Mystakidou K, Befon S, Kouskouni E, Gerolymatos K, Georgaki S, Tsilika E, Vlahos L
Pain Relief and Palliative Care Unit, Areteion Hospital, University of Athens, Greece.
Anticancer Res. 2001 May-Jun;21(3C):2225-30.
Fentanyl is a synthetic opioid, suitable for transdermal delivery, offering an interesting solution as a step 3 opioid in cancer pain treatment. The purpose of the study was to carefully investigate: 1) the feasibility of the direct conversion from codeine to TTS fentanyl, in patients already receiving codeine and requiring strong opioids for their analgesia; 2) the safety of 25 microg/hour incremental steps and at shorter than 72-hour intervals, if clinically required.
130 patients were judged eligible for the study. All the patients were receiving 280-360 mg or more of codeine and required strong opioid for their analgesia. The study lasted 56 days. The initial dose was 25 microg/hour. TTS fentanyl for all patients. Data assessments were made on baseline, day 1, day 2, day 3, in the hospital and thereafter on days 7, 14, 21, 28, 42 and 56. After the patch application, all the patients were given an immediate release oral morphine (5 mg) every 4-6 hours for the first 12 hours and then if needed only as rescue doses. The patients remained in the hospital for the first three days of the study where follow-up (pain score, satisfaction, side effects etc.). was recorded by the palliative care team and by daily cards.
The itnitial dose of fentanyl was 25 microg/hour while the mean dose on day 3 was 45.9 microg/hour. All the patients required upward titration of the study medication during follow-up visits. On day 56 the mean dose of fentanyl was 87.4 microg/hour. Mean pain intensity decreased from an initial 5.96 on the baseline to 0.83 on day 3. Karnofsky scale measurements between treatment phases revealed non-significant changes. The rate of overall satisfaction was quite high. Nine patients discontinued the study due to inadequate pain relief or side effects between day 7 and day 28, while five patients died between day 28 and day 56. Constipation, nausea and vomiting were the most common side effects. Skin reaction was relatively mild and acceptable during the study.
Under controlled conditions, TTS fentanyl seems to be feasible for direct conversion from mild to strong opioids and additionally, 25 microg/hour incremental steps day by day can be made by palliative care specialists, if clinically required for cancer pain management.
芬太尼是一种合成阿片类药物,适用于经皮给药,为癌症疼痛治疗中作为三级阿片类药物提供了一种有趣的解决方案。本研究的目的是仔细调查:1)对于已经接受可待因且镇痛需要强效阿片类药物的患者,直接从可待因转换为透皮贴剂芬太尼的可行性;2)如果临床需要,每小时增加25微克且间隔短于72小时的安全性。
130名患者被判定符合研究条件。所有患者均接受280 - 360毫克或更多的可待因,且镇痛需要强效阿片类药物。研究持续56天。初始剂量为每小时25微克。所有患者均使用芬太尼透皮贴剂。在基线、第1天、第2天、第3天在医院进行数据评估,此后在第7天、第14天、第21天、第28天、第42天和第56天进行评估。贴敷贴片后,所有患者在最初12小时内每4 - 6小时给予一次即释口服吗啡(5毫克),然后仅在需要时作为急救剂量。患者在研究的前三天住院,在此期间由姑息治疗团队通过每日卡片记录随访情况(疼痛评分、满意度、副作用等)。
芬太尼的初始剂量为每小时25微克,而第3天的平均剂量为每小时45.9微克。所有患者在随访期间均需要向上滴定研究用药。在第56天,芬太尼的平均剂量为每小时87.4微克。平均疼痛强度从基线时的初始5.96降至第3天的0.83。治疗阶段之间的卡氏评分测量显示无显著变化。总体满意度较高。9名患者在第7天至第28天之间因疼痛缓解不足或出现副作用而退出研究,5名患者在第28天至第56天之间死亡。便秘、恶心和呕吐是最常见的副作用。在研究期间,皮肤反应相对较轻且可接受。
在可控条件下,芬太尼透皮贴剂似乎可用于从轻度阿片类药物直接转换为强效阿片类药物,此外,如果癌症疼痛管理临床需要,姑息治疗专家可每天以每小时增加25微克的剂量递增。