鞘内单次与连续输注吗啡镇痛对晚期癌痛患者吗啡用量及白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α水平的影响

Effects of single and continuous intrathecal morphine infusion on morphine dosage and levels of interleukin-1β,interleukin-6 and tumor necrosis factor-αin patients with advanced cancer pain

目的探讨经鞘内单次与连续输注吗啡镇痛对晚期癌痛患者吗啡用量及白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)水平的影响。方法纳入90例晚期癌痛患者,患者均行鞘内输注系统镇痛治疗,随机数字表法分为经鞘内单次输注吗啡组(A组,n=42)和经鞘腔内连续输注吗啡组(B组,n=48)。比较两组患者平均生存期,治疗后第1、30天鞘内吗啡剂量,鞘内治疗前及治疗后第14、30天疼痛评分[视觉模拟评分法(VAS)]与血清炎性因子(IL-1β、IL-6、TNF-α)水平及不良反应发生情况。结果两组患者平均生存期[(120.43±30.79)d比(121.95±38.90)d]及治疗后第1天鞘内吗啡剂量[(0.82±0.15)mg/d比(0.80±0.18)mg/d]差异均无统计学意义(t=0.203、0.568,P>0.05),A组治疗第30天鞘内吗啡剂量小于B组[(1.09±0.14)mg/d比(1.21±0.24)mg/d]差异有统计学意义(t=2.854,P<0.05);两组治疗后第14、30天疼痛VAS评分及血清IL-1β、IL-6、TNF-α水平均明显低于治疗前,差异有统计学意义(P<0.05)[VAS评分:A组,(3.36±0.91)分比(7.93±1.10)分,t=19.751、(3.19±0.66)分比(7.93±1.10)分,t=23.809;B组,(3.22±1.05)分比(7.67±1.15)分,t=21.473、(3.22±0.83)分比(7.67±1.15)分,t=21.200,血清IL-1β:A组,(15.36±4.07)pg/ml比(19.87±5.43)pg/ml,t=5.259、(14.86±4.47)pg/ml比(19.87±5.43)pg/ml,t=4.212;B组,(15.12±3.56)pg/ml比(20.01±5.46)pg/ml,t=6.087、(15.00±3.12)pg/ml比(20.01±5.46)pg/ml,t=5.100,血清IL-6:A组,(102.61±31.21)pg/ml比(162.36±47.44)pg/ml,t=6.956、(97.74±18.22)pg/ml比(162.36±47.44)pg/ml,t=9.267;B组,(101.55±27.46)pg/ml比(167.92±38.16)pg/ml,t=8.852、(97.69±21.79)pg/ml比(167.92±38.16)pg/ml,t=10.759,血清TNF-α:A组,(118.68±28.88)pg/ml比(232.73±49.92)pg/ml,t=12.995、(115.24±25.84)pg/ml比(232.73±49.92)pg/ml,t=14.345;B组,(122.33±26.96)pg/ml比(236.27±38.91)pg/ml,t=15.451、(115.15±21.13)pg/ml比(236.27±38.91)pg/ml,t=18.516];两组组间治疗后各时间点VAS评分及血清IL-1β、IL-6、TNF-α水平差异均无统计学意义(P>0.05)[VAS评分:(3.36±0.91)分比(3.22±1.05)分,t=0.671、(3.19±0.66)分比(3.22±0.83)分,t=0.188,血清IL-1β:(15.36±4.07)pg/ml比(15.12±3.56)pg/ml,t=0.298、(14.86±4.47)pg/ml比(15.00±3.12)pg/ml,t=0.174,血清IL-6:(102.61±31.21)pg/ml比(101.55±27.46)pg/ml,t=0.171、(97.74±18.22)pg/ml比(97.69±21.79)pg/ml,t=0.012,血清TNF-α:(118.68±28.88)pg/ml比(122.33±26.96)pg/ml,t=0.620、(115.24±25.84)pg/ml比(115.15±21.13)pg/ml,t=0.005]。A组恶心呕吐、皮肤瘙痒、尿潴留发生率均低于B组[16.67%比39.58%、4.76%比18.75%、2.38%比14.58%],差异有统计学意义(χ2=5.726、4.085、4.118,P<0.05)。结论经鞘内单次与连续输注吗啡对晚期癌痛患者镇痛效果相当,均可下调IL-1β、IL-6、TNF-α水平,但单次输注吗啡用量更小,不良反应更少。

Objective To explore the effects of single and continuous intrathecal infusion of morphine on the dosage of morphine and the levels of interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in patients with advanced cancer pain.Methods Totally,90 patients with advanced cancer pain in the hospital were enrolled and all patients received intrathecal infusion system analgesia.Among the patients,42 cases who were given single intrathecal infusion of morphine were included in group A,and 48 cases who were treated with continuous intrathecal infusion of morphine were assigned to group B.The average survival time,intrathecal morphine dose on the 1st day and 30th day,pain degree[visual analogue scale(VAS)]and levels of serum inflammatory factors(IL-1β,IL-6,TNF-α)before intrathecal treatment and on the 14th day and 30th day after treatment and occurrence of adverse reactions were compared between the two groups.Results There was no significant difference in the average survival time and intrathecal morphine dose in the 1st of treatment between the two groups[(120.43±30.79)d vs.(121.95±38.90)d,(0.82±0.15)mg/d vs.(0.80±0.18)mg/d,t=0.203,0.568,P>0.05],and intrathecal morphine dose in the 30th day in group A was less than that in group B[(1.09±0.14)mg/d vs.(1.21±0.24)mg/d,t=2.854,P<0.05].The VAS score and serum levels of IL-1β,IL-6 and TNF-αon the 14th day and 30th day after treatment in the two groups were reduced as compared with those before treatment[VAS score:group A,(3.36±0.91)points vs.(7.93±1.10)points,t=19.751,(3.19±0.66)points vs.(7.93±1.10)point,t=23.809;group B,(3.22±1.05)points vs.(7.67±1.15)points,t=21.473,(3.22±0.83)points vs.(7.67±1.15)points,t=21.200,IL-1β:group A,(15.36±4.07)vs.(19.87±5.43)pg/ml,t=5.259,(14.86±4.47)vs.(19.87±5.43)pg/ml,t=4.212;group B,(15.12±3.56)vs.(20.01±5.46)pg/ml,t=6.087,(15.00±3.12)vs.(20.01±5.46)pg/ml,t=5.100,IL-6:group A,(102.61±31.21)vs.(162.36±47.44)pg/ml,t=6.956,(97.74±18.22)vs.(162.36±47.44)pg/ml,t=9.267;group B,(101.55±27.46)vs.(167.92±38.16)pg/ml,t=8.852,(97.69±21.79)vs.(167.92±38.16)pg/ml,t=10.759,TNF-α:group A,(118.68±28.88)vs.(232.73±49.92),t=12.995,(115.24±25.84)vs.(232.73±49.92)pg/ml,t=14.345;group B,(122.33±26.96)vs.(236.27±38.91)pg/ml,t=15.451,(115.15±21.13)vs.(236.27±38.91)pg/ml,t=18.516,P<0.05],but there were no statistically significant differences in VAS score and serum levels of IL-1β,IL-6 and TNF-αat each time point between the two groups[VAS score:(3.36±0.91)points vs.(3.22±1.05)points,t=0.671,(3.19±0.66)points vs.(3.22±0.83)points,t=0.188,IL-1β:(15.36±4.07)vs.(15.12±3.56)pg/ml,t=0.298,(14.86±4.47)vs.(15.00±3.12)pg/ml,t=0.174,IL-6:(102.61±31.21)vs.(101.55±27.46)pg/ml,t=0.171,(97.74±18.22)vs.(97.69±21.79)pg/ml,t=0.012,TNF-α:(118.68±28.88)vs.(122.33±26.96)pg/ml,t=0.620,(115.24±25.84)vs.(115.15±21.13)pg/ml,t=0.005,P>0.05].The incidence rates of nausea and vomiting,skin pruritus and urinary retention in group A were lower than in group B[16.67%vs.39.58%,4.76%vs.18.75%,2.38%vs.14.58%,χ2=5.726,4.085,4.118,P<0.05].Conclusion Single and continuous intrathecal morphine infusion have the same analgesic effect on patients with advanced cancer pain,and both can down-regulate the levels of IL-1β,IL-6 and TNF-α,but single intrathecal morphine infusion has lower dosage and fewer toxic and side effects.