盐酸右美托咪定对重症肌无力手术患者血流动力学及炎性因子的影响

Effects of dexmedetomidine hydrochloride on hemodynamics and inflammatory factors in patients with myasthenia gravis

目的探讨不同剂量的盐酸右美托咪定对重症肌无力手术患者血流动力学及炎性因子的影响。方法选取择期行胸腔镜下胸腺切除术的重症肌无力患者40例,入选标准:ASA分级Ⅰ~Ⅱ级,年龄18~65岁,性别不限,根据盐酸右美托咪定(DEX)术中持续泵入速度的不同,将研究对象随机分为4组:0. 9%氯化钠溶液对照组(C组)、0. 2μg·kg^(-1)·h^(-1)DEX组(D1组)、0. 4μg·kg^(-1)·h^(-1)DEX组(D2组)、0. 6μg·kg^(-1)·h^(-1)DEX组(D3组),每组10例。D1组、D2组、D3组在麻醉诱导前10 min静脉输注DEX 1μg/kg,随后分别以0. 2μg·kg^(-1)·h^(-1)、0. 4μg·kg^(-1)·h^(-1)、0. 6μg·kg^(-1)·h^(-1)输注至手术结束,C组0. 9%氯化钠溶液对照。全麻诱导后,泵入丙泊酚3~5 mg·kg^(-1)·h^(-1),盐酸瑞芬太尼0. 1~0. 2μg·kg^(-1)·h^(-1),间断静脉注射顺阿曲库铵,维持BIS值于40~60。以上4组患者分别于麻醉前(T0)、插管即刻(T1)、单肺通气30 min(T2)、单肺通气90 min(T3)、术后2 h(T4)记录平均动脉压(MAP)和心率(HR),记录心血管不良反应发生率(MAP <70 mm Hg或HR <50次/min),T0、T1、T2、T3、T4点抽取颈内静脉血5 ml,采用酶联免疫吸附法测血清肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)水平。结果 4组患者的一般情况(年龄、性别、BIS、ASA、补液量、出液量、手术时长)比较差异无统计学意义(P> 0. 05)。血流动力学指标HR:与C组比较,D2组T4时HR明显降低(P <0. 05),D3组T3、T4时HR明显降低(P <0. 05);与D1组比较,D2组T4时HR明显降低(P <0. 05),D3组T3、T4时HR明显降低(P <0. 05);与D2组比较,D3组T3、T4时HR明显降低(P <0. 05)。与T0比较,T3时D3组HR明显降低(P <0. 05); T4时C组、D1组HR明显增高(P <0. 05)。MAP:与C组比较,D2组T4时MAP明显降低(P <0. 05),D3组T2、T3、T4时MAP明显降低(P <0. 05);与D1组比较,D2组T4时MAP明显降低(P <0. 05),D3组T2、T3、T4时MAP明显较低(P <0. 05);与D2组比较,D3组T2、T3、T4时MAP明显降低(P <0. 05)。与T0比较,T2、T3、T4时D3组MAP明显降低(P <0. 05); T4时C组、D1组MAP明显增高(P <0. 05)。心血管不良反应发生率:与C组、D1组、D2组比较,D3组术中血压降低,心动过缓发生率明显增加(P <0. 05);炎性因子TNF-α:与C组比较,D1组T1时TNF-α降低(P <0. 05),D2、D3组T1、T2、T3、T4时TNF-α降低(P <0. 05);与D1组比较,D2组T3、T4时TNF-α降低(P <0. 05),D3组T2、T3、T4时TNF-α降低(P <0. 05);与D2组比较,D3组各时间点TNF-α无差异(P> 0. 05)。与T0比较,在各时间点4组TNF-α均增高(P <0. 05)。IL-6:与C组比较,D1组T1、T2、T3时IL-6降低(P <0. 05),D2、D3组T1、T2、T3、T4时IL-6降低(P <0. 05);与D1组比较,D2、D3组T3、T4时IL-6降低(P <0. 05);与D2组比较,D3组各时间点IL-6无差异(P> 0. 05)。与T0比较,各时间点4组IL-6均增高(P <0. 05)。结论重症肌无力患者胸腔镜胸腺切除手术中,使用0. 4μg·kg^(-1)·h^(-1)的盐酸右美托咪定能够稳定血流动力学,抑制炎性反应。

Objective To investigate the effects of different doses of dexmedetomidine hydrochloride （DEX） on hemodynamics and inflammatory factors in patients with myasthenia gravis. Methods Forty patients with myasthenia gravis who underwent elective thoracoscopic thymectomy were enrolled in our study. The inclusion criteria were as follows： the American Society of anesthesiologists （ASA） grade Ⅰ-Ⅱ, aged 18-65 years, and male or female. According to different continuous intravenous pumping speed of DEX, the patients were randomly divided into four groups： saline control group （group C）, 0.2μg·kg^-1·h^-1DEX group （group D1）, 0.4μg·kg^-1·h^-1DEX group （group D2）, and 0.6μg·kg^-1·h^-1DEX group （group D3）, with 10 cases in each group. The patients in group D1, D2 and D3 were intravenously infused with DEX 1 μg/kg 10 min before anesthesia induction, followed by 0.2μg·kg^-1·h^-1and 0.4μg·kg^-1·h^-1, and 0.6μg·kg^-1·h^-1, respectively until the end of surgery. Those in group C were given 0.9% sodium chloride solution as control group. After induction of general anesthesia, propofol 3-5mg·kg^-1·h^-1and remifentanil hydrochloride 0.1- 0.2μg·kg^-1·h^-1were pumped in, accompanied by intermittent injection of cis-atracurium, maintaining a BIS value between 40 and 60. Mean arterial pressure （MAP）, heart rate （HR）, the incidence of cardiovascular adverse reactions （MAP〈70mm Hg or HR〈50 times/min） were recorded in the above groups before anesthesia （T0）, immediate intubation （T1）, 30 min after single-lung ventilation （T2）,80 min after single-lung ventilation （T3）, and at 2 h after surgery （T4）. Internal jugular vein blood （5 ml） was collected at T0, T1, T2, T3, and T4. Serum tumor necrosis factor （TNF-α） and interleukin-6 （IL-6） levels were measured by enzyme-linked immunosorbent assay （ELISA）. Results There was no significant difference in the general condition （age, gender, BIS, ASA, rehydration fluid, fluid output, duration of surgery） between the groups （ P 〉0.05）. Hemodynamic index HR was as follows： as compared with that in group C, HR was decreased significantly at T4 in group D2 （ P 〈0.05）, and at T3 and T4 in group D3 （ P 〈0.05）; as compared with that in group D1, HR was significantly decreased at T4 in group D2 （ P 〈 0.05 ）, and at T3 and T4 in group D3 （ P 〈0.05）. As compared with that in group D2, HR was significantly decreased at T3 and T4 in group D3 （ P 〈0.05）.As compared with that at T0, HR in group D3 was significantly decreased at T3 （ P 〈 0.05 ）, and HR in group C and D1 was significantly increased at T4 （ P 〈0.05）. In terms of MAP, as compared with that in group C, MAP was significantly decreased at T2 in group D2 （ P 〈0.05）, and at T2, T3 and T4 in group T3 （ P 〈0.05）. As compared with that in group D1, MAP was significantly lower at T4 in group D2 （ P 〈0.05）, and at T3, T3, T4 in group D3 （ P 〈0.05）. As compared with that in group D2, MAP was significantly decreased at T2, T3, T4 in group D3 （ P 〈0.05）. As compared with that at T0, MAP in group D3 was significantly decreased at T2, T3 and T4 （ P 〈0.05）. However, MAP was significantly increased at T4 in group C and D1 （ P 〈0.05）. As for the incidence of cardiovascular adverse reactions,the blood pressure during surgery was decreased and incidence of bradycardia was significantly increased in group D3, as compared with that in group C, D1 and D2 （ P 〈0.05）. With respect to inflammatory factor TNF-α, as compared with that in group C, TNF-α was decreased at T1 in group D1 （ P 〈0.05）, and at T1, T2, T3 and T4 in group D2 and D3 （ P 〈0.05）. As compared with that in group D1, TNF-α was decreased at T3 and T4 in group D2 （ P 〈0.05）, and at T3, T3 and T4 in group D3 （ P 〈0.05）. As compared with that in group D2, no significant difference was found in TNF-α in group D3 at every time point （ P 〉0.05）. In addition, compared with T0, TNF-α was increased in each group at each time point （ P 〈0.05）. As for IL-6, as compared with that in group C, IL-6 was decreased at T1, T2 and T3 in group D1 （ P 〈0.05）, and at T1, T2, T3 and T4 in group D2 and D3 （ P 〈0.05）. As compared with that in group D1, IL-6 was decreased at T3 and T4 in group D2 and group D3 （ P 〈0.05）. There were no significant differences in IL-6 levels at every time point between group D2 and group D3 （ P 〉0.05）. As compared with those at T0, IL-6 levels were increased in every group at the other time point （ P 〈 0.05）. Conclusion In patients with myasthenia gravis undergoing thoracoscopic thymectomy, DEX at 0.4μg·kg^-1·h^-1can stabilize hemodynamics and inhibit inflammatory response.