From the Division of Pain Medicine, Department of Anesthesiology, University of Utah, Salt Lake City, Utah.
Anesth Analg. 2020 Apr;130(4):1035-1044. doi: 10.1213/ANE.0000000000004276.
Opioids remain the mainstay of cancer pain management but are associated with systemic toxicity. In refractory cancer pain, intrathecal therapy (ITT) is associated with improved pain control, reduced systemic side effects, and improved survival. It has been assumed that ITT decreases systemic serum opioid levels and their associated toxicity, but there are limited data to support this assumption. This study hypothesizes that serum opioid levels decrease with ITT. Secondary objectives include comparative measures of pain, bowel function, and other cancer-related symptoms.
Fifty-one cancer patients undergoing ITT for cancer pain were recruited in a prospective observational study. Daily oral morphine equivalency (OME) dose, serum opioid levels, Brief Pain Inventory (BPI), MD Anderson Symptom Inventory (MDASI), and a constipation questionnaire were obtained at the time of implant, and 4 and 8 weeks postoperatively.
Average baseline daily OME was 375 mg (median, 240; interquartile range, 150-405; range, 0-3160), mean serum morphine concentration was 53.7 ng/mL (n = 17), and mean oxycodone concentration was 73.7 ng/mL (n = 20). At 4 weeks, 87.5% of patients had discontinued non-IT opioids, and 53% had undetectable (<2 ng/mL) serum opioid concentrations. At 8 weeks, 92% remained off all non-IT opioids and 59% had undetectable serum opioid levels. IT morphine doses >4.2 mg/d were invariably associated with detectable serum levels; with doses <4.2 mg, morphine was undetectable in 80% of subjects. IT hydromorphone doses >6.8 mg/d were detectable in the serum. Using linear mixed model analyses, there were statistically significant decreases in the mean "worst pain," "average pain," and MD Anderson symptom severity and interference scores at 4 and 8 weeks. This change was independent of serum opioid levels; when analyzed separately, there was no difference in the pain scores of subjects with detectable serum opioid levels compared to those with undetectable levels at 4 and 8 weeks. Constipation ranked as "quite a bit" or "very much" decreased from 58.7% to 19.2% of subjects at week 4 (P < .001) and to 37.5% at 8 weeks (P = .23). A very low complication rate was observed.
ITT for cancer pain was associated with a marked reduction in serum opioid concentrations, with the majority of patients having undetectable serum levels. Reducing serum opioid concentrations in cancer patients may have implications with respect to restoring bowel function, improving fatigue, and promoting the integrity of antitumor immune function and warrants further study.
阿片类药物仍然是癌症疼痛管理的主要药物，但与全身毒性有关。在难治性癌症疼痛中，鞘内治疗（IT）与改善疼痛控制、减少全身副作用和提高生存率有关。人们一直认为 IT 会降低血清阿片类药物水平及其相关毒性，但目前的数据支持这一假设。本研究假设 IT 会降低血清阿片类药物水平。次要目标包括疼痛、肠道功能和其他癌症相关症状的比较测量。
51 例癌症患者因癌症疼痛接受 IT 治疗，采用前瞻性观察研究。在植入时以及术后 4 周和 8 周，获得每日口服吗啡等效剂量（OME）、血清阿片类药物水平、简明疼痛量表（BPI）、MD 安德森症状量表（MDASI）和便秘问卷。
平均基线每日 OME 为 375mg（中位数，240；四分位距，150-405；范围，0-3160），平均血清吗啡浓度为 53.7ng/ml（n=17），平均羟考酮浓度为 73.7ng/ml（n=20）。4 周时，87.5%的患者已停止使用非 IT 阿片类药物，53%的患者血清阿片类药物浓度无法检测到（<2ng/ml）。8 周时，92%的患者仍未使用任何非 IT 阿片类药物，59%的患者血清阿片类药物浓度无法检测到。IT 吗啡剂量>4.2mg/d 时，血清中均能检测到可检测到的水平；IT 吗啡剂量<4.2mg/d 时，80%的患者吗啡无法检测到。IT 氢吗啡酮剂量>6.8mg/d 时，血清中可检测到。采用线性混合模型分析，4 周和 8 周时，平均“最痛”、“平均疼痛”和 MD 安德森症状严重程度和干扰评分均有统计学显著下降。这种变化与血清阿片类药物水平无关；单独分析时，4 周和 8 周时，血清阿片类药物水平可检测到的患者与不可检测到的患者的疼痛评分无差异。便秘从 58.7%降至 4 周时的 19.2%（P<0.001）和 8 周时的 37.5%（P=0.23），在 4 周时有“相当多”或“非常多”的患者。并发症发生率非常低。
鞘内治疗癌症疼痛与血清阿片类药物浓度显著降低有关，大多数患者的血清水平无法检测到。降低癌症患者的血清阿片类药物浓度可能会对恢复肠道功能、改善疲劳、促进抗肿瘤免疫功能的完整性产生影响，值得进一步研究。
Zotero 插件