Opioid Rotation from High-Dose Morphine to Transdermal Buprenorphine (Transtec®) in Chronic Pain Patients

Abstract:   Opioid rotation is increasingly becoming an option to improve pain management especially in long-term treatment. Because of insufficient analgesia and intolerable side effects, a total of 42 patients (23 male, 19 female; mean age 64.1 years) suffering from severe musculoskeletal (64%), cancer (21%) or neuropathic (19%) pain were converted from high-dose morphine (120 to >240 mg/day) to transdermal buprenorphine. The dose of buprenorphine necessary for conversion (at least 52.5 µg/h) was titrated individually by the treating physician. No conversion recommendations were given and the treating physician used his or her own judgment for dose adjustment. Pain relief, overall satisfaction and quality of sleep (very good, good, satisfactory, poor, or very poor), and the incidence and severity of adverse drug reactions over a period of at least 10 weeks and up to 1 year was assessed. Following rotation, patients experiencing good/very good pain relief increased from 5% to 76% ( P  < 0.001). Only 5% reported insufficient relief. Relief was achieved with buprenorphine alone in 77.4%, while 17% needed an additional opioid for breakthrough pain. Sleep quality (good/very good) increased from 14% to 74% ( P  < 0.005). Adverse effects were reported in 11.9%, mostly because of local irritation, did not result in termination of therapy. Neither tolerance nor refractory effect following rotation from morphine to buprenorphine was noted. Conversion tables with a fixed conversion ratio are of limited value in patients treated with high-dose morphine.     

盐酸丁丙诺啡复合布比卡因用于老年患者术后硬膜外自控镇痛的疗效观察

[目的]观察丁丙诺啡复合布比卡因用于老年患者术后硬膜外自控镇痛(PCEA)的疗效及不良反应.[方法]70～85岁膀胱癌或前列腺增生患者60例,随机分为A、B、C三组,术毕均采用硬膜外自控镇痛,其中A组配方为吗啡5 mg 0.75%布比卡因15 mL 0.9%氯化钠溶液稀释至100 mL,B组、C组分别将吗啡改为丁丙诺啡0.45 mg或0.3 mg.观察术毕(t1)、术后3 h(t2)、6 h(t3)、12 h(t4)、24 h(t5)、拔除PCA时(t6)的心率(HR),平均动脉压(MAP),血氧饱和度(SpO2);视觉模拟评分(VAS),Ramsay镇静评分(RSS);t1～t6 PCA按压次数及总用量;不良反应.[结果]三组HR、MAP、SpOz及VAS无明显差别;A组患者RSS在t3、t4高于术毕,且从t3～t6 B,C两组明显低于A组,C组明显低于术毕(P＜0.01);PCA按压次数C组明显多于B和A组(P＜0.01),总用药量C组＞B组＞A组(P＜0.01);A组有较多的恶心呕吐病例(P＜0.01),有4例患者出现嗜睡现象(P＜0.05),但无明显呼吸抑制.[结论]丁丙诺啡复合布比卡因能安全有效用于老年患者术后PCEA,其中以丁丙诺啡0.45 mg配方较为适宜.     

Efficacy and Safety of Buprenorphine Transdermal System (BTDS) for Chronic Moderate to Severe Low Back Pain: A Randomized, Double-Blind Study

In this enriched design study, 1,160 opioid-experienced patients with chronic, moderate to severe low back pain entered an open-label run-in period; 660 demonstrated analgesic benefit from and tolerability to buprenorphine transdermal system 20 mcg/hour (BTDS 20) treatment and were randomized to receive either BTDS 20, BTDS 5 mcg/hour (BTDS 5), or the active control (immediate release oxycodone 40-mg/day) during an 84-day double-blind phase. The primary endpoint, “average pain in the last 24 hours” during double-blind weeks 4, 8, and 12, was significantly lower for patients receiving BTDS 20 compared with patients receiving BTDS 5 (P < .001, treatment difference of −.67). A treatment difference of −.75 in favor of oxycodone 40 mg/day versus BTDS 5 (P < .001) indicated the assay sensitivity of the study. Four sensitivity analyses, secondary, and exploratory analyses supported the results of the primary analysis. Incidences of treatment-emergent adverse events were 56% during the open-label period, and 59, 77, and 73% for the BTDS 5, BTDS 20, and oxycodone 40 mg/day treatment groups, respectively, during the double-blind phase. One death considered unrelated to study treatment occurred in a patient receiving BTDS 10 during the run-in period. BTDS 20 treatment was demonstrated to be efficacious and generally well tolerated.

Perspective

This article presents results of a pivotal Phase 3 study that assesses a new treatment for the management of chronic low back pain: a transdermal patch containing the opioid buprenorphine (BTDS). In this active controlled, superiority study with an enriched design, BTDS 20 was found to be efficacious and generally well tolerated.     

The Use of Transdermal Buprenorphine in Complex Regional Pain Syndrome: A Report of Two Cases

Management of complex regional pain syndrome (CRPS) can be challenging. Various pharmacological approaches have produced mixed results. Buprenorphine activates mu-opioid receptors and antagonizes kappa and delta receptors, acts at N-methyl-d-aspartate (NMDA) receptor, and is an orphan-related ligand-1 receptor agonist. It is available in transdermal patches that last for up to 7 days. This report describes two patients with refractory CRPS who were treated with transdermal buprenorphine. The patients experienced approximately 50% reduction in pain intensity scores. Application site rash that occurred was managed with topical steroid spray used before applying the patch.     

Reduction in Pulmonary Embolism after Total Joint Arthroplasty: Three Years of Experience with Extended‐Release Epidural Morphine

A retrospective analysis of 659 patients who had undergone a hip or knee arthroplasty was undertaken to determine the incidence of pulmonary embolism (PE) during the 48‐hour period following surgery. Data related to pain control, concomitant medications, length of stay, and adverse reactions were also collated. Patients were evenly divided between those receiving extended‐release epidural morphine (EREM: n = 327; mean dose 9.7 mg, range 5 mg to 15 mg) or a control group receiving other treatment for postoperative pain (control: n = 332; 44% of controls had an epidural catheter in place). The incidence of PE was significantly higher in the control group than in the EREM group (control: n = 6 or 1.80% vs. EREM: n = 0). Pain control (by a 10‐point verbal numerical rating scale) was significantly improved in the EREM group compared with the control group 48 hours after surgery (2.3 ± 1.8 vs. 4.7 ± 2.6) and length of stay was significantly reduced (3.9 ± 1.5 days vs. 4.5 ± 2.0 days). Adverse event profiles of the EREM and control groups were consistent with prior published studies with EREM. The use of EREM following lower extremity joint arthroplasty may be associated with a significant reduction in the incidence of PE.     

Comparison of Epidural Depo-Medrol vs. Aqueous Betamethasone in Patients with Low Back Pain

Abstract: Despite the popularity of epidural steroid injections for low back pain, there still remains a lack of consensus on which type of steroid to inject. Most comparison studies regarding epidural steroids are based on an assumption that different types of steroids are equal as long as equipotent doses are utilized. In the spring of 2002, a national shortage of all depo steroids allowed the authors to compare epidural methylprednisolone (Depo‐Medrol) to a non depo form of betamethasone in patients with low back pain. Patients who received epidural methylprednisolone (Depo‐Medrol) reported significant reduction in pain ratings as well as disability scores after 4 weeks, while patients receiving betamethasone showed no significant difference in pain or disability scores. This study shows that the aqueous steroid betamethasone is not an effective alternative to the commonly used depo‐steroid methylprednisolone (Depo‐Medrol) when injected epidurally in patients with lumbar pain. The study also shows that the anti‐inflammatory effect of a depo‐steroid can be greater than a non‐depo steroid, even at equipotent doses. This should be an important factor to consider when reviewing epidural steroid outcome studies, where the type of steroid might affect results as much as other variables such as route of administration, volume of injectate, or use of fluoroscopy.     

舒芬太尼复合罗哌卡因用于开胸术后硬膜外镇痛的疗效

【目的】观察舒芬太尼或芬太尼复合罗哌卡因用于开胸手术后硬膜外自控镇痛（PCEA）的临床镇痛效果和安全性。【方法】ASAⅠ～Ⅱ级,全麻复合连续硬膜外阻滞麻醉行开胸手术病人70例,随机分为两组（n=35）,使用0．75μg／ml舒芬太尼（S组）或3μg／ml芬太尼（F组）复合0．125％罗哌卡因,术后行PCEA。镇痛泵设定持续背景剂量2mL／h、PCA每次0．5mL,锁定时间15min。观察病人术后镇痛效果,记录术后4h、8h、12h、24h、48h各时间点的疼痛评分（VAS）、镇静评分、PCA使用次数、不良反应和病人满意度。【结果】S组术后8h、24h和48hVAS评分明显低于F组（P〈0．05）;S组各时间点镇静评分均明显大于F组（P〈0．05）;S组PCA按压次数显著低于F组（P〈0．05）;S组病人对PCA的满意度明显高于F组（P〈0．05）。两组恶心、呕吐发生率低,呼吸抑制相比无明显差异。【结论】舒芬太尼复合罗哌卡因用于开胸手术后PCEA,镇痛安全有效,镇痛镇静效果优于芬太尼,不良反应程度较轻。     

Spinal Cord Stimulation (SCS) in Peripheral Ischemic Pain

Between 1982 and 1987,45 patients suffering from painful symptomatology caused by peripheral vascular disease, not curable by medical or surgical therapy, were implanted with epidural neurological stimulators. Measurements used in evaluating the effectiveness of the method were pain control, walking distance, and development of trophic problems. With most patients, we noted a satisfactory and long-lasting degree of pain control. Walking distance increased to a surprising degree. Trophic lesions smaller than 3 sq cm healed, while lesions of greater size required amputation of the limb. Transcutaneous oxygen tension (TcpO₂) was used to study the efects of SCS on peripheral circulation in implanted patients. In addition, TcpO₂ was calculated in 15 patients before and during the percutaneous test to predict the efectiveness of SCS. Regression of painful symptomatology was achieved only in patients whose TcpO_2b improved during the course of the testing. Therefore, this method provides an objective measure for the implantation of a neurostimulator     

不同浓度舒芬太尼复合布比卡因持续硬膜外输注在开胸术后的镇痛效果观察

目的观察不同浓度舒芬太尼复合0.125%布比卡因持续硬膜外输注在开胸术后的镇痛效果和安全性.方法将30例ASA Ⅱ～Ⅲ级、行胸外科手术的患者随机分为3组,分别用0.125%布比卡因复合0.25μg/ml舒芬太尼（A组）、0.50 μg/ml舒芬太尼（B组）和0.75μg/ml舒芬太尼（C组）.术前,于T7～T8行硬膜外穿刺置管,手术结束后接入镇痛泵行持续硬膜外输注镇痛,观察术后6 h、12 h、24 h和48 h的疼痛视觉模拟评分（VAS）、辅助药用量和镇静、恶心、呕吐、皮肤瘙痒、呼吸抑制等副作用.结果B组和C组各个时段的VAS评分和48 h的辅助镇痛用药量两组间无显著性差异,但均低于A组（P＜0.05）.A组和B组的瘙痒评分均低于C组（P＜0.05）,但两组间无显著性差异.各组均无严重的呼吸抑制发生.结论 0.50 μg/ml的舒芬太尼复合0.125%布比卡因持续硬膜外输注在开胸术后可取得较满意的镇痛效果且副作用较小.     

罗哌卡因复合芬太尼用于腹腔镜下胃癌根治术后硬膜外自控镇痛效果观察

目的 分析罗哌卡因复合芬太尼用于腹腔镜下胃癌根治术后硬膜外自控镇痛的效果.方法 收集2017年5月—2020年8月行腹腔镜下胃癌根治术109例的临床资料.按照不同术后镇痛用药分为A组57例和B组52例,A组给予罗哌卡因复合芬太尼硬膜外自控镇痛,B组给予罗哌卡因硬膜外自控镇痛.比较两组围术期指标、疼痛视觉模拟评分(VAS...     

脑血管病合并心电图改变的观察及护理

通过对３４５例脑系科患者的临床观察,发现合并有心电图改变者约占６３％,经过心脏监测及加强心功能的观察及护理,减少了脑血管病患者心脏方面的合并症,提高了治愈率,减少了死亡率。     

硬膜外埋入式输注系统外接持续输入泵用于晚期癌痛的临床研究

目的:探讨硬膜外埋入式输注系统外接持续输入泵(PCA)用于晚期癌痛的疗效、可行性及安全性。方法:46例中、重度晚期癌痛患者采用硬膜外埋入式输注系统外接PCA注药镇痛,PCA总容量为250 ml,设定维持量、单次冲击量、锁定时间等参数。记录患者术前1 d、术后3 h、3 d、15 d和30 d VAS评分及术前1 d、术后7 d、15 d、30 d疼痛对生活质量影响评分,并观察镇痛后恶心、呕吐、便秘、尿潴留的发生率。结果:治疗后46例患者VAS评分及疼痛对生活质量影响评分均明显降低(P0.05),术后少数患者出现尿潴留、皮肤瘙痒、恶心呕吐,但与术前比较无明显差异(P0.05)。结论:硬膜外埋入式输注系统外接PCA在晚期癌症镇痛中疗效确切,患者生活质量明显改善,不良反应少,值得临床推广。     

Aprepitant vs. Multimodal Prophylaxis in the Prevention of Nausea and Vomiting following Extended‐Release Epidural Morphine

Background: Extended‐release epidural morphine (EREM) is an effective option for postoperative analgesia following major orthopedic surgery; however, postoperative nausea/vomiting (PONV) is a recognized limitation. The incidence of PONV following prophylactic aprepitant, a neurokinin‐1 antagonist, was compared with prophylactic multimodal antiemetic therapy in patients receiving EREM for postoperative analgesia following unilateral primary total knee arthroplasty (TKA). Methods: Prospectively collected quality assurance data were examined with Institutional Review Board approval. A sequential, open‐label, active matched case‐control study compared PONV following EREM in patients receiving ondansetron and dexamethasone, and either metoclopramide, diphenhydramine, or prochlorperazine every 6 hours for the 48‐hour study period, to patients receiving aprepitant 40 mg given as a single oral dose in the preoperative holding area. Cases were matched for procedure (TKA), age, epidural morphine dose, and known major risk factors for PONV (sex, smoking, previous PONV/motion sickness). Results: Twelve consecutive patients (3 male; 9 female) receiving aprepitant prior to EREM were matched to 12 patients of the same sex of similar age (range 51 to 84 years.) and EREM dose (range 5 to 12.5 mg) receiving the multimodal regime. The incidence of PONV was significantly less for the aprepitant group where 3 of 12 (25%) had PONV compared with 9 of 12 (75%) in the multimodal group (P = 0.039, Fisher's Exact Test; odds ratio = 0.11; 95% CI: 0.018 to 0.706, P = 0.03). Conclusion: While aprepitant significantly reduced the incidence of PONV compared with a multimodal antiemetic regime, used alone it did not eliminate PONV.     

The Influence of Pain Sensitivity on the Treatment Outcome of Transforaminal Epidural Steroid Injection in Patients with Lumbar Spinal Stenosis

The aim of this study was to investigate the effect of individual pain sensitivity on the results of transforaminal epidural steroid injection (TFESI) for the patients with lumbar spinal stenosis (LSS). Seventy‐seven patients with LSS were included in this study. Prospectively planned evaluations were performed twice consecutively before and 2 months after TFESI. These included a detailed medical history, a physical examination, and completion of a series of questionnaires, including pain sensitivity questionnaire (PSQ), Oswestry disability index (ODI), and visual analog scale (VAS) for back and leg pain. The correlations were analyzed among variables between total PSQ/PSQ‐moderate/PSQ‐minor and pain and disability level measured by VAS for back/leg pain and ODI both before and 2 months after TFESI. Two months after TFESI, there were significant decreases in VAS for back/leg pain and ODI compared with those before injection. Before injection, VAS for back pain and leg pain was highly associated with the PSQ scores including total PSQ and PSQ subscores after adjustment for age, BMI, and grade of canal stenosis. However, any subscores of PSQ and total PSQ scores were not correlated with either VAS for back pain/leg pain or ODI 2 months after TFESI with adjustment made to age, BMI, gender, and grade of canal stenosis. This study highlights that individual pain sensitivity does not influence the outcomes of TFESI treatment in patients with LSS, even though pain sensitivity has a significant negative correlation with symptom severity of LSS.     

Gender Disparity in Analgesic Treatment of Emergency Department Patients with Acute Abdominal Pain

Objectives:  Oligoanalgesia for acute abdominal pain historically has been attributed to the provider's fear of masking serious underlying pathology. The authors assessed whether a gender disparity exists in the administration of analgesia for acute abdominal pain.
Methods:  This was a prospective cohort study of consecutive nonpregnant adults with acute nontraumatic abdominal pain of less than 72 hours' duration who presented to an urban emergency department (ED) from April 5, 2004, to January 4, 2005. The main outcome measures were analgesia administration and time to analgesic treatment. Standard comparative statistics were used.
Results:  Of the 981 patients enrolled (mean age ± standard deviation [SD] 41 ± 17 years; 65% female), 62% received any analgesic treatment. Men and women had similar mean pain scores, but women were less likely to receive any analgesia (60% vs. 67%, difference 7%, 95% confidence interval [CI] = 1.1% to 13.6%) and less likely to receive opiates (45% vs. 56%, difference 11%, 95% CI = 4.1% to 17.1%). These differences persisted when gender-specific diagnoses were excluded (47% vs. 56%, difference 9%, 95% CI = 2.5% to 16.2%). After controlling for age, race, triage class, and pain score, women were still 13% to 25% less likely than men to receive opioid analgesia. There was no gender difference in the receipt of nonopioid analgesia. Women waited longer to receive their analgesia (median time 65 minutes vs. 49 minutes, difference 16 minutes, 95% CI = 3.5 to 33 minutes).
Conclusions:  Gender bias is a possible explanation for oligoanalgesia in women who present to the ED with acute abdominal pain. Standardized protocols for analgesic administration may ameliorate this discrepancy.