盐酸羟考酮缓释片联合普瑞巴林治疗糖尿病性神经痛的临床观察

目的研究盐酸羟考酮缓释片联合普瑞巴林治疗中重度糖尿病性神经痛的疗效及不良反应。方法将56例糖尿病性神经痛患者随机分成联合用药组(A)与单一用药组(B),每组28例。A组应用盐酸羟考酮缓释片联合普瑞巴林治疗,B组单纯应用盐酸羟考酮缓释片治疗,观察比较两组患者疼痛程度、疼痛缓解程度、疼痛缓解率、盐酸羟考酮缓释片使用剂量及药物不良反应等。结果两组糖尿病性神经痛患者疼痛均明显缓解,经4周治疗后,A组的疼痛程度及疼痛缓解率明显高于B组(VAS评分:A组1.2±0.4,B组2.9±0.4;疼痛缓解率:A组96.4%,B组75%),差异有统计学意义(P<0.05);同时可以减少盐酸羟考酮缓释片的使用量,两组分别为(31.9±4.4)mg、(41.1±5.5)mg,两组比较差异有统计学意义(P<0.05)。两组患者的药物不良反应主要表现为恶心呕吐、便秘、头晕、口干及尿潴留,其中A组头晕及口干症状的发生率高于B组,治疗7、14、21、28 d头晕的发生率:A组为57.1%、46.4%、35.7%、28.6%,B组为21.4%、14.3%、14.3%、3.6%,口干的发生率:A组为28.6%、42.9%、17.9%、10.7%,B组为25.0%、17.9%、10.7%、3.6%,两组比较差异有统计学意义(P<0.05)。结论盐酸羟考酮缓释片联合普瑞巴林治疗中重度糖尿病性神经痛疗效确切,安全可行。     

腹腔镜胆囊切除术患者在PACU应用羟考酮注射液镇痛疗效观察

目的:观察腹腔镜胆囊切除患者术后在麻醉恢复室(PACU)应用羟考酮注射液(奥诺美)镇痛的疗效及安全性。方法:随机选择ASAⅠ或Ⅱ级腹腔镜胆囊切除术后视觉模拟评分(VAS)为7分及以上的患者60例,分为两组各30例;镇痛组患者给予羟考酮注射液5 mg稀释至5 ml经静脉注射,对照组患者给予0.9%Na Cl注射液5 ml经静脉注射,采用VAS疼痛评分。并记录注药前及注药后每隔5 min的NT值。同时观察患者生命体征变化,以及恶心、呕吐、呼吸抑制等不良反应。结果:镇痛组患者在注药5 min后VAS评分明显下降,于20 min后降至0分;而对照组患者在注药10 min后VAS评分已升至10分,直至离开PACU;镇痛组患者在注药10 min后出现NT值一过性下降,但很快恢复;镇痛组患者的生命体征注药后无明显变化,未延长患者在PACU的滞留时间;不良反应无明显增多。结论:羟考酮注射液可安全用于腹腔镜胆囊切除患者术后镇痛,适合于PACU的镇痛管理。     

丙泊酚靶控输注时羟考酮抑制气管插管反应的半数有效剂量

目的测定丙泊酚靶控输注时羟考酮抑制气管插管反应的半数有效剂量(ED_(50))。方法择期全麻下手术的患者,性别不限,年龄18~65岁,BMI 18.5~24.9kg/m~2,ASAⅠ或Ⅱ级,MallampatiⅠ或Ⅱ级。静脉顺序注射羟考酮、靶控输注丙泊酚血浆浓度4μg/ml,BIS60时,静注罗库溴铵0.9mg/kg后行气管插管机械通气。采用改良Dixon序贯法进行试验,羟考酮起始剂量0.2mg/kg。若气管插管反应阳性,则下一例增加剂量;反之,则降低剂量,相邻剂量比值为1∶1.1。气管插管反应阳性的标准:插管后2min内MAPmax或HRmax较基础值≥20%。采用加权概率法计算羟考酮抑制气管插管反应的ED_(50)、ED_(95)及其相应的95%可信区间(CI)。结果共有27例患者完成正式研究。羟考酮抑制气管插管反应的ED_(50)为0.204 mg/kg,(95%CI 0.175~0.249 mg/kg),ED_(95)为0.342mg/kg(95%CI 0.287~0.409mg/kg)。结论血浆靶控输注丙泊酚4μg/ml时,羟考酮抑制气管插管反应的ED_(50)为0.204mg/kg,ED_(95)为0.342mg/kg。     

羟考酮对肱骨骨折术后镇痛的影响

目的观察羟考酮对肱骨骨折术后镇痛的影响。方法择期喉罩插管全麻复合臂丛阻滞麻醉下肱骨骨折切开复位内固定术患者60例,男46例,女14例,随机均分为羟考酮组(O组)和吗啡组(M组)。分别于麻醉前(T0)、术后1h(T1)、3h(T2)、24h(T3)和48h(T4)抽取外周静脉血,应用酶联免疫吸附试验(ELISA)检测血清IL-2水平,记录MAP、SpO2、VAS评分及不良反应。结果与T0时比较,T2~T4时O组血清IL-2水平明显升高(P0.05),而T1、T2、T4时M组血清IL-2水平明显降低(P0.05)。与M组比较,T2~T4时O组血清IL-2水平明显升高(P0.05)。两组MAP、SpO2和VAS评分和不良反应差异均无统计学意义。结论吗啡、羟考酮均可有效减轻术后疼痛。与吗啡抑制IL-2分泌相反,羟考酮可明显增加肱骨内固定手术患者术后IL-2的分泌。     

羟考酮联合氟比洛芬酯用于骨科术后镇痛中的效果研究

目的:分析羟考酮联合氟比洛芬酯用于骨科术后镇痛中的临床疗效与安全性,为骨科手术镇痛提供临床研究。方法:选择2013年4月至2014年5月期间行骨科手术的80例患者,按照采用的镇痛方法将其分为对照组和实验组,每组40例,实验组患者术后连接羟考酮联合氟比洛芬酯配镇痛泵进行镇痛(盐酸羟考酮50 mg+氟比洛芬酯250 mg+生理盐水至100 m L),对照组患者术后连接地佐辛联合氟比洛芬进行镇痛(地佐辛25 mg+氟比洛芬酯250 mg+生理盐水至100 m L)。观察两组患者术后镇痛的VAS、BCS与Ramsay评分的差异性;分析两组患者总体满意度的差别;比较两组患者术后镇静不良反应的状况。结果:实验组术后镇静1 h、3 h、5 h、7 h的VAS、BCS评分明显高于对照组,组间比较差异均有统计学意义(P<0.05),术后12 h、24 h以及48 h的VAS、BCS评分和对照组比较差异无统计学意义(P>0.05);实验组患者术后1 h、3 h、5 h、7 h、12 h、24 h以及48 h的Ramsay评分与对照组比较差异无统计学意义(P>0.05);实验组患者I级、II级满意率高于对照组患者(P<0.05),III级、IV级满意率低于对照组患者(P<0.05);两组患者术后镇静发生的头晕、恶心、呕吐、皮肤瘙痒、呼吸异常、以及其他不良反应发生率比较差异无统计学意义(P>0.05)。结论:羟考酮联合氟比洛芬酯用于骨科术后镇痛,能够明显改善患者的VAS、BCS评分,显著提高患者镇痛总体满意度,安全可靠,是一种值得在临床上推广使用的骨科术后镇痛方法。     

不同剂量羟考酮对腹部手术后急性疼痛的抑制作用

目的探讨不同剂量羟考酮对腹部手术后急性疼痛的抑制作用。方法择期全麻下行腹部手术患者60例,ASAⅠ或Ⅱ级,年龄30~70岁,随机均分为四组:羟考酮0.05mg/kg组(OL组)、羟考酮0.1mg/kg组(OM组)、羟考酮0.2mg/kg组(OH组)和对照组(C组)。两组麻醉诱导采用静脉注射咪达唑仑0.03mg/kg、丙泊酚2.0~2.5μg/kg、顺阿曲库铵0.2mg/kg、舒芬太尼0.6μg/kg;麻醉维持采用瑞芬太尼5~10μg·kg-1·h-1、丙泊酚4~6mg·kg-1·h-1、顺阿曲库铵0.1mg·kg-1·h-1。关腹时羟考酮组给予相应剂量的羟考酮抑制术后疼痛。于患者清醒后行NRS评分(对所有NRS大于4分者给予羟考酮镇痛),记录患者苏醒时间、清醒后的疼痛数字评分、镇痛持续时间、以及恶心、呕吐、瘙痒等不良反应的发生情况。结果与C组比较,OH组患者苏醒时间明显延长,OL、OM和OH组患者的NRS评分均明显降低,镇痛持续时间明显延长(P<0.05或P<0.01);与OL组比较,OM和OH组NRS评分明显降低,镇痛持续时间明显延长(P<0.05)。结论在关腹前给予羟考酮具有抑制腹部手术后疼痛的作用,但0.1mg/kg的羟考酮最适宜,既能达到良好的镇痛效果,同时又不影响患者的苏醒。     

A Randomized Clinical Trial of Nefopam versus Ketorolac Combined With Oxycodone in Patient-Controlled Analgesia after Gynecologic Surgery

Objectives: Nefopam is a centrally-acting non-opioid analgesic, which has no effect on bleeding time and platelet aggregation. There has been no study about nefopam and oxycodone combination for postoperative analgesia. In this study, we present efficacy and side effects of nefopam/oxycodone compared with ketorolac/oxycodone in patient-controlled analgesia (PCA) after gynecologic surgery.Methods: 120 patients undergoing gynecologic surgery were divided randomly into two groups: Nefopam group treated with oxycodone 1 mg and nefopam 1 mg bolus; and Ketorolac group treated with oxycodone 1 mg and ketorolac 1.5 mg bolus. After the operation, a blinded observer assessed the pain with a numeric rating scale (NRS), infused PCA dose and sedation score at 1, 4, 24, and 48 h, nausea, vomiting, headache, shivering, pruritus and delirium at 6, 24 and 48 h, and satisfaction at 48 h after the operation.Results: Nefopam group showed less nausea than Ketorolac group within 6 h after the operation. There were no significant differences in demographic data and other complications between both groups. At 48 h after operation, satisfaction and the infused PCA volumes of Nefopam group (34.0± 19.7 ml) showed no significant differences compared to Ketorolac group (30.7± 18.4 ml, P-value= 0.46).Conclusion: Nefopam showed a similar efficacy and lower incidence of nausea within 6 h after the operation to that of ketorolac in PCA. Nefopam may be a useful analgesic drug for the opioid-based PCA after gynecologic surgery. Further evaluation of accurate equivalent dose of nefopam as well as pharmacokinetics of bolus administration is required.     

Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain

ABSTRACT

Objective: To assess the long-term efficacy, tolerability and safety of polymer-coated extended- release morphine sulfate (P-ERMS) (KADIAN) compared with controlled-release oxycodone HCl (CRO) (OxyContin) in treating chronic, nonmalignant, moderate to severe pain in a community- based outpatient population.

Design: Phase IV, prospective, randomized, open-label.

Participants: Adults (N = 112) with chronic, nonmalignant, moderate to severe pain with visual numeric scale (VNS) scores ≥ 4 (0 = no pain; 10 = worst pain).

Interventions: Patients were randomized to receive either P-ERMS once-daily (QD) dosing or CRO twice-daily (BID) dosing for a 24‐week treatment period. Upward titration of dose and switching P-ERMS to BID or CRO to thrice-daily (TID) dosing was allowed Weeks 2–24.

Main outcome measures: Quality of life (Physical [PCS] and Mental [MCS] Component Summary scores of the SF-36v2 Health Survey), pain and sleep scores (0–10), and patient and clinician assessments of current therapy (–4 to +4).

Results: Patients in both treatment groups experienced significant improvements in PCS scores (P-ERMS, +2.6; CRO, +3.1; p < 0.05 vs. baseline); patients taking CRO also demonstrated improvements in MCS scores (+4.7, p < 0.05 vs. baseline). Both groups attained significant reductions from baseline to 24 weeks in pain (P-ERMS, –2.0; CRO, –1.4; p ≤ 0.001 vs. baseline); the reduction with P-ERMS was clinically meaningful (as defined by at least a 2‐point reduction in VNS score). Patients attained significant improvement in sleep scores (P-ERMS, –2.6; CRO, –1.6; p < 0.001 vs. baseline; p < 0.05, P-ERMS vs. CRO). At Week 24, both groups indicated significantly increased patient (P-ERMS, +2.6; CRO, +1.7; p < 0.001 vs. baseline) and clinician (P-ERMS, +4.0; CRO, +3.1; p < 0.001 vs. baseline) global assessments of therapy. After 24 weeks, all patients on P-ERMS were dosing within the FDA-approved frequencies (65% QD, 35% BID); 56% of patients on CRO dosed BID, but 38% dosed TID and 6% dosed four times daily (QID). Most common adverse events were constipation, nausea, and somnolence, with no significant difference between treatment groups.

Conclusions: P-ERMS and CRO both relieved chronic nonmalignant pain in this community-based population; however, patients taking P-ERMS dosed in accordance with FDA-approved frequencies (QD/BID); 44% of those taking CRO dosed more frequently (TID/QID).     

Voriconazole drastically increases exposure to oral oxycodone

Objective  We investigated the effect of voriconazole on the pharmacokinetics and pharmacodynamics of oxycodone. Methods  Twelve healthy subjects ingested either voriconazole or placebo for 4 days in a randomized, cross-over study. On day 3, they ingested 10 mg oxycodone. Timed plasma samples were collected for the measurement of oxycodone, noroxycodone, oxymorphone, noroxymorphone and voriconazole up to 48 h, and pharmacodynamic effects were recorded. Results  When voriconazole was taken at the same time as oxycodone, the mean area under the plasma concentration-time curve (AUC_0–∞) of oxycodone increased 3.6-fold (range 2.7- to 5.6-fold), peak plasma concentration 1.7-fold and elimination half-life 2.0-fold (p < 0.001) when compared to placebo. The AUC_0-∞ ratio of noroxycodone to oxycodone was decreased by 92% (p < 0.001), and that of oxymorphone increased by 108% (p < 0.01). Pharmacodynamic effects of oxycodone were modestly increased by voriconazole. Conclusions  Voriconazole inhibits the CYP3A-mediated N-demethylation of oxycodone, drastically increasing exposure to oral oxycodone. Clinically, lower doses of oxycodone may be needed during voriconazole treatment to avoid opioid-related adverse effects especially after repeated dosing.