Long acting local anesthesia and preventive analgesia—difficulty of prove on clinical trial
Editorial Commentary

长效局部麻醉药和预防性镇痛——临床试验验证的困难性

Katsuhisa Sunada

Department of Dental Anesthesiology, The Nippon Dental University School of Life Dentistry, Tokyo, Japan

Correspondence to: Katsuhisa Sunada, DDS, PhD. Department of Dental Anesthesiology, The Nippon Dental University School of Life Dentistry, Tokyo, Japan. Email: katsu.sunada@nifty.com.

Comment on: Amorim KS, Gercina AC, Ramiro FMS, et al. Can local anesthesia with ropivacaine provide postoperative analgesia in extraction of impacted mandibular third molars? A randomized clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol 2021;131:512-8.

Received: 01 November 2021; Accepted: 12 November 2021; Published: 30 June 2022.

doi: 10.21037/joma-21-14

得益于麻醉药和麻醉方法的不断改进，如今，患者在拔牙时几乎不会感到疼痛。然而，术后疼痛仍然给许多患者带来不适和痛苦。拔牙后，医生常开具非甾体类抗炎药（Nonsteroidal anti-inflammatory drugs，NSAIDs）和处方类阿片类药物，但NSAIDs可能会导致胃溃疡，患有胃肠道疾病的患者需谨慎使用；有些患者阿司匹林不耐受，因此无法使用这类药物。这使患者术后镇痛药物的选择成为了一个难题。另外，医生也不会开具足量的阿片类药物，因为其具有成瘾性。因此，人们正在研究缓解术后疼痛的替代方法。动物研究已经探索了预防性镇痛的使用（也称为超前镇痛），也报告了充分的术前镇痛可以有效缓解术后疼痛[1-4]。但相关临床研究的结果却存在分歧，有些报告称预防性镇痛有效[5,6]，但也有报告否定这一结论[7-9]。产生分歧的原因可能是研究个体疼痛阈值和心理因素的差异。

Amorim等人关于“下颌第三磨牙阻生牙拔牙的术后镇痛：一项随机临床试验”的研究表明，长效局麻药罗哌卡因对术后镇痛有效[10]。该研究采用交叉法比较了在需要削骨的双侧下颌第三磨牙（Pell和Gregory分类为Ⅱ-B）拔除术中，使用0.75%罗哌卡因和2%利多卡因加1:100 000肾上腺素的术后疼痛情况。麻醉药通过局部浸润麻醉、颊神经阻滞和下牙槽神经阻滞给药。依靠患者随访的临床研究常常会出现数据缺失的情况。该研究的作者每隔30分钟会给每位患者打一次电话，询问麻醉效果。因此，获得的数据是可靠的。研究者发现，使用0.75%罗哌卡因的平均麻醉持续时间为445.7±58分钟（平均值±标准差），明显长于使用2%利多卡因加1:100 000肾上腺素的213.8±41分钟。这一结果与Ogura等人[11]的研究结果相似。此外，Amorim等人发现，患者在接受2%利多卡因加1:100 000肾上腺素后24小时内，其术后VAS疼痛评分没有明显降低，而患者在接受0.75%罗哌卡因后8小时内，其VAS评分明显降低。给予0.75%罗哌卡因时，安乃近的总用量和使用频率也明显降低。特别是在第72个小时，接受0.75%罗哌卡因的患者中没有人使用安乃近，而在使用2%利多卡因加1:100 000肾上腺素后，有20名患者使用了安乃近。因此，作者得出结论，0.75%的罗哌卡因发挥了预防性镇痛作用，减轻了拔除阻生第三磨牙后的疼痛。笔者（KS）同意与2%利多卡因加1:100 000肾上腺素相比，0.75%罗哌卡因对缓解拔牙后疼痛更有效，但无法明确得知这一效果是否如作者所述是预防性镇痛的直接结果。

疼痛刺激会降低周围神经元的阈值并刺激中枢神经系统。因此，预防性镇痛通过防止疼痛输入至神经系统而获得镇痛效果。另一方面，长效局麻药延长了术后镇痛效果持续的时间，因此可以减少镇痛药的使用剂量。此外，长效镇痛可以帮助患者迅速恢复口腔功能，包括咬合和吞咽，而且由于伤口部位的血液灌注增加，炎症和疼痛也能更快消失。总之，与预防性镇痛相比，长效局麻药能在更大程度上减少镇痛药用量，这一点不可否认。预防性镇痛的临床研究需要比较无痛拔牙的患者和在麻醉不充分的情况下拔牙的患者的术后疼痛程度，但由于伦理方面的原因，这种研究不能进行。这可能是预防性镇痛难以在临床环境中验证的原因。

作者引用了Johansson等人的一项研究，该研究的结论是，罗哌卡因在术后初期有明显的、与剂量有关的镇痛作用，但找不到支持术前浸润镇痛减少长期疼痛的理论依据[12]。本研究还讨论了0.75%罗哌卡因的血管收缩作用，以及加入肾上腺素的效果。作者引用了过去的临床研究，这些研究表明罗哌卡因具有收缩血管的特性[13,14]，而肾上腺素有助于延长利多卡因等麻醉药血管扩张的作用时间[15,16]。另一方面，Yamashiro等人报告称，0.5%罗哌卡因没有血管收缩作用，在大鼠的实验研究中，加入肾上腺素后，罗哌卡因在上颌组织中的浓度增加了3倍[17]。Fujita等人也报告称，与2%利多卡因相比，加入肾上腺素的0.5%罗哌卡因在增加大鼠上颌组织麻醉药物浓度中的影响更大[18]。笔者认为，本研究中0.75%罗哌卡因给药后出现大量出血的原因是0.75%罗哌卡因没有血管收缩作用。基于这些原因，笔者认为在罗哌卡因中加入肾上腺素可以增强麻醉效果，提供长效麻醉，并减少术后出血。当然，正如作者所言，关于罗哌卡因加肾上腺素在口腔手术和一般牙科中的应用，还需要进行更多的临床研究。然而，笔者个人认为，罗哌卡因加肾上腺素会是一种有效的牙科麻醉方案。

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Oral and Maxillofacial Anesthesia. The article did not undergo external peer review.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://joma.amegroups.com/article/view/10.21037/joma-21-14/coif). The author has no conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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译者介绍
徐天意
上海交通大学医学院硕士，现就职于上海交通大学医学院附属第九人民医院。（更新时间：2022/9/2）
审校介绍
夏明
Journal of Oral and Maxillofacial Anesthesia （JOMA）执行主编。上海交通大学医学院附属第九人民医院麻醉科副主任医师，副教授，硕士研究生导师；麻醉学博士，博士后。现担任中华口腔医学会口腔麻醉学专业委员会全国常务委员、上海市疼痛科临床质量控制中心专家委员会委员、中华口腔医学会镇静镇痛分会全国委员等学术职务。（更新时间：2022/9/2）

（本译文仅供学术交流，实际内容请以英文原文为准。）

doi: 10.21037/joma-21-14
Cite this article as: Sunada K. Long acting local anesthesia and preventive analgesia—difficulty of prove on clinical trial. J Oral Maxillofac Anesth 2022;1:18.

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