Haeseler Gertrud, Schaefers Dirk, Prison Natalie, Ahrens Jörg, Liu Xiaofei, Karch Annika
Department of Anesthesia, Katholisches Klinikum Ruhrgebiet Nord (KKRN) GmbH, Hervester Str. 57, D-45768, Marl, Germany.
Department of orthopedic and trauma surgery, KKRN, Hervester Str. 57, D-45768, Marl, Germany.
BMC Anesthesiol. 2017 Jul 11;17(1):91. doi: 10.1186/s12871-017-0383-6.
High post-operative pain scores after "minor" orthopedic/trauma surgery are in part attributed to inadequate prescription of opioid analgesics. Novel concepts aiming to achieve sufficient analgesia while minimizing opioid-related side effects by avoiding fluctuating plasma levels are based on perioperative oral administration of extended-release opioids beginning with the first dose pre-operatively. This is the first study to evaluate analgesic efficacy and side effect rates of extended-release tapentadol compared to oxycodone/naloxone following orthopedic/trauma surgery.
This randomized, observer-blinded, active-controlled prospective clinical trial had 2 co-primary endpoints: (1) Analgesic efficacy: Mean pain level on a numeric rating scale (NRS) from 0 to 10 during exercise over 5 days. (2) Safety: Side effect sum score of the following events: Nausea, vomiting, constipation, sedation, vertigo, somnolence. The study was powered to detect superiority of tapentadol for at least one endpoint pending statistical proof of non-inferiority for both endpoints in a first step.
Two hundred sixty-six trauma patients were randomized to receive either tapentadol (n = 133) or oxycodone/naloxone (n = 133). Analgesic efficacy: Mean (±SD) daily pain levels in the first five post-operative days were 2.8 ± 1.3 in both groups. Mean maximum pain intensity during exercise in the first 24 h after surgery was 3.8 ± 1.9 (tapentadol) and 3.8 ± 2.1 (oxycodone/naloxone). Statistically tapentadol was non-inferior but not superior to oxycodone/naloxone.
Vomiting on day 1 occurred in 11%, constipation in 35% of the tapentadol patients and in 16% and 30% of the oxycodone/naloxone patients (p = 0.60 and 0.33), respectively. The incidence of sedation/ vertigo was <10%, that of somnolence <2% in both groups (p > 0.3, respectively). The sum score of side effect events was 51% in the tapentadol vs. 49% in the oxycodone/naloxone group; risk difference 3% [95% CI, -8 to 14%]; p = 0.6). Non-inferiority of tapentadol could not be concluded as the pre-defined non-inferiority margin was exceeded.
With both concepts, mean maximum pain intensity during exercise within the first 24 h after orthopedic/trauma surgery was reduced to a score of <4. This analgesic efficacy came at the cost of mainly gastro-intestinal side effects. Thus, we now use a prophylaxis against nausea and vomiting and pre-emptive laxatives as part of these concepts.
https://eudract.ema.europa.eu (EudraCT- Nr. 2011-003238-15 ); October 24th, 2012.
“小型”骨科/创伤手术后较高的术后疼痛评分部分归因于阿片类镇痛药的处方不足。旨在通过避免血浆水平波动来实现充分镇痛同时将阿片类药物相关副作用降至最低的新观念，是基于从术前第一剂开始围手术期口服缓释阿片类药物。这是第一项评估骨科/创伤手术后缓释曲马多与羟考酮/纳洛酮相比的镇痛效果和副作用发生率的研究。
这项随机、观察者盲法、活性对照前瞻性临床试验有2个共同主要终点：（1）镇痛效果：术后5天运动期间数字评分量表（NRS）上0至10的平均疼痛水平。（2）安全性：以下事件的副作用总分：恶心、呕吐、便秘、镇静、眩晕、嗜睡。该研究旨在检测曲马多在至少一个终点上的优越性，第一步是两个终点均需有非劣效性的统计学证据。
266名创伤患者被随机分为接受曲马多（n = 133）或羟考酮/纳洛酮（n = 133）。镇痛效果：两组术后头五天的平均（±标准差）每日疼痛水平均为2.8±1.3。术后头24小时运动期间的平均最大疼痛强度在曲马多组为3.8±1.9，羟考酮/纳洛酮组为3.8±2.1。从统计学上看，曲马多不劣于但也不优于羟考酮/纳洛酮。
曲马多组第1天呕吐发生率为11%，便秘发生率为35%；羟考酮/纳洛酮组呕吐发生率为16%，便秘发生率为30%（p分别为0.60和0.33）。两组镇静/眩晕发生率<10%，嗜睡发生率<2%（p均>0.3）。副作用事件总分在曲马多组为51%，羟考酮/纳洛酮组为49%；风险差异为3%[95%置信区间，-8至14%]；p = 0.6）。由于超过了预先定义的非劣效性界限，无法得出曲马多非劣效的结论。
采用这两种方法，骨科/创伤手术后头24小时运动期间的平均最大疼痛强度均降至<4分。这种镇痛效果是以主要的胃肠道副作用为代价的。因此，我们现在在这些方法中使用预防恶心和呕吐以及预防性泻药。
https://eudract.ema.europa.eu（欧盟临床试验注册号：2011 - 003238 - 15）；2012年10月24日。
