硫酸吗啡栓治疗中重度癌痛的临床疗效与安全性研究

Studies on clinical efficacy and safety of morphine sulfate suppositories in treatment of moderate to severe cancer pain

目的:探讨硫酸吗啡栓治疗中重度癌痛的临床疗效与安全性。方法:采用多中心、随机、双盲、安慰剂对照试验方法。2005年3月至2006年3月期间中重度癌痛患者132例纳入研究。患者分为2组:治疗组(66例)和对照组(66例)。治疗组中男35例,女31例,平均年龄(52.8±11.9)岁,对照组中男46例,女20例,平均年龄(58.2±10.9)岁。治疗组患者经肛门给予硫酸吗啡栓(20mg)1枚和口服安慰剂1片,对照组患者口服硫酸吗啡片(20mg)1片和经肛门给予安慰剂栓1枚。待患者再出现中度疼痛时,再第2次给药。每日用药剂量不超过100mg,共给药7d。评价硫酸吗啡栓的镇痛效果和不良反应。结果:治疗组和对照组用药前用目测划线分级法测定的疼痛强度分别为7.1±1.3和6.8±1.2,差异无统计学意义(P>0.05)。2组患者用药后15、30min及1.0、1.5、2.0、3.0、4.0、6.0h的疼痛强度均较用药前下降。用药前疼痛强度和用药后各时间点疼痛强度的差值如下:第1次用药后,治疗组分别为0.80±1.33、2.09±1.77、3.27±1.92、4.14±2.05、4.26±2.13、3.70±2.09、3.27±2.11及2.88±2.35,对照组分别为0.74±1.41、1.97±1.93、3.15±2.11、3.82±2.16、3.95±2.13、3.52±2.12、3.00±2.19及2.70±2.23;第2次用药后,治疗组分别为0.92±1.37、5.35±1.53、3.05±1.94、3.38±1.85、3.70±2.02、3.52±2.00、3.05±2.06及2.84±2.22、,对照组分别为0.72±1.03、4.95±1.49、2.77±1.84、3.27±1.98、3.27±1.95、3.05±1.77、2.67±1.68及2.25±1.88。2组用药前后疼痛强度的差异均有统计学意义(均P<0.001),但2组间疼痛强度的差异无统计学意义(均P>0.05)。治疗组和对照组第1次用药后2h镇痛的有效率均为71.21%,疼痛强度分别为2.74与2.86,用药后6h疼痛强度均为4.12;治疗组与对照组第2～7天用药次数分别为2.54～2.97与2.52～3.03。2组用药后2h和6h的有效率、疼痛强度及用药次数比较差异均无统计学意义(均P>0.05)。2组不良反应发生率均为27.27%。治疗组和对照组的主要不良反应分别为呕吐(13.64%与9.09%),恶心(10.61%与10.61%),便秘(6.06%和7.58%),嗜睡(3.03%与6.06%),头晕(3.03%与6.06%),皮肤瘙痒(1.52%与1.52%),组间比较差异无统计学意义(P>0.05),其中治疗组发生复视1.52%,肛门下坠1.52%;对照组发生呼吸抑制1.52%,指尖抽搐1.52%。结论:硫酸吗啡栓对癌痛的镇痛效果与硫酸吗啡片相似,是一种安全有效能良好耐受的治疗中重度癌痛的剂型。

Objective： To investigate clinical efficacy and safety of morphine sulfate suppositories in treatment of moderate to severe cancer pain. Methods： A multicentre randomized double-blind, placebo-controlled study was conducted. Form March 2005 to March 2006, a total of 132 patients with moderate to severe cancer pain was enrolled in the study. The patients were divided into two groups： the treatment group （66 cases） and the control group （66 cases）. The treatment group comprised 35 men and 31 women with average age （ 52.8 ± 11.9 ） years. The control group comprised 46 men and 20 women with average age （ 58.2± 10.9 ） years. The patients in the treatment group were administered 1 morphine sulfate 20mg suppository by rectum and 1 placebo tablet by mouth. The patients in the control group were administered 1 morphine sulfate 20mg tablet by mouth and 1 placebo suppository by rectum. The oatients were administered the second dose when the moderate oain recurred. The daily dose was not more than 100 mg. The duration of treatment was 7 days. The analgesic efficacy and adverse reactions to morphine sulfate suppositories were assessed. Results： Baseline pain intensity measured with visual analogue scale in the treatment and control groups was 7. 1 ± 1.3 and 6. 8 ±1.2, respectively. The difference was not statistically significant （P 〉 0.05 ）. The pain intensity in patients in both groups decreased 15 and 30 minutes, 1.0, 1.5, 2.0, 3.0, 4.0, and 6.0 hours after administration, compared with before administration. The difference in pain intensity between before administration and at different time points after administration was as follows： after the first administration, it was respectively 0.80 ± 1.33, 2.09 ± 1.77, 3.27± 1.92, 4.14± 2.05, 4.26 ± 2.13, 3.70 ± 2.09, 3.27 ±2.11, and 2.88 ±2.35 in the treatment group and 0.74 ± 1.41, 1.97 ± 1.93,3.15 ± 2.11,3.82 ± 2.16, 3.95 ± 2.13, 3.52 ± 2.12, 3.00 ± 2.19, and 2.70 ± 2.23 in the control group; after the second administration, it was respectively 0.92 ± 1.37, 5.35 ± 1.53, 3.05 ± 1.94, 3.38 ± 1.85, 3.70± 2.02, 3.52 ± 2.00, 3.05 ± 2.06, and 2.84 ± 2.22 in the treatment group and 0.72 ± 1.03, 4.95 ± 1.49, 2.77 ± 1.84, 3.27 ± 1.98, 3.27 ± 1.95, 3.05 ± 1.77, 2.67 ± 1.68, and 2.25 ± 1.88 in the control group. The differences in pain intensity before and after treatment in both groups were statistically significant （ all P 〈 0. 001 ）. But there was no statistically significant difference in the pain intensity between the two groups （ all P 〉 0.05 ）. The response rate to analgesia in both groups was 71.21%, the pain intensity in the treatment and control groups was respectively 2.74 and 2.86 two hours after the first injection and 4.12 six hours after the first injection. The times of administration in the treatment and control groups were respectively 2.54-2.97 and 2.52-3.03 from day 2 to day 7. The differences in the response rate, pain intensity, and times of administration between both groups were not statistically significant 2 and 6 hours after administration （ all P 〉 0.05 ）. The incidence of adverse reactions was 27.27% in both groups. The main adverse reactions in the treatment and control groups were vomiting （ 13.64% vs 9.09% ） , nausea （ 10.61% vs 10.61% ）, constipation （6.06% vs 7.58% ）, somnolent （3.03% vs 6.06% ）, dizziness （3.03% vs 6.06% ）, skin pruritus （ 1.52% vs 1.52% ）. The differences between both groups were not statistically significant （ P 〉 0.05 ）. Diplopia （ 1.52% ） and rectal tenesmus （ 1.52% ） occurred in the treatment group; respiratory depression （ 1.52% ） and finger tip convulsion （ 1.52% ） occurred in the control group. Conclusion： Analgesic efficacy of morphine sulfate suppositories is similar to morphine sulfate tablets. It is a more tolerable, safe, and effective dosage form for treatment of moderate to severe cancer pain.