Scalp Infiltration With Dexamethasone Plus Ropivacaine for Post-craniotomy Pain

Pre-emptive Scalp Infiltration With Dexamethasone Lipid Microsphere Plus Ropivacaine for Postoperative Pain After Craniotomy

According to recent studies, patients following craniotomy suffer more than minimal pain; two-thirds of patients experienced moderate to severe pain. Postoperative pain most often occurs within 48 hours after surgery. Local infiltration of anesthesia is the most simple and effective analgesia. However, the analgesic effect only lasts for a short-time after surgery, and it cannot adequately meet the needs of postoperative analgesia after craniotomy. Several studies have shown that the mixture of dexamethasone with local anesthetics could reduce the postoperative pain scores better than local anesthetics alone. Lipid microsphere is a relatively new drug delivery system. It is an artificial lipid emulsion. Studies have shown that dexamethasone lipid microsphere, the dexamethasone palmitate emulsion (D-PAL emulsion), has stronger anti-inflammatory effect than dexamethasone. Therefore, the investigators hypothesize that the pre-emptive scalp infiltration with dexamethasone lipid microsphere plus ropivacaine could achieve superior postoperative pain-relief compared to ropivacaine alone for patients undergoing craniotomy.

Study Overview

• Status: Active, not recruiting
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Dexamethasone lipid microsphere plus ropivacaine; Drug: Ropivacaine alone

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fang Luo, M.D.; Phone Number: +86 13611326978; Email: 13611326978@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients scheduled for elective craniotomy under general anesthesia;
• Age 18-64 years;
• American Society of Anesthesiologists (ASA) physical status of I or II;
• Anticipated tracheal extubation, full recovery and cooperation within 2 hours postoperatively
• Patients required to fix their head in a head clamp during the operation.

Exclusion Criteria:

• Previous history of craniotomy;
• Plan to delay extubation or no plan to extubate;
• Patients who cannot use the patient-controlled analgesia (PCA) device;
• Patients who cannot comprehend the instructions of a numeric rating scale (NRS) before craniotomy;
• Body mass index (BMI) <15 or >35;
• Allergy to dexamethasone, lipid microsphere, opioids or ropivacaine;
• History of drug abuse or excessive alcohol, chronic opioids use (more than 2 weeks), or use of any sedative or analgesic before surgery;
• History of uncontrolled epilepsy, psychiatric disorders or chronic headache;
• Pregnant or at breastfeeding;
• Symptomatic cardiopulmonary, liver or renal dysfunction or combined with diabetes or other systemic dysfunction;
• Glasgow Coma Scale <15 before the surgery;
• Intracranial hypertension;
• Peri-incisional infection;
• Patients who have received chemoradiotherapy before the surgery or expected to receive postoperative chemoradiotherapy according to the preoperative imaging.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The dexamethasone lipid microsphere plus ropivacaine group	Drug: Dexamethasone lipid microsphere plus ropivacaine; Local scalp infiltration solution will consist of 30ml miscible liquids containing 8 mg dexamethasone lipid microsphere, 150mg ropivacaine and normal saline.; Other Names: ropivacaine plus D-PAL
Active Comparator: The ropivacaine alone group	Drug: Ropivacaine alone; Local scalp infiltration solution will consist of 30ml miscible liquids containing 150mg ropivacaine and normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pain NRS scores at 24 h after craniotomy	The numeral rating scale allows a person to describe the intensity of the pain as a number usually ranging from 0 to 10, where "0" means "no pain" and "10" means pain as "bad as it could be".	At 24 hours after the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The first time the patients press the PCA button	Patients will use PCA device for postoperative analgesia. When the patients feel pain, the PCA button will be pressed. The PCA device will provide a bolus of 2μg sufentanil with a 10 minutes lock-out time, and the maximum dose of sufentanil will be limited to 8μg/h.	Within 24, 48,72 hours postoperatively
The number of patients who didn't press the PCA button	Patients will use PCA device for postoperative analgesia. When the patients feel pain, the PCA button will be pressed. The PCA device will provide a bolus of 2μg sufentanil with a 10 minutes lock-out time, and the maximum dose of sufentanil will be limited to 8μg/h.	Within 24, 48, 72 hours postoperatively
The number of times patients press the PCA button	Patients will use PCA device for postoperative analgesia. When the patients feel pain, the PCA button will be pressed. The PCA device will provide a bolus of 2μg sufentanil with a 10 minutes lock-out time, and the maximum dose of sufentanil will be limited to 8μg/h.	Within 24, 48, 72 hours postoperatively
The NRS score	The numeral rating scale allows a person to describe the intensity of the pain as a number usually ranging from 0 to 10, where "0" means "no pain" and "10" means pain as "bad as it could be".	At 2 hours, 4 hours, 12 hours, 48 hours, 72 hours, 1 month, and 3 months after the operation
The incidence of PONV	Postoperative nausea and vomiting: 0 represents absent; 1 represents nausea without treatment; 2 represents nausea in need of treatment; 3 represents vomiting	Within 24, 48, 72 hours after surgery
Time to first rescue analgesia with OC/APAP after surgery	Patients will be given an oral supplementary tablet of oxycodone (OC)/acetaminophen (APAP) 5/325-mg (MallinckrodtInc.USA) for rescue analgesia when NRS score > 4 after receiving four times of bolus with the PCA device. OC/ APAP will be prescribed at an interval of at least 6 h until the end of our study.	At 2 hours, 4 hours, 8 hours, 24 hours and 48 hours postoperatively
Duration of hospitalization	From the date of the surgery until the date of discharge	From the date of the surgery until the date of discharge, assesses up to 7 days
WHOQOL-BREF scores	The World Health Organization QoL abbreviated version scale consists of 26 items and involves 4 aspects: A. Physical health (7 items); B. Psychological health (6 items); C. Social relationships (3 items); D. Environment (8 items). Other two items measure the patients' quality of life and general health. The average score for each domain can range from 4 to 20, and the higher the score, the better the quality of life.	At 1 month and 3 months after surgery
Wound healing scores	Wound healing scores： 1 represents skin fully healed, no infection, hair regrowth along wound; 2 represents skin ≤3cm in total not healed, ≤0.5cm margin of redness, hair ≤3cm not regrowthing; 3 represents skin >3cm not healed, more redness or superficial pus, >3-6cm not regrowthing hair; 4 represents areas of necrosis ≤3cm, deep infection, >6cm not regrowthing hair; 5 represents areas of necrosis >3cm.	At 1 and 3 months after surgery
POSAS scores	The Patient and Observer Scar Assessment Scale consists of two scales: the observer scale and the patient scale. Both scales contain six items that are scored numerically. Each of the six items on both scales has a 10-step score, with 10 indicating the worst imaginable scar or sensation. The total score of both scales consists of adding the scores of each of the six items (range, 6 to 60). The lowest score, 6, reflects normal skin, whereas the highest score, 60, reflects the worst imaginable scar.	At 3 months after surgery
Adverse events	Steroid-hormone related complications, such as wound infection, wound edema, delayed wound healing, pulmonary infections, gastric ulcers, local atrophy or infection, embolic events and so on	Through the whole follow-up, an average of 3 months
Cumulative sufentanil consumption by PCA device	A Patient Controlled Analgesia (PCA) device containing sufentanil 200μg and ondansetron 16 mg in 100 ml saline will be set up to deliver 1 mL as an intravenous bolus with a 10-min lockout interval after craniotomy. The maximum dose will be limited to 8 μg per hour, and there will be no initial dose or background infusion. Patients will be advised to push the analgesic demand button if they feel pain and to repeat it until the pain is relieved.	During 24hours, 48 hours and 72 hours postoperatively

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Fang Luo, M.D., Beijing Tian Hospital; Principal Investigator: Wei Zhang, MD, Beijing Tian Hospital

Publications and helpful links

General Publications

• Gottschalk A, Berkow LC, Stevens RD, Mirski M, Thompson RE, White ED, Weingart JD, Long DM, Yaster M. Prospective evaluation of pain and analgesic use following major elective intracranial surgery. J Neurosurg. 2007 Feb;106(2):210-6. doi: 10.3171/jns.2007.106.2.210.
• Zhou H, Ou M, Yang Y, Ruan Q, Pan Y, Li Y. Effect of skin infiltration with ropivacaine on postoperative pain in patients undergoing craniotomy. Springerplus. 2016 Jul 26;5(1):1180. doi: 10.1186/s40064-016-2856-3. eCollection 2016.
• Jia Y, Zhao C, Ren H, Wang T, Luo F. Pre-emptive scalp infiltration with dexamethasone plus ropivacaine for postoperative pain after craniotomy: a protocol for a prospective, randomized controlled trial. J Pain Res. 2019 May 24;12:1709-1719. doi: 10.2147/JPR.S190679. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Actual): September 26, 2023
• Study Completion (Estimated): December 25, 2023

Study Registration Dates

• First Submitted: July 19, 2020
• First Submitted That Met QC Criteria: July 22, 2020
• First Posted (Actual): July 28, 2020

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 18, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anesthetics, Local; Dexamethasone; Ropivacaine
• Other Study ID Numbers: KY-2018-034-02-8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No