A comparison of Depodur™, a novel, single-dose extended-release epidural morphine, with standard epidural morphine for pain relief after lower abdominal surgery
A comparison of Depodur™, a novel, single-dose extended-release epidural morphine, with standard epidural morphine for pain relief after lower abdominal surgery
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DOI：
10.1213/01.ane.0000145009.03574.78
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发表时间：
2005-04-01
影响因子：
5.7
通讯作者：
Manvelian, G
中科院分区：
文献类型：
--
作者：
Gambling, D;Hughes, T;Manvelian, G
在这项随机、对照、剂量范围研究中，我们评估了一种新型单剂量硬膜外缓释吗啡（Depodur（TM））在下腹部手术患者中的镇痛效果。541例患者被随机分配到6个硬膜外治疗前约30分钟管理之一。6种治疗为5 mg标准硬膜外硫酸吗啡（MS）（活性对照药物）; 5 mg单次给药硬膜外缓释吗啡（EREM）（剂量对照）;以及10、15、20和25 mg单次给药EREM。主要研究目的是评估EREM 10、15、20或25 mg单次给药与EREM 5 mg单次给药在术后疼痛管理方面的疗效。这是通过绘制线性剂量-反应关系来完成的，以评估手术后48小时的术后IV患者自控镇痛（PCA）芬太尼消耗量。次要安全性和有效性分析比较了10、15、20和25 mg单次给药EREM组与5 mg单次给药EREM组，并比较了每个单次给药EREM组与5 mg MS。如剂量-反应关系所示，术后48小时内IV芬太尼的使用量呈剂量相关性减少（估计斜率，-22.2; P = 0.0002）。接受10、20和25 mg单剂量EREM治疗的患者使用的IV芬太尼显著减少（平均值+/- SD：995 +/- 987 μ g，P = 0.0446; 972 +/- 982 μ g，P = 0.0221;和683 +/- 620 μ g，P < 0.0001）与5 mg单剂量EREM组（1218 +/- 894 μ g）相比。在给药后48小时，单次给药EREM患者（13%）比MS患者（2%）显著更多（P < 0.01）不需要IV芬太尼。尽管所有治疗组都可以使用PCA芬太尼，MS组中PCA芬太尼的使用频率更高，但单剂量EREM 15、20和25 mg组的患者报告疼痛强度评分显著降低，对疼痛缓解的满意度更高。总体而言，单剂量EREM耐受性良好，97%的不良事件被评为轻度至中度。正如预期的那样，报告的不良事件与其他硬膜外阿片类药物（即，恶心、呕吐、瘙痒和低血压）。总之，这项对照研究表明，单剂量EREM可提供长达48小时的术后镇痛，但大多数患者仍需要补充突破性疼痛。在本研究的背景下，单次给药EREM的副作用特征是可接受和可预测的。
In this randomized, controlled, dose-ranging study, we evaluated the analgesic efficacy of a novel single-dose extended-release epidural morphine (Depodur (TM)) in patients undergoing lower abdominal surgery. Five-hundred-forty-one patients were randomly assigned to one of six epidural treatments administered approximately 30 min before surgery. The 6 treatments were 5 mg of standard epidural morphine sulfate (MS) (active comparator); 5 mg of single-dose extended-release epidural morphine (EREM) (dose control); and 10, 15, 20, and 25 mg of single-dose EREM. The main study objective was to assess the efficacy of single-dose EREM 10, 15, 20, or 25 mg versus single-dose EREM 5 mg for the management of postoperative pain. This was done by plotting a linear dose-response relationship to assess postoperative IV patient-controlled analgesia (PCA) fentanyl consumption for breakthrough pain for 48 h after surgery. Secondary safety and efficacy analyses compared the 10-, 15-, 20-, and 25-mg single-dose EREM groups with the 5-mg single-dose EREM group and compared each single-dose EREM group with 5 mg of MS. As shown by the dose-response relationship, there was a dose-related reduction in the use of postoperative IV fentanyl through 48 h (estimated slope, -22.2; P = 0.0002). Patients treated with 10, 20, and 25 mg of single-dose EREM used significantly less IV fentanyl (mean +/- SD: 995 +/- 987 mu g, P = 0.0446; 972 +/- 982 mu g, P = 0.0221; and 683 +/- 620 mu g, P < 0.0001, respectively) through 48 h after surgery compared with the 5-mg single-dose EREM group (1218 +/- 894 mu g). At 48 h post-dose, significantly more single-dose EREM patients (13%) than MS patients (2%) had required no IV fentanyl (P < 0.01). Although all treatment groups had access to PCA fentanyl and there was more frequent PCA fentanyl use in the MS group, patients in the single-dose EREM 15, 20, and 25 mg groups reported significantly lower pain-intensity scores and greater satisfaction with their pain relief. Overall, single-dose EREM was well tolerated, with 97% of adverse events rated as mild to moderate. As expected, the adverse events reported were consistent with those of other epidural opioids (i.e., nausea, vomiting, pruritus, and hypotension). In conclusion, this controlled study demonstrated that single-dose EREM can provide up to 48 h of postoperative analgesia, but supplementation for breakthrough pain is still required in most patients. Within the context of this study, the side effect profile of single-dose EREM was acceptable and predictable.