Description

This study aims to compare the analgesic efficacy and safety of hydrochloride bupivacaine versus liposomal bupivacaine in patients undergoing elective cranial surgery. The protocol is designed to rigorously assess pain management outcomes, recovery quality, and potential complications through a randomized, single-blind, controlled trial.

Study Design and Methodology After a comprehensive screening process, eligible patients are randomized into two groups: the control group receiving hydrochloride bupivacaine and the experimental group receiving a combination of hydrochloride bupivacaine and liposomal bupivacaine. Randomization was implemented using a pre-generated data list to ensure allocation concealment and minimize selection bias. The single-blind design ensures that patients are unaware of their group assignment, while clinicians administering the drugs are informed to ensure proper preparation and delivery.

Preoperative Assessment

Prior to surgery, all subjects undergo a thorough evaluation, including:

1. Neurological Assessment: Consciousness levels are assessed using the Glasgow Coma Scale (GCS).
2. Laboratory Testing: Electrocardiograms, routine blood tests (e.g., RBC, WBC, hemoglobin, platelet count), and liver/kidney function tests (e.g., ALT, AST, serum creatinine, BUN) are performed to confirm eligibility and detect any underlying conditions.
3. Pain and Recovery Familiarization： Patients are introduced to the Numeric Rating Scale (NRS) for pain, the Objective Pain Assessment Scale (OBAS), and the Quality of Recovery-15 (QoR15) scale to standardize postoperative data collection.

Anesthesia and Intraoperative Protocol Upon admission to the operating room, inclusion/exclusion criteria are re-evaluated, and baseline vitals (SPO2, BP, ECG) are monitored. Peripheral intravenous and arterial lines are established for drug administration and invasive blood pressure monitoring.

1. General Anesthesia Induction:

Induction agents include midazolam/remimazolam, propofol, sufentanil, and rocuronium/cisatracurium.

Endotracheal intubation is performed after 3 minutes of induction, followed by mechanical ventilation with a tidal volume of 6-8 ml/kg and a respiratory rate of 10-12 breaths/min to maintain end-tidal CO2 at 30-40 mmHg.

2. Maintenance of Anesthesia:

Anesthesia is maintained with sevoflurane, propofol, remifentanil, and either cisatracurium or rocuronium.

Dexamethasone (5 mg) and betamethasone (4 mg) are routinely administered during induction to reduce inflammation and nausea.

To avoid confounding variables, non-steroidal anti-inflammatory drugs, additional opioids (e.g., dezocine, norfentanyl), and dexmedetomidine are excluded.

3. Scalp Nerve Blocks： Scalp nerve blocks are performed bilaterally before the surgical incision to enhance analgesia. The blocks target six major nerve groups (e.g., superior orbital, supraorbital, zygomatic-temporal, auriculotemporal, greater occipital, and lesser occipital nerves) using precise anatomical landmarks and standardized volumes of local anesthetic.

Drug Preparation and Administration Control Group: 20 ml of 0.75% hydrochloride bupivacaine is diluted with 10 ml saline and divided into three 10 ml doses.

Experimental Group: 10 ml of 0.75% hydrochloride bupivacaine is mixed with 15 ml of 1.33% liposomal bupivacaine and 5 ml saline, also divided into three 10 ml doses.

The prepared solutions are administered during nerve blocks under aseptic conditions.

Recovery and Extubation Postoperatively, sedatives are discontinued, and muscle relaxation is reversed with either neostigmine (1-2 mg) and atropine (0.5-1 mg) or sugammadex (2 mg/kg). Extubation is performed when patients achieve a score of >9 on Godet et al.'s scoring criteria. Patients are monitored in the Post-Anesthesia Care Unit (PACU) for 1 hour.

Postoperative Rescue Analgesia Rescue analgesia is provided if NRS scores are ≥4, with intravenous non-steroidal anti-inflammatory drugs or other clinically appropriate interventions. All rescue analgesia events are documented.

Measures to Minimize Bias Randomization: Ensures equal distribution of confounding factors between groups.

Blinding: Subjects are blinded to their group assignment to reduce placebo effects.

Standardized Assessment Tools: NRS, OBAS, and QoR15 scales are used to objectively evaluate pain and recovery outcomes.

Clinical Indicator Assessment

Primary and secondary outcomes are measured at predefined postoperative time points:

Primary Endpoint: Resting AUC-NRS scores within 48 hours postoperatively (PACU discharge, 4 hours post-op, 8 hours post-op, and on POD1 at 8:30, 12:00, and 16:00).

Secondary Endpoints:

Coughing AUC-NRS scores within 48 hours postoperatively. Resting NRS scores at PACU discharge and on POD1-3. OBAS scores, QoR15 scores, and incidence of postoperative complications (e.g., nausea, vomiting, nerve block-related issues).

Subject Selection and Withdrawal Detailed inclusion and exclusion criteria ensure the recruitment of a homogenous study population. Subjects may withdraw at any time, and procedures are in place to document and address missed visits and loss to follow-up.

Sample Size and Statistical Power A total of 218 subjects are required to achieve adequate statistical power, accounting for potential dropouts. This sample size is calculated based on the primary endpoint to detect clinically significant differences between groups.