Effect of erector spinae plane block on overall benefit of analgesia after esophagectomy: a randomized controlled trial protocol

Abstract

Introduction

Management of postoperative pain following esophagectomy is challenging. This study aims to investigate the analgesic efficacy and overall clinical benefit of erector spinae plane block (ESPB) using either liposomal bupivacaine or ropivacaine in patients undergoing esophagectomy.

Patients and Methods

This single-center, randomized, double-blind, placebo-controlled trial will be conducted at the First Affiliated Hospital of Soochow University. Eighty-four adult patients scheduled for transthoracic esophagectomy will be randomized (1:1:1) to receive a preoperative ultrasound-guided ESPB using either liposomal bupivacaine, ropivacaine, or normal saline placebo. All patients will receive standardized general anesthesia and postoperative patient-controlled intravenous analgesia with sufentanil. The primary outcome is the mean Overall Benefit of Analgesia Score (OBAS) over postoperative days 1 to 5, a multidimensional tool integrating pain, opioid-related side effects, and patient satisfaction. Secondary outcomes include the OBAS on each of the first 5 postoperative days, cumulative opioid consumption during postoperative 5 days, incidence of major in-hospital complications, length of postoperative hospital stay, and 5-year overall survival.

Discussion

Utilizing the OBAS to comprehensively assess analgesic benefit, the findings of this trial will guide evidence-based refinement of multimodal analgesia for patients undergoing esophagectomy.

Trial registration

Chinese Clinical Trial Registry (ChiCTR2500099481; registered on March 25, 2025)

Introduction

Esophagectomy remains the cornerstone treatment for esophageal malignancies and end-stage benign diseases [1]. However, these procedures are associated with substantial surgical trauma, significant postoperative pain, and high rates of postoperative complications [2–4]. Inadequate analgesia may impair respiratory effort, delay mobilization, and increase the risk of pulmonary infections and anastomotic leakage [5].

Multimodal analgesia, including regional techniques, has been applied to reduce opioid consumption and related adverse effects. Erector spinae plane block (ESPB), first described by Forero et al. in 2016 [6], has emerged as a promising fascial plane block for thoracic and abdominal surgeries [7–9]. Preliminary studies suggested that ESPB reduced early postoperative pain and opioid use after esophagectomy [10,11]. Despite its potential, direct comparisons between different local anesthetics in ESPB for esophagectomy are lacking. Ropivacaine is widely used due to its favorable safety profile and intermediate duration (6–12 h). Liposomal bupivacaine, a sustained-release formulation, provides prolonged analgesia for up to 72 h and may enhance postoperative pain management [12].

Traditional outcome measures (e.g. visual analogue scale for pain, opioid consumption) fail to capture the multidimensional nature of postoperative analgesic benefit. The Overall Benefit of Analgesia Score (OBAS) is a multidimensional evaluation tool that comprehensively integrates pain intensity, side effects of opioids, and patient satisfaction, offering a more holistic assessment [13]. Herein, we describe the first randomized, double-blind, placebo-controlled trial to evaluate the effect of ESPB using either liposomal bupivacaine or ropivacaine in patients undergoing esophagectomy, with the OBAS as the primary endpoint.

Patients and methods

Study design, ethics, and registration

This is a single-center, prospective, randomized, double-blind, placebo-controlled trial with three parallel groups (liposomal bupivacaine, ropivacaine, and normal saline placebo). This study will be conducted at the First Affiliated Hospital of Soochow University, Suzhou, China. The protocol was approved by the Institutional Ethics Committee (Approval No. 2025-218) and registered on the Chinese Clinical Trial Registry (ChiCTR2500099481; principal investigator: Ke Peng; https://www.chictr.org.cn/showproj.html?proj=266783).

Figure 1 illustrates the flow diagram of this trial. We will recruit 84 patients from April 2025 to September 2026, with a 5-year survival follow-up until September 2031. The study will be conducted in accordance with the Declaration of Helsinki. All subjects will provide written informed consent. The study design and protocol are reported in compliance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement (Supplement 1).

Figure 1.

Flow diagram of this trial. Participant numbers (n = X) will be inserted upon recruitment completion.

Patients

Inclusion criteria are: (1) age ≥ 18 years, (2) ASA physical status I–III, (3) scheduled for elective transthoracic esophagectomy (thoracotomy or thoracoscopy/artificial pneumothorax combined with laparoscopy or laparotomy), and (4) provision of written informed consent. Exclusion criteria are: (1) severe cardiopulmonary, hepatic, or renal dysfunction, (2) allergy to study medications or history of local anesthetic toxicity, (3) chronic pain, neuropathic pain, or long-term analgesic use, (4) psychiatric disorders, or (5) inability to understand the assessment scales.

Randomization and blinding

Randomization will be performed using a computer-generated random number table, with a 1:1:1 ratio, permuted blocks of sizes 3 and 6, and stratified by surgical approach (thoracotomy vs. thoracoscopy). Immediately before induction, an independent research nurse will open the next sequentially numbered, opaque, sealed envelope to assign each participant to the liposomal bupivacaine, ropivacaine, or normal saline group. This nurse will prepare the allocated drug in an identical 50 mL syringe inside the anesthetic preparation room, cover the syringe with an opaque sleeve, and carry it to the operating room. After ultrasound-guided needle placement, the nurse will inject the solution through a catheter concealed beneath opaque drapes. Patients, anaesthesiologists, surgeons, and outcome assessors will remain blinded to treatment assignment.

Anesthesia and study interventions

In the operating room, patients will be monitored with electrocardiography, non-invasive blood pressure, pulse oximetry (SpO₂), surgical pleth index (SPI), and bispectral index (BIS). An arterial line will be inserted under local anesthesia for continuous blood pressure monitoring. After preoxygenation with 100% oxygen via a face mask (5 L/min), general anesthesia will be induced with intravenous sufentanil 0.3 μg/kg and propofol 1.5–2 mg/kg. After loss of consciousness, rocuronium 0.6 mg/kg will be administered to facilitate tracheal intubation under video laryngoscopy. Mechanical ventilation will be initiated in a volume-controlled mode (tidal volume 6–8 mL/kg, respiratory rate 12–15 breaths/min) with 50–80% inspired oxygen to maintain SpO₂ ≥ 93% and end-tidal CO₂ at 35–40 mmHg.

Before surgery, an experienced attending anesthesiologist will perform an ultrasound-guided ESPB at the T7–8 level with the patient in the lateral decubitus position, as described in our recent study [14]. The liposomal bupivacaine group will receive 266 mg liposomal bupivacaine diluted in 40 mL normal saline; the ropivacaine group will receive 150 mg (0.375%) ropivacaine in 40 mL normal saline; and the control group will receive 40 mL normal saline alone.

Anesthesia will be maintained with inhalational sevoflurane 1–3% and intermittent sufentanil 0.1–0.2 μg/kg to maintain BIS 40–60 and surgical pleth index 20–50 [15]. Flurbiprofen axetil 50 mg will be intravenously administered during surgery. All patients will receive patient-controlled intravenous analgesia (PCIA) with sufentanil 100 μg in 100 mL 0.9% saline (background infusion 1 mL/h, bolus 2 mL, lockout 10 min). No additional regional blocks will be used perioperatively.

Primary and secondary outcomes

The primary outcome is the mean of five daily OBAS values collected on postoperative days 1 to 5. The OBAS is a simple, multi-dimensional, validated tool that assesses overall analgesic benefit by integrating seven items: pain intensity, opioid-related side effects (vomiting, itching, sweating, freezing, dizziness), and patient satisfaction [13]. The total score ranges from 0 to 28, with lower scores indicating greater overall benefit.

Secondary outcomes include (1) the OBAS at each day of postoperative 5 days; (2) cumulative opioid consumption during postoperative 5 days; (3) incidence of major in-hospital complications (anastomotic leakage, mechanical ventilation > 48 h, pulmonary infection, renal failure, reoperation, and death), (4) length of postoperative hospital stay, and (5) 5-year overall survival.

Data collection

Patient enrollment, study interventions, and outcome assessment will be conducted in accordance with the SPIRIT guideline (Table 1). Demographic and baseline data include age, sex, weight, height, body mass index, ASA physical status, smoking status, history of abdominal or thoracic surgery, preoperative chemoradiotherapy, preoperative blood pressure and heart rate, hemoglobin level, albumin level, comorbidities, and preoperative medications. Anesthesia and surgical data include dose of anesthetics (propofol, sufentanil, sevoflurane, esketamine, dexmedetomidine, etc.), hemodynamic values from entering the operating room to the end of surgery, hypotension (mean blood pressure < 65 mmHg with interventions), bradycardia (heart rate < 50 beats/min with interventions), types of surgery, amount of fluids, transfusion, urine output, blood loss, duration of surgery, length of recovery room stay, intensive care unit (ICU) admission, and length of ICU stay. C-reactive protein will be measured perioperatively in patients undergoing esophagectomy. These data will be extracted from the electronic anesthesia information system and electronic medical records. Postoperative outcome data will be collected using the case report forms by independent researchers blinded to group allocation. An independent data monitoring committee will supervise the study as it progresses to safeguard participant welfare and the reliability of the data collected.

Table 1.

Schedule of patient enrollment, study interventions, and outcome assessment according to SPIRIT statement.

	Study period
	Enrollment	Allocation	Post-allocation							Closeout
Timepoint	Preoperative visit	Before induction	Before surgery	Day 1	Day 2	Day 3	Day 4	Day 5	Hospital discharge	5 year
Enrollment
Inclusion criteria	×
Exclusion criteria	×
Written informed consent	×
Baseline data	×
Randomization		×
Allocation		×
Study interventions
Liposomal bupivacaine			×
Ropivacaine			×
Normal saline			×
Outcome assessment
Pain intensity				×	×	×	×	×
Opioid-related adverse effects				×	×	×	×	×
Patient satisfaction				×	×	×	×	×
Cumulative opioid use								×
Postoperative complications									×
Length of hospital stay									×
5-y survival										×

According to SPIRIT 2013 statement of defining standard protocol items for clinical trials.

Sample size estimation

No prior OBAS data exist for esophagectomy. Our pilot observation in 14 patients undergoing esophagectomy yielded a mean ± standard deviation (SD) OBAS of 4.7 ± 2.2 over the first 5 postoperative days. To detect a 1-point difference among three equal-sized groups with a common SD of 2.2, 75 patients (25 per group) will provide 80% power at α = 0.05 (two-sided). Allowing 10% attrition, we will recruit 84 patients (28 per group). PASS 2023 is used for sample size calculation.

Statistical analysis

Data will be analyzed using SPSS 25.0 (IBM SPSS, Chicago, IL, USA). Continuous data will be presented as mean ± SD or median (interquartile range) depending on the distribution, whereas dichotomous data will be presented as number (percentage). Demographic and baseline characteristics will be analyzed with descriptive statistics only. Data during anesthesia and surgery will be analyzed using one-way analysis of variance (ANOVA), Kruskal-Wallis test, or χ² test, as appropriate.

For the primary analysis, one-way ANOVA will be used, followed by Tukey test to correct for multiple comparisons, and multiplicity adjusted P values will be reported for each comparison; mean difference with 95% confidence intervals between groups will be analyzed. Secondary outcomes are prespecified as exploratory and hypothesis-generating; therefore, no multiplicity adjustment was applied, keeping the statistical focus on the primary outcome. The 5-year survival rate will be reported separately, after the completion of the final follow-up. Data on perioperative CRP will be reported in an exploratory mechanistic analysis.

Primary analysis will be intention-to-treat, including all randomized patients who undergo surgery and have at least one postoperative OBAS assessment, regardless of protocol adherence. The mean of the available daily OBAS values will be calculated, assuming data are missing completely at random and will not be imputed. Patients without any OBAS data will be excluded. A per-protocol sensitivity analysis will include only patients who complete all five daily assessments and have no major protocol deviations. The significance level is a two-sided P value < 0.05.

Discussion

This is the first randomized, double-blind, placebo-controlled trial to assess the effect of ultrasound-guided ESPB with liposomal bupivacaine or ropivacaine for patients undergoing transthoracic esophagectomy. By using the mean OBAS as the primary endpoint, we will capture not only pain intensity but also opioid-related side-effects and patient satisfaction during the first 5 postoperative days. We expect that ESPB using both local anesthetics will lead to lower mean OBAS compared with normal saline placebo, and that the sustained-release liposomal formulation will confer additional benefit over ropivacaine by extending analgesia up to 72 h, thereby improving postoperative analgesia.

Esophagectomy is associated with severe pain and high morbidity. Effective postoperative analgesia is essential to enhance recovery and reduce complications. While opioids remain the mainstay of postoperative acute pain management, their side effects such as nausea, vomiting, bowel dysfunction, and respiratory depression limit their use. Regional anesthesia techniques, including thoracic epidural analgesia, paravertebral block, and ESPB, have emerged as key components of multimodal analgesia to optimize pain control while minimizing opioid-related adverse events [16,17]. ESPB exerts its effect by blocking conduction in the dorsal rami of the spinal nerves when local anesthetic is deposited in the erector spinae plane, thereby providing postoperative pain relief. However, high-quality randomized controlled trials remain scarce, especially direct comparisons between liposomal bupivacaine and ropivacaine in ESPB for esophagectomy. This underscores the need for well-designed studies to clarify the comparative effectiveness of these agents and guide clinical practice.

Key strengths of this trial include the use of the validated, multidimensional OBAS to assess pain intensity, opioid-related adverse effects, and patient satisfaction in a single metric which has been widely used in various types of surgical procedures [18–23]; the randomized, double-blind, placebo-controlled design minimizes performance and detection bias; and a standardized perioperative protocol of anesthesia and sufentanil PCIA further limits possible confounding. Although the trial is powered for analgesic endpoints, 5-year overall survival will be captured as an exploratory outcome, acknowledging that perioperative analgesia and opioid-sparing may modulate immune function and inflammatory responses, which have been associated with cancer recurrence and long-term survival after oncologic surgery [24,25]. On the other hand, potential limitations include the single-center design and lack of psychological assessments. Future multicenter trials should validate these findings and explore the role of ESPB in enhanced recovery pathways for patients undergoing major surgery.

In conclusion, the results of this trial will provide high-quality evidence on whether ESPB with liposomal bupivacaine or ropivacaine improves overall analgesic benefit after esophagectomy. Findings are expected to inform evidence-based, patient-centered perioperative analgesia and may support wider adoption of ESPB in major thoracic surgery.

Funding Statement

This work will be supported by the National Natural Science Foundation of China (82471290) and Suzhou Basic Research Pilot Project (SSD2024082). The funders have no role in study design, data collection, data analysis, interpretation, or manuscript writing.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics and dissemination

The Institutional Ethics Committee approved this clinical trial (Approval No. 2025-218) on March 18, 2025. Thereafter, the protocol was registered at the Chinese Clinical Trial Registry (ChiCTR2500099481) on March 25, 2025. All subjects will provide written informed consent, and all study implementations will follow the Declaration of Helsinki. We will submit the study results for publication in major peer-reviewed journals.

Data availability statement

The full protocol, dataset, statistical plan, and informed consent materials are available via contacting the corresponding author after the formal publication of this trial. No new data has been generated during the study.