便秘通治疗慢性非癌性疼痛患者阿片类药物相关便秘的临床研究

目的:评价便秘通治疗慢性非癌性疼痛患者出现阿片类药物相关便秘(OIC)的疗效及安全性。方法:将138例慢性非癌性疼痛OIC患者按随机数字表法分为便秘通组和乳果糖组,每组69例。便秘通组口服便秘通水丸10 g,2次/日,乳果糖组口服乳果糖口服溶液15 ml,2次/日,疗程均为12 w。观察患者自发排便(SBM)、完全自发排便(CSBM)、不费力SBM情况,测定血清胃动素(MTL)、血管活性肠肽(VIP)、生长抑素(SS)水平。总结出每周至少出现3次SBM或与基线相比每周至少增加1次SBM反应者的例数,记录治疗后首次出现SBM的中位时间、治疗出现的不良反应、治疗前后临床阿片类戒断量表(COWS)评分和11点数字评定量表(NRS)评分。结果:便秘通组SBM反应者47例(68. 1%)多于乳果糖组的34例(49. 3%)(χ^2=5. 0 5 1,P=0. 025);便秘通组SBM、CSBM、不费力SBM明显高于乳果糖组(P <0. 05);便秘通组第一次出现SBM的中位时间为18 h短于乳果糖组的31 h(χ^2=5. 348,P=0. 021)。治疗后两组MTL水平均有升高趋势,但对比差异无统计学意义(P=0. 097),两组VIP、SS水平均明显下降且便秘通组明显低于乳果糖组(P <0. 05)。两组不良反应(TEAEs)对比,便秘通组9例(13. 0%),乳果糖组7例(10. 1%),差异无统计学意义(χ^2=0. 283,P=0. 595)。便秘通组和乳果糖组在基线、首剂用药前1 d、用药后1、15、29、57、85 d COWS评分、NRS评分比较,差异无统计学意义(P> 0. 05)。结论:便秘通治疗慢性非癌性疼痛患者OIC疗效较乳果糖好,其机制可能与便秘通增加VIP、SS水平有关,安全性不劣于乳果糖,且未促进阿片类药物戒断综合症和影响镇痛疗效。

Clinical Efficacy of Bianmitong in the Treatment of Opioid Related Constipation in Patients with Chronic Noncancer Pain

Objective: To evaluate the efficacy and safety of opioid-related constipation( OIC) in patients with chronic non-cancerous pain treated with Bianmitong. Methods: 138 patients of OIC with chronic non-cancerous pain were randomly divided into Bianmitong group and lactulose group,69 cases in each group. In Bianmitong group,10 g Bianmitongshui pills were given orally 2 times/day,while 15 ml lactulose was given orally 2 times/day in lactulose group,the course of the treatment was 12 weeks. The spontaneous defecation( SBM),complete spontaneous defecation( CSBM),effortless SBM in patients were observed,the levels of MTL,VIP and SS were determined. Then the number of cases with at least 3 SBMs per week or at least 1 SBM response per week compared to baseline was summarized. The median time to SBM,the adverse effects of treatment,the clinical opioid withdrawal scale( COWS) score,and the 11-point numerical rating scale( NRS) score before and after treatment were recorded. Results : 4 7 cases( 6 8. 1 %) of the SBM responders in Bianmitong group were more than 3 4 cases( 49. 3%) in lactulose group( χ^2= 5. 051,P = 0. 025). SBMs,CSBMs,effortless SBMs in Bianmitong group were significantly higher than in the lactulose group( p < 0. 05). The median time of SBM in Bianmitong group was 18 h,which was shorter than 31 h in the lactulose group( χ^2= 5. 348,P = 0. 021). The MTL levels were increased in both groups,with no significant difference between them( P = 0. 097). The levels of VIP and SS were decreased,while the changes in Bianmitong group showed more significant difference than that in lactulose group. For TEAEs,There were 9 cases( 13. 0 %) in Bianmitong group and 7 cases( 10. 1%) in the lactulose group,the difference was not statistically significant( χ^2= 0. 283,P = 0. 595). There was no significant difference in the COWS score and NRS score between the two groups at baseline,1 day before the first dose,1 d,15 d,29 d,57 d and 85 d after treatment( P > 0. 05). Conclusion: The efficacy of Bianmitong in the treatment of chronic non-cancerous pain is better than that of lactulose,its mechanism may be related to increasing the levels of VIP and SS. The safety is not inferior to lactulose. It does not promote opioid withdrawal syndrome and affect the analgesic effect.