The Analgesic Effect of Scalp Nerve Block Using Bupivacaine Liposomes for Postoperative Pain Relief After Craniotomy

Study Purpose

After undergoing craniotomy, 60% to 84% of neurosurgery patients experience moderate to severe acute pain, primarily in the first 48 hours. This pain is mostly superficial, affecting the muscles and soft tissues around the skull. Poor pain management can lead to complications such as restlessness, nausea, hypertension, increased intracranial pressure, and prolonged recovery, potentially resulting in chronic headaches. Opioids are commonly used to manage this pain but can cause significant side effects like sedation, nausea, and increased intracranial pressure, which can mask serious conditions. Non-opioid medications and scalp infiltration techniques can help but may not provide sufficient pain relief for the duration needed. Currently, multimodal analgesia, particularly scalp nerve blocks, is advocated in neurosurgical recovery practices. These blocks are effective and simpler to perform, but the effects of long-acting local anesthetics, like bupivacaine, typically last only 24 hours. Since pain often persists longer than that, there is a need for better pain management strategies. Liposome bupivacaine is a new long-acting local anesthetic approved by the FDA, offering pain relief for up to 72 hours compared to regular bupivacaine's 8-hour duration. Its effectiveness has been confirmed in various nerve block procedures, but it has not been reported for scalp nerve blocks. This study aims to investigate whether liposome bupivacaine scalp nerve blocks can provide long-lasting postoperative pain relief, promote quicker recovery, and reduce complications in neurosurgery patients.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Age ≥ 18 years.
  • - ASA I-III.
  • - Scheduled for elective cranial surgery.
  • - Informed consent from the patient or legal representative.

Exclusion Criteria:

  • - Preoperative Glasgow score < 15.
  • - Preoperative headache with NRS ≥ 4.
  • - Anticipated postoperative sedation or extubation difficulties requiring mechanical ventilation.
  • - Inability to understand the numerical rating scale (NRS) - Allergies or contraindications to amide local anesthetics, opioids, or NSAIDs.
  • - Long-term opioid or corticosteroid treatment (> 2 weeks) - History of drug abuse in the past 2 years.
  • - Daily alcohol consumption exceeding 3 standard doses.
  • - Mental or cognitive disorders affecting perioperative assessment.
  • - Contraindications for nerve blocks, including infection or tumors at the puncture site, diagnosed diabetic peripheral neuropathy, or inability to cooperate.
  • - Severe liver dysfunction (Child-Pugh class C), severe renal dysfunction (requiring dialysis preoperatively), or severe heart failure (METS < 4) - Pregnant or breastfeeding women.
  • - History of craniotomy or pre-existing pathological pain conditions (e.g., migraines, trigeminal neuralgia) - Incisions for craniotomy extending beyond the area covered by the scalp nerve blocks.
- Participation in other clinical trials

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT07049094
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 4
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Zhejiang University
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries China
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain Tumor Adult, Cerebrovascular Disease
Additional Details

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.

Arms & Interventions

Arms

Experimental: scalp nerve block with 0.25% hydrochloride bupivacaine and 0.67% bupivacaine liposome solution

In this group, patients use 0.25% hydrochloride bupivacaine and 0.67% bupivacaine liposome solution for scalp nerve block

Active Comparator: scalp nerve block with 0.50% hydrochloride bupivacaine

In this group, patients use 0.50% hydrochloride bupivacaine for scalp nerve block

Interventions

Drug: - scalp nerve block with 0.25% hydrochloride bupivacaine and 0.67% bupivacaine liposome solution

Using 0.25% hydrochloride bupivacaine and 0.67% bupivacaine liposome solution for scalp nerve block

Drug: - scalp nerve block with 0.50% hydrochloride bupivacaine

Using 0.50% hydrochloride bupivacaine for scalp nerve block

Contact a Trial Team

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International Sites

Hangzhou 1808926, Zhejiang 1784764, China

Status

Recruiting

Address

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou 1808926, Zhejiang 1784764, 310000

Site Contact

Diansan Su, phD

[email protected]

+8618616514088

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