Marinangeli Franco, Ciccozzi Alessandra, Aloisio Luca, Colangeli Antonello, Paladini Antonella, Bajocco Chiara, Coaccioli Stefano, Varrassi Giustino
Department of Anesthesiology and Pain Medicine, L'Aquila University, L'Aquila, Italy.
Pain Pract. 2007 Dec;7(4):307-12. doi: 10.1111/j.1533-2500.2007.00155.x. Epub 2007 Nov 6.
The aim of the study was to facilitate dose escalation of strong opioids. In this randomized open-label study the influence of tramadol on dose adjustment of transdermal fentanyl in advanced cancer pain control was prospectively evaluated. Seventy patients affected by intractable cancer disease with visual analog scale (VAS) score >3 were enrolled. Thirty-five patients were treated conventionally with increasing transdermal fentanyl dosage as required (group F) and 35 patients received oral tramadol added to their transdermal fentanyl before each increment of the transdermal opioid dosage (group T). Pain control was equally satisfactory in the two groups. VAS scores at baseline (T: 4.36 +/- 1.53; F: 4.51 +/- 1.36; n.s.) and at the end of the study (T: 1.8 +/- 1.6; F: 1.6 +/- 1.5; n.s.) did not differ. However, in the tramadol group this level of pain control was achieved with much slower dose escalation of fentanyl. The mean application time of the fentanyl-Transdermal Therapeutic System patch for each dosage (25, 50, 75 microg/hour) was significantly greater in patients receiving tramadol. No patient in group T escalated to the 100 microg/hour patch, while in 12 patients of group F the 100 microg/hour patch was applied after a 75 microg/hour patch mean application period of 18.6 +/- 4.7 days. The number of fentanyl-TTS dosage changes was significantly lower in group T (1.2 +/- 0.4 vs. 2.3 +/- 0.5; P < 0.05). The mean total duration of treatment in group T, was 37.1 +/- 11.6 days. The amount of fentanyl used at study end was 56.6 +/- 11.2 microg/hour plus 141.1 +/- 151.9 mg tramadol per day (median: 200 mg/day) in group T patients compared with 84.1 +/- 12.2 microg/hour in group F patients (P < 0.05). The combination of a strong opioid with a weak opioid to treat severe cancer pain allowed a more gradual increase of analgesic delivery than was possible using fentanyl-TTS alone, minimizing periods of under- and overdosing. In addition, it considerably slowed the pace of fentanyl dose escalation. In conclusion, this TTS fentanyl-tramadol analgesic protocol provides a useful alternative to the usual treatment of cancer pain with fentanyl-TTS alone, especially in case of quick progression of disease and pain.
本研究的目的是促进强效阿片类药物的剂量递增。在这项随机开放标签研究中，前瞻性评估了曲马多对晚期癌症疼痛控制中透皮芬太尼剂量调整的影响。纳入了70例视觉模拟量表（VAS）评分>3的顽固性癌症患者。35例患者按需要常规增加透皮芬太尼剂量进行治疗（F组），35例患者在每次增加透皮阿片类药物剂量前，在透皮芬太尼基础上加用口服曲马多（T组）。两组的疼痛控制同样令人满意。基线时（T组：4.36±1.53；F组：4.51±1.36；无显著差异）和研究结束时（T组：1.8±1.6；F组：1.6±1.5；无显著差异）的VAS评分无差异。然而，在曲马多组，达到这种疼痛控制水平时芬太尼剂量递增要慢得多。接受曲马多治疗的患者，每种剂量（25、50、75微克/小时）的芬太尼透皮治疗系统贴片的平均使用时间显著更长。T组没有患者升级到100微克/小时的贴片，而F组有12例患者在75微克/小时贴片平均使用18.6±4.7天后使用了100微克/小时的贴片。T组芬太尼透皮贴剂剂量变化的次数显著更少（1.2±0.4对2.3±0.5；P<0.05）。T组的平均总治疗持续时间为37.1±11.6天。研究结束时，T组患者每天使用的芬太尼量为56.6±11.2微克/小时加141.1±151.9毫克曲马多（中位数：200毫克/天），而F组患者为84.1±12.2微克/小时（P<0.05）。强效阿片类药物与弱效阿片类药物联合用于治疗重度癌症疼痛，与单独使用芬太尼透皮贴剂相比，能使镇痛药物的给药增加更为渐进，减少了用药不足和用药过量的时间。此外，它还大大减缓了芬太尼剂量递增的速度。总之，这种芬太尼-曲马多透皮贴剂镇痛方案为单用芬太尼透皮贴剂治疗癌症疼痛的常规方法提供了一种有用的替代方案，尤其是在疾病和疼痛快速进展的情况下。
