麻醉因素对胸腔镜肺癌根治术患者肺损伤的影响：右美托咪定混合罗哌卡因胸椎旁神经阻滞联合全麻的效果

Effect of anesthesia factor on lung injury in patients undergoing thoracoscopic radical lung cancer surgery ： combination of thoracic paravertebral block with dexmedetomidine mixed with ropivacaineand general anesthesia

目的研究麻醉因素对胸腔镜肺癌根治术患者肺损伤的影响，评价右美托咪定混合罗哌卡因胸椎旁神经阻滞（TPVB）联合全麻的效果。 方法择期胸腔镜下行肺癌根治术患者100例，性别不限，年龄18～64岁，体重指数18～25 kg/m2，ASA分级Ⅱ或Ⅲ级。采用随机数字表法分为5组（n＝20）：全麻组（G组） 、罗哌卡因TPVB联合全麻组（R组）、右美托咪定静脉输注联合全麻组（Div组）、右美托咪定静脉输注＋罗哌卡因TPVB联合全麻组（Div＋R组）和右美托咪定混合罗哌卡因TPVB联合全麻组（Dtp＋R组）。R组超声引导下行TPVB，根据手术切口的肋间隙位置选择两点法阻滞，每个穿刺点分别注入0.5%罗哌卡因10 ml；Div组静脉输注右美托咪定0.5 μg/kg，输注时间10 min；Div＋R组静脉输注右美托咪定，行TPVB；Dtp＋R组TPVB药物为右美托咪定0.5 μg/kg混合罗哌卡因。随后麻醉诱导，静脉输注丙泊酚和瑞芬太尼维持麻醉。记录术中丙泊酚和瑞芬太尼用量、低氧血症、低血压、心动过缓等的发生情况；于肺肿瘤切除离体即刻切取肺肿瘤周边正常肺组织，Western blot法检测肺组织低氧诱导因子-1α（HIF-1α）、BCL2和腺病毒E1B19KD相互作用蛋白3（BNIP3）和自噬蛋白微管相关蛋白1轻链3Ⅱ型（LC3Ⅱ）表达；采用ELISA法检测TNF-α和IL-6含量，Tunnel法评价细胞凋亡情况，计算凋亡指数；光镜下观察病理学结果，行肺损伤评分。 结果Div＋R组和Dtp＋R组丙泊酚用量较其余3组减少，G组和Div组瑞芬太尼用量较其余3组增加（P〈0.05）；与G组比较，R组和Div组高血压和心动过速发生率降低（P〈0.05）；与Div＋R组比较，R组、Div组和Dtp＋R组低血压发生率降低（P〈0.05）；与R组比较，Div组和Div＋R组心动过缓发生率升高（P〈0.05）；与G组和R组比较，Div组、Div＋R组和Dtp＋R组细胞凋亡指数、肺组织TNF-α、IL-6含量和损伤评分降低，HIF-1α、BNIP3和LC3Ⅱ表达上调（P〈0.05）；与Div组比较，Div＋R组和Dtp＋R组肺组织TNF-α含量和损伤评分降低，HIF-1α和LC3Ⅱ表达上调，Dtp＋R组IL-6含量降低（P〈0.05）。 结论右美托咪定混合罗哌卡因TPVB联合全麻减轻胸腔镜肺癌根治术患者肺损伤的效果较好。

Objective To investigate the effect of anesthesia factor on lung injury in patients un- dergoing thoracoscopic radical lung cancer surgery and to evaluate efficacy of combination of thoracic para- vertebral block （TPVB） with dexmedetomidine mixed with ropivacaine and general anesthesia. Methods One hundred patients of both sexes, aged 18-64 yr, with body mass index of 18-25 kg/m2, of AmericanSociety of Anesthesiologists physical status Ⅱ or m, scheduled for elective thoracoscopic radical lung cancer surgery, were divided into 5 groups （n = 20 each） using a random number table： general anesthesia group （group G）, TPVB with ropivacaine combined with general anesthesia group （group R）, intravenously in- fused dexmedetomidine combined with general anesthesia group （ group Div）, intravenously infused dexme- detomidine plus TPVB with ropivacaine combined with general anesthesia group （ group Div ＋ R）, and TPVB with dexmedetomidine mixed with ropivacaine combined with general anesthesia group （group Dtp＋ R）. In group R, TPVB was performed under ultrasound guidance, two-point method was selected accord- ing to the position of intercostal space at surgical incision, and 0. 5% ropivacaine 10 ml was injected into each puncture site. Dexmedetomidine 0. 5 μg/kg was intravenously infused over 10 min in group Div. Dexmedetomidine was intravenously infused for TPVB in group Div＋R. TPVB solution contained dexmedeto- midine 0. 5 μg/kg and ropivacaine in group Dtp＋R. Anesthesia was then induced and maintained by IV in- fusion of propofol and remifentanil. The intraoperative consumption of propofol and remifentanil and develop- merit of adverse reactions such as hypoxemia, hypotension and bradycardia were recorded. Normal lung tis- sues around the tumor margin were obtained immediately after tumor resection for determination of the ex- pression of hypoxia-inducible factor 1 alpha （HIF-la）, BCL2/adenovirus E1B 19kDa interacting protein 3 （BNIP3） and mierotubule-associated protein 1 light chain 3 11 （LC3 Ⅱ ） （by Western blot）, contents of tumor necrosis factor-alpha （TNF-a） and interleukin-6 （IL-6） in lung tissues （by enzyme-linked immu- nosorbent assay） and cell apoptosis （by TUNEL） and for examination of the pathological changes （with a light microscope） which were scored. Apoptosis index was calculated. Results The amount of propofol consumed was significantly lower in Div＋R and Dtp＋R groups than in the other three groups, and the a- mount of remifentanil consumed was significantly higher in G and Div groups than in the other three groups （P〈0. 05）. The incidence of hypertension and tachycardia was significantly lower in R and Div groups than in group G （P〈0. 05）. The incidence of hypotension was significantly lower in R, Div and Dtp＋R groups than in group Div＋R （P〈0. 05）. The incidence of bradycardia was significantly higher in Div and Div＋R groups than in group R （P〈0. 05）. Compared with G and R groups, apoptosis index, contents of TNF-a and IL-6 and lung injury scores were significantly decreased, and the expression of HIF-la, BNIP3 and LC3 Ⅱ was up-regulated in Div, Div＋R and Dtp＋R groups （P〈0. 05）. Compared with group Div, the TNF-a content and lung injury scores were significantly decreased, and the expression of HIF-la and LC3 Ⅱ was up-regulated in Div＋R and Dtp＋R groups, and the IL-6 content was significantly decreased in group Dtp＋R （P〈0.05）. Conclusion Combination of TPVB with dexmedetomidine mixed with ropivacaine and general anesthesia produces better efficacy in reducing lung injury in patients undergoing thoracoscopic radi- cal lung cancer surgery.