危重型新型冠状病毒肺炎患者体外生命支持应用时机及模式选择的专家建议

新型冠状病毒肺炎在中国武汉地区流行并蔓延,部分病例需要进行体外膜氧合辅助(extracorporeal membrane oxygenation,ECMO).为了指导ECMO在新型冠状病毒肺炎救治中的应用,中国医师协会体外生命支持专业委员会组织国内相关专家对ECMO应用时机及辅助模式的选择方面制定了有关建议.本建议书以既往ECMO相关临床研究及国际体外生命支持组织推荐建议为基础,并结合新型冠状病毒肺炎特点对ECMO模式选择进行了相关推荐.     

新型冠状病毒肺炎药物治疗的思考

新型冠状病毒肺炎(new coronavirus pneumonia,NCP)正在中国引起严重疫情,截至发稿之日,全国确诊人数已逾4万.冠状病毒已经在全世界范围内引起数次疫情,但此次疫情的来势之迅猛及传染性之强前所未有.我们对引起此次疫情的病原体——2019新型冠状病毒知之甚少,目前在国际上发表的临床研究文章或为单中心研究,或为回顾性分析.我们结合在新冠肺炎一线的救治体会及相关发表的研究成果,给大家分享新冠肺炎的治疗经验.抗病毒药物方面,目前仍无特效药物,利巴韦林和干扰素联合用药由于其治疗中东呼吸综合征(MERS)有效,仍被我国新冠肺炎诊疗方案推荐;洛匹那韦/利托那韦和瑞德西韦的疗效有待随机对照临床试验(randomized controlled trial,RCT)评价;糖皮质激素的短期应用(1~2 mg·kg-1·d-1,3~5 d)被我国诊疗方案推荐,但仍需RCT进一步证实;本次新冠肺炎合并细菌感染较少,应当避免盲目使用抗菌药物,尤其避免联用广谱抗菌药物.     

激素治疗能够降低重症COVID-19患者病死率？结论尚早

糖皮质激素在新型冠状病毒肺炎（COVID-19）治疗中的应用备受关注,多项关于COVID-19中激素应用的临床研究结果依次发布,结合目前研究进展,谨慎、全面地解读研究结果,对于指导临床应用具有重要意义。     

评价膈肌功能指导慢性阻塞性肺疾病患者撤机的可行性研究

Objective To evaluate the predictive performance of neuro-mechanical coupling (NMC) and neuro-ventilatory coupling (NVC) in the weaning outcome in patients with chronic obstructive pulmonary disease (COPD). Methods Sixteen patients were enrolled when the criteria for their first spontaneous breathing trial (SBT) was met. A 30-minute SBT was attempted, with the measurement of electrical activity of the diaphragm (Edi) , NMC, NVC, NVC ×NMC, index of rapid shallow breathing (f/Vt) , airway occlusion pressure (P0.1) and f/Vt ×P0.1 at 0, 5 and 30 min. The receiver operating characteristic (ROC) curve was calculated to evaluate the predictive performance of each index. Results Successful weaning(S group) was observed in 6 patients while weaning failure(F group) in 10 patients. (1)The predictive capacity of Edi: at 30 min of SBT, Edi showed higher values in the F group (P ＜ 0. 05), the area under the ROC curves(AUC) was 0. 817(P ＜0. 05). (2) The predictive capacity of NVC and NMC:at 5, 30 min of SBT, NVC and NMC showed higher values in the S group (P ＜0. 05); at 30 min of SBT NVC presented the largest AUC than any other time of SBT (0. 822, P ＜ 0. 05), while the AUC of NMC was 0. 800 (P ＞ 0. 05). (3) The predictive capacity of NVC × NMC: at 30 min of SBT, the AUC of NVC × NMC was larger than NVC (0. 864, P ＜ 0. 05) , showing greater sensitivity (100. 0%) and specificity (83. 3%) .(4) The predictive capacity of f/Vt and P0.1: f/Vt and f/Vt × P0.1 presented poor predictive performance in the failed patients. Conclusions Edi, NVC and NVC × NMC were good predictor for the weaning outcome in patients with COPD.     

热湿交换器和加温湿化器对呼吸机相关性肺炎发生率影响的荟萃分析

目的 探讨热湿交换器(HME)与加温湿化器(HH)是否可降低机械通气患者呼吸机相关性肺炎(VAP)的发生。方法 通过计算机检索和手工检索PubMed、Cochrane数据库,收集1990年1月1日至2010年9月1日关于HME与HH对机械通气患者VAP影响的随机对照研究(RCT),按Cochrane协作网推荐的方法,对HME与HH预防机械通气患者VAP的发生率进行荟萃分析(Meta分析)。结果 共纳入11篇RCT文献,其中HME组1 121例,HH组1 101例,两组VAP发生率分别为14.2％(159/1 121)和15.9％(175/1 101),相对危险度(RR)=0.88,95％可信区间(95％CI)0.72～1.07,P=0.21,表明与HH相比,HME并不降低机械通气患者VAP的发生率。筛选机械通气时间＞7 d的RCT进行亚组分析,共纳入8篇文献,其中HME组834例,HH组859例,VAP发生率分别为15.2％(127/834)和17.5％(150/859),RR=0.84,95％CI0.58～1.23,P=0.37,表明在机械通气时间＞7d的患者中,HME同样不降低VAP的发生率。结论 HME并不降低机械通气患者VAP的发生率,即使在机械通气时间超过7d的患者也是如此。由于有关的RCT数量相对较少、质量较低（缺少盲法）,需要高质量的大规模RCT进一步证实。     

神经调节辅助通气对急性呼吸窘迫综合征兔呼吸机相关性膈肌功能障碍的影响

目的 探讨神经调节辅助通气(NAVA)对ARDS呼吸机相关性膈肌功能障碍(VIDD)的预防作用.方法 将20只成年新西兰大白兔按随机数字表法分为对照组、容量控制通气组(VC组)、压力支持通气组(PSV组)和NAVA通气组(NAVA组),每组5只.VC、PSV及NAVA组在机械通气4 h后取膈肌标本,对照组麻醉后立即取膈肌标本.测定各组膈肌中丙二醛、超氧化物歧化酶(SOD)以及还原型谷胱甘肽(GSH)含量,观察各组膈肌纤维病理结构的改变.结果 (1)丙二醛:NAVA组膈肌中丙二醛含量为(0.28±0.19)nmol/mg,与对照组的(0.15±0.06)nmol/mg、PSV组的(0.30±0.11)nmol/mg比较,差异无统计学意义(F=2.730,P＞0.05);VC组膈肌中丙二醛含量为(0.40±0.16)nmol/mg,明显高于对照组(P＜0.05).(2)SOD:NAVA组膈肌中SOD含量为(94±9)U/mg,与对照组的(111±12)U/mg、PSV组的(93±4)U/mg比较,差异无统计学意义(F=4.422,P＞0.05);VC组膈肌中SOD含量为(80±21)U/mg,明显低于对照组(P＜0.05).(3)GSH:NAVA组膈肌中丙二醛含量为(5.6±1.0)mg/g,与对照组的(5.3±1.0)mg/g、PSV组的(4.5±1.2)mg/g比较,差异无统计学意义(F=3.001,P＞0.05);VC组膈肌中GSH含量为(3.3±1.7)mg/g,明显低于对照组(P＜0.05).(4)光镜观察:VC组出现肌纤维变性、坏死,部分肌纤维萎缩;NAVA、PSV组以及对照组肌纤维形态基本正常.(5)电镜观察:VC组肌原纤维断裂,线粒体肿胀;NAVA组、PSV组以及对照组超微结构无明显异常.(6)膈肌纤维横截面积:NAVA组平均肌纤维横截面积(像素)为2573±278,与对照组的3070+175、PSV组的2508±670比较,差异无统计学意义(F=1.775,P＞0.05);VC组Ⅱ型肌纤维横截面积为2210±971,明显低于对照组的3477±187(P＜0.05).结论 与控制通气相比较,NAVA可减轻ARDS膈肌氧化应激、膈肌萎缩和膈肌结构损伤,NAVA较控制通气更能预防VIDD.

Abstract：

Objective To evaluate the effect of neurally adjusted ventilatory assist (NAVA) on prevention of ventilator-induced diaphragmatic dysfunction (VIDD) in ARDS rabbits.Methods Twenty New Zealand white rabbits were randomly divided into 4 groups: ( 1 ) control group ( n = 5 ); ( 2 ) Volume control (VC) group ( n = 5 ); ( 3 ) Pressure support ( PSV ) group ( n = 5 ); (4) NAVA group ( n = 5 ).In VC, PSV and NAVA groups, the rabbits were killed and the diaphragm was removed after 4 hours of ventilation.Animals in the control group were not mechanically ventilated, and the diaphragm was also removed immediately after anesthetizing.In all rabbits, malondialdehyde ( MDA), superoxide disrmutase (SOD) and glutathione(GSH) of diaphragm were measured.Structure of diaphragm was observed by light microscope, electron microscope, constituent ratio and mean cross-sectional area (CSA) of diaphragm fiber.Results (1)MDA: Compared with the control [(0.15 ±0.06)nmol/mg], PSV group[(0.30 ±0.11)nmol/mg], there was no significant difference in MDA of diaphragm in NAVA group [( 0.28 ± 0.19 )nmol/mg] (F = 2.730, P ＞ 0.05).MDA in VC group [(0.40 ±0.16)nmol/mg] was significantly higher than the control group (P＜0.05).(2) SOD: Compared with control [( 111 ± 12) U/mg], PSV group [(93 ± 4) U/mg], there was no significant difference in SOD of diaphragm in NAVA group [( 94 ± 9 )U/mg] (F=4.422,P ＞0.05).SOD in VC group [(80 ±21 )U/mg] was significantly lower than the control group(P ＜0.05).(3)GSH: Compared with control [(5.3 ± 1.0)mg/g] and PSV group [(4.5 ±1.2)mg/g], there was no significant difference in GSH of diaphragm in NAVA group [(5.6 ± 1.0) mg/g](F =3.001 ,P ＞ 0.05 ).GSH in VC group [(3.3 ± 1.7)mg/g] is significantly lower than control and NAVA groups ( P ＜ 0.05 ).( 4 ) Light microscope: In VC group, many changes were observed in the muscle, such as myofibrosis, necrosis, and some of muscle fibers became atrophy, but these were no obvious changes of pathological structure in control, PSV or NAVA groups.(5)Electron microscope: In control, PSV and NAVA groups, the ultrastructure of diaphragm was normal Different from the above 3 groups, some abnormal ultrastructure was observed in VC group, including disrupted myofibrils, swollen mitochondria.(6)CSA of diaphragm fiber: Compared with control and PSV group, there was no significant difference in CSA of diaphragm fiber in NAVA group ( P ＞ 0.05 ); The CSA of type Ⅱ fibers in VC group was markedly lower than control group ( P ＜ 0.05 ) .Conclusions Compared with volume control ventilation, NAVA may mitigate diaphragmatic oxidative stress, atrophy and injury, and prevent VIDD better than VC.     

体外膜肺氧合对成人急性呼吸窘迫综合征患者预后影响的Meta分析和系统评价

目的 探讨体外膜肺氧合(ECMO)对急性呼吸窘迫综合征(ARDS)患者预后的影响.方法 计算机检索和手工检索收集1966-2010年ECMO治疗成人ARDS的英文和中文临床研究,按纳入与排除标准选择文献,提取资料,采用RevMan 5.0软件对数据进行Meta分析,对ECMO临床研究进行系统评价.结果 共纳入3篇随机对照研究,随机效应模型显示ECMO不降低成人重症ARDS患者病死率[RR=0.95(95%CI:0.76-1.18),P=0.64],但按发表时间的累积Meta分析显示ECMO呈现保护性效应;与以往临床研究相比,最近一项观察性临床研究显示ECMO明显降低甲型H1N1流感导致的重症ARDS患者病死率.结论 现有研究尚不能证实ECMO能改善成人ARDS患者预后,但对于病因可逆的重症ARDS患者早期应用ECMO可取得较好临床效益.

Abstract：

Objective To investigate the effects of extracorporeal membrane oxygenation (ECMO) on survival of adult from acute respiratory distress syndrome (ARDS). Method We searched Pubmed, Embase, Cochrane Library, Web of Science databases to find relevant literatues on ECMO in treatment of ARDS, which are reported from January 1966 to June 2010. Meta analyses was performed. Results Three papers about randomized controlled trial (RCT) of evaluating ECMO in patients with severe ARDS were enrolled for analyses. Meta-analysis of the three randomized controlled trials revealed ECMO did not decrease the mortality of ARDS patients. However, the cumulative meta-analysis of randomized trials showed ECMO had a protective effect on patients with ARDS. The most recent observational studies suggested that ECMO significantly decreased the mortality of ARDS caused by H1 N1 viral pneumonia. Conclusions There is no evidence to prove the benefit of ECMO in patients with ARDS. However, ECMO should be considered to use in early stage of ARDS as a last rescue resort for potentially reversible severe acute respiratory failure. Further investigation of large sample of high quality RCTs is needed.     

呼吸机管路更换对呼吸机相关肺炎影响的荟萃分析

目的 评价呼吸机管路更换对呼吸机相关肺炎( ventilator-associated pneumonia,VAP)的影响.方法 通过计算机检索和手工检索全面收集国内外1995-2010年机械通气患者更换呼吸机管路的随机对照试验(RCT),按Cochrane协作网推荐的方法对呼吸机相关肺炎发生率作Meta分析.结果 共纳入9篇文献,患者总数20 326人.纳入6篇文献进行Meta分析发现每2到3d更换呼吸机管路VAP的发生率为4.05％,每7d更换呼吸机管路VAP的发生率为3.65％,与每2到3d更换呼吸机管路相比,每7d更换呼吸机管路呼吸机相关肺炎发生率的RR值为0.77 [0.54,1.09](P=0.14);纳入3篇文献进行分析发现每7d更换呼吸机管路VAP的发生率为15.89％,大于14 d更换呼吸机管路VAP的发生率为14.9％,与每7天更换呼吸机管路相比,大于14 d更换呼吸机管路呼吸机相关肺炎发生率的RR值为0.98 [0.69,1.39] (P=0.91).结论 定期更换呼吸机管路并不能降低机械通气患者呼吸机相关肺炎的发生率.     

严重感染患者外周血中树突状细胞的变化及意义

严重感染及感染性休克是全身性感染（sepsis）导致的以器官功能损害为特征的复杂临床综合征,在ICU患者的发病率高达25％。近年来,尽管抗感染治疗及器官功能支持技术取得了长足的进步,但严重感染的病死率仍高达30％～70％。严重感染的发病机制复杂,免疫功能的紊乱参与严重感染的发生与发展。树突状细胞（DCs）在启动机体免疫应答中发挥关键性作用。近年研究显示,严重感染患者外周血DCs数量及功能呈现明显动态改变,并与病情严重程度及预后相关。因此监测严重感染的危重病患者外周血DCs改变具有重要的临床意义。     

神经调节辅助通气对AECOPD患者呼吸功的影响

目的探讨不同外源性呼气末正压（extrinsic positive end expiratory pressure,PEEPe）条件下,神经调节辅助通气（neurally adjusted ventilatory assist,NAVA）对慢性阻塞性肺疾病急性加重（acute exacerbation of chronicobstructive pulmonary disease,AECOPD）患者呼吸功及触发功的影响。 方法以2012年5月至2013年5月入住东南大学附属中大医院ICU、静态内源性呼气末正压（intrinsic positive end-expiratory pressure,PEEPi）（PEEPi_stat）≥5 cm H2O（1 cm H2O=0.098 kPa）的AECOPD患者为研究对象。本研究方案已通过东南大学附属中大医院伦理委员会批准（批准号：2010ZDLL018.0）,并与患者签署了知情同意书。将控制通气下PEEPe由0升至40%PEEPi_stat,总呼气末正压（total-PEEP）不增加的患者作为呼气流速受限（expiratory flow limitation,EFL）组,增加的患者为呼气阻力（expiratory resistance,Re）增高组。共纳入AECOPD患者12例,其中EFL组6例,Re组6例。患者分组后调节镇静深度至Ramsay3分,在PEEPe设定为0、40%、80%、120%PEEPi_stat条件下,随机进行支持力度相同压力支持通气（pressure support ventilation,PSV）及NAVA通气。通过NAVA压力限定实现NAVA与PSV支持水平的等效性。监测食道内压（esophageal pressure,Pes）、膈肌电活动（electrical activity diaphragm,EAdi）,采集流速、压力波形并计算呼吸功（PTPes_ins）和触发功（PTPes_tri）。测量参数在通气模式和PEEPe水平之间的比较采用两因素的重复测量方差分析。在NAVA或PSV模式下,不同PEEPe水平之间的多重比较采用SNK检验。 结果2组患者年龄与急性生理与慢性健康评分II（acute physidogy and chronic health evaluation,APACHE II）等一般情况无显著差异。① NAVA与PSV支持水平的等效性：NAVA通气时可以获得与PSV通气类似的方波压力-时间曲线,且与PSV相比NAVA通气时呼吸频率、吸气时间、气道峰值压、平均气道压均无显著差异（t=0.720,0.817,0.621,1.579,均P>0.05）。② NAVA对呼吸功影响：在相同PEEPe水平下NAVA通气时呼吸功明显低于PSV通气（t=3.816,3.117,2.758,2.572,均P<0.05）。PEEPe由0逐渐增至120%PEEPi_stat时,在NAVA及PSV模式下,EFL组患者呼吸功均显著下降（t=4.629,4.431,4.165,5.082,均P<0.05）;RE组患者呼吸功无显著变化（F=8.12,7.64,均P>0.05）。③ NAVA对触发功的影响：相同PEEPe水平下,NAVA通气触发功明显低于PSV通气（t=4.624,4.431,4.165,5.082,均P<0.05）。PEEPe由0逐渐增至120%PEEPi_stat时,NAVA模式下EFL组及RE组患者触发功均无显著变化（F=5.71,5.93,均P>0.05）;PSV模式下,EFL组患者触发功显著下降（F=16.21,P<0.05）;RE组患者随着PEEPe增加触发功无明显变化（F=6.12,P>0.05）。 结论与PSV相比,NAVA通气显著降低AECOPD患者的呼吸功及触发功。NAVA通气时触发功不受PEEPe的影响,PSV通气时增加PEEPe可降低呼气流速受限患者的触发功。