鞘内输注氢吗啡酮与其联合氯胺酮和加巴喷丁治疗难治性癌痛的效果分析

Analysis of efficacy of intrathecal infusion of hydromorphone and its combination with ketamine and gabapentin in the treatment of refractory cancer pain

目的探讨鞘内连续输注吗啡、氢吗啡酮以及氢吗啡酮联合氯胺酮和加巴喷丁治疗难治性癌痛鼻咽癌患者的疗效和不良反应。方法选取2022年1—6月呼和浩特市第一医院接受治疗的伴有难治性癌痛晚期鼻咽癌患者并进行随机分组。吗啡组(M组)接受鞘内连续输注吗啡治疗;氢吗啡酮组(HM组)接受鞘内连续输注氢吗啡酮治疗;氢吗啡酮+氯胺酮组(HM+KET组)接受鞘内连续输注氢吗啡酮联合静脉输注氯胺酮治疗;氢吗啡酮+氯胺酮+加巴喷丁组(HM+KET+GBP组)接受鞘内连续输注氢吗啡酮联合静脉输注氯胺酮和口服加巴喷丁治疗。持续记录并比较不同药物治疗组患者的疼痛数字评分法(NRS)评分、24 h内爆发性癌痛次数、匹兹堡睡眠质量指数(PSQI)评分、不良反应以及生存状况。结果共纳入204例患者,男149例(73.0%),女55例(27.0%)患者,平均年龄为(45.8±9.9)岁。其中M组101例,HM组34例,HM+KET组34例,HM+KET+GBP组35例,各组患者临床症状、血液参数和病理类型资料比较,差异均无统计学意义(P>0.05)。治疗前,各组NRS评分、24 h内爆发性癌痛次数和PSQI评分比较,差异均无统计学意义(P>0.05);HM组患者治疗后所有时点的NRS评分、PSQI评分显著低于M组,24 h内暴发性疼痛次数少于M组患者;HM+KET+GBP组患者治疗后1 d、3 d、7 d、15 d和1个月的NRS评分低于HM组和HM+KET组,治疗后所有时点24 h内暴发性疼痛次数少于HM组和HM+KET组,治疗后1个月和2个月的PSQI评分低于HM组和HM+KET组,差异均有统计学意义(P<0.05)。安全性分析显示,HM组患者的便秘发生率低于M组,HM+KET+GBP组患者恶心呕吐、便秘、嗜睡和皮肤瘙痒发生率均低于HM组和HM+KET组,差异有统计学意义(P<0.05)。生存分析显示,HM组比M组的患者具有更长的总生存期(P=0.042)。结论鞘内输注氢吗啡酮治疗难治性癌痛鼻咽癌患者有较大优势,且氢吗啡酮联合氯胺酮和加巴喷丁疗效更好。

Objective To investigate the difference in the efficacy of continuous intrathecal infusion of morphine,hydromorphone,and their combination with ketamine and gabapentin in the treatment of refractory cancer pain in patients with nasopharyngeal cancer.Methods Late-stage nasopharyngeal cancer patients with refractory cancer pain treated at the First Hospital of Hohhot from January 2022 to June 2022 were selected and randomized into four groups.The M group received a continuous intrathecal infusion of morphine.The HM group underwent continuous intrathecal infusion of hydromorphone.The HM+KET group received continuous intrathecal infusion of hydromorphone in combination with intravenous infusion of ketamine.The HM+KET+GBP drug group underwent continuous intrathecal infusion of hydromorphone in combination with intravenous infusion of ketamine and oral administration of gabapentin.The patients'numeric rating scale(NRS)pain scores,frequency of explosive cancer pain episodes in 24 hours,Pittsburgh sleep quality index(PSQI)scores,and survival status were recorded and compared.Results A total of 204 patients were enrolled,with 149 males(73.0%)and 55 females(27.0%),with an average age of(45.8±9.91)years old.Among them,there were 101 cases in the M group,34 cases in the HM group,34 cases in the HM+KET group,and 35 cases in the HM+KET+GBP group.The clinical symptoms,blood parameters,and pathological types of patients in each group were compared,and the differences were not statistically significant(P>0.05).Before treatment,there was no statistically significant difference in NRS score,number of sudden cancer pain within 24 hours,and PSQI score among the groups(P>0.05).The NRS score and PSQI score of the HM group patients were significantly lower than those of the M group at all time points after treatment,and the number of episodes of sudden pain within 24 hours was less than that of the M group patients;The NRS scores of patients in the HM+KET+GBP group were lower than those in the HM group and HM+KET group at 1 day,3 days,7 days,15 days,and 1 month after treatment.At all time points after treatment,the number of episodes of pain within 24 hours was lower than that in the HM group and HM+KET group.The PSQI scores at 1 month and 2 months after treatment were lower than those in the HM group and HM+KET group,and the differences were statistically significant(P<0.05).The safety analysis showed that the incidence of constipation in the HM group was lower than that in the M group.The incidence of nausea,vomiting,constipation,drowsiness,and skin itching in the HM+KET+GBP group were lower than those in the HM group and HM+KET group,the differences were statistically significant(P<0.05).Survival analysis showed that patients in the HM group had a longer overall survival time than those in the M group(P=0.042).Conclusion Intrathecal infusion of hydromorphone showed significant advantages in treating refractory cancer pain in nasopharyngeal cancer patients.The combination of hydromorphone,ketamine,and gabapentin demonstrated better efficacy.