The Local Infiltration Therapy (LIT) Trial for Pain Control Following Hip Fracture Fixation

老年性髋部骨折是一个日益突出的公共健康问题，有30多万人骨折 每年在美国境内持续存在，预计到2050年将超过100万。这些骨折改变了生活 对于老年患者来说，持续的术后并发症可能会严重削弱他们的身体素质。术后 疼痛可通过增加术后并发症的风险而成为不良结局的重要驱动因素，包括 精神错乱与死亡率、发病率和预后的增加有关，持续超过指标 住院治疗。疼痛控制经常使用阿片类药物，老年患者尤其如此。 容易受到副作用的影响，这些副作用包括嗜睡、精神错乱、恶心、呕吐、 尿潴留和呼吸抑制。此外，在当前的情况下，阿片类药物的使用增加 阿片类药物的流行更令人担忧，老年患者与其他年龄段的患者一样容易受到影响。因此， 减少这些患者的阿片类药物的使用对于减少并发症和最终改善至关重要。 对这群应得的患者的结果。一项试点、双盲、多中心、安慰剂对照试验 我们最近进行了，我们报告了髋部骨折固定术后阿片类药物的使用减少，并减少了 使用脂质体布比卡因进行疼痛视觉模拟评分(VAS)。在后续的回溯性研究中， 我们证明使用常用药物的注射鸡尾酒(可乐定， 肾上腺素、罗比卡因、托拉多)阿片类药物的使用也出现了类似的、可能更大的减少 疼痛VAS与脂质体布比卡因比较。注射鸡尾酒的成本低于注射鸡尾酒 商业脂质体布比卡因，可能是一种比脂质体布比卡因更具成本效益的替代品。 考虑到这些发现和关节置换文献中对这两种方式的广泛支持，评估 改善髋部骨折人群预后的方法对于帮助预防并发症和 这些患者的预后很差。该提案旨在启动并完成多中心的规划， 使用安慰剂进行双盲非自卑试验，以确定效应大小，以检验我们的假设 药房配制的鸡尾酒不亚于市售的布比卡因脂质体，而且当地 注射疗法可以改善髋部骨折固定术后的疼痛控制。我们将利用现有的研究 临床站点之间的关系，以完成方案，优化程序，准备预算，制定 礼宾表格，优化招聘程序，制定标准程序手册，执行监管 提交材料，并在必要时招募更多的地点，以完成拟议的试验。鉴于……的严重性 与疼痛控制不佳、成功规划和完成这项试验相关的并发症可能 介绍一种不含阿片类药物，适应性广，资源最少的疼痛控制方法。

Geriatric hip fractures are an increasingly prominent public health problem with more than 300,000 fracture sustained within the U.S. each year and predicted over 1,000,000 by 2050. These fractures are life changing in elderly patients and sustaining a post-operative complication can be severely debilitating. Post-operative pain can be a significant driver of poor outcome via an increased risk of post-operative complications, including delirium which is associated with increased mortality, morbidity and outcome which persists beyond index hospitalization. Pain control is frequently managed with opioids which elderly patients are particularly susceptible to the negative side-effects they entail, which include somnolence, delirium, nausea, vomiting, urinary retention and respiratory depression. Additionally, increased opioid use in the context of the current opioid epidemic is further concerning and elderly patients are just as susceptible as other age groups. Thus, decreasing opioid use in these patients is paramount in decreasing complications and ultimately improving outcome for this deserving group of patients. In a pilot, double-blinded, multi-centered placebo-controlled trial we recently conducted, we reported a decreased use of opioids following hip fracture fixation and decreased pain visual analog scores (VAS) with the usage of liposomal bupivacaine. In a follow-up retrospective study, we demonstrated that the use of an injection cocktail of commonly available medications (Clonidine, Epinephrine, Ropivacaine, Toradol) demonstrated a similar and possibly greater decrease of opioid use and pain VAS when compared to liposomal bupivacaine. The injection cocktail is associated with less cost than the commercial liposomal bupivacaine and may be a more cost-effective alternative to liposomal bupivacaine. Given these findings and large support for both of these modalities in the arthroplasty literature, evaluation of the approach to improve outcomes in the hip fracture population is crucial to helping prevent complications and poor outcomes in these patients. This proposal aims to initiate and complete the planning of a multi-center, double-blind, non-inferiority trial with placebo for effect size determination to test our hypotheses that a pharmacy prepared cocktail is not inferior to a commercially available liposomal bupivacaine, and that local injection therapy can improve pain control following hip fracture fixation. We will utilize existing research relationships between clinical sites to complete the protocol, optimize procedures, prepare a budget, develop protocol forms, optimize recruitment procedures, develop a standard procedures manual, perform regulatory submissions and recruit additional sites as necessary to complete the proposed trial. Given the severity of complications associated with poor pain control, successful planning and completion of this trial can potentially introduce a method of pain control which is opioid free and widely adaptable with minimal resources.