Background. Oliceridine, an investigational IV opioid, is a first-in-class G-protein selective agonist at the μ-opioid receptor. The G-protein selectivity results in potent analgesia with less recruitment of β-arrestin, a signaling pathway associated with opioid-related adverse events (ORAEs). In randomized controlled studies in both hard and soft tissue models yielding surgical pain, oliceridine provided effective analgesia with a potential for an improved safety and tolerability profile at equianalgesic doses to morphine. The phase 3, open-label, single-arm, multicenter ATHENA trial demonstrated the safety, tolerability, and effectiveness of oliceridine in moderate to severe acute pain in a broad range of patients undergoing surgery or with painful medical conditions warranting use of an IV opioid. This retrospective, observational chart review study compared respiratory depression events associated with oliceridine administration as found in the ATHENA trial to a control cohort treated with conventional opioids. Methods. Patients at 18 years of age or older, who underwent colorectal, orthopedic, cardiothoracic, bariatric, or general surgeries between June 2015 and May 2017 in 11 sites participating in the ATHENA trial who received postoperative analgesia either with IV oliceridine or with IV conventional opioids (e.g., morphine alone or in combination with other opioids) (CO cohort); and had a hospital stay >48 hours, were included in this retrospective analysis. Data from the ATHENA trial was used for the oliceridine cohort; and additional baseline characteristics were collected from medical charts. Data from medical charts were collected for all CO cohort patients. The two cohorts were balanced using an inverse probability weighting method. The primary outcome was the incidence of operationally defined opioid-induced respiratory depression (OIRD) in the two cohorts. Secondary outcomes included between-group comparison of the incidence of OIRD events among a subset of high-risk patients. Results. OIRD was significantly less in the oliceridine cohort compared to the CO cohort (8.0% vs. 30.7%; odds ratio: 0.139) (95% confidence interval [CI] 0.09–0.22; ). Likewise, the incidence of OIRD was lower among high-risk patients in the oliceridine cohort (9.1% vs. 34.7%; odds ratio: 0.136) (95% CI [0.09–0.22]; ) compared to the CO cohort. Conclusion. In this retrospective chart review study, patients receiving IV oliceridine for moderate to severe acute pain demonstrated a lower incidence of treatment emergent OIRD compared to patients who were treated with IV morphine either alone or with concomitant administration of other opioids.

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与吗啡相比，使用奥利替丁进行术后呼吸抑制的发生率低：回顾性图表分析

背景。Oliceridine，一种研究IV阿片样物质，是在第一的一流G蛋白选择性激动剂μ阿片受体。G蛋白选择性导致强效镇痛，β募集较少-arrestin，与阿片相关不良事件（ORAE）相关的信号通路。在产生手术疼痛的硬组织和软组织模型中的随机对照研究中，奥利替丁可提供有效的镇痛作用，并具有在以吗啡为等效镇痛剂量的情况下改善安全性和耐受性的潜力。开放标签，单臂，多中心ATHENA的3期临床试验表明，在许多接受手术或疼痛医疗条件（需要使用阿片类阿片类药物）的患者中，奥利替丁在中度至重度急性疼痛中的安全性，耐受性和有效性。这项回顾性，观察性图表回顾性研究比较了ATHENA试验中发现的与奥利替丁给药相关的呼吸抑制事件与常规阿片类药物治疗的对照组。方法。在2015年6月至2017年5月期间，在参加ATHENA试验的11个地点接受大肠，骨科，心胸，肥胖症或普通外科手术的18岁或18岁以上患者，接受静脉输注奥利替丁或静脉内常规阿片类药物的术后镇痛（例如，吗啡单独使用或与其他阿片类药物联合使用（CO队列）；回顾性分析包括住院时间超过48小时的患者。来自ATHENA试验的数据用于奥利替丁队列；并且从医学图表中收集了其他基线特征。从医学图表中收集了所有CO队列患者的数据。使用逆概率加权方法对两个队列进行了平衡。主要结果是两个队列中可明确定义的阿片类药物引起的呼吸抑制（OIRD）的发生率。次要结果包括一组高危患者中OIRD事件发生率的组间比较。结果。相比于CO队列，奥利替丁组的OIRD显着更少（8.0％vs. 30.7％；优势比：0.139）（95％置信区间[CI] 0.09-0.22； P <0.05）。）。同样，在奥利替丁组高危患者中，OIRD的发生率较低（分别为9.1％和34.7％；优势比：0.136）（95％CI [0.09-0.22]；）与CO队列相比。结论。在这项回顾性图表审查研究中，与单独使用IV吗啡或同时使用其他阿片类药物治疗的患者相比，接受IV来水芹油治疗中度至重度急性疼痛的患者显示出紧急OIRD的治疗发生率较低。