早期应用神经肌肉阻断剂治疗严重脓毒症合并急性呼吸窘迫综合征的临床研究

Clinical study of early use of neuromuscular blocking agents in patients with severe sepsis and acute respiratory distress syndrome

目的 观察早期应用神经肌肉阻断剂（NMBA）治疗严重脓毒症合并急性呼吸窘迫综合征（ARDS）的临床效果.方法 采用前瞻性临床研究方法,选择2012年7月至2013年9月广西壮族自治区柳州市人民医院重症监护病房（ICU）收治的96例严重脓毒症合并ARDS患者,根据ARDS柏林定义分为重度ARDS组（48例）及中度ARDS组（48例）,各组再按随机数字表法分为治疗组与对照组,每组24例.所有患者按照2008年国际严重脓毒症与感染性休克治疗指南给予综合治疗,并在镇静,镇痛基础上行气管插管机械通气;治疗组在机械通气开始时给予负荷剂量维库溴铵0.1mg/kg后以0.05 mg· kg^-1·h^-1持续静脉泵入24 ～ 48 h.比较两组患者治疗前和治疗48 h后急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分、序贯器官衰竭评分（SOFA）、氧合指数（paO2/FiO2）、中心静脉血氧饱和度（ScvO2）、动脉血乳酸（Lac）、C-反应蛋白（CRP）水平及21d病死率.结果 在中度或重度ARDS患者中,治疗组与对照组治疗前APACHEⅡ评分、SOFA评分、PaO2/FiO2、ScvO2、Lac、CRP比较差异均无统计学意义.在重度ARDS患者中,治疗组治疗48 h后APACHEⅡ评分、SOFA评分、PaO2/FiO2、ScvO2、Lac的改善均较对照组明显[APACHEⅡ评分（分）：16.58±2.41比19.79±3.52,t=3.679,P=0.010; SOFA评分（分）：12.04±2.17比14.75±3.26,t=3.385,P=0.010;PaO2/FiO2（mmHg,1mmHg=0.133 kPa）：159.31±22.57比131.81±34.93,t=3.239,P=0.020; ScvO2：0.673±0.068比0.572±0.142,t=3.137,P=0.030;Lac（mmol/L）：3.10±1.01比4.39±1.72,t=3.161,P=0.030],而CRP差异无统计学意义（mg/L：180.91±37.14比174.66±38.46,t=0.572,P=0.570）;且治疗组21d病死率明显低于对照组[20.8％ （5/24）比50.0％（12/24）,Х^2=4.463,P=0.035].在中度ARDS患者中,治疗组与对照组治疗48 h后,除CRP无明显变化外,各指标均有所改善,但两组间各项指标比较差异无统计学意义（均P＞0.05）;治疗组21d病死率略低于对照组,但差异也无统计学意义[16.7％（4/24）比25.0％（6/24）,Х^2=0.505,P=0.477].结论 早期使用NMBA治疗严重脓毒症合并重度ARDS患者,不仅能有效改善病情严重程度,且能够降低21d病死率.

Objective To observe the clinical effects of early use of neuromuscular blocking agents （NMBA） in patients with severe sepsis and acute respiratory distress syndrome （ARDS）.Methods A prospective study was conducted.96 patients with severe sepsis and ARDS admitted from July 2012 to September 2013 to intensive care unit （ICU） of Liuzhou People＇s Hospital in Guangxi Zhuang Autonomous Region were enrolled and divided into severe ARDS group （n=48） and moderate ARDS group （n=48） according to the Berlin definition of ARDS.Then patients in each group were randomly divided into treatment group （n =24） and control group （n=24）.All patients with diagnosis in accordance with the 2008 international septic shock and severe sepsis treatment guidelines were provided with comprehensive treatment and mechanical ventilation on the basis of analgesia and sedation.The patients in treatment group were given a loading dose of vecuronium during mechanical ventilation,started with 0.1 mg/kg up to 0.05 mg ·kg^-1·h^-1 for continuous intravenous infusion for 24-48 hours.The acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ） score,sequential organ failure assessment （SOFA）,arterial oxygenation index （PaOfFiO2）,central venous oxygen saturation （ScvO2）,arterial blood lactate （Lac）,C-reactive protein （CRP） levels of two groups were compared before treatment and 48 hours after treatment,and 21-day mortality rate was finally compared.Results In moderate or severe ARDS group,there were no statistically significant difference in APACHE Ⅱ score,SOFA score,PaO2/FiO2,ScvO2,Lac and CRP before treatment between two groups.APACHE Ⅱ score,SOFA score,PaO2/FiO2,ScvO2,and Lac 48 hours after treatment were significantly improved in severe ARDS group compared with control group [APACHE Ⅱ score：16.58 ± 2.41 vs.19.79 ± 3.52,t=3.679,P=0.010; SOFA score：12.04 ± 2.17 vs.14.75 ±3.26,t=3.385,P=0.010; PaO2/FiO2 （mmHg,1 mmHg=0.133 kPa）：159.31 ±22.57 vs.131.81 ± 34.93,t=3.239,P=0.020; ScyO2：0.673 ± 0.068 vs.0.572 ± 0.142,t=3.137,P=0.030; Lac （mmol/L）：3.10 ± 1.01 vs.4.39 ± 1.72,t=3.161,P=0.030],while the value of CRP （mg/L） showed no significant difference （180.91 ±37.14 vs.174.66 ± 38.46,t=0.572,P=0.570）.21-day mortality in treatment group was significantly lower than that in control group [20.8% （5/24） vs.50.0% （12/24）,Х^2=4.463,P=0.035].In moderate ARDS group,each of the above clinical parameters were improved in both groups expect for CRP at 48 hours after treatment,but the indexes showed no statistically significant difference between two groups （all P〉0.05）.21-day mortality rate in the treatment group was slightly lower than that in the control group which showed no statistically significant difference [16.7% （4/24） vs.25.0%（6/24）,Х^2=0.505,P=0.477].Conclusion The early use of NMBA treatment of patients with severe sepsis and severe ARDS cannot only improve the severity but also reduce 21-day mortality.