Flurbiprofen Axetil as an Adjuvant to Pre-emptive Scalp Infiltration

Study Overview
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Brief Summary
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Post-craniotomy pain remains a major challenge in patient care following neurosurgery.Flurbiprofen axetil (FA), as an injectable nonselective cyclooxygenase inhibitor, is a widely prescribed NSAID for postoperative pain. As FA is highly lipophilic by merging into emulsified lipid microspheres, it has a high affinity to the surgical incision and inflammatory tissues to achieve targeted drug therapy and prolonged duration of action, thus providing a basis for its local use to achieve efficacy and safety comparable to or greater than systemic administration. In this study, we attempt to evaluate the clinical effects of FA as an adjunct to ropivacaine in pre-emptive scalp infiltration to prevent or reduce pain after craniotomy.

Official Title
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Flurbiprofen Axetil as an Adjuvant to Pre-emptive Scalp Infiltration for Post-craniotomy Pain

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: FA plus ropivacaine
* Drug: ropivacaine alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age minimum 18 years; ASA physical status of I - II; Body mass index (BMI) of 15 - 30; Scheduled for supratentorial craniotomy under general anesthesia; Anticipated tracheal extubation, recovery of consciousness and orientation within 2 hours after craniotomy. Exclusion Criteria: Glasgow Coma Scale <15; Unable to use the PCIA device or comprehend the pain NRS; History of opioid dependence, chronic headache or intake of any drugs with known analgesic properties within the 24 hours before surgery; History of craniotomy or scalp infection; Any contraindication to flurbiprofen axetil, such as gastrointestinal ulcer, coagulation disorders, renal dysfunction, heart failure and ischemic heart disease; History of allergy to any drug used in the study; Pregnancy and breastfeeding.

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: ropivacaine plus FA<br>5 mL FA (50 mg; by Beijing Taide Pharmaceutical Co., Ltd) and 15 mL of 1% ropivacaine (Nai Le Pin 10mg/mL; by AstraZeneca AB, Sweden) diluted to a total volume of 30 mL in normal saline | Drug: FA plus ropivacaine<br>* Th group will receive 0.17% FA and 0.5% ropivacaine for pre-emptive scalp infiltration at about 30 min before surgical incision. The assigned solution was injected along the planned surgical incision and pin fixation sites of the Mayfield head holder, using a 22-gauge needle introduced throughout the entire thickness of the scalp at a 45° angle.<br>|
| Active Comparator: ropivacaine alone<br>15 mL of 1% ropivacaine diluted to a total volume of 30 mL in normal saline | Drug: ropivacaine alone<br>* The ropivacaine alone group will receive 0.5% ropivacaine alone for pre-emptive scalp infiltration at about 30 min before surgical incision. The assigned solution was injected along the planned surgical incision and pin fixation sites of the Mayfield head holder, using a 22-gauge needle introduced throughout the entire thickness of the scalp at a 45° angle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total consumption of sufentanil with PCIA device at 48 hours postoperatively. | A postoperative Patient Controlled Intravenous Analgesia (PCIA) pump containing sufentanil 200μg in 100 mL saline will be administered from admission to the PACU until postoperative 48 hours. The PCIA pump will be set for 0.5 mL bolus doses with a lockout time of 15 min without initial dose or continuous infusion. The maximum dose will be limited to 2 mL (sufentanil 4 μg) per hour. | at 48 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total consumption of sufentanil with PCIA pump at 24 hours after craniotomy | A postoperative Patient Controlled Intravenous Analgesia (PCIA) pump containing sufentanil 200μg in 100 mL saline will be administered from admission to the PACU until postoperative 48 hours. The PCIA pump will be set for 0.5 mL bolus doses with a lockout time of 15 min without initial dose or continuous infusion. The maximum dose will be limited to 2 mL (sufentanil 4 μg) per hour. | at 24 hours postoperatively | 
| Time to first PCIA button press after craniotomy | A postoperative Patient Controlled Intravenous Analgesia (PCIA) pump containing sufentanil 200μg in 100 mL saline will be administered from admission to the PACU until postoperative 48 hours. The PCIA pump will be set for 0.5 mL bolus doses with a lockout time of 15 min without initial dose or continuous infusion. The maximum dose will be limited to 2 mL (sufentanil 4 μg) per hour. | after craniotomy | 
| Pain NRS scores at 2 hours after craniotomy | 0 indicates no pain and 10 indicates the worst pain imaginable | at 2 hours after craniotomy | 
| Pain NRS scores at 4 hours after craniotomy | 0 indicates no pain and 10 indicates the worst pain imaginable | at 4 hours after craniotomy | 
| Pain NRS scores at 12 hours after craniotomy | 0 indicates no pain and 10 indicates the worst pain imaginable | at 12 hours after craniotomy | 
| Pain NRS scores at 24 hours after craniotomy | 0 indicates no pain and 10 indicates the worst pain imaginable | at 24 hours after craniotomy | 
| Pain NRS scores at 48 hours after craniotomy | 0 indicates no pain and 10 indicates the worst pain imaginable | at 48 hours after craniotomy | 
| Pain NRS scores at 1 mon after craniotomy | 0 indicates no pain and 10 indicates the worst pain imaginable | at 1 mon after craniotomy | 
| Pain NRS scores at 3 mons after craniotomy | 0 indicates no pain and 10 indicates the worst pain imaginable | at 3 mons after craniotomy | 
| The time to first prescription of OC/APAP after craniotomy | In the ward, if a patient scores > 4 in pain NRS after receiving a maximum dose of 2 mL per hour from PCIA device, an oral supplementary tablet of oxycodone (OC)/acetaminophen (APAP) (5/325 mg; by MallinckrodtInc, USA) will be prescribed as a rescue analgesic at an interval of at least 6 hours. | up to 48 hours after craniotmy | 
| Hospital duration after craniotomy | The duration from end of surgery to discharge from hospital | From surgery day until the discharge date from hospital, assessed up to one week | 
| WHOQOL-BREF score | It is a questionnaire consisting of social relationships, physical health, psychological health, environment, overall QoL and general health. The mean score of each domain ranges between 4 and 20. A higher score indicates a better QoL | at 1month after craniotomy | 
| WHOQOL-BREF score | It is a questionnaire consisting of social relationships, physical health, psychological health, environment, overall QoL and general health. The mean score of each domain ranges between 4 and 20. A higher score indicates a better QoL | at 3 months after craniotomy | 
| PONV scores | It is rated as: 0, absent; 1, nausea not requiring treatment; 2, nausea requiring treatment; 3, vomiting | at 24 hours after surgery | 
| PONV scores | It is rated as: 0, absent; 1, nausea not requiring treatment; 2, nausea requiring treatment; 3, vomiting | at 48 hours after surgery | 
| Wound healing score | It is rated as excellent, good and suboptimal | at 1 month after craniotomy | 
| Wound healing score | It is rated as excellent, good and suboptimal | at 3 months after craniotomy | 
| Patient and Observer Scar Assessment Scale | It consists of 2 numeric scales regarding the observer component (6 items) and the patient component (6 items). All included items are scored on the same 10-point scale. And a higher score represents a poorer scar quality. | at 1 month after craniotomy | 
| Patient and Observer Scar Assessment Scale | It consists of 2 numeric scales regarding the observer component (6 items) and the patient component (6 items). All included items are scored on the same 10-point scale. And a higher score represents a poorer scar quality. | at 3 months after craniotomy | 
| The occurrence of other AEs | Other AEs include cerebral hematoma, respiratory depression, gastrointestinal ulcerations and perforation, renal risks, coagulation dysfunction, allergic reaction and wound infection, oozing, hemorrhage, burning sensation and mild pruritus | throughout both the treatment and follow-up periods (up to 3 months) |