氟比洛芬酯联合肺保护性通气对胸腔镜肺癌根治术病人术后细胞免疫功能的影响

Effect of flurbiprofen axetil combined with lung-protective ventilation on postoperative cellular immune function in patients undergoing thoracoscopic radical resection of lung cancer

目的探讨氟比洛芬酯联合肺保护性通气对胸腔镜肺癌根治术病人术后细胞免疫功能的影响。方法择期全麻下行胸腔镜肺癌根治术病人80例,术前肺功能检查无明显异常,ASA分级Ⅰ或Ⅱ级,年龄35~64岁,性别不限,BMI 18~28 kg/m^2,采用随机数字表法分为4组(n=20):常规通气组(C组)、氟比洛芬酯联合常规通气组(F+C组)、肺保护性通气组(P组)和氟比洛芬酯联合肺保护性通气组(F+P组)。F+C组和F+P组麻醉诱导前5 min静脉注射氟比洛芬酯2 mg/kg。4组均采用容量控制通气模式,常规机械通气参数:双肺通气时VT 10 ml/kg,通气频率10~12次/min,单肺通气时VT 8 ml/kg,通气频率13~16次/min;肺保护性机械通气参数:双肺通气时VT 8 ml/kg,通气频率12~14次/min;单肺通气时PEEP 5 cmH2O,VT 6 ml/kg,通气频率14~16次/min。术毕行PCIA,C组和P组配方为舒芬太尼100 μg+昂丹司琼16 mg,用生理盐水稀释至100 ml;F+C组和F+P组配方为舒芬太尼100 μg+氟比洛芬酯2 mg/kg+昂丹司琼16 mg,用生理盐水稀释至100 ml。4组背景输注速率2 ml/h,PCA剂量0.5 ml,锁定时间15 min,镇痛至术后24 h,维持VAS评分≤3分。当VAS评分>3分时,静脉注射曲马多2 mg/kg。分别于麻醉诱导前(T0)、术毕(T1)、术后24 h(T2)、术后72 h(T3)和术后1周(T4)时抽取中心静脉血样2 ml,采用流式细胞术测定T淋巴细胞亚群CD3^+、CD4^+、CD8^+和NK细胞水平,计算CD4^+/CD8^+比值。结果与T0时比较,C组、F+C组和P组T1-3时CD3^+细胞、CD4^+细胞、NK细胞的水平和CD4^+/CD8^+比值降低,F+P组T1,2时CD3^+细胞、CD4^+细胞、NK细胞的水平和CD4^+/CD8^+比值降低(P<0.05)。与C组比较,其余3组T1-3时CD3^+细胞、CD4^+细胞、NK细胞的水平和CD4^+/CD8^+比值升高(P<0.05)。与F+C组或P组比较,F+P组T1-3时CD3^+细胞、CD4^+细胞、NK细胞的水平和CD4^+/CD8^+比值升高(P<0.05)。结论氟比洛芬酯联合肺保护性通气可改善胸腔镜肺癌根治术病人术后细胞免疫功能,其效果优于单独应用氟比洛芬酯或肺保护性通气。

Objective To investigate the effect of flurbiprofen axetil combined with lung-protective ventilation on postoperative cellular immune function in the patients undergoing thoracoscopic radical resection of lung cancer. MethodsEighty American Society of Anesthesiologists physical status Ⅰor Ⅱ patients of both sexes, with no abnormal lung function during the preoperative examination, aged 35-64 yr, with body mass index of 18-28 kg/m^2, scheduled for elective thoracoscopic radical resection of lung cancer under general anesthesia, were divided into 4 groups(n=20 each)using a random number table method: conventional mechanical ventilation group(group C), flurbiprofen axetil combined with conventional mechanical ventilation group(group F+ C), lung-protective ventilation group(group P)and flurbiprofen axetil combined with lung-protective ventilation group(group F+ P). Flurbiprofen axetil 2 mg/kg was intravenously injected at 5 min before induction of anaesthesia in F+ C and F+ P groups.Patients were mechanically ventilated in volume-controlled mode in four groups.Conventional ventilator settings were adjusted with tidal volume(VT)10 ml/kg and respiratory rate 10-20 breaths/min during two-lung ventilation and with VT 8 ml/kg and respiratory rate 13-16 breaths/min during one-lung ventilation.Lung-protective ventilator settings were adjusted with VT 8 ml/kg and respiratory rate 12-14 breaths/min during two-lung ventilation and with positive end-expiratory pressure 5 cmH2O, VT 6 ml/kg and respiratory rate 14-16 breaths/min during one-lung ventilation.All patients received patient-controlled intravenous analgesia(PCIA)at the end of surgery until 24 h after surgery.PCIA solution contained sufentanil 100 μg and ondansetron 16 mg in 100 ml of normal saline in group C and group P. PCIA solution contained sufentanil 100 μg, flurbiprofen axetil 2 mg/kg and ondansetron 16 mg in 100 ml of normal saline in group F+ C and group F+ P.The PCIA pump was set up with a 0.5 ml bolus dose, a 15-min lockout interval and background infusion at a rate of 2 ml/h.Visual analog scale score was maintained ≤3.When visual analog scale score >3, tramadol 2 mg/kg was intravenously injected.Before induction of anesthesia(T0), at the end of surgery(T1), at 24 and 72 h after surgery(T2, 3)and at 1 week after surgery(T4), blood samples were collected from the central vein for measurement of the levels of T lymphocyte subsets CD^3+, CD^4+, CD8^+ and NK cells.The CD^4+/CD8^+ ratio was calculated. ResultsCompared with the baseline at T0, the levels of CD^3+, CD^4+ and NK cells and CD^4+/CD8^+ ratio were significantly decreased at T1-3 in C, F+C and P groups and at T1, 2 in group F+ P(P<0.05). Compared with group C, the levels of CD^3+, CD^4+ and NK cells and CD^4+/CD8^+ ratio were significantly increased at T1-3 in the other three groups(P<0.05). Compared with group F+C or group P, the levels of CD^3+, CD4^+ and NK cells and CD^4+/CD8^+ ratio were significantly increased at T1-3 in group F+ P(P<0.05). ConclusionFlurbiprofen axetil combined with lung-protective ventilation improves postoperative cellular immune function and provides better efficacy than either alone in the patients undergoing thoracoscopic radical resection of lung cancer.