丙泊酚和七氟烷对单肺通气下行食管癌根治术患者炎症反应及肺功能的影响
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摘要
背景与目的
随着胸科手术技术的发展,为防止手术侧肺分泌物或血液进入健侧肺,确保气道通畅,防止交叉污染,提供良好术野,减轻对肺实质的损伤,要求手术中将两侧肺分隔,并能进行单肺通气。单肺通气技术(One-lung ventilation,OLV)应运而生,并广泛应用于胸科手术的临床麻醉中。但是做为一种非生理性通气模式,单肺通气过程中可引发多种病理生理过程,如肺内分流,通气血流比例失调,气道峰压增加及肺缺血—再灌注等生理紊乱,诱发局部和全身应激反应及炎性细胞因子(Cytokine,CK)释放,最终导致全身或肺部并发症,甚至发生急性肺损伤(Acute lung injury,ALI)。随着对其发病机制及病理生理过程的深入认知,临床预防和治疗意识及措施也相应提高。通过麻醉干预的手段尽量避免或减轻围术期麻醉及手术操作中各种因素导致的ALI成为临床麻醉工作者关注的热点。
丙泊酚和七氟醚均是目前临床常用的全麻药物,各具优势。现有的研究结果显示丙泊酚和七氟烷均对单肺通气所致肺损伤有一定的保护作用。本研究拟通过麻醉深度监测,在相同麻醉深度下比较丙泊酚与七氟烷对单肺通气下行食管癌根治术患者中性粒细胞核因子-κB和白介素-1,以及血流动力学和肺功能的影响,评价哪种药物更有利于减轻单肺通气下胸科手术所造成的应激反应,为临床合理用药提供理论参考。
材料与方法
左侧开胸食管癌根治术患者40例,年龄40～65岁,性别不拘,体重指数18kg/m2-25kg/m2,ASA I或Ⅱ级。随机分为丙泊酚麻醉组(P组)和七氟烷麻醉组(S组),每组20例。
术前无糖尿病、高血压、血液病及其他代谢障碍性疾病史,无长期使用糖皮质激素、三环类抗抑郁药、抗生素史,未服用维生素类药,无严重感染性疾病,术前检查心血管、肝、肾、肺功能未见异常,血常规检查中性粒细胞计数及分类数值均在正常范围。术前未行放疗或化疗,预计手术时间在4小时以内,术中无大出血(输注血液制品)。
术前准备：术前常规禁食水8h,所有患者不用术前药。入室后常规监测ECG、 BP、SPO2、PETCO2,开放右上肢静脉通路,局麻下行右侧桡动脉穿刺置管(肝素抗凝保留,供采集血样及监测动脉有创血压用)。采用Narcotrend麻醉深度监测仪监测麻醉深度。
麻醉方法：静脉注射咪达唑仑0.08～0.12mg/kg、舒芬太尼0.1～1.0μg/kg、依托咪脂0.2～0.6mg/kg和苯磺酸阿曲库铵0.15mg/kg麻醉诱导,经口插入右双腔支气管导管,并采用纤维支气管镜定位,男性采用F37气管导管,女性采用F35气管导管,气管插管后行机械通气,吸入氧浓度100%,氧流量1.0～1.5L/min,VT6-8ml/kg,RR10～14次/min,吸呼比1：2,OLV时通气参数基本不变,仅调节通气频率(RR12～16次/min),维持PETCO235～40mm Hg (1mm Hg=0.133kPa)。
麻醉维持：P组静脉输注丙泊酚4-8mg·kg-1·min-1,S组吸入1%-3%七氟烷,2组均静脉输注瑞芬太尼,术中根据情况间断静脉注射顺苯磺酸阿曲库铵维持肌松。麻醉期间保持瑞芬太尼的输注速度恒定(0.2μg· kg-1·min-1),根据麻醉深度调控丙泊酚和七氟烷用量,维持Narcotrend指数40～50,心率及平均动脉压在基础值±20%范围内波动。不使用血管活性药物,术中静脉输注乳酸林格氏液和羟乙基淀粉130/0.4,比例为3：1,手术结束前5min停用丙泊酚、七氟烷及瑞芬太尼。
于气管插管后5min(T0)、单肺通气开始时(T1)、单肺通气后30min(T2)、60min(T3)、90min(T4)、恢复双肺通气时(T5)、恢复双肺通气后10min(T6)及手术结束时(T7),采桡动脉血,分离提取中性粒细胞核蛋白,用凝胶电泳迁移率改变分析法(EMSA)测定中性粒细胞NF-κB活性,并测定血浆白细胞介素-1(IL-1)浓度。同时记录各时点动脉血气分析结果、心率(HR)及血压(BP),并根据血气分析结果计算肺泡-动脉氧分压差(PA-aO2)、氧合指数(OI)和呼吸指数(RI)。
统计学处理采用SPSS17.0统计软件进行统计分析,正态分布的计量资料以均数±准差(x±s)表示,组间比较采用成组t检验,组内比较采用重复测量设计的方差分析。计数资料比较采用x2检验。检验水准为α=0.05。
结果
2组患者一般资料各指标及麻醉时间、手术时间、单肺通气时间比较差异无统计学意义(P>0.05)。
与T0时比较,S组患者T3,4时PA-ao2增加；与T0时比较,两组患者T2,3,4,5时OI下降(P<0.05)；与T0比较,两组患者T2,3,4,5时RJ增加(P<0.05)；与S组比较,P组T3,4,6,7时RI降低(P<0.05)。
与T0时比较,两组患者T3,6时血浆IL-1浓度均明显升高(P<0.05)；与T0时比较,S组T7时血浆IL-1浓度升高(P<0.05)：与S组比较,P组T2,3,6,7时血浆IL-1浓度降低(P<0.05)。
与T0时比较,两组患者T6,7时NF-κB DNA结合活性升高(P<0.05)；与S组比较,P组T1,7时NF-κB DNA结合活性降低(P<0.05)。
结论
丙泊酚和七氟烷都能较好地维持单肺通气下行食管癌根治术患者术中麻醉深度及血流动力学的稳定状态,但与七氟烷麻醉相比,丙泊酚麻醉更有利于减轻食管癌根治术患者术中炎症反应,且肺损伤的程度较轻。
Background and Objective
With the development of the thoracic surgical technique, which aim to keep airway unobstructed, avoid cross contamination, provide ideal surgical field, and relieve the injury of lung tissue, it requires to separate the two sides of the lung, and ventilate to one side. One-lung ventilation, is widely used in thoracic surgery in the above background.But as a non-physiological ventilation mode, one-lung ventilation can result in many physiological disorders, just as intrapulmonary shunt, ventilation ratil of blood disorders, higher airway pressure and ischemia-reperfusion in lung and so on. All this pathological changes can be the inducement of stress response and systemic inflammatory response, leading to the release of variety of cytokines(CK), finally giving rise to local or systemic complications, in severe cases, it can also lead to acute lung injury(ALI). As to the further understanding of it's pathogenesis and pathophysiological procedure, the consciousness and measures to prevent and cure is rising to a high step.The problem of how to avoid or release the degree of the lung injury which resulted from the possible perioperative factors become a subject extensively concerned.
Both of propofol and sevoflurane are widely used in clinical anesthesia, and the results from present research show that propofol and sevoflurane have protective effects on lung injury induced by the one-lung ventilation. In a randomized controlled clinical trial, guided with the Narcotrend index, to make sure the two groups were under the same anesthetic depth, we compared the activity of Nuclear Transcription Factor-KappaB (NF-κB) and interleukin-1(IL-1) concentration in plasm, haemodynamic effects and the change of lung function in patients undergoing esophagpgastrostomy, so as to evaluate which drugs is more beneficial to reduce the injury caused by thoracic surgery during one-lung ventilation, and to arrive at the ultimate aim of providing reasonable reference for clinical anesthesia.
Materials and Methods
Forty adult patients with cancer of the esophagus scheduled for esophagogastrostomy with one-lung ventilation, ASA Ⅰ～Ⅱ grade, aged40to65years old, no limitations to genders, body mass index was18kg/m2-25kg/m2. Preoperative tests show that heart, liver and kidney functions had no obvious abnormalities, excluding diabetes, hypertension, hematopathy and other metabolic disorders, three weeks without taking goucocorticoid, tricyclic antidepressants, nonsteroidal anti-inflammatory drug or vitamins. None of these patients received preoperative treatment, preoperative blood examination show neutrophil count and percentage were with normal limits. No intraoperative bleeding no transfusion blood products, and the operative time between one hour and four hours. All the patients were randomly and equally allocated to two group, group P and group S.
Preoperative preparation:Nothing Per-os8hours. All patients included in trials used nothing premedication before anesthesia. After entering the operating room, monitor vital signs of patients with PHILIPs multi-function monitor, including electrocardiogram (ECG), blood pressure (BP), heart rate (HR), pulse oxygen saturation (SpO2) and end-tidal carbon dioxide partial pressure (PETCO2). Open peripheral venous access, puncture the right radial artery under local anesthesia, to measure the directly arterial pressure and obtain blood samples. Connect Narcotrend index monitor.
Induction of anesthesia is performed in two groups by titrated infusion of midazolam (0.08-0.12mg/kg), sufentanil (0.1-1.0μg/kg), etomidate (0.2～0.6mg/kg) and cisatracurium besilate (0.15mg/kg). After muscle relaxant completely effective,inserted a right double-lumen endobronchial tube and fixed position with the bronchofiberscope. Anesthesia maintenance were respectively practiced in two groups, group P received propofol (4-8mg·kg-1·min-1), and group S received sevoflurane anesthesia (inhaled1%-3%). In both group remifentanil (0.2μg·kg-1·min-1) was continuous intravenous infusion, and cisatracurium besilate was injected intermittently to remain the muscle relaxation. The propofol infusion speed and the concentration of sevoflurane inhalation was adjusted in accordance to the intraoperative Narcotrend index value and hemodynamic changes.
Peripheral blood samples were taken from the right radial artery after the induction of anesthesia and intubation(T0),at the beginning of one-lung ventilation (OLV)(T1),30min (T2),60min (T3),90min (T4) after OLV, returing to two-lung ventilation (TLV)(T5),10min following resuming of TLV (T6), at the end of surgery (T7). DNA-binding activity of NF-κB was investigated with EMS A (Electrophoretic Mobility Shift Assay) from nuclear protein fractions of peripheral nertrophils, and plasma concentratons of interleukin-1(IL-1) were examined by ELISA. We also compare the data of PA-aO2(Alveolar-arterial oxggen difference), OI (oxygenation index) and RI (respiratory index).
Statistical software package (SPSS17.0) was used for data analysis. All numerical variables were expressed as mean±standard deviation. Group t test was used to test the difference between groups. Repeated measurement analysis of variance was used to test the difference for continuous variables within groups. Qualitative variables were analysed with Chi-square test. The statistical significance test criterion is α=0.05.
Results
Heart rate (HR), mean arterial pressure (MAP) were not notably different in the two groups.
Higher PA-aO2were detected at T3and T4in group S in comparison to the TO point, Lower OI and higher RI were detected from T2to T5in both group in comparison to the TO point, and there were significantly higher RI in group S at T3,T4,T6and T7in relation to group P.
At T2, T3, T6, T7, the plasma level of IL-1was higher in group S, and the difference between two groups was significantly different. And in both group, the concentrations at T3and T6was statistically higher than other points.
The activity of NF-κB kept rising to a high level at T6and T7in both group, and at T7,the activity of NF-κB was higher in group S and had statistical significance (P<0.05).
Conclusions
These data suggest that pro-inflammatory reactions during OLV were influenced by type of general anaesthesia.Propofol appears more likely to attenuate the pro-inflammatory response and the degree of lung injury than sevoflurane during thoracic surgery.
随着胸科手术技术的发展,为防止手术侧肺分泌物或血液进入健侧肺,确保气道通畅,防止交叉污染,提供良好术野,减轻对肺实质的损伤,要求手术中将两侧肺分隔,并能进行单肺通气。单肺通气技术(One-lung ventilation,OLV)应运而生,并广泛应用于胸科手术的临床麻醉中。但是做为一种非生理性通气模式,单肺通气过程中可引发多种病理生理过程,如肺内分流,通气血流比例失调,气道峰压增加及肺缺血—再灌注等生理紊乱,诱发局部和全身应激反应及炎性细胞因子(Cytokine,CK)释放,最终导致全身或肺部并发症,甚至发生急性肺损伤(Acute lung injury,ALI)。随着对其发病机制及病理生理过程的深入认知,临床预防和治疗意识及措施也相应提高。通过麻醉干预的手段尽量避免或减轻围术期麻醉及手术操作中各种因素导致的ALI成为临床麻醉工作者关注的热点。
丙泊酚和七氟醚均是目前临床常用的全麻药物,各具优势。现有的研究结果显示丙泊酚和七氟烷均对单肺通气所致肺损伤有一定的保护作用。本研究拟通过麻醉深度监测,在相同麻醉深度下比较丙泊酚与七氟烷对单肺通气下行食管癌根治术患者中性粒细胞核因子-κB和白介素-1,以及血流动力学和肺功能的影响,评价哪种药物更有利于减轻单肺通气下胸科手术所造成的应激反应,为临床合理用药提供理论参考。
材料与方法
左侧开胸食管癌根治术患者40例,年龄40～65岁,性别不拘,体重指数18kg/m2-25kg/m2,ASA I或Ⅱ级。随机分为丙泊酚麻醉组(P组)和七氟烷麻醉组(S组),每组20例。
术前无糖尿病、高血压、血液病及其他代谢障碍性疾病史,无长期使用糖皮质激素、三环类抗抑郁药、抗生素史,未服用维生素类药,无严重感染性疾病,术前检查心血管、肝、肾、肺功能未见异常,血常规检查中性粒细胞计数及分类数值均在正常范围。术前未行放疗或化疗,预计手术时间在4小时以内,术中无大出血(输注血液制品)。
术前准备：术前常规禁食水8h,所有患者不用术前药。入室后常规监测ECG、 BP、SPO2、PETCO2,开放右上肢静脉通路,局麻下行右侧桡动脉穿刺置管(肝素抗凝保留,供采集血样及监测动脉有创血压用)。采用Narcotrend麻醉深度监测仪监测麻醉深度。
麻醉方法：静脉注射咪达唑仑0.08～0.12mg/kg、舒芬太尼0.1～1.0μg/kg、依托咪脂0.2～0.6mg/kg和苯磺酸阿曲库铵0.15mg/kg麻醉诱导,经口插入右双腔支气管导管,并采用纤维支气管镜定位,男性采用F37气管导管,女性采用F35气管导管,气管插管后行机械通气,吸入氧浓度100%,氧流量1.0～1.5L/min,VT6-8ml/kg,RR10～14次/min,吸呼比1：2,OLV时通气参数基本不变,仅调节通气频率(RR12～16次/min),维持PETCO235～40mm Hg (1mm Hg=0.133kPa)。
麻醉维持：P组静脉输注丙泊酚4-8mg·kg-1·min-1,S组吸入1%-3%七氟烷,2组均静脉输注瑞芬太尼,术中根据情况间断静脉注射顺苯磺酸阿曲库铵维持肌松。麻醉期间保持瑞芬太尼的输注速度恒定(0.2μg· kg-1·min-1),根据麻醉深度调控丙泊酚和七氟烷用量,维持Narcotrend指数40～50,心率及平均动脉压在基础值±20%范围内波动。不使用血管活性药物,术中静脉输注乳酸林格氏液和羟乙基淀粉130/0.4,比例为3：1,手术结束前5min停用丙泊酚、七氟烷及瑞芬太尼。
于气管插管后5min(T0)、单肺通气开始时(T1)、单肺通气后30min(T2)、60min(T3)、90min(T4)、恢复双肺通气时(T5)、恢复双肺通气后10min(T6)及手术结束时(T7),采桡动脉血,分离提取中性粒细胞核蛋白,用凝胶电泳迁移率改变分析法(EMSA)测定中性粒细胞NF-κB活性,并测定血浆白细胞介素-1(IL-1)浓度。同时记录各时点动脉血气分析结果、心率(HR)及血压(BP),并根据血气分析结果计算肺泡-动脉氧分压差(PA-aO2)、氧合指数(OI)和呼吸指数(RI)。
统计学处理采用SPSS17.0统计软件进行统计分析,正态分布的计量资料以均数±准差(x±s)表示,组间比较采用成组t检验,组内比较采用重复测量设计的方差分析。计数资料比较采用x2检验。检验水准为α=0.05。
结果
2组患者一般资料各指标及麻醉时间、手术时间、单肺通气时间比较差异无统计学意义(P>0.05)。
与T0时比较,S组患者T3,4时PA-ao2增加；与T0时比较,两组患者T2,3,4,5时OI下降(P<0.05)；与T0比较,两组患者T2,3,4,5时RJ增加(P<0.05)；与S组比较,P组T3,4,6,7时RI降低(P<0.05)。
与T0时比较,两组患者T3,6时血浆IL-1浓度均明显升高(P<0.05)；与T0时比较,S组T7时血浆IL-1浓度升高(P<0.05)：与S组比较,P组T2,3,6,7时血浆IL-1浓度降低(P<0.05)。
与T0时比较,两组患者T6,7时NF-κB DNA结合活性升高(P<0.05)；与S组比较,P组T1,7时NF-κB DNA结合活性降低(P<0.05)。
结论
丙泊酚和七氟烷都能较好地维持单肺通气下行食管癌根治术患者术中麻醉深度及血流动力学的稳定状态,但与七氟烷麻醉相比,丙泊酚麻醉更有利于减轻食管癌根治术患者术中炎症反应,且肺损伤的程度较轻。
Background and Objective
With the development of the thoracic surgical technique, which aim to keep airway unobstructed, avoid cross contamination, provide ideal surgical field, and relieve the injury of lung tissue, it requires to separate the two sides of the lung, and ventilate to one side. One-lung ventilation, is widely used in thoracic surgery in the above background.But as a non-physiological ventilation mode, one-lung ventilation can result in many physiological disorders, just as intrapulmonary shunt, ventilation ratil of blood disorders, higher airway pressure and ischemia-reperfusion in lung and so on. All this pathological changes can be the inducement of stress response and systemic inflammatory response, leading to the release of variety of cytokines(CK), finally giving rise to local or systemic complications, in severe cases, it can also lead to acute lung injury(ALI). As to the further understanding of it's pathogenesis and pathophysiological procedure, the consciousness and measures to prevent and cure is rising to a high step.The problem of how to avoid or release the degree of the lung injury which resulted from the possible perioperative factors become a subject extensively concerned.
Both of propofol and sevoflurane are widely used in clinical anesthesia, and the results from present research show that propofol and sevoflurane have protective effects on lung injury induced by the one-lung ventilation. In a randomized controlled clinical trial, guided with the Narcotrend index, to make sure the two groups were under the same anesthetic depth, we compared the activity of Nuclear Transcription Factor-KappaB (NF-κB) and interleukin-1(IL-1) concentration in plasm, haemodynamic effects and the change of lung function in patients undergoing esophagpgastrostomy, so as to evaluate which drugs is more beneficial to reduce the injury caused by thoracic surgery during one-lung ventilation, and to arrive at the ultimate aim of providing reasonable reference for clinical anesthesia.
Materials and Methods
Forty adult patients with cancer of the esophagus scheduled for esophagogastrostomy with one-lung ventilation, ASA Ⅰ～Ⅱ grade, aged40to65years old, no limitations to genders, body mass index was18kg/m2-25kg/m2. Preoperative tests show that heart, liver and kidney functions had no obvious abnormalities, excluding diabetes, hypertension, hematopathy and other metabolic disorders, three weeks without taking goucocorticoid, tricyclic antidepressants, nonsteroidal anti-inflammatory drug or vitamins. None of these patients received preoperative treatment, preoperative blood examination show neutrophil count and percentage were with normal limits. No intraoperative bleeding no transfusion blood products, and the operative time between one hour and four hours. All the patients were randomly and equally allocated to two group, group P and group S.
Preoperative preparation:Nothing Per-os8hours. All patients included in trials used nothing premedication before anesthesia. After entering the operating room, monitor vital signs of patients with PHILIPs multi-function monitor, including electrocardiogram (ECG), blood pressure (BP), heart rate (HR), pulse oxygen saturation (SpO2) and end-tidal carbon dioxide partial pressure (PETCO2). Open peripheral venous access, puncture the right radial artery under local anesthesia, to measure the directly arterial pressure and obtain blood samples. Connect Narcotrend index monitor.
Induction of anesthesia is performed in two groups by titrated infusion of midazolam (0.08-0.12mg/kg), sufentanil (0.1-1.0μg/kg), etomidate (0.2～0.6mg/kg) and cisatracurium besilate (0.15mg/kg). After muscle relaxant completely effective,inserted a right double-lumen endobronchial tube and fixed position with the bronchofiberscope. Anesthesia maintenance were respectively practiced in two groups, group P received propofol (4-8mg·kg-1·min-1), and group S received sevoflurane anesthesia (inhaled1%-3%). In both group remifentanil (0.2μg·kg-1·min-1) was continuous intravenous infusion, and cisatracurium besilate was injected intermittently to remain the muscle relaxation. The propofol infusion speed and the concentration of sevoflurane inhalation was adjusted in accordance to the intraoperative Narcotrend index value and hemodynamic changes.
Peripheral blood samples were taken from the right radial artery after the induction of anesthesia and intubation(T0),at the beginning of one-lung ventilation (OLV)(T1),30min (T2),60min (T3),90min (T4) after OLV, returing to two-lung ventilation (TLV)(T5),10min following resuming of TLV (T6), at the end of surgery (T7). DNA-binding activity of NF-κB was investigated with EMS A (Electrophoretic Mobility Shift Assay) from nuclear protein fractions of peripheral nertrophils, and plasma concentratons of interleukin-1(IL-1) were examined by ELISA. We also compare the data of PA-aO2(Alveolar-arterial oxggen difference), OI (oxygenation index) and RI (respiratory index).
Statistical software package (SPSS17.0) was used for data analysis. All numerical variables were expressed as mean±standard deviation. Group t test was used to test the difference between groups. Repeated measurement analysis of variance was used to test the difference for continuous variables within groups. Qualitative variables were analysed with Chi-square test. The statistical significance test criterion is α=0.05.
Results
Heart rate (HR), mean arterial pressure (MAP) were not notably different in the two groups.
Higher PA-aO2were detected at T3and T4in group S in comparison to the TO point, Lower OI and higher RI were detected from T2to T5in both group in comparison to the TO point, and there were significantly higher RI in group S at T3,T4,T6and T7in relation to group P.
At T2, T3, T6, T7, the plasma level of IL-1was higher in group S, and the difference between two groups was significantly different. And in both group, the concentrations at T3and T6was statistically higher than other points.
The activity of NF-κB kept rising to a high level at T6and T7in both group, and at T7,the activity of NF-κB was higher in group S and had statistical significance (P<0.05).
Conclusions
These data suggest that pro-inflammatory reactions during OLV were influenced by type of general anaesthesia.Propofol appears more likely to attenuate the pro-inflammatory response and the degree of lung injury than sevoflurane during thoracic surgery.
引文
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