Scalp Infiltration With Dexamethasone Plus Ropivacaine for Post-craniotomy Pain

Overview

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.

Full Title of Study: “Pre-emptive Scalp Infiltration With Dexamethasone Lipid Microsphere Plus Ropivacaine for Postoperative Pain After Craniotomy”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Prevention
  • Masking: Double (Participant, Outcomes Assessor)
• Study Primary Completion Date: May 1, 2023

Interventions

• 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.
• Drug: Ropivacaine alone
  • Local scalp infiltration solution will consist of 30ml miscible liquids containing 150mg ropivacaine and normal saline

Arms, Groups and Cohorts

• Experimental: The dexamethasone lipid microsphere plus ropivacaine group
• Active Comparator: The ropivacaine alone group

Clinical Trial Outcome Measures

Primary Measures

• The pain NRS scores at 24 h after craniotomy
  • Time Frame: At 24 hours after the operation
  • 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”.

Secondary Measures

• The first time the patients press the PCA button
  • Time Frame: Within 24, 48,72 hours postoperatively
  • 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.
• The number of patients who didn’t press the PCA button
  • Time Frame: Within 24, 48, 72 hours postoperatively
  • 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.
• The number of times patients press the PCA button
  • Time Frame: Within 24, 48, 72 hours postoperatively
  • 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.
• The NRS score
  • Time Frame: At 2 hours, 4 hours, 12 hours, 48 hours, 72 hours, 1 month, and 3 months after the operation
  • 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”.
• The incidence of PONV
  • Time Frame: Within 24, 48, 72 hours after surgery
  • Postoperative nausea and vomiting: 0 represents absent; 1 represents nausea without treatment; 2 represents nausea in need of treatment; 3 represents vomiting
• Time to first rescue analgesia with OC/APAP after surgery
  • Time Frame: At 2 hours, 4 hours, 8 hours, 24 hours and 48 hours postoperatively
  • 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.
• Duration of hospitalization
  • Time Frame: From the date of the surgery until the date of discharge, assesses up to 7 days
  • From the date of the surgery until the date of discharge
• WHOQOL-BREF scores
  • Time Frame: At 1 month and 3 months after surgery
  • 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.
• Wound healing scores
  • Time Frame: At 1 and 3 months after surgery
  • 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.
• POSAS scores
  • Time Frame: At 3 months after surgery
  • 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.
• Adverse events
  • Time Frame: Through the whole follow-up, an average of 3 months
  • 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
• Cumulative sufentanil consumption by PCA device
  • Time Frame: During 24hours, 48 hours and 72 hours postoperatively
  • 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 64 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Beijing Tiantan Hospital
• Provider of Information About this Clinical Study
  • Principal Investigator: Fang Luo, Director of Department of Day Surgery and Pain Management – Beijing Tiantan Hospital
• Overall Official(s)
  • Fang Luo, M.D., Principal Investigator, Beijing Tian Hospital
  • Wei Zhang, MD, Principal Investigator, Beijing Tian Hospital
• Overall Contact(s)
  • Fang Luo, M.D., +86 13611326978, 13611326978@163.com

References

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.

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.

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.