Sandler A N, Baxter A D, Katz J, Samson B, Friedlander M, Norman P, Koren G, Roger S, Hull K, Klein J
Department of Anesthesiology, Toronto Hospital, University of Toronto, Ontario, Canada.
Anesthesiology. 1994 Nov;81(5):1169-80; discussion 26A. doi: 10.1097/00000542-199411000-00010.
A randomized, double-blind, placebo-controlled trial was conducted to assess the analgesic, pharmacokinetic, and clinical respiratory effects of 72-h application of two transdermal fentanyl (TTSF) patch sizes in patients undergoing abdominal hysterectomy.
TTSF patches releasing 50 micrograms/h (TTSF-50) or 75 micrograms/h (TTSF-75) fentanyl or placebo patches were applied to 120 women 2 h before abdominal hysterectomy under general anesthesia. Postoperatively, all patients had access to supplemental morphine using patient-controlled analgesia pumps. Each patient was attended continuously by a research nurse for 8 h on the night before surgery and for 84 h after patch application. The following data were collected: visual analog scale pain scores, supplementary analgesia, fentanyl plasma concentration (4-h intervals), continuous hemoglobin saturation (pulse oximetry), respiratory pattern (continuous respiratory inductive plethysmography), and adverse effects (nausea, vomiting, pruritus). Data analysis included analysis of variance, Kruskal-Wallis, and chi-squared. P < 0.05 was considered significant.
There were no demographic differences among groups. Visual analog scale pain scores were significantly lower for the TTSF-75 group, and supplemental morphine was significantly decreased in the TTSF-75 group in the postanesthesia care unit and for both the TTSF-50 and the TTSF-75 group for 8-48 h postoperatively. Between 5 and 36 h, the TTSF groups had significantly increased abnormal respiratory pattern including apneic episodes (tidal volume of less than 100 ml for more than 15 s) and episodes of slow respiratory rate (less than 8 breaths/min persisting for more than 5 min) and significantly increased requirement for oxygen supplementation. Nine patients in the TTSF groups were withdrawn because of severe respiratory depression compared to none in the placebo group. No significant between-group differences were present in the incidence of nausea, vomiting, or pruritus. Although fentanyl plasma concentration was higher in the TTSF-75 group than in the TTSF-50 group, the differences were not significant. Fentanyl plasma concentration decreased significantly 48 h after patch application.
Application of TTSF patches 2 h preoperatively is associated with moderate supplementary opioid requirements for analgesia in the early postoperative period and ongoing opioid supplementation for at least 72 h. Although good analgesia is the result of this combination therapy, it is associated with a high incidence of respiratory depression requiring intensive monitoring oxygen supplementation, removal of the TTSF patches in approximately 11% of the patients and opioid reversal with naloxone in approximately 8% of the patients.
开展了一项随机、双盲、安慰剂对照试验，以评估两种不同规格的透皮芬太尼（TTSF）贴剂在接受腹部子宫切除术患者中持续应用72小时的镇痛、药代动力学及临床呼吸效应。
在全身麻醉下于腹部子宫切除术2小时前，将释放50微克/小时（TTSF-50）或75微克/小时（TTSF-75）芬太尼的TTSF贴剂或安慰剂贴剂应用于120名女性患者。术后，所有患者可使用患者自控镇痛泵补充吗啡。术前一晚及贴剂应用后84小时，由一名研究护士持续照料每位患者。收集以下数据：视觉模拟评分法疼痛评分、补充镇痛情况、芬太尼血浆浓度（每4小时一次）、持续血红蛋白饱和度（脉搏血氧饱和度测定）、呼吸模式（持续呼吸感应体积描记法）及不良反应（恶心、呕吐、瘙痒）。数据分析包括方差分析、Kruskal-Wallis检验及卡方检验。P<0.05被视为具有统计学意义。
各组间人口统计学特征无差异。TTSF-75组的视觉模拟评分法疼痛评分显著更低，且在麻醉后护理单元中TTSF-75组的补充吗啡量显著减少，术后8至48小时TTSF-50组和TTSF-75组的补充吗啡量均显著减少。在5至36小时期间，TTSF组异常呼吸模式显著增加，包括呼吸暂停发作（潮气量小于100毫升持续超过15秒）及呼吸频率减慢发作（呼吸频率小于8次/分钟持续超过5分钟），且吸氧需求显著增加。TTSF组有9名患者因严重呼吸抑制退出试验，而安慰剂组无此情况。恶心、呕吐或瘙痒的发生率在组间无显著差异。虽然TTSF-75组的芬太尼血浆浓度高于TTSF-50组，但差异无统计学意义。贴剂应用48小时后，芬太尼血浆浓度显著下降。
术前2小时应用TTSF贴剂与术后早期适度的补充阿片类药物镇痛需求及持续至少72小时的阿片类药物补充有关。虽然这种联合治疗可产生良好的镇痛效果，但与呼吸抑制的高发生率相关，需要密切监测吸氧情况，约11%的患者需移除TTSF贴剂，约8%的患者需用纳洛酮逆转阿片类药物作用。
