Long-term oral opioid therapy in patients with chronic nonmalignant pain.

In contrast to the use of opioids for the treatment of acute and chronic cancer pain, the administration of chronic opioid therapy for pain not due to malignancy remains controversial. We describe 100 patients who were chronically given opioids for treatment of nonmalignant pain. Most patients experienced neuropathic pain or back pain. We used sustained-release dihydrocodeine, buprenorphine, and sustained-release morphine. Pain reduction was measured with visual analogue scales (VAS), and the Karnofsky Performance Status Scale was used to assess the patient's function. Good pain relief was obtained in 51 patients and partial pain relief was reported by 28 patients. Only 21 patients had no beneficial effect from opioid therapy. There was a close correlation between the sum and the peak VAS values (r = 0.983; p less than 0.0001) and pain reduction was associated with an increase in performance (p less than 0.0001). The most common side effects were constipation and nausea. There were no cases of respiratory depression or addiction to opioids. Our results indicate that opioids can be effective in chronic nonmalignant pain, with side effects that are comparable to those that complicate the treatment of cancer pain.     

曲马多与阿米替林治疗带状疱疹后遗神经痛的疗效比较

目的：研究曲马多对带状疱疹后遗神经痛的临床疗效、剂量控制以及主要的不良反应。方法：将50例带状疱疹后遗痛患者分为曲马多组（n=30）和阿米替林组（n=20）,对患者的疼痛程度（visual analog scale,VAS）、疼痛缓解程度、不良反应、日常生活等进行8周的随访。结果：曲马多治疗后8周VAS较治疗前显著下降（P〈0.01）。第1～3周曲马多较阿米替林能够更好的减轻患者的疼痛程度（P〈0.05）。第4～8周两者疗效无显著差异（P〉0.05）。曲马多最常见的不良反应为便秘、乏力、恶心及嗜睡;80%的患者用曲马多后生活质量得到改善。结论：曲马多或阿米替林都能够减轻带状疱疹后遗神经痛。曲马多能够快速的缓解患者疼痛,疗效稳定。大部分患者可以耐受曲马多的不良反应且生活质量得到了改善。曲马多可以作为带状疱疹后遗神经痛的主要镇痛药物。     

Impact of cancer-related symptom synergisms on health-related quality of life and performance status

To identify the impact of multiple symptoms and their co-occurrence on health-related quality of life (HRQOL) dimensions and performance status (PS), 115 outpatients with cancer, who were not receiving active cancer treatment and were recruited from a university hospital in Sao Paulo, Brazil completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the Beck Depression Inventory, and the Brief Pain Inventory. Karnofsky Performance Status scores also were completed. Application of TwoStep Cluster analysis resulted in two distinct patient subgroups based on 113 patient experiences with pain, depression, fatigue, insomnia, constipation, lack of appetite, dyspnea, nausea, vomiting, and diarrhea. One group had multiple and severe symptom subgroup and another had less symptoms and with lower severity. Multiple and severe symptoms had worse PS, role functioning, and physical, emotional, cognitive, social, and overall HRQOL. Multiple and severe symptom subgroup was also six times as likely as lower severity to have poor role functioning; five times more likely to have poor emotional; four times more likely to have poor PS, physical, and overall HRQOL; and three times as likely to have poor cognitive and social HRQOL, independent of gender, age, level of education, and economic condition. Classification and Regression Tree analyses were undertaken to identify which co-occurring symptoms would best determine reduction in HRQOL and PS. Pain and fatigue were identified as indicators of reduction on physical HRQOL and PS. Fatigue and insomnia were associated with reduction in cognitive; depression and pain in social; and fatigue and constipation in role functioning. Only depression was associated with reduction in overall HRQOL. These data demonstrate that there is a synergic effect among distinct cancer symptoms that result in reduction in HRQOL dimensions and PS.     

Comparison of the antiemetic efficacy of tropisetron and droperidol with patient-given tramadol

We compared the antiemetic efficacy of tropisetron versus droperidol in women given tramadol after total hysterectomy. Forty patients were randomly allocated to group 1 (n = 20, tropisetron 0.05 mg/kg intravenously) or group 2 (n = 20, droperidol 15 micrograms/kg intravenously). Tramadol infusion (intravenously), for post-operative analgesia, was started at fascia closure. Incidences of post-operative nausea and vomiting, pain intensity, tramadol use, and the need for a rescue antiemetic (metoclopramide 10 mg) were recorded 0 h, 2 h, 6 h, 12 h, 24 h and 48 h post-operatively. Vomiting and nausea incidences were reported fewer in group 1 than in group 2, but statistical significance was only reached for vomiting incidence 6 h post-operation. Tropisetron seems to have better antiemetic properties than droperidol in patients receiving tramadol because of the length of its duration of action. Further studies, investigating alternative ways of managing post-operative nausea and vomiting, and the use of tramadol for post-operative analgesia, are needed.     

曲马朵缓释片用于肺癌术后镇痛效果观察

[目的]观察曲马朵缓释片和曲马朵普通片治疗肺癌术后疼痛的疗效.[方法]将30例病人随机分成实验组和对照组,实验组给予曲马朵缓释片100 mg,12 h 口服1次;对照组给予曲马朵普通片50 mg,6 h口服1次.[结果]曲马朵缓释片与曲马朵普通片镇痛效果相同,组间差异无统计学意义.[结论]曲马朵缓释片对肺癌术后中度急性疼痛的镇痛效果确切.     

曲马多和芬太尼用于鼻内镜术后病人自控镇痛

目的比较鼻内镜手术后使用曲马多或芬太尼进行自控镇痛的镇痛效果及不良反应。方法手术患者88例。随机分为曲马多组42例和芬太尼组46例。两组均全麻下行鼻内镜手术。术毕苏醒后送麻醉术后恢复室（PACU），使用曲马多或芬太尼进行自控镇痛（PCA）。术后48h分时点观察病人的一般情况，疼痛、头晕、恶心呕吐、食欲及睡眠等指标。结果术后次日晨（8Am）和术后48h，曲马多组的视觉模拟评分（VAS）明显低于芬太尼组（P〈0．01）；术后次日晨（8Am）、术后24h和48h曲马多组病人的按压次数明显少于芬太尼组；曲马多组术后48h静脉镇痛使用的总药量明显少于芬太尼组（P〈0．01），头晕的发生率高于芬太尼组（P〈0．05）。结论鼻内镜手术后镇痛使用PCA，曲马多的效果优于芬太尼。     

The Addition of Tramadol as a Second Opioid May Improve Pain Relief in Severe Osteoarthritis: A Prospective Study

Background: Opioid combination has been shown to reduce the need for escalating doses for the treatment of cancer pain. A prospective study was planned to evaluate the addition of tramadol to a stronger opioid for the treatment of severe pain as a result of osteoarthritis, previously uncontrolled by non‐opioid analgesics or weak opioids. Methods: All subjects received tramadol 200 mg and tizanidine 2 mg. At 2 weeks, tramadol was discontinued for patients still reporting poor pain relief (effectiveness ≤50%), and a stronger opioid was titrated to a morphine equivalent amount (MEA) of 40–60 mg orally. After two additional weeks, patients were then divided into two groups: the Strong Opioid Group (SO) and the Tramadol plus the Strong Opioid Group (TSO). The SO group was allowed to escalate opioid dose for lack of effectiveness; the TSO group received tramadol 150 mg daily, thereafter additional strong opioid titration was allowed. Results: A total of 74 patients were studied: SO (n = 40) and TSOG (n = 34). All patients eventually achieved pain relief quality, with both groups reporting similar Karnofsky Performance Scale effectiveness. The SO group achieved satisfactory pain relief (>50%) at an average daily oral MEA of 120 mg. TSO subjects achieved satisfactory pain relief (>50%) at an average daily oral MEA of 95 mg. Discussion: The addition of tramadol provided a synergistic effect resulting in a 30‐mg decrease in necessary morphine equivalents with fewer opioid‐related adverse effects.     

伍用不同剂量氟哌啶对曲马多PCEA术后镇痛效应的影响

研究不同剂量量氟哌啶对曲马多病人自控硬膜外镇痛（ＰＣＥＡ）效应及副作用的影响。方法：择期手术３２０例随机分为四组,Ａ组（ｎ＝８０）：１％曲马多＋０．１５％丁哌卡因（对照组）;Ｂ组（ｎ＝８０）：１％曲马多＋０．１５％丁哌卡因＋０．００５％氟哌啶;Ｃ组（ｎ＝８０）：１％曲马多＋０．１５％丁哌卡因＋０．０１％氟哌啶;Ｄ组（ｎ＝８０）：１％曲马多＋０．１５％丁哌卡因＋０．０１５％氟哌啶。上述各组按比例配制     

曲马多和吗啡术后镇痛对肿瘤病人免疫功能的影响

目的 :探讨曲马多、吗啡术后镇痛对肿瘤病人免疫功能的影响。方法 :选取子宫颈癌病人30例 ,常规全麻下行子宫颈癌根治手术 ,术后随机分成两组 (T组和M组 ) ,分别给予曲马多和吗啡进行术后镇痛 ,于术前、术毕给予镇痛药前和给予镇痛药 2h后抽取病人静脉血测定血清T淋巴细胞增殖率、NK细胞活性及病人VAS评分。结果 :两组病人均达到满意的镇痛效果 ,术毕两组病人T淋巴细胞增殖率均明显下降 (P <0 .0 5 ) ,M组持续到术后 2h ,而T组则于术后 2h恢复到术前水平 ,两组间有显著差异 (P <0 .0 5 )。给予镇痛药 2h后NK细胞活性 ,M组无明显变化而T组则有明显增高。结论 :曲马多用于术后镇痛更有利于病人免疫功能的恢复     

Hydrocodone/acetaminophen and tramadol chlorhydrate combination tablets for the management of chronic cancer pain: a double-blind comparative trial

OBJETIVES: The purpose of this study was to compare the analgesic efficacy and tolerability of opioids hydrocodone and tramadol in the relief of cancer pain. METHODS: One hundred and eighteen patients with chronic cancer pain participated in a double-blind, randomized controlled trial. Sixty-two patients received hydrocodone and 56 patients received tramadol. RESULTS: Hydrocodone/acetaminophen was effective in relieving pain in 56.5% of the patients at the starting dose of 25 mg/2500 mg/d. An additional 14.5% of the patients responded to a double dose, and the remaining 29% of patients did not experience any pain relief from hydrocodone administration. One dose of tramadol at 200 mg/d produced pain relief in 62% of the patients and alleviated pain in another 11% of patients at a dose of 400 mg/d, and remaining 27% of patients did not experience pain relief from tramadol. No significant statistical difference in the analgesic efficacy of tramadol clorhydrate and hydrocodone/acetaminophen was found. The groups differed significantly in the incidence of side effects like nausea (P=0.03; relative risk (RR), 1.69; confidence interval (IC) 95%, 1.03-2.77), vomiting (P=0.02; RR, 2.21; IC 95%, 1.14-4.32), dizziness (P=0.03; RR, 2.12; IC 95%, 1.17-3.86), loss of appetite (P=0.02; RR, 3.27; IC 95%, 1.12-9.55) and weakness (P=0.019; RR, 7.75; IC 95%, 0.98-61.05). CONCLUSIONS: There was no superior analgesic efficacy with the administration of hydrocodone/acetaminophen when compared to patients receiving tramadol in the relief of cancer pain. Tramadol produced more mild side effects than hydrocodone.     

氟比洛芬酯和曲马多超前镇痛用于腹腔镜胆囊切除术的临床比较

目的 比较研究氟比洛芬酯和曲马多超前镇痛用于腹腔镜胆囊切除术的效果及不良反应.方法 择期行腹腔镜胆囊切除手术患者42例,随机分为氟比洛芬酯组(A组)、曲马多组(B组)及氯化钠溶液对照组(C组),每组各14例.术前10 min,A组静脉注射氟比洛芬酯50 mg,B组静脉注射曲马多100 mg,C组静脉注射氯化钠溶液5ml.术后随访24 h,记录生命体征、疼痛程度和恶心呕吐情况.结果 各时间点3组患者的生命体止差异无统计学意义;A组与B组各时间点视觉模拟评分(VAS)差异无统计学意义,但两组分别与C组比较VAS评分均显著降低(P<0.05);B组与A、C组比较,术后恶心呕吐(PONV)的发生率明显升高(P<0.05).结论 氟比洛芬酯和曲马多超前镇痛应用于腹腔镜胆囊切除术,能明显减缓术后疼痛,氟比洛芬酯与曲马多相比恶心呕吐的不良反应小,因而更具优势.     

Comparative study of tramadol versus NSAIDS as intravenous continuous infusion for managing postoperative pain

We compared the analgesic efficacy and safety of tramadol, a new pure agonistic central analgesic, with that of three nonsteroidal anti-inflammatory drugs (NSAIDs) in the control of postoperative pain. A total of 160 patients undergoing abdominal hysterectomy participated in this randomized, double-blind study. Four treatment groups were established: tramadol, metamizole, ketorolac, and lysine clonixinate, with 40 patients in each group. Analgesics were administered using continuous infusion plus patient-controlled analgesia. During this 24-hour study, pain was assessed by using a visual analog scale. The number of boluses required per patient, the number of patients requiring supplementary analgesia, the presence of nausea or vomiting, the need for antiemetics, and an evaluation of overall efficacy also were recorded during the first 24 hours after surgery. The analgesic efficacy of tramadol was found to be greater than that of the three NSAIDs. Tramadol also was statistically significantly better than the other three agents with regard to the number of boluses required per patient (1.6 versus 4.4 for metamizole, 4.5 for ketorolac, and 5.3 for lysine clonixinate) and the number of patients requiring supplementary analgesia (1 patient versus 5 for metamizole, 11 for ketorolac, and 11 for lysine clonixinate). Nausea and vomiting were common in all four groups, especially in patients treated with metamizole, but the need for antiemetics was significantly lower with tramadol and lysine clonixinate. With regard to overall efficacy, as rated by the physician, excellent and very good results were obtained in 79.5% of the patients in the tramadol group, compared with 57.5%, 57.5%, and 50% of those in the metamizole, ketorolac, and lysine clonixinate groups, respectively (P < 0.05 or better). The results of this study confirm that tramadol, a central analgesic, is better for controlling postoperative pain than the NSAIDs with which it was compared.     

氯诺昔康及曲马多行术后自控镇痛的临床应用

目的评价氯诺昔康及曲马多用于患者术后自控镇痛(PCA)的安全性及有效性,寻找较好的术后自控镇痛方法从而减轻术后护理的工作量和提高患者术后护理质量。方法50例在全麻下行胆囊切除术和单侧乳癌根治术的患者,随机分为氯诺昔康组(L组)和曲马多组(T组),每组各25例。将所配制药液注入PCA泵,PCA泵给药速率为2ml/h,术毕时启动PCA泵进行镇痛,术毕前予首量。镇痛结束时,由患者完成疼痛的评分,记录PCA期间出现的副作用。结果L组患者的镇痛效果优于T组,差异有统计学意义。T组恶心与呕吐的发生率为36.0%,L组为8.0%,T组明显高于L组(P<0.05)。结论氯诺昔康术后自控镇痛的效果优于曲马多,恶心、呕吐少,能减少术后护理工作量,更适用于治疗术后急性疼痛。     

术前口服曲马多在神经外科手术超前镇痛的应用

目的:观察颅脑手术病人术前口服不同剂量曲马多对术后镇痛的效果以及副作用的发生率,探讨曲马多用于神经外科手术超前镇痛的合理用量.方法:采用随机、双盲、平行对比的研究方法,择期神经外科全麻颅脑手术患者175例,随机分为三组:安慰剂组、曲马多100mg组、曲马多200mg组.各组药物分别于术前2h口服.所有病人术后采用相同剂量的曲马多PCA镇痛.于术后48h内定时观察VAS疼痛评分,记录镇痛药用量、副作用.结果:术后VAS疼痛评分各组间无统计学差异,术后4h内安慰剂组疼痛例数高于超前镇痛组(P＜0.05).口服曲马多各剂量组术后恶心呕吐发生率以曲马多200mg组较高.结论:口服曲马多用于神经外科手术有明确的超前镇痛作用,术前口服曲马多100mg术后镇痛效果好,术后恶心及呕吐发生率较低,是较适宜的术前口服剂量.     

Interactions in the antinociceptive effect of tramadol in mice: an isobolographic analysis

Tramadol is a widely-used analgesic for pre- and post-operative pain which has a different pharmacological profile to that of classical opioids, since it does not induce respiratory depression, constipation, sedation, tolerance or dependence. However, tramadol frequently produces nausea and vomiting as side-effects. In the present study, the interactions between tramadol and several adrenergic and serotonergic compounds with antinociceptive activity were studied by isobolographic analysis. Antinociceptive activity was evaluated using the acetic acid writhing test in mice. Dose-response curves for the antinociceptive effect of tramadol, prazosin, clonidine, xylamine, clomipramine and cyproheptadine were obtained, and ED₅₀S were calculated for isobolographic analysis, which was performed by administration of fixed-ratios of tramadol with each of these drugs, given both systemically and intrathecally. The isobolograms of all combinations tested, either systemically or intrathecally showed superadditivity. The synergies observed with these combinations suggest a complex modulation of the descending noradrenergic and serotonergic systems that exert inhibitory influences on the transmission of nociceptive information, probably in addition to effects on receptors in the primary neurons of the spinal cord. The co-administration of analgesic drugs that produce superadditivc effects constitutes a significant new avenue for the treatment of pain, since a similar level of antinociception can be obtained with considerable reductions in the dose of each analgesic.     

Orale Opiattherapie bei Patienten mit “nicht-malignen” Schmerzen

Opioids are given for acute intra- and postope-rative pain relief or for chronic cancer pain. In the literature there are only rare and contradictory reports on the oral administration of opioids for chronic non-malignant pain. However, there is no reason to withhold strong analgesics for patients with severe pain. When all other thrapeutic measures fail to control pain, patients with non-malignant pain can also be treated by opioids. We report 70 patients with severe pain who were given opioids as the ultima ratio in pain therapy: 50 received buprenorphine sublingual tablets, 13 received morphine sustained release tablets and the remaining 7 were treated with other opioids. The mean daily dose was 1.45 mg buprenorphine or 87.6 mg morphine. The dosage increased in 12 of the 50 patients treated with buprenorphine while 5 of the 13 morphine patients needed increasing dosage. The other patients had a constant dosage after the initial period of dose-finding. In more than 50% the pain could be effectively controlled by oral opioids. The general performance status (Karnofsky) increased from 63.6% to 74.1%. The typical side effects were constipation and nausea. Prophylaxis of constipation is most important during opioid therapy. No case of respiratory depression or opioid addiction was registered. Our results show that patients with musculo-skeletal and deafferentation pain respond better to opioids than patients with headache. Negative results were observed in some patients with neuropathic pain. The results of the study show that opioids are justifiable for the treatment of non-malignant pain and can be given without danger over a long period of time. Side effects are controlled by additional medication. The principle of opioid administration is prophylaxis of pain -therefore, they should be given "by the clock". Opioids are not only indicated in malignant illness, but also according to severity of pain and by the failure of other measures to control pain.     

Slow-release tramadol for treatment of chronic malignant pain – an open multicenter trial

 Patients with moderate to severe cancer pain and insufficient pain relief from nonopioid analgesics were treated with slow-release tramadol for initial dose finding and as a long-term treatment. Immediate-release tramadol was provided for the treatment of breakthrough pain and a standard nonopioid analgesic (1000 mg naproxen daily) was given as suggested for step 2 of the WHO analgesic ladder. Ninety of 146 patients (62%) completed the 6-week trial period. Drop-outs were due to adverse events (20%), inadequate pain relief (9%), or both (2.5%), death due to the underlying disease (4%), low patient compliance (2%) or other reasons. Average and maximal pain intensity decreased from day 1 to day 4. The number of patients with good and complete pain relief increased from 43% after week 1 to 71% after week 6 with maximum daily doses of tramadol up to 650 mg. However, 70% of the patients still needed less than 400 mg tramadol per day in week 6. Most patients (86%) experienced adverse events during the study period. Some common side effects of opioids, such as fatigue, dizziness, and constipation, decreased in frequency over the 6 weeks. The frequency of other adverse events such as nausea, vomiting and sweating did not change. Slow-release tramadol provided fast and efficient pain relief in almost two-thirds of patients both during initial dose finding and during long-term treatment, improving treatment options in step 2 of the WHO analgesic ladder. Published online: 31 May 2000     

Tramadol/acetaminophen for the treatment of acute migraine pain: findings of a randomized, placebo-controlled trial

OBJECTIVE: To compare tramadol/acetaminophen (APAP) and placebo for the management of acute migraine pain. BACKGROUND: Tramadol/APAP tablets reduced moderate-to-moderately severe acute pain in controlled studies of other painful conditions. METHODS: This randomized, double-blind, placebo-controlled, parallel group study enrolled adults with migraine pain as per International Headache Society criteria. Subjects took tramadol/APAP (total dose, 75 mg/650 mg) or placebo for a typical migraine with moderate-to-severe pain. Severity of pain and migraine-related symptoms were recorded before study medication and at 0.5, 1, 2, 3, 4, 6, and 24 hours after study medication. RESULTS: Efficacy analyses included 305 subjects (154 tramadol/APAP and 151 placebo). Treatment response was higher for tramadol/APAP than a placebo at 2 hours after dosing (55.8% vs. 33.8%, P < .001) and at every other assessment from 30 minutes (12.3% vs. 6.6%) through 6 hours (64.9% vs. 37.7%) (all P< or = .022). Subjects in the tramadol/APAP group were more likely than those in the placebo group to be pain-free at 2 hours (22.1% vs. 9.3%), 6 hours (42.9% vs. 25.2%), and 24 hours (52.7% vs. 37.9%) (all P< or = .007). Two hours after dosing, moderate-to-severe symptoms that were less common for tramadol/APAP than placebo included photophobia (34.6% vs. 52.2%, P= .003) and phonophobia (34.3% vs. 44.9%, P = .008), but not migraine-related nausea (38.5% vs. 29.4%, P= .681). Treatment-related adverse events included nausea, dizziness, vomiting, and somnolence. CONCLUSIONS: Tramadol/APAP reduces the severity of pain, photophobia, and phonophobia associated with migraine headache, but does not reduce migraine-associated nausea. Tramadol/APAP might be an appropriate option for the management of moderate-to-severe migraine headache.     

鞘内注药用于重度宫颈癌疼痛治疗的临床观察

目的观察鞘内注药治疗重度顽固性晚期宫颈癌疼痛患者的临床效果。方法选择60例ASAⅠ-Ⅲ级,经第二、三阶梯治疗效果欠佳重度晚期宫颈癌疼痛患者分为观察组（鞘内注药组）和对照组（美施康定组）,每组30例。观察组鞘内注药（硬膜外患者自控镇痛）每单元300 mL,混合液每单元药物含0.75%盐酸罗哌卡因60 mL,舒芬太尼300μg,氟哌啶5 mg、昂旦司琼20 mg,2 mL·h^-1泵注,对照组按照三阶梯规范口服硫酸吗啡控释片。运用视觉模拟评分法（VAS）评估治疗疗效,并不断调整治疗剂量。结果观察组患者经治疗后疼痛明显减轻,VAS为（1.86±1.42）分,生活质量明显改善,与镇痛前比较差异有显著的统计学意义（P〈0.01）,与对照组比较差异有统计学意义（P〈0.05）;部分患者可发生轻度的恶心呕吐,便秘,尿潴留等不良反应,无需特殊治疗。结论鞘内注药配合肿瘤化疗或放射治疗重度晚期宫颈癌疼痛患者效果满意、安全、不良反应少。     

酮咯酸氨丁三醇联合曲马多用于下肢骨科手术后静脉自控镇痛的临床研究

目的观察联合酮咯酸氨丁三醇和曲马多用于下肢骨科手术后患者静脉自控镇痛的疗效。方法选择80例ASA(Ⅰ～Ⅱ)级择期在椎管内麻醉行下肢骨科手术的患者,随机分为2组:PCIA:曲马多组(A组)40例;曲马多复合酮咯酸氨丁三醇组(B组)40例。观察术后24h内(6h、12h、18h、24h)VAS评分、PCA按压次数、不良反应情况。结果术后6h、12hB组VAS评分低于A组,2组患者恶心、呕吐、头晕、头痛等不良反应无明显差异,PCA按压次数减少。结论酮咯酸氨丁三醇联合曲马多用于术后镇痛,可增强单用曲马多的镇痛效果,并且减少其用量,静脉自控镇痛效果好,而并不增加恶心、呕吐、头晕、头痛等不良反应发生率。