Opioid-Sparing Effects of Flurbiprofen Axetil as an Adjuvant to Ropivacaine in Pre-Emptive Scalp Infiltration for Post-Craniotomy Pain: Study Protocol for a Multicenter, Randomized Controlled Trial

Abstract

Background

Pain after craniotomy remains a poorly controlled problem that is mainly caused by the inflammatory reaction at the incision site. Nowadays, systemic opioids use, as first-line analgesics, is often limited because of adverse effects. Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug merged into emulsified lipid microspheres, which represent a strong affinity to inflammatory lesions. Local administration of flurbiprofen into a surgical wound has induced enhanced analgesic efficacy and few systemic or local adverse effects after oral surgery. However, the impact of local FA, as a non-opioid pharmacologic alternative, remains elusive on postoperative pain in craniotomy. In this study, we presume that pre-emptive infiltration of scalp with FA as an adjuvant to ropivacaine can lead to less sufentanil consumption postoperatively in patient controlled intravenous analgesia (PCIA) compared with ropivacaine alone.

Methods/Design

We design a multicenter, randomized controlled study that will enroll 216 subjects who are planned to receive supratentorial craniotomy. Patients will receive pre-emptive infiltration of scalp either with 50 mg FA and 0.5% ropivacaine, or with 0.5% ropivacaine alone. Primary outcome is total consumption of sufentanil with PCIA device at 48 h postoperatively.

Discussion

This is the first study attempting to explore the analgesic and safety profile of local FA as an adjuvant to ropivacaine for incisional pain in patients undergoing craniotomy. It will provide additional insights into the opioid-sparing analgesia pathways by local administration of NSAIDs for neurosurgery.

Keywords:

• flurbiprofen axetil
• pre-emptive analgesia
• scalp infiltration
• opioid-sparing
• craniotomy
• postoperative pain

Abbreviations

FA, flurbiprofen axetil; NSAIDs, nonsteroidal anti-inflammatory drugs; PCIA, patient-controlled intravenous analgesia; IC, informed consent; BMI, body mass index; CRF, case report form; HR, heart rate; BP, blood pressure; BIS, bispectral index; SpO2, pulse oximetry; PACU, Post Anesthesia Care Unit; NRS, numerical rating scale; SOMC, Short Orientation Memory Concentration; POSAS, Patient and Observer Scar Assessment Scale; WHOQOL-BREF, World Health Organization QoL abbreviated version; PONV, postoperative nausea and vomiting; OC/APAP, oxycodone/acetaminophen; DMC, Data Monitoring Committee; AE, adverse events.

Data Sharing Statement

The datasets used and analyzed during this study are available from corresponding author Fang Luo on request.

Ethics Approval and Informed Consent

This trial will be performed in accordance with “Declaration of Helsinki”. The ethics approval (KY-2018-034-02-10) has been obtained from the Ethics Committee of Beijing Tiantan Hospital. All participants will sign the IC to participate before enrollment.

Author Contributions

Wei Zhang and Chunzhao Li have equally contributed to the protocol. They are regarded as co-first authors. All authors have made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas. All authors have taken part in drafting, revising or critically reviewing the article and approved the final manuscript to be published. All authors have agreed on the journal to which the article has been submitted and agreed to be accountable for all aspects of the work.

Disclosure

All authors declare that they have no competing interests.

Additional information

Funding

There is no funding to report.