Scalp Infiltration With Dexamethasone Plus Ropivacaine for Post-craniotomy Pain

Study Overview
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Brief Summary
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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.

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

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Dexamethasone lipid microsphere plus ropivacaine
* Drug: Ropivacaine alone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |