Explanation for the choice of comparators

At Peking Union Medical College Hospital, the standard perioperative pain management for patients undergoing open liver resection involves multimodal analgesia without regional anaesthesia. After surgery, patients typically receive opioid-based PCIA with additional medications such as non-steroid anti-inflammatory drug, acetaminophen, tramadol, and extra opioid as needed. This standard regimen is used as comparator to evaluate whether the EOI plane block provides superior postoperative analgesia, reduces opioid consumption, and improves recovery after surgery.

To maintain blinding, all participants will receive local infiltration anaesthesia with 1 ml of 1% lidocaine. Participants in the intervention group will then receive EOI plane block, while those in the control group will not receive any block.

Intervention description

Before surgery, participants will be placed in pre-anaesthesia room for monitoring, including non-invasive blood pressure, continuous electrocardiography, and pulse oximetry. Supplemental oxygen will be provided via nasal cannula. One to 2 mg of midazolam will be administered. A radial arterial catheter will be placed for continuous arterial blood pressure monitoring and arterial blood gas analysis during operation. Blood samples for ropivacaine plasma concentration testing will also be obtained through this catheter.

Participants will be placed in the supine position, and their skin will be disinfected with povidone-iodine 5% solution. A linear ultrasound transducer (6–13 MHz, X-Porte, SonoSite, Bothell, MA, USA) will be covered by sterile sleeve. Ultrasound-guided EOI plane block will be performed as described previously [17]. In brief, the transducer will be placed slightly medial to the anterior axillary line between the sixth and seventh ribs on the right side. The cranial end of transducer points slightly medially, while the caudal end laterally. The local anaesthetic will be administered between the external oblique and intercostal muscles. Participants in the EOI plane block group will receive a single shot of 30 ml of 0.375% ropivacaine after a subcutaneous infiltration anaesthesia with 1 ml of 1% lidocaine. Participants in the control group will receive only the subcutaneous infiltration anaesthesia with 1 ml of 1% lidocaine.

Approximately 30 min after local anaesthetic injection, participants will be transferred to the operating room. Monitoring will include electrocardiography, pulse oximetry, bispectral index, and invasive blood pressure. General anaesthesia will be induced with propofol (2–2.5 mg/kg), sufentanil (0.15 μg/kg), and rocuronium (0.6 mg/kg), followed by endotracheal intubation and mechanical ventilation. Two to 3 vol% sevoflurane/oxygen/air mix inhalation, sufentanil (0.1 μg/kg/h), remifentanil (0.1–0.2 μg/kg/min), and rocuronium (0.1–0.2 mg/kg /h) will be applied to maintain anaesthesia. Hemodynamic fluctuation will be kept within 20% of baseline values.

Criteria for discontinuing or modifying allocated interventions

Participants may withdraw from the study at any stage. The risks associated with ultrasound-guided EOI plane block are considered low, as no publication reported the complications. In the event of complications, appropriate medical treatment will be administered. Participant who wishes to continue despite any issues will remain in their original study group,

Strategies to improve adherence to interventions

The interventions and tests related to ropivacaine plasma concentration will be provided at no cost. Additionally, participants will benefit from enhanced postoperative pain management, which often increases their engagement and adherence to the study. The ultrasound-guided EIO blocks will be performed exclusively in the operating room, and any other regional blocks performed perioperatively will be documented in the electric system. This ensures that any deviations from the allocated procedures can be identified, allowing for effective monitoring of adherence.

Relevant concomitant care permitted or prohibited during the trial

Any postoperative pain management including opioid, non-steroid anti-inflammatory drug, acetaminophen, tramadol, and other medicines are permitted. However, any form of regional anaesthesia is prohibited, including wound infiltration, transversus abdominis plane block, quadratus lumborum blocks, paravertebral blocks, erector spinae plane blocks, and thoracic epidural analgesia.

Provisions for post-trial care

The ultrasound-guided EOI plane block is generally a safe procedure. If a participant experiences an injury related to this clinical trial, it will be documented, evaluated, and treated with appropriate medical care. The costs of such care will be covered by Clinical Trial Insurance.

Outcomes Primary outcomeSecondary outcomes include (1)

NRS pain scores at rest and during movement at postoperative 6, 24, 48, and 72 h, and during movement at postoperative 3 h.

(2)

Perioperative opioid consumption.

(3)

Remedial analgesics within 72 h postoperatively.

(4)

PCIA pump usage within 72 h postoperatively.

(5)

Recovery milestones, including time to removal of urinary catheter, time to first ambulation, time to first flatus, and length of hospital stay.

(6)

Postoperative side effects, such as nausea, vomiting, dizziness, drowsiness, and pruritus.

(7)

Block-related complications, including pneumothorax, local anaesthetic systemic toxicity, and hematoma.

Exploratory outcomeParticipant timeline

The participant timeline is shown in Fig. 2.

Fig. 2

Schedule of enrolment, interventions, and assessment (SPIRIT figure). EOI, external oblique intercostal

Sample size

The sample size was calculated based on data from a pilot study with 8 participants, which indicated that resting pain score at 3 h postoperatively was 3.5 (± 1.3) in the control group and 2.8 (± 0.5) in the intervention group. To achieve a statistical power of 0.80 with a two-sided α level of 0.05, a minimal sample of 33 participants per group was required. Accounting for a dropout rate of approximately 10%, we plan to recruit 37 participants per group.

Recruitment

Participants are all inpatients scheduled for elective open liver surgery. The day before the surgery, an investigator will review the list of scheduled operation to identify potential subjects. Those who meet all inclusion criteria and none of the exclusion criteria will be eligible for the study. The investigator will introduce this study to the participants and their families. Informed consent will be obtained subsequently. Close cooperation between anaesthesiology and liver surgery departments ensures effective participant enrolment.