Effect of deuteration on the single dose pharmacokinetic properties and postoperative analgesic activity of methadone

Although methadone is effective in the management of acute pain, the complexity of its absorption-distribution-metabolism-excretion profile limits its use as an opioid of choice for perioperative analgesia. Because deuteration is known to improve the pharmacokinetic, pharmacodynamic and toxicological properties of some drugs, here we characterized the single dose pharmacokinetic properties and post-operative analgesic efficacy of d₉-methadone.The pharmacokinetic profiles of d₉-methadone and methadone administered intravenously to CD-1 male mice revealed that deuteration leads to a 5.7- and 4.4-fold increase in the area under the time-concentration curve and maximum concentration in plasma, respectively, as well as reduction in clearance (0.9 ± 0.3 L/h/kg vs 4.7 ± 0.8 L/h/kg). The lower brain-to-plasma ratio of d₉-methadone compared to that of methadone (0.35 ± 0.12 vs 2.05 ± 0.62) suggested that deuteration decreases the transfer of the drug across the blood-brain barrier. The estimated LD₅₀ value for a single intravenous dose of d₉-methadone was 2.1-fold higher than that for methadone. Moreover, d₉-methadone outperformed methadone in the efficacy against postoperative pain by primarily activating peripheral opioid receptors. Collectively, these data suggest that the replacement of three hydrogen atoms in three methyl groups of methadone altered its pharmacokinetic properties, improved safety, and enhanced its analgesic efficacy.     

The effect of massage therapy on pain after surgery: A comprehensive meta-analysis

BackgroundFindings on the usefulness of massage therapy (MT) in postoperative pain management are often inconsistent among studies.ObjectivesThis study’s aim is to conduct a meta-analysis of randomized controlled trials (RCT) to clarify the effects of massage therapy in the treatment of postoperative pain.MethodsThree databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) were searched for RCTs published from database inception through January 26, 2021. The primary outcome was pain relief. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. The random-effect model was used to calculate the effect sizes and standardized mean difference (SMD) with 95 % confidential intervals (CIs) as a summary effect. The heterogeneity test was conducted through I². Subgroup and sensitivity analyses were used to explore the source of heterogeneity. Possible publication bias was assessed using visual inspection of funnel plot asymmetry.ResultsThe analysis included 33 RCTs and showed that MT is effective in reducing postoperative pain (SMD, −1.32; 95 % CI, −2.01 to −0.63; p = 0.0002; I² = 98.67 %). A similar significant effect was found for both short (immediate assessment) and long terms (assessment performed 4–6 weeks after the MT). Remarkably, we found neither the duration per session nor the dose had an impact on the effect of MT and there seemed to be no difference in the effects of different MT types. In addition, MT seemed to be more effective for adults. Furthermore, MT had better analgesic effects on cesarean section and heart surgery than orthopedic surgery.LimitationsPublication bias is possible due to the inclusion of studies in English only. Additionally, the included studies were extremely heterogeneous. Double-blind research on MT is difficult to implement, and none of the included studies is double-blind. There was some heterogeneity and publication bias in the included studies. In addition, there is no uniform evaluation standard for the operation level of massage practitioners, which may lead to research implementation bias.ConclusionsMT is effective in reducing postoperative pain in both short and long terms.     

Variabilidad del uso intraoperatorio de cristaloides y asociación con los resultados postoperatorios: análisis post hoc de dos estudios prospectivos y multicéntricos de cohortes

BackgroundThe optimal regimen for intravenous administration of intraoperative fluids remains unclear. Our goal was to analyze intraoperative crystalloid volume administration practices and their association with postoperative outcomes.MethodsWe extracted clinical data from two multicenter observational studies including adult patients undergoing colorectal surgery and total hip (THA) and knee arthroplasty (TKA). We analyzed the distribution of intraoperative fluid administration. Regression was performed using a general linear model to determine factors predictive of fluid administration. Patient outcomes and intraoperative crystalloid utilization were summarized for each surgical cohort. Regression models were developed to evaluate associations of high or low intraoperative crystalloid with the likelihood of increased postoperative complications, mainly acute kidney injury (AKI) and hospital length of stay (LOS).Results7,580 patients were included. The average adjusted intraoperative crystalloid infusion rate across all surgeries was to 7.9 (SD 4) mL/kg/h. The regression model strongly favored the type of surgery over other patient predictors. We found that high fluid volume was associated with 40% greater odds ratio (OR 1.40; 95% confidence interval1.01-1.95, p = 0.044) of postoperative complications in patients undergoing THA, while we found no associations for the other types of surgeries, AKI and LOSConclusionsA wide variability was observed in intraoperative crystalloid volume administration; however, this did not affect postoperative outcomes.     

不同剂量羟考酮PCEA与PCIA用于前列腺术后镇痛效果比较

【摘要】 目的 探讨不同剂量羟考酮通过患者硬膜外自控镇痛（PCEA）与患者静脉自控镇痛（PCIA）用于前列腺术后的镇痛效果。 方法 选取在2018年1月~2020年1月期间于我院行前列腺术的210例患者，采用随机数字表法将患者分成A1、A2、A3、B1、B2、B3 6组，每组各35例。其中A1、A2、A3组术后镇痛采用PCIA方案，分别使用0.6mg/kg、0.8mg/kg、1.0mg/kg的羟考酮+托烷司琼10mg+0.9%氯化钠溶液至100mL；B1、B2、B3术后镇痛采取PCEA方案，分别使用0.6mg/kg、0.8mg/kg、1.0mg/kg的羟考酮+托烷司琼10mg+0.9%氯化钠溶液至100mL。比较手术前（T0）、术后6h(T1)、术后12h(T2)、术后24h(T3)及术后48h(T4)6组患者的生命体征、视觉疼痛模拟评分（VAS）及不良反应的发生情况。 结果 各组患者在不同时间点的MAP、HR及SPO2的水平比较差异无统计学意义（P＞0.05）。B1、B2、B3组患者分别在T1、T2、T3、T4时间的VAS评分显著低于A1、A2、A3组（均P＜0.05），A2、A3组患者分别在T1、T2、T3、T4时间的VAS评分显著低于A1组（均P＜0.05），B2、B3组患者分别在T1、T2、T3、T4时间的VAS评分显著低于B1组（均P＜0.05）。B1、B2、B3不良反应的发生率分别显著低于A1、A2、A3组（均P＜0.05）。B1、B2不良反应的发生率显著低于A2、A3组（P＜0.05），且A3组不良反应的发生率显著高于A1、A2，B3组的不良反应的发生率显著高于B1、B2组（均P＜0.05）。 结论 对前列腺手术患者术后，不同剂量羟考酮PCEA的镇痛效果及不良反应发生率均显著优于不同剂量羟考酮的PCIA，且当羟考酮的剂量为0.8mg/kg时，效果最佳。     

Incidence and risk factors for Chyle leak after pancreatic surgery for cancer: A comprehensive systematic review

BackgroundChyle leak (CL) is a clinically relevant complication after pancreatectomy. Its incidence and the associated risk factors are ill defined, and various treatments options have been described. There is no consensus, however, regarding optimal management. The present study aims to systematically review the literature on CL after pancreatectomy.MethodsA systematic review from PubMed, Scopus and Embase database was performed. Studies using a clear definition for CL and published from January 2000 to January 2021 were included. The PRISMA guidelines were followed during all stages of this systematic review. The MINORS score was used to assess methodological quality.ResultsLiterature search found 361 reports, 99 of which were duplicates. The titles and abstracts of 262 articles were finally screened. The references from the remaining 181 articles were manually assessed. After the exclusions, 43 articles were thoroughly assessed. A total of 23 articles were ultimately included for this review. The number of patients varied from 54 to 3532. Incidence of post pancreatectomy CL varied from 1.3% to 22.1%. Main risk factors were the extent of the surgery and early oral or enteral feeding. CL dried up spontaneously or after conservative management within 14 days in 53% to 100% of the cases.ConclusionsThe extent of surgery is the most common predictor of risk of CL. Conservative treatment has been shown to be effective in most cases and can be considered the treatment of choice. We propose a management algorithm based on the current available evidence.     

风险前瞻应对模式在肝破裂围手术期患者中的应用

目的探讨风险前瞻应对模式在肝破裂术后患者并发症预防中的应用效果。方法采用便利抽样法,于2019年1月—2020年12月选取在河南省人民医院肝胆外科收治的130例肝破裂患者作为研究对象。将2020年1—12月就诊的65例肝破裂患者作为研究组,采用风险前瞻应对模式进行干预,将2019年1—12月就诊的65例肝破裂患者作为对照组,采用常规方式进行干预。比较两组肝破裂患者手术耐受优良率、术后并发症发生情况及护理满意度。结果研究组患者手术耐受优良率为95.38%(62/65),高于对照组的80.00%(52/65),研究组患者术后并发症总发生率为7.69%(5/65),低于对照组患者的21.54%(14/65),研究组患者护理满意度为95.38%(62/56),高于对照组患者的83.08%(54/65),以上差异均有统计学意义(均P<0.05)。结论在肝破裂围手术期开展风险前瞻应对模式不仅能够提高患者手术耐受性,降低术后并发症发生率,促进护患关系和谐发展。     

不同修复方法修复口腔颌面部肿瘤术后缺损的效果比较

目的探讨不同修复方法修复口腔颌面部肿瘤术后缺损的效果。方法选取口腔颌面部肿瘤根治术后缺损患者89例,根据最终选取的修复方案分为A组(n=49)和B组(n=40),A组给予股前外侧嵌合皮瓣修复,B组给予串联皮瓣修复。观察2组手术情况,采用华盛顿大学头颈肿瘤生活质量量表(UW-QOL)对患者术后生活质量进行评价,检测唾液中唾液酸(SA)及癌胚抗原(CEA)水平。结果A组手术时间、胃管拔除时间和经口进食时间分别为(6.30±1.19)h、(19.77±2.81)d和(20.32±2.19)d,明显少于B组(P<0.05);但A组皮瓣制作时间为(1.20±0.28)h,明显多于B组(P<0.05)。A组术后6个月UW-QOL量表中外观、吞咽、咀嚼、言语、肩功能、情绪评分分别为(63.29±4.54)分、(54.93±5.03)分、(47.12±6.02)分、(64.49±4.33)分、(82.20±5.43)分和(75.50±7.20)分,明显高于B组(P<0.05)。A组和B组术后6个月UW-QOL量表中疼痛、活动、娱乐、味觉、唾液及焦虑评分比较差异无统计学意义(P>0.05)。A组修复后1个月唾液中SA和CEA分别为(7.29±1.33)ng/dl和(50.04±16.62)ng/ml,明显低于B组(P<0.05)。A组血管危险发生率为2.04%,明显低于B组(P<0.05)。A组和B组感染、皮瓣坏死发生率差异比较无统计学意义(P>0.05)。结论相比较串联皮瓣修复,股前外侧嵌合皮瓣修复口腔颌面部肿瘤根治术后缺损有较好的效果,可以改善患者生活质量。