The impact of compliance with an enhanced recovery after surgery protocol on short-term outcomes in patients undergoing hepatectomy

Abstract

Background

Enhanced recovery after surgery (ERAS) protocols are multimodal, evidence-based pathways designed to attenuate the surgical stress response and accelerate recovery. While ERAS principles have been successfully applied in various surgeries, the impact of overall protocol compliance on outcomes after liver resection, a procedure with unique physiological demands, requires further elucidation. This study aimed to assess the effect of adherence to an ERAS protocol on short-term postoperative outcomes in patients undergoing hepatectomy.

Materials and methods

This retrospective analysis included 156 patients who underwent elective hepatectomy at a single center from 2020 to 2024. All patients were managed according to a standardized 20-item ERAS protocol. Overall compliance was calculated as the percentage of protocol elements delivered per patient. Patients were stratified into high-compliance, defined as 70% or greater, with 98 patients, and low-compliance, defined as less than 70%, with 58 patients, based on the median compliance rate. Primary outcomes were postoperative complications within 30 days, graded by the Clavien-Dindo classification, and length of postoperative hospital stay. Secondary outcomes included time to first flatus, postoperative ileus, readmission rate, and Comprehensive Complication Index.

Results

The high-compliance group demonstrated significantly fewer overall complications, 24.5% versus 50.0%, and major complications, 6.1% versus 19.0%. The median length of stay was substantially shorter in the high-compliance group, 6 days compared to 9 days. Multivariate analysis identified high ERAS compliance as an independent protective factor against major complications, with an odds ratio of 0.32, and prolonged length of stay, with an odds ratio of 0.24. Time to gastrointestinal recovery was also faster in the high-compliance group. The overall readmission rate was similar between groups.

Conclusions

High overall compliance with a multimodal ERAS protocol is independently associated with reduced postoperative morbidity and shorter hospital stay following hepatectomy. These findings underscore the importance of strict adherence to ERAS elements throughout the perioperative journey. Efforts should be directed towards optimizing compliance through multidisciplinary teamwork and patient engagement to maximize the benefits of ERAS pathways in liver surgery.

Nomenclature

ASA

American society of anesthesiologists

AUC

Area under the curve

BMI

Body mass index

CCI

Comprehensive complication index

CI

Confidence interval

ERAS

Enhanced recovery after surgery

IQR

Interquartile range

LOS

Length of stay

OR

Odds ratio

PONV

Postoperative nausea and vomiting

SD

Standard deviation

Introduction

Liver resection remains the cornerstone of curative-intent treatment for primary and secondary hepatic malignancies [1]. Contemporary perioperative management has significantly evolved, yet hepatectomy continues to pose a substantial physiological insult, with postoperative complication rates reported between 20% and 40% even in high-volume centers [2]. These complications, ranging from surgical site infections and postoperative ileus to life-threatening liver failure and sepsis, not only impede immediate recovery and prolong hospitalization but also may adversely affect long-term oncological outcomes and survival [3], [4]. The imperative to develop and refine strategies that effectively mitigate surgical stress and promote rapid, uncomplicated convalescence is therefore a central focus in modern hepatobiliary surgery, driving the adoption of standardized care pathways [5].

The enhanced recovery after surgery (ERAS) paradigm represents a transformative shift in perioperative care, moving away from traditional, often dogmatic practices towards a holistic, evidence-based, and multimodal approach [6]. Since their inception in colorectal surgery, ERAS protocols have been systematically adapted and validated across a spectrum of surgical specialties, including major hepatic resection [7]. These comprehensive protocols encompass a bundle of interventions spanning the entire perioperative timeline. Core elements typically include structured preoperative counseling and nutritional optimization, avoidance of prolonged fasting and mechanical bowel preparation, standardized anesthetic regimens favoring short-acting agents and multimodal opioid-sparing analgesia, goal-directed fluid management, emphasis on minimally invasive techniques, prompt removal of catheters and drains, and the enforced initiation of early oral intake and mobilization [8]. The synergistic objective of these components is to blunt the catabolic stress response and associated organ dysfunction, thereby preserving physiological reserve and accelerating functional recovery [9].

While the individual elements constituting ERAS for liver surgery are supported by growing evidence, and several international society guidelines have been promulgated [7], [10], the consistent translation of these evidence-based items into daily clinical practice remains a formidable challenge. A pivotal, and sometimes underemphasized, determinant of the success of an ERAS pathway is not merely its existence as a document but the actual degree of adherence or compliance achieved by the entire multidisciplinary care team and the patient themselves [11]. Compelling evidence from other surgical domains increasingly indicates that higher overall compliance with ERAS protocols is correlated in a dose-response manner with superior clinical outcomes [12], [13]. However, within the specific context of hepatectomy-a procedure characterized by unique metabolic demands, fluid shifts, and potential for distinct complications such as post-hepatectomy liver failure-the quantitative impact of aggregate ERAS compliance on short-term outcomes warrants more robust and definitive characterization, with the existing literature sometimes presenting conflicting results or being constrained by limited sample sizes [14], [15].

Moreover, the operational definition of high versus low compliance is heterogeneous across studies, and the optimal compliance threshold associated with a significant clinical benefit in the setting of liver surgery is not yet standardized [16]. A considerable number of prior investigations have dichotomized the analysis into ERAS versus traditional care, rather than evaluating outcomes across a continuum of compliance. This binary approach potentially obscures the full efficacy of ERAS, as suboptimal adherence might lead to the erroneous conclusion that the pathway itself is ineffective [17]. Consequently, a meticulous, quantitative analysis of compliance and its graded relationship with patient outcomes is essential to validate the ERAS concept in hepatectomy and to pinpoint specific targets for quality improvement initiatives within the pathway [18].

This study was therefore designed to address this evidence gap by conducting a rigorous evaluation of the impact of overall compliance with a comprehensive, 20-item ERAS protocol on short-term postoperative outcomes in a consecutive, well-characterized cohort of patients undergoing hepatectomy. We hypothesized that higher overall compliance with the ERAS protocol would be independently associated with a significant reduction in postoperative complications and a shorter length of hospital stay, even after adjusting for pertinent patient- and surgery-related confounding factors.

Materials and methods

Study design and population

This single-center, retrospective cohort study was approved by Affiliated Hospital of Jiangnan University Review Board with a waiver of informed consent. We screened the electronic medical records of all adult patients, 18 years or older, who underwent elective hepatectomy between January 1, 2020, and December 31, 2024. The initial search, based on procedure codes, identified 183 potential cases. The patient selection process is detailed in Fig. 1. Exclusion criteria were emergency surgery, combined resection of other major organs such as simultaneous colorectal or pancreatic resection, American Society of Anesthesiologists (ASA) physical status class V, and incomplete medical records precluding accurate calculation of ERAS compliance. The final study cohort consisted of 156 patients.

Fig. 1.

Patient selection flowchart. The diagram illustrates the stepwise inclusion and exclusion process leading to the final study cohort of 156 patients.

The ERAS protocol and compliance assessment

A standardized, institution-specific ERAS protocol for hepatectomy, comprising 20 key evidence-based elements, was fully implemented across the department in January 2020. The elements were logically categorized into preoperative, intraoperative, and postoperative phases, as detailed in Table 1. Data for each element were systematically extracted from anesthesia records, nursing charts, physician progress notes, and medication administration records. Patient compliance was calculated as the percentage of successfully delivered protocol elements. For example, a patient who missed four elements had a compliance of 80%. The median compliance rate of the entire cohort was 70%, which was chosen as the cutoff for dichotomization based on its use as a common threshold in prior ERAS compliance studies [19] and because it represented a natural division in our data distribution. Additionally, a sensitivity analysis using alternative cutoffs (65% and 75%) yielded consistent direction of effects, supporting the robustness of the 70% threshold. Based on this median, patients were dichotomized into a high-compliance group (≥70%) and a low-compliance group (<70%) for the primary comparative analysis.

Table 1.

The 20-item Enhanced Recovery After Surgery protocol for hepatectomy and overall compliance rates.

Phase	ERAS element	Description	Overall compliance, %
Preoperative	Preoperative counseling	Structured information on ERAS pathway and expectations	88.5
	No bowel preparation	Avoidance of mechanical bowel preparation	95.5
	Carbohydrate loading	Oral carbohydrate drink 2–3 h pre-anesthesia	72.4
	No prolonged fasting	Solid food until 6 h, clear fluids until 2 h before surgery	91.0
	Preemptive analgesia	Administration of preemptive non-opioid analgesics	84.0
	Thromboprophylaxis	Pharmacological prophylaxis administered preoperatively	96.2
Intraoperative	Standardized antibiotic prophylaxis	Timely administration of antibiotics	98.7
	Short-acting anesthesia	Use of short-acting anesthetic agents	94.9
	PONV prophylaxis	Multimodal antiemetic prophylaxis	90.4
	Normothermia	Active warming to maintain core temperature > 36 °C	86.5
	Goal-directed fluid therapy	Use of stroke volume variation or other parameters to guide fluid administration	65.4
	Avoidance of salt/water overload	Restrictive intraoperative fluid strategy	70.5
	Minimally invasive approach	Laparoscopic or robotic resection attempted	58.3
	No routine abdominal drainage	Avoidance of drain placement or early removal by postoperative day 3	62.8
Postoperative	Multimodal, opioid-sparing analgesia	Regular non-opioid analgesics; opioids only as rescue	78.2
	Early removal of urinary catheter	Removal on postoperative day 1 or 2	75.6
	Early oral intake	Clear fluids on day 0, solid food on day 1	81.4
	Early mobilization	Mobilization out of bed for at least 2 h on postoperative day 1	69.9
	Prevention of ileus	Use of chewing gum or laxatives if no bowel movement by day 2	66.0
	Audit and feedback	Regular review of compliance and outcomes within the team	N/A

PONV, Postoperative nausea and vomiting. Compliance for the audit and feedback element was not calculated per patient.

Data collection

Data were collected using a standardized, pre-piloted electronic case report form. Baseline demographic and clinical variables included age, gender, body mass index (BMI), ASA classification, specific comorbidities such as diabetes and cardiovascular disease, primary diagnosis indicating hepatectomy, and preoperative serum albumin level. Surgery-related variables encompassed the type of hepatectomy, classified as minor for resection of fewer than three Couinaud segments versus major for resection of three or more segments, surgical approach, total duration of surgery from incision to closure, and intraoperative estimated blood loss.

Outcome measures

The primary outcomes were postoperative complications occurring within 30 days after surgery, graded according to the Clavien-Dindo classification, and length of postoperative hospital stay (LOS) [20]. Complications of Grade II, requiring pharmacological treatment, and above were considered clinically relevant. Major complications were specifically defined as Grade III or higher, requiring surgical, endoscopic, or radiological intervention, or life-threatening. The Comprehensive Complication Index (CCI) was also calculated, providing a continuous scale from 0 to 100 that integrates all complications weighted by their severity [21]. Secondary outcomes included time to first flatus in days, incidence of postoperative ileus defined as the need for nasogastric tube insertion after surgery or failure to tolerate oral diet by postoperative day 4 in the absence of mechanical obstruction, and 30-day readmission rate to any hospital.

Statistical analysis

Data analysis used SPSS 28.0 and R 4.3.0. Continuous data are shown as mean ± SD or median [IQR], and categorical data as n (%). Group comparisons used t, Mann-Whitney U, Chi-square, or Fisher's exact tests. Multivariate logistic regression identified predictors of major complications and prolonged hospital stay (>7 days). Variables with a P value less than 0.1 in univariate analysis and clinically relevant factors were included in the models. Results are reported as adjusted odds ratios with 95% confidence intervals, with statistical significance set at p < 0.05.

Results

Patient characteristics and perioperative data

The final cohort of 156 patients had a median overall ERAS compliance of 70%. Based on this median, 98 patients were classified into the high-compliance group and 58 into the low-compliance group. The baseline demographic and clinical characteristics were well-balanced between the two groups, with no statistically significant differences observed in age, gender, BMI, ASA status distribution, prevalence of key comorbidities, or preoperative serum albumin levels (Table 2). Similarly, all key perioperative variables, including the proportion of major hepatectomies performed, the utilization of a minimally invasive approach, the mean operation time, and the median estimated blood loss, were comparable between the groups.

Table 2.

Baseline demographic and perioperative characteristics.

Characteristic	Total (n = 156)	High compliance (n = 98)	Low compliance (n = 58)	P value
Age, years, mean ± SD	62.5 ± 10.8	61.8 ± 11.2	63.8 ± 10.1	0.265
Male sex, n (%)	89 (57.1)	54 (55.1)	35 (60.3)	0.520
BMI, kg/m2, mean ± SD	24.1 ± 3.5	23.9 ± 3.4	24.4 ± 3.7	0.387
ASA classification, n (%)				0.688
I / II	112 (71.8)	72 (73.5)	40 (69.0)
III / IV	44 (28.2)	26 (26.5)	18 (31.0)
Preoperative Albumin, g/L, mean ± SD	38.5 ± 4.2	38.8 ± 4.0	38.0 ± 4.5	0.241
Major hepatectomy, n (%)	67 (43.0)	40 (40.8)	27 (46.6)	0.485
Minimally invasive approach, n (%)	62 (39.7)	43 (43.9)	19 (32.8)	0.169
Operation time, min, mean ± SD	215 ± 78	208 ± 75	228 ± 82	0.112
Blood loss, ml, median (IQR)	400 (200–650)	380 (180–600)	450 (250–700)	0.095

BMI, Body mass index; ASA, American Society of Anesthesiologists; IQR, Interquartile range.

Comparative analysis of postoperative outcomes

The analysis of postoperative outcomes revealed significant advantages for the high-compliance group across multiple domains (Table 3). The overall incidence of any complication was markedly lower in the high-compliance group, at 24.5% compared to 50.0%. The high-compliance group had a lower rate of major complications (6.1%) than the comparison group (19.0%). The median CCI was also significantly lower in the high-compliance group. The median postoperative LOS was three days shorter in the high-compliance group. Regarding gastrointestinal recovery, the time to first flatus was significantly shorter in the high-compliance group, and the incidence of postoperative ileus was substantially lower. The 30-day readmission rates were low and comparable between the two groups.

Table 3.

Comparison of postoperative outcomes between groups.

Outcome	Total (n = 156)	High compliance (n = 98)	Low compliance (n = 58)	P value
Any complication (Clavien-Dindo ≥II), n (%)	53 (34.0)	24 (24.5)	29 (50.0)	<0.001
Major complication (Clavien-Dindo ≥III), n (%)	17 (10.9)	6 (6.1)	11 (19.0)	0.012
Comprehensive Complication Index, median (IQR)	0 (0–20.9)	0 (0–8.7)	8.7 (0–26.2)	0.002
Length of stay, days, median (IQR)	7 (6–10)	6 (5–8)	9 (7–12)	<0.001
Time to first flatus, days, mean ± SD	2.7 ± 1.0	2.5 ± 0.9	3.1 ± 1.2	0.001
Postoperative ileus, n (%)	13 (8.3)	4 (4.1)	9 (15.5)	0.012
30-day readmission, n (%)	9 (5.8)	5 (5.1)	4 (6.9)	0.744

Data are presented as n (%), mean ± standard deviation, or median (interquartile range). P values are from Student's t-test, Mann-Whitney U test, Chi-square test, or Fisher's exact test as appropriate. CCI, Comprehensive Complication Index; IQR, interquartile range; LOS, length of stay.

Independent predictors of adverse outcomes

Multivariate logistic regression analyses were performed to isolate the independent effect of ERAS compliance (Table 4). For the outcome of major complications, high ERAS compliance remained a strong and statistically significant independent protective factor after adjustment, with an adjusted odds ratio of 0.32. Major hepatectomy was confirmed as a significant independent risk factor. For the outcome of prolonged LOS, high ERAS compliance was again a powerful independent protective factor, with an adjusted odds ratio of 0.24. Other significant independent predictors for prolonged LOS included undergoing a major hepatectomy and the occurrence of any complication.

Table 4.

Multivariate logistic regression analysis for independent predictors of major complications and prolonged length of stay.

Outcome/variable	Adjusted OR	95% CI	P value
Major complication (Clavien-Dindo ≥III)
High ERAS Compliance	0.32	0.12–0.83	0.019
Major Hepatectomy	3.55	1.25–10.10	0.017
Prolonged LOS (>7 days)
High ERAS Compliance	0.24	0.11–0.51	<0.001
Major Hepatectomy	4.12	1.99–8.54	<0.001
Any Complication (Clavien-Dindo ≥II)	5.88	2.78–12.44	<0.001

OR, Odds ratio; CI, Confidence interval; LOS, Length of stay. Reference categories are Low ERAS Compliance, Minor Hepatectomy, and No Complication/Clavien-Dindo I.

Subgroup analysis by hepatectomy extent

To assess the consistency of the ERAS compliance effect across different surgical complexities, a prespecified subgroup analysis was performed based on the extent of hepatectomy (Fig. 2). The beneficial effect of high ERAS compliance on reducing the rate of major complications was consistently observed in both the minor and major hepatectomy subgroups. In patients undergoing minor hepatectomy, the major complication rate was 4.2% in the high-compliance group versus 12.9% in the low-compliance group. Notably, the absolute risk reduction was more pronounced in the major hepatectomy subgroup, where the major complication rate was 7.5% in the high-compliance group compared to 25.9% in the low-compliance group. This suggests that patients undergoing more extensive resections, who are at inherently higher risk, may derive even greater benefit from high adherence to the ERAS pathway.

Fig. 2.

Subgroup analysis of major complication rates (Clavien-Dindo ≥III) stratified by hepatectomy type and ERAS compliance group. The bars represent the percentage of patients experiencing a major complication within each subgroup. The number atop each bar indicates the actual patient count.

Dose-response relationship between compliance and outcomes

To further elucidate the relationship between protocol adherence and clinical outcomes, the entire cohort was analyzed by quartiles of ERAS compliance (Q1: <65%, Q2: 65–70%, Q3: 70–78%, Q4: >78%). A clear, monotonic dose-response relationship was observed between increasing compliance and decreasing rates of both overall and major complications (Fig. 3). The rate of overall complications decreased steadily from 54.8% in the lowest compliance quartile (Q1) to 21.2% in the highest quartile (Q4). Similarly, the rate of major complications demonstrated a graded decline, from 19.4% in Q1 to 4.9% in Q4. This graded association provides strong supportive evidence for a causal link between protocol adherence and improved outcomes, reinforcing the concept that the benefits of ERAS are cumulative and dependent on the degree of implementation.

Fig. 3.

Dose-response relationship between ERAS compliance quartiles and postoperative complication rates. Q1: <65%, Q2: 65–70%, Q3: 70–78%, Q4: >78%. The line graph depicts the declining trend in complication rates with increasing ERAS protocol adherence.

Discussion

This rigorous retrospective cohort study provides compelling evidence that high overall compliance with a comprehensive ERAS protocol is a powerful, independent determinant of superior short-term outcomes following hepatectomy. The principal finding that adherence to at least 70% of the protocol elements conferred a profound reduction in the odds of major complications and prolonged hospitalization underscores that the efficacy of ERAS is critically dependent on the fidelity of its execution. These results robustly support the paradigm that the benefits of ERAS exhibit a clear dose-response relationship, where greater adherence yields incrementally better results [12], [13]. This insight is pivotal for clinical practice, as it shifts the quality improvement focus from the simple adoption of an ERAS pathway to the active measurement and optimization of compliance [22].

The primary innovation of this investigation lies in its granular, quantitative methodology for assessing ERAS compliance and its direct linkage to outcomes. Unlike numerous prior studies that primarily compare historical cohorts, we conducted a meticulous, element-by-element audit of a 20-item pathway [18], [23]. Our multivariate analysis is particularly illuminating; after controlling for established risk factors, high ERAS compliance emerged as one of the most potent independent predictors for a favorable outcome. This indicates that the synergistic effect of the ERAS bundle confers a protective benefit that transcends inherent surgical risks, effectively modulating the patient's physiological response to the operative insult [9], [24]. The mechanisms through which high compliance mediates its beneficial effects are multifactorial and synergistic. Preoperative elements, such as counseling and carbohydrate loading, work to reduce anxiety and shift the metabolic state [25], [26]. Intraoperative strategies minimize hemodynamic lability and inflammation [27], [28]. Postoperatively, opioid-sparing analgesia, early enteral nutrition, and proactive mobilization act in concert to preserve gastrointestinal function and mitigate insulin resistance [29], [30]. The marked reduction in postoperative ileus and accelerated time to flatus observed are direct clinical manifestations of this approach. The broad reduction in complications likely stems from the aggregate effects of reduced opioid use, optimized fluid management, and early mobilization [31], [32].

Our demonstration of a clear dose-response relationship powerfully reinforces the concept of cumulative benefit from adhering to multiple protocol elements [13]. It suggests that each successfully implemented component contributes incrementally to the overall outcome. This finding encourages multidisciplinary teams to strive for excellence across all phases of care. Auditing compliance rates for individual elements serves as an invaluable tool for identifying targetable bottlenecks within the pathway [10], [33]. Future efforts should leverage real-time compliance data for continuous performance feedback. Notwithstanding its compelling findings, this study has limitations. First, its retrospective, single-center design carries risks of residual confounding. Although we adjusted for several patient- and surgery-related variables, unmeasured confounders such as individual surgeon experience, subtle variations in intraoperative technique, or unrecorded patient frailty could have influenced outcomes. However, the consistency of results across subgroups and the dose-response relationship strengthen the validity of the association between compliance and outcomes. Second, the generalizability of our findings, including the specific compliance threshold, may be limited and requires external validation. Third, our study was not powered to definitively deconstruct the ERAS bundle to identify the most critical elements. Larger, prospective, multi-center studies are warranted to delineate the core active ingredients of ERAS for hepatectomy. Future research should also explore the impact on long-term oncological outcomes and investigate strategies to enhance patient engagement.

Conclusion

In conclusion, this study establishes that high overall compliance with a multimodal ERAS protocol is a powerful, independent determinant of significantly improved short-term outcomes after hepatectomy. The demonstrated dose-response relationship underscores the critical importance of meticulous protocol execution. We advocate for the routine integration of ERAS pathways into liver surgical practice, coupled with continuous auditing of compliance rates as a key performance indicator. Future efforts should focus on overcoming barriers to full protocol implementation, ensuring all patients can reliably attain the full benefits of enhanced recovery.

CRediT authorship contribution statement

Yan Zhang: Writing – review & editing, Writing – original draft, Visualization, Validation, Software, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Jingyan Gu: Visualization, Validation, Supervision, Software, Resources, Investigation, Data curation. Jie Song: Visualization, Validation, Supervision, Software, Project administration, Investigation, Formal analysis. Yun Pan: Writing – review & editing, Supervision, Resources, Methodology, Investigation, Formal analysis, Data curation.

Ethical approval

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The study was approved by Affiliated Hospital of Jiangnan University. All patients provided written informed consent for FMT treatment and data analysis.

Funding

None.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.