鞘内吗啡与氢吗啡酮轮替治疗慢性顽固性疼痛：不对称交叉耐受与转换比例分析

Intrathecal Morphine and Hydromorphone Rotation in Chronic Refractory Pain: Analysis of Asymmetric Cross-Tolerance and Conversion Ratios

摘要:

摘 要 目的：探讨鞘内阿片类药物轮替的转换比例、转换原因及转换后结局。方法：回顾纳入2020年1月至2025年9月在中日友好医院疼痛科接受SynchroMed II鞘内药物输注系统（Medtronic, Minneapolis, MN, USA）植入治疗并进行鞘内阿片类药物轮替的慢性顽固性疼痛患者，描述并分析其疼痛特点、轮替原因、轮替时间、转换比例和轮替后结局。结果：共纳入患者23例，癌痛患者18例和非癌痛患者5例。氢吗啡酮轮替为吗啡的平均起始转换比例为3.25，吗啡轮替为氢吗啡酮的平均起始转换比例为7.50；当达到有效镇痛剂量时，上述转换比例分别为3.70和5.75。吗啡轮替至吗啡联合舒芬太尼时，吗啡和舒芬太尼的起始转换比例分别为3600、1330和2000，有效镇痛转换比例对应为3180、350和1310，转换比例存在明显个体差异。因镇痛不佳进行轮替者22例，其中疼痛未明显改善者2例，均为中枢痛，其余患者镇痛满意；因阿片类相关不良反应水肿进行轮替者1例，轮替至氢吗啡酮后水肿减轻。结论：鞘内阿片药物轮替是改善慢性顽固性疼痛患者镇痛效果、缓解阿片相关不良反应（如水肿）的有效策略；吗啡与氢吗啡酮之间存在不对称交叉耐受现象；吗啡轮替至吗啡联合舒芬太尼时，需考虑个体间差异，采用保守的起始转换比例。

Abstract:

Abstract Objective: To investigate the conversion ratios, indications and clinical outcomes of intrathecal opioid rotation in patients with chronic refractory pain. Methods: We retrospectively reviewed patients with chronic refractory pain who underwent implantation of a SynchroMed II intrathecal drug delivery system (Medtronic, Minneapolis, MN, USA) at the Department of Pain Medicine, China–Japan Friendship Hospital between January 2020 and September 2025 and subsequently underwent intrathecal opioid rotation. Pain characteristics, indications for rotation, timing of rotation, conversion ratios, and post-rotation outcomes were described and analyzed. Results: A total of 23 patients were included, comprising 18 patients with cancer-related pain and 5 with non-cancer pain. The mean initial conversion ratio from hydromorphone to morphine was 3.25, whereas that for rotation from morphine to hydromorphone was 7.50. At the effective analgesic dose, the corresponding conversion ratios were 3.70 and 5.75, respectively. In patients rotated from morphine to morphine combined with sufentanil, the initial morphine-to-sufentanil conversion ratios were 3600, 1330, and 2000, with corresponding effective analgesic ratios of 3180, 350 and 1310, demonstrating marked interindividual variability. Among the 22 patients who underwent opioid rotation due to inadequate analgesia, pain did not improve significantly in 2 patients, both of whom had central pain, while satisfactory analgesia was achieved in the remaining patients. One patient underwent rotation due to opioid-related edema, which improved after rotation to hydromorphone. Conclusion: Intrathecal opioid rotation is an effective strategy to improve analgesic efficacy and alleviate opioid-related adverse effects (e.g., edema) in patients with chronic refractory pain. Asymmetric cross-tolerance exists between morphine and hydromorphone. When rotating from morphine to a combination of morphine and sufentanil, individual variability must be considered, and a conservative initial conversion ratio should be adopted.