Xueye Han,1 Yixuan Yang,2 Tong Ren,3 Nan Ji,3 Fang Luo2 

1Department of Anesthesiology and Pain Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100027, People’s Republic of China; 2Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China

Correspondence: Fang Luo, Department of Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China, Tel +86 010 59976664, Fax +86 010 67050177, Email 13611326978@163.com Nan Ji, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China, Tel +86 010 59976516, Email jinan@bjtth.org

Objective: The current landscape is characterized by a dearth of effective, safe, simple, and noninvasive methods for preventing pain following craniotomy. This clinical trial seeks to evaluate the efficacy profile of preemptive application of a topical 5% lidocaine patch in alleviating post-craniotomy pain.
Methods: This was a multi-centric, prospective randomized placebo-controlled triple-blind clinical trial. Eligible patients were randomly assigned to either the masked intervention group, who received lidocaine 5% white hydrogel plasters (N = 90), or the placebo control group who received plain hydrogel plasters of the same pattern, size, appearance and material as L5Ps, but free of lidocaine (N = 90). Primary outcome was the pain intensity (Visual Analogue Scale at 24 h) after craniotomy. Secondary outcomes included: intra-operative analgesics consumption, pain intensity, cumulative rescue analgesics consumption, sleeping scores, adverse effects such as skin reactions, etc. The intention-to-treat analyses and the per-protocol analyses were used.
Results: There were no statistically significant differences in the VAS scores at 24 h after craniotomy (P = 0.539). However, subgroup analysis for female and male patients showed that statistically significant differences were found in VAS scores in male patients (0 [0, 3] in the masked intervention group at 24 h after craniotomy and 3 [1, 4.5] in the placebo control group, P = 0.017). There were no obvious side effects directly associated with preemptive L5P.
Conclusion: Preemptive lidocaine 5% plaster as a safe technique was not found to be effective in reducing post-craniotomy pain, but potential gender disparities in the outcomes of this method warrant further investigation.
Trial Registration: ClinicalTrials.Gov (NCT 04169854).

Keywords: craniotomy, lidocaine 5% plaster, postoperative pain, triple-blind, randomized controlled trial