氢吗啡酮鞘内药物输注系统在难治性癌痛患者中有效性和安全性的研究

SAFETY AND EFFICACY OF HYDROMORPHONE IN INTRATHECAL DRUG DELIVERY SYSTEM FOR REFRACTORY CANCER PAIN

摘要:

摘 要 目的： 探讨氢吗啡酮鞘内药物输注系统（intrathecal drug delivery system ，IDDS）在难治性癌痛患者中应用的有效性和安全性。 方法： 选取行IDDS植入术难治性癌痛患者 42 例，数字随机分为吗啡对照组（M组，n=21 ）和氢吗啡酮观察组（HM组，n= 21），对照组鞘内使用吗啡患者自控镇痛(patient-controlled analgesia, PCA)，观察组鞘内使用氢吗啡酮PCA。记录并统计两组硬膜外测试前1天（T0）、鞘内PCA后1天（T1d）、出院时（Tdis）、鞘内PCA后1月（T1m）、2月（T2m）、3月（T3m）患者的数字疼痛评分（numerical rating scale,NRS）、阿片类药物日消耗量、日爆发痛频次、患者的生活质量和测试前与出院时不良反应发生率。 结果： 鞘内PCA后两组患者的 NRS评分各观察点组间和组内比较无统计学差异，与T0比较均显著降低 (P＜0.01)。随着治疗时间的延长，鞘内PCA后各观察点两组患者鞘内阿片类药物日消耗量呈逐步上升趋势，两组组内T3m与T1d和Tdis相比阿片类药物用量显著增加(P＜0.05),组间各观察点比较无统计学差异。日爆发痛频次随着治疗时间的延长，呈逐步增加趋势，组内T3m与T1d和Tdis相比爆发痛次数显著增加(P＜0.05)。两组患者鞘内 PCA 治疗后生活质量评分较测试前均得到显著改善(P＜0.01)，组间比较无统计学差异。两组患者便秘、恶心呕吐、嗜睡副作用，Tdis较T0得到显著改善(P＜0.01)，HM组出院时较M组，恶心呕吐显著降低(P＜0.05)。M组4例患者在治疗期间，因日增加吗啡剂量仍然疼痛控制不佳，施行氢吗啡酮药物轮换，轮换后疼痛缓解达20～50%。结论：氢吗啡酮鞘内镇痛效力与吗啡相当，可安全有效应用于IDDS难治性癌痛镇痛，并可能成为吗啡耐受或出现严重不良反应时良好的替代药物。

Abstract:

Abstract Objective: To investigate the safety and efficacy of Hydromorphone in intrathecal drug delivery system(IDDS) for refractory cancer pain. Methods:Forty-two patients suffering refractory cancer pain after IDDS implantation were randomly divided into morphine control group(M group, n=21) and hydromorphone observation group(HM group, n=21). Patients in control group were intathecally received morphine patient-controlled analgesia (PCA) with a electronical pump, while patients in observation group were given hydromorphone PCA. The patient' s numerical rating scale (NRS) score, daily consumption of opioids(The dose of hydromorphone was converted into morphine to be calculated by the rotation 1:5) and frequency of breakthrough pain(BTP), quality of life scores and side effects were recorded at the day before epidural trialing (T0) and one day (T1d), time of discharge (Tdis), one month (T1m), two months (T2m) ,three months (T3m)after intrathecal PCA to assess the safety and efficacy. Results: There was no significant difference in NRS score between the two groups after intrathecal PCA,and it was significantly lower than that before epidural trailing (P<0.01).The daily consumption of opioids after intrathecal PCA showed a gradual escalation during the follow-up period, and Compared with T1d and Tdis, the dose of T3m increased significantly in the two groups(P<0.05). The frequency of daily BTP increased gradually with the prolongation of treatment time. The quality of life score (EORTC QLQ-C30 Chinese version) was significantly improved after intrathecal PCA treatment in both groups compared with T0(P<0.01). The quality of life score in HM group was higher than that in M group after treatment,but there was no significant difference between the two groups. The side effects of constipation, nausea and vomiting,drowsiness in the two groups were significantly improved at the time of discharge compared with those before epidural trailing (P<0.01). The incidence of nausea and vomiting in the HM group were significantly lower than those in the M group (P<0.05).Four patients excluded from the observation in M group consumed morphine rapidly per day and had inadequate analgesia(NRS≥7), at the same time,Hydromorphone rotation was intathecally performed and analgesic response was relieved by 20% to 50%. Conclusion: Intrathecal hydromorphone analgesia is as effective as morphine .It can be safely and effectively used in the analgesia of refractory cancer pain in IDDS, and may be a good alternative for morphine tolerance or severe side effects.