Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Pharmacotherapy. 2012 Sep;32(9 Suppl):19S-26S. doi: 10.1002/j.1875-9114.2012.01183.x.
Local anesthetics are a cornerstone of multimodal pain control strategies in the surgical setting as they have a long history of use and an established safety profile. Although effective, their duration of action is relatively short, which usually leads to the use of other agents, such as opioids, for effective postsurgical pain control in most patients. A medical need exists to extend the duration of analgesia with local anesthetics to help reduce the reliance on opioids in the postsurgical setting. Liposomal bupivacaine uses a product delivery platform to release bupivacaine slowly over 96 hours after infiltration at the surgical site. Liposomal bupivacaine was compared with placebo in two pivotal, multicenter, randomized, double-blind, parallel-group trials in 189 adults undergoing soft-tissue surgery (hemorrhoidectomy) and 193 adults undergoing orthopedic surgery (bunionectomy). Among patients undergoing hemorrhoidectomy, liposomal bupivacaine significantly reduced cumulative pain scores for up to 72 hours (primary end point) as measured by the area under the curve of pain scores on the numeric rating scale (p<0.0001), reduced overall opioid consumption (p ≤ 0.0006), increased the proportion of patients who did not receive opioids (p<0.0008), delayed time to first opioid by more than 13 hours (p<0.0001), and was associated with significantly higher rates of patient satisfaction (p=0.0007) compared with placebo. Similarly, in patients undergoing bunionectomy, liposomal bupivacaine significantly reduced total consumption of rescue opioids (p=0.0077) and cumulative pain scores as measured by the area under the curve of pain scores on the numeric rating scale (p=0.0005) during the first 24 postsurgical hours (primary end point) relative to placebo. Furthermore, liposomal bupivacaine also significantly delayed the time to first use of opioid rescue (p<0.0001) and increased the proportion of patients requiring no rescue opioid treatment (p ≤ 0.0404) compared with placebo. The most common adverse events with liposomal bupivacaine were nausea, vomiting, and constipation. No adverse effects on the QTc interval or cardiac safety signal have been detected in the clinical trial development program (823 patients) when liposomal bupivacaine was infiltrated into the surgical site. The beneficial effects of liposomal bupivacaine on postsurgical pain management and opioid use, significantly reducing both, are likely to translate into improved clinical and economic outcomes.
局部麻醉药是手术中多模式疼痛控制策略的基石，因为它们具有悠久的使用历史和既定的安全性。尽管有效，但它们的作用持续时间相对较短，这通常导致在大多数患者中使用其他药物，如阿片类药物，以有效控制术后疼痛。医疗上需要延长局部麻醉药的镇痛持续时间，以帮助减少术后对阿片类药物的依赖。脂质体布比卡因利用产品输送平台，在手术部位浸润后 96 小时内缓慢释放布比卡因。脂质体布比卡因在两项关键的、多中心、随机、双盲、平行组试验中与安慰剂进行了比较，共纳入 189 例接受软组织手术（痔切除术）的成年人和 193 例接受骨科手术（拇囊炎切除术）的成年人。在接受痔切除术的患者中，脂质体布比卡因在长达 72 小时（主要终点）内显著降低累积疼痛评分，这是通过数字评分量表上的疼痛评分曲线下面积来衡量的（p<0.0001），减少了总体阿片类药物用量（p ≤ 0.0006），增加了不使用阿片类药物的患者比例（p<0.0008），首次使用阿片类药物的时间延迟超过 13 小时（p<0.0001），并且与安慰剂相比，患者满意度显著提高（p=0.0007）。同样，在接受拇囊炎切除术的患者中，脂质体布比卡因在术后前 24 小时内显著减少了阿片类药物解救药物的总消耗量（p=0.0077）和通过数字评分量表上的疼痛评分曲线下面积衡量的累积疼痛评分（p=0.0005）（主要终点）与安慰剂相比。此外，脂质体布比卡因还显著延迟了首次使用阿片类药物解救的时间（p<0.0001），并增加了不需要阿片类药物解救治疗的患者比例（p ≤ 0.0404）与安慰剂相比。脂质体布比卡因最常见的不良反应是恶心、呕吐和便秘。在临床研发计划（823 例患者）中，将脂质体布比卡因注入手术部位时，未检测到 QTc 间期或心脏安全性信号的不良影响。脂质体布比卡因对术后疼痛管理和阿片类药物使用的有益影响，显著减少了两者，可能会转化为改善的临床和经济结果。
