Harvard Medical School, Boston, MA.
Harvard School of Dental Medicine, Boston, MA.
J Surg Res. 2021 Aug;264:510-533. doi: 10.1016/j.jss.2021.02.024. Epub 2021 Apr 13.
Background The opioid crisis has prompted surgeons to search for alternative postoperative methods of analgesia. Liposomal bupivacaine is a long-acting local anesthetic formulation used for pain, potentially reducing opioid use. Evaluation of liposomal bupivacaine as a viable alternative for pain management is needed. The objective was to assess the efficacy of randomized clinical trials (RCTs) of liposomal bupivacaine in postoperative pain management and opioid consumption. Material and Methods The authors extracted RCTs comparing liposomal bupivacaine versus placebo or active comparators for postoperative pain or opioid reduction from PubMED/MEDLINE, Cochrane Library, and ClinicalTrials.gov. Exclusion criteria included nonhuman studies, non-RCTs, pooled studies, and inability to access full text. The following variables were abstracted: surgical specialty, number of subjects, pain and opioid outcomes, and authors' financial conflicts of interest. Results We identified 77 published RCTs, of which 63 studies with a total of 6770 subjects met inclusion criteria. Liposomal bupivacaine did not demonstrate significant pain relief compared to placebo or active agents in 74.58% of RCTs. Of the studies evaluating narcotic use, liposomal bupivacaine did not show a reduction in opioid consumption in 85.71% of RCTs. Liposomal bupivacaine, when compared to standard bupivacaine or another active agent, yielded no reduction in opioid use in 83.33% and 100.00% of studies, respectively. Clinical trials with a financial conflict of interest relating to the manufacturer of liposomal bupivacaine were significantly more likely to show pain relief (OR: 14.31 [95% CI, 2.8, 73.10], P = 0.0001) and decreased opioid consumption (OR: 12.35 [95% CI 1.40, 109.07], P = 0.0237). Of the 265 unpublished RCTs on ClinicalTrials.gov, 47.54% were withdrawn, terminated, suspended, or completed without study results available. Conclusions The efficacy of liposomal bupivacaine for providing superior postoperative pain control relative to placebo or another active agent is not supported by a majority of RCTs. Underreporting of trial results and bias due to underlying financial relationships amongst authors are two major concerns that should be considered when evaluating the available evidence.
阿片类药物危机促使外科医生寻找替代术后镇痛的方法。脂质体布比卡因是一种长效局部麻醉制剂，用于止痛，可能减少阿片类药物的使用。需要评估脂质体布比卡因作为一种可行的疼痛管理替代方案。目的是评估脂质体布比卡因在术后疼痛管理和阿片类药物消耗方面的随机临床试验 (RCT) 的疗效。
作者从 Pubmed/MEDLINE、Cochrane 图书馆和 ClinicalTrials.gov 中提取了比较脂质体布比卡因与安慰剂或活性对照剂用于术后疼痛或减少阿片类药物的 RCT。排除标准包括非人类研究、非 RCT、汇总研究以及无法获取全文。提取了以下变量：手术专业、受试者数量、疼痛和阿片类药物结果以及作者的财务利益冲突。
我们确定了 77 项已发表的 RCT，其中 63 项研究共 6770 名受试者符合纳入标准。在 74.58%的 RCT 中，脂质体布比卡因与安慰剂或活性药物相比并未显示出显著的疼痛缓解作用。在评估阿片类药物使用的研究中，在 85.71%的 RCT 中，脂质体布比卡因并未显示出阿片类药物消耗减少。与标准布比卡因或另一种活性药物相比，脂质体布比卡因在分别为 83.33%和 100.00%的研究中并未减少阿片类药物的使用。与脂质体布比卡因制造商有关的财务利益冲突的临床试验更有可能显示出疼痛缓解（OR：14.31 [95%CI，2.8，73.10]，P=0.0001）和减少阿片类药物消耗（OR：12.35 [95%CI 1.40，109.07]，P=0.0237）。ClinicalTrials.gov 上的 265 项未发表的 RCT 中，有 47.54%撤回、终止、暂停或完成，而没有研究结果。
脂质体布比卡因在提供优于安慰剂或另一种活性药物的术后疼痛控制方面的疗效，并未得到大多数 RCT 的支持。试验结果的漏报和作者之间潜在的财务关系导致的偏倚是在评估现有证据时应考虑的两个主要问题。
