]	0.044
mNUTRIC	4.0 [3.0–5.0]	4.0 [3.0–5.0]	0.102
Admission diagnosis			0.108
Heart failure	12 (20.7)	26 (44.8)
Ischemic heart disease	16 (27.6)	14 (24.1)
Valve disease	12 (20.7)	8 (13.8)
Aortic disease	10 (17.2)	6 (10.3)
Arrythmia	1 (1.7)	1 (1.7)
Pulmonary hypertension, embolism	2 (3.4)	2 (3.4)
Other	5 (8.6)	1 (1.7)
Hemodynamic and therapeutic status at EN initiation
Mean arterial pressure (mmHg)	74.8 [63.7–85.2]	82.3 [76.7–91.1]	0.009
Heart rate (beats/min)	84.5 [71.1–98.0]	86.0 [70.0–99.0]	0.897
Mechanical circulatory support (n)
IABP	11 (19.0)	9 (15.5)	0.806
VA-ECMO	13 (22.4)	13 (22.4)	1.000
Impella	11 (19.0)	10 (17.2)	1.000
LVAD	1 (1.7)	0 (0.0)	1.000
Catecholamine use (n)
DOA	6 (10.3)	2 (3.4)	0.272
DOB	20 (34.4)	26 (44.8)	0.343
AD	0 (0.0)	2 (3.4)	0.496
NAD	8 (13.8)	14 (24.1)	0.236
Catecholamine dosage (μg/kg/min)
DOA	2.50 [2.00–4.35]	2.70 [2.05–3.35]	0.867
DOB	3.00 [2.28–4.12]	2.35 [1.83–3.38]	0.085
NAD	0.07 [0.03–0.08]	0.50 [0.27–0.75]	<0.001

HbA1c data were available for 50 patients in the pre-protocol group and 26 patients in the post-protocol group. MAP and HR data at EN initiation were available for 38 patients in the pre-protocol group and 54 patients in the post-protocol group. Data are expressed as median [interquartile range]. AD, adrenaline; APACHE II, Acute Physiology and Chronic Health Evaluation II; BMI, body mass index; CCU, Cardiac Care Unit; DOA, dopamine; DOB, dobutamine; eGFR, estimated glomerular filtration rate; EN, enteral nutrition; HR, heart rate; IABP, intra-aortic balloon pump; LVAD, left ventricular assist device; MAP, mean arterial pressure; mNUTRIC, modified Nutrition Risk in the Critically Ill; NAD, noradrenaline; SOFA, Sequential Organ Failure Assessment; VA-ECMO, veno-arterial extracorporeal membrane oxygenation.

Safety of Nutritional Protocol

Table 2 summarizes the gastrointestinal complications. Vomiting occurred in 5.2% of pre-protocol and 8.5% of post-protocol patients (P=0.717). Diarrhea decreased from 22.4% to 12.0% (P=0.219). The incidence of bowel ischemia was 6.9% in the pre-protocol group and 1.7% in the post-protocol group (P=0.364). Hemodynamic monitoring from Day −3 to Day +3 (Figure 3) showed MAP consistently above the protocol-defined threshold of 65 mmHg and no abrupt HR changes after EN initiation.

Table 2.

Frequencies of Vomiting, Diarrhea, and Bowel Ischemia

Complication	Pre-protocol (N=58)	Post-protocol (N=58)	P value
Vomiting	3 (5.2%)	5 (8.5%)	0.717
Diarrhea	13 (22.4%)	7 (12.0%)	0.219
Bowel ischemia	4 (6.9%)	1 (1.7%)	0.364

Data are expressed as n (%).

Figure 3.

Hemodynamic changes (mean arterial pressure (MAP) and heart rate (HR)) around enteral nutrition (EN) initiation. (A) Time course of MAP from Day −3 to Day +3 relative to EN initiation in the pre-protocol and post-protocol cohorts. The dashed line denotes the prespecified safety threshold of MAP=65 mmHg for EN initiation. Group-level values remained at or above this threshold without post-initiation deterioration. (B) Time course of HR from Day −3 to Day +3 relative to EN initiation in the pre-protocol and post-protocol cohorts.

Efficacy of Nutritional Protocol

The time to initiating EN was significantly shorter in the post-protocol group compared with the pre-protocol group (median 39.5 h [IQR, 20.0–69.5] vs. median 76.0 h [IQR, 48.5–141.5]; P<0.001, Wilcoxon test) (Figure 4). As shown in Figure 5, the total energy adequacy did not differ significantly between groups, whereas enteral energy adequacy was higher in the post-protocol group from Day 2 to Day 6 (all P≤0.001), peaking on Day 5 (40.8% vs. 12.3%, P<0.001), and became similar by Day 7. Total protein adequacy was higher in the post-protocol group from Day 3 to Day 6, with the largest difference on Day 5 (62.2% vs. 31.0%, P<0.001). Enteral protein adequacy was higher from Day 2 to Day 7 (all P<0.001 for Days 2–6, P=0.034 for Day 7), again peaking on Day 5 (49.8% vs. 8.4%, P<0.001) (Supplementary Table 2).

Figure 4.

Comparison of time to initiate enteral nutrition (EN) in the pre-protocol (n=47) and post-protocol (n=57) groups. N differs due to missing data from patients without EN initiation during CCU stay. Box plots show the median (horizontal line), interquartile range (box), and range up to 1.5×interquartile range (whiskers).

Figure 5.

Adequacy of energy and protein intake during first 7 days in the Cardiac Care Unit. (A) Total energy adequacy (enteral plus parenteral nutrition, EN+PN). (B) Enteral energy adequacy (EN only). (C) Total protein adequacy (EN+PN). (D) Enteral protein adequacy (EN only). Box plots indicate the median (horizontal line), interquartile range (box), range up to 1.5×interquartile range (whiskers); × in boxes=mean. Blue boxes: pre-protocol group; red boxes: post-protocol group.

Exploratory Clinical Outcomes

In the overall cohort of 116 mechanically ventilated patients, the median CCU stay was 12.5 days [IQR, 9.0–30.2] in the pre-protocol group and 17.5 days [IQR, 12.0–28.8] in the post-protocol group (P=0.103). The median number of ventilator-free days was 18.5 [IQR, 1.3–23.0] vs. 17.5 [IQR, 0.0–22.0], respectively (P=0.183). The in-hospital mortality rate was 20.7% vs. 17.2%; logistic regression showed no significant difference (OR 0.80, 95% CI 0.31–2.03, P=0.636), confirmed by Fisher’s exact test (P=0.813).

MCS Subgroup Findings

In the predefined subgroup of patients who received MCS (pre-protocol group: n=27; post-protocol group: n=19; total n=46), the time to EN initiation was significantly shorter in the post-protocol group (median 41.0 h [IQR, 26.5–68.0]) compared with the pre-protocol group (median 72.0 h [IQR, 55.0–100.0]; P=0.005, Wilcoxon test), consistent with the overall cohort. Nutritional adequacy of both energy and protein during the first 7 days was consistently higher in the post-protocol group, with statistical significance reached for multiple days, particularly for EN (Supplementary Table 3). Regarding clinical outcomes, the median CCU stay was longer in the post-protocol group (23.0 days [IQR, 18.5–44.5]) than in the pre-protocol group (14.0 days [IQR, 10.5–32.0]; P=0.014). The number of ventilator-free days tended to be lower in the post-protocol group (6.0 days [IQR, 0.0–15.5]) compared with the pre-protocol group (15.0 days [IQR, 0.0–22.0]; P=0.158). The in-hospital mortality rate was 29.6% in the pre-protocol group and 26.3% in the post-protocol group, with no significant difference (OR 0.85; 95% CI, 0.23–3.15; P=0.806), and Fisher’s exact test confirmed this result (P=1.000). The incidence of gastrointestinal complications did not differ significantly between groups (Table 3).

Table 3.

Frequencies of Vomiting, Diarrhea, and Bowel Ischemia Under Mechanical Circulatory Support

Complication	Pre-protocol (N=27)	Post-protocol (N=19)	P value
Vomiting	1 (3.7%)	4 (21.1%)	0.144
Diarrhea	6 (22.2%)	3 (15.8%)	0.716
Bowel ischemia	3 (11.1%)	0 (0.0%)	0.257

Data are expressed as n (%).

Sensitivity Analysis for Protocol Adherence

In the sensitivity analysis restricted to protocol-adherent patients in the post-protocol group (n=37), baseline characteristics were generally comparable between adherent and non-adherent patients (Supplementary Table 3). Time to EN initiation was significantly shorter in the adherent group compared with the pre-protocol group (28.0 h [IQR, 16.0–46.0] vs. 76.0 h [IQR, 48.5–141.5]; P<0.001). Enteral energy adequacy was significantly higher from Day 2 through Day 6 (all P<0.001), with the largest difference on Day 5 (12.3% [IQR, 0.0–41.0] vs. 63.2% [IQR, 36.5–91.9]; P<0.001). Total protein adequacy and enteral protein adequacy were also significantly higher from Day 3 through Day 6 (all P<0.001), with the most pronounced difference on Day 5 (total protein: 31.0% [IQR, 10.5–59.8] vs. 83.8% [IQR, 52.9–131.6]; enteral protein: 8.4% [IQR, 0.0–35.8] vs. 83.4% [IQR, 46.7–121.3]; both P<0.001). The incidence of gastrointestinal adverse events did not differ significantly between the adherent post-protocol group and the pre-protocol group: vomiting occurred in 8.1% vs. 5.2% of patients (P=0.675), diarrhea in 13.5% vs. 22.4% (P=0.421), and bowel ischemia in 0% vs. 6.9% (P=0.154).

Discussion

Rationale for Protocol Development

This protocol was designed to prioritize patient safety while advancing EN cautiously. For initiation, we set a MAP threshold of 65 mmHg, higher than the 60 mmHg suggested for cardiogenic shock, and a GRV threshold of 200 mL/8 h, lower than the 500 mL/6 h used in some guidelines, based on multidisciplinary consensus informed by existing guidelines and expert opinion.^2,18,19 In the absence of high-level evidence specific to critically ill cardiovascular patients, these conservative, practical thresholds were chosen to minimize the risk of gastrointestinal hypoperfusion or feeding intolerance while ensuring feasibility across diverse hospital settings. A structured complication management algorithm and the use of prokinetic agents such as metoclopramide were incorporated to enhance EN tolerance and prevent adverse events.^2,19 As for formula selection, a peptide-based product was chosen to improve absorption in patients with intestinal edema, a common feature of heart failure, and because it reduces GRV vs. whole-protein formulas.²⁰ In addition, a high-calorie formula (1.5 kcal/mL) was selected to meet energy requirements while limiting fluid volume, which is essential in heart failure management. Based on these factors, Peptamen AF was implemented in the protocol.

Implications for Early EN Implementation

Early EN within 48 h of ICU admission is widely recommended by critical care guidelines across multiple countries,^1–4 and supported by large-scale studies, including Japan’s national database analyses.^11,12 These studies demonstrate reductions in multiple organ failure, ICU/hospital stay, and mortality rates, with notable benefits in high-risk groups such as VA-ECMO patients¹¹ and ventilated shock patients on low- or medium-dose noradrenaline.¹² In our cohort, 43.1% received noradrenaline and 22.4% VA-ECMO, underscoring the relevance of early EN in unstable cardiovascular patients. Although traditionally avoided due to concerns over gastrointestinal hypoperfusion, recent evidence supports the survival benefit of early EN. We implemented a structured protocol to overcome perceived barriers, reducing the median time to EN initiation from 76.0 to 39.5 h, and enabling most patients to start within the 48-h guideline target. Continuous MAP and HR monitoring from 3 days before to after EN confirmed MAP remained ≥65 mmHg with no abrupt HR changes, supporting the hemodynamic safety of protocol-based early EN.

Practical Balance Between EN and PN

Optimal nutrition delivery in critically ill patients remains a challenge, as both EN and PN have distinct advantages and risks. In our study, the pre-protocol group showed a high dependence on PN, whereas after protocol implementation, energy and protein adequacy from EN alone was significantly higher from Day 2 onward. This improvement was likely attributable, at least in part, to the higher protein content of the EN formula used in the protocol (Peptamen AF, 6.3 g/100 kcal) compared with the commonly used PN formula (Elneopa-NF No.1, standard-protein [3.6 g/100 kcal], standard-energy [1.0 kcal/mL] formula; Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan). EN requires gradual volume advancement and is frequently interrupted for clinical procedures; indeed, on Day 7, total energy delivery in the study cohort was slightly reduced due to such interruptions. However, a randomized trial found no increase in extubation failure rates when EN was continued until extubation compared with fasting for 6 h with gastric suctioning (17.2% vs. 17.5%),²¹ suggesting that routine discontinuation may be unnecessary.

PN, by contrast, can be initiated at full volumes immediately, but carries a risk of overfeeding. In the pre-protocol group, some patients exceeded 150% adequacy, and the EPaNIC trial similarly reported prolonged ICU stay and increased complications in patients receiving combined EN and PN,²² likely due to overfeeding. Acute-phase overfeeding may be harmful by suppressing autophagy, a process essential for recovery.^23,24 Such concerns about PN-related harms have historically contributed to guidelines recommending EN over PN.¹⁹ However, in its 2022 revision, ASPEN reclassified PN as equivalent to EN provided early initiation is ensured, based on large trials (CALORIES,²⁵ NUTRIREA-2²⁶) showing no significant differences in mortality or infection rates between the 2 routes.⁴ These findings underscore that the timing and appropriateness of nutritional support are more important than the specific delivery route. Our protocol achieved a balance, promoting gradual EN advancement while avoiding PN-related overfeeding, and a flexible, patient-centered integration of both EN and PN may represent the most effective approach moving forward.

Exploratory Clinical Outcomes and Implications

Exploratory analyses of CCU stay, ventilator-free days, and in-hospital deaths revealed no significant group differences. Given the retrospective design and limited sample size, these findings should be interpreted with caution. Although the protocol clearly improved process outcomes such as earlier initiation and greater adequacy of enteral feeding, its impact on clinical outcomes remains uncertain. Importantly, the absence of excess complications suggests that protocol implementation did not compromise patient safety. In the predefined MCS subgroup, EN was initiated earlier and achieved greater nutritional adequacy without an increase in gastrointestinal complications, suggesting potential applicability even in patients receiving advanced circulatory support. However, the longer CCU stay observed in the post-protocol group should be interpreted cautiously, as this exploratory finding may have been influenced by the small sample size, higher baseline severity, and residual confounding. Given these limitations, the clinical significance of this result remains uncertain, and larger, prospective studies will be required to clarify the impact of protocol-based early EN in this high-risk subgroup.

Study Limitations

First, this was a single-center, retrospective study with a relatively small sample size, which limits the generalizability of the findings and increases susceptibility to bias. In addition, the study was underpowered to detect rare but clinically important safety events such as bowel ischemia. Nevertheless, the findings may serve as a pilot for a future multicenter trial. When expanding to multiple centers, balancing standardization with adaptation to local practices will be essential to enhance adherence and effectiveness. Second, in the post-protocol group, adherence to the EN protocol was only 63.8%, and non-adherence was determined at the discretion of the attending physician. Such variability in implementation may have introduced selection bias and reduced the internal validity of group comparisons. Furthermore, patients in the post-protocol group had significantly higher APACHE II scores at baseline, suggesting greater illness severity. These differences raise the possibility of residual confounding, and the observed effects may partly reflect underlying patient heterogeneity rather than the protocol itself. Third, the primary endpoints were process measures (i.e., timing of EN initiation and nutritional adequacy) rather than hard clinical outcomes such as death or ICU length of stay. These represent important first steps for evaluating feasibility and safety, but future studies should examine their impact on long-term outcomes such as ICU-acquired weakness. Fourth, target energy intake was calculated using a simple weight-based equation rather than indirect calorimetry (IC). This approach was consistent with ESPEN and ASPEN guidelines^3,4 when IC is unavailable. Nevertheless, the use of IC may enable more precise determination of energy targets and has been associated with improved 60-day mortality rates in critically ill patients.²⁷ If feasible, future protocol revisions should incorporate IC to optimize individualized energy targets. Finally, as a retrospective pilot study, no formal sample size calculation was performed, and the study was underpowered to detect rare but clinically important adverse events such as bowel ischemia. Confirmation of safety will require adequately powered prospective multicenter studies.

Conclusions

Our study demonstrated that implementing a structured EN protocol in cardiovascular critical care was feasible and improved the timing and adequacy of enteral feeding without increasing gastrointestinal complications, including bowel ischemia. These findings address a common concern regarding the safety of early EN in critically ill cardiovascular patients. However, the study was not powered to detect differences in clinical outcomes such as death, ventilator-free days, or CCU stay, and these effects remain uncertain. Confirmation in larger, prospective, multicenter studies will be required to establish the protocol’s impact on patient-centered outcomes.

Acknowledgments

The authors thank Ayaka Murakami, Tomoe Yamamoto, Ayako Fukao, and Yoko Inoue for their invaluable support in data collection and management.

Sources of Funding

None.

Disclosures

The authors declare that there are no conflicts of interest or sources of funding related to this manuscript.

IRB Information

This study was approved by the Osaka Keisatsu Hospital Ethical Committee (Approval No. 1646).

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circrep.CR-25-0113

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