肖贞良严重ARDS的治疗策略.ppt

1、严重ARDS的治疗策略,成都军区总医院 肖贞良,什么是ARDS?,中华医学会重症医学分会。急性肺损伤/急性呼吸窘迫综合征诊断和治疗指南(2006)。Ch in Crit Care M ed,Dec 2006,Vo l. 18,No112,ALI/ARDS 是在严重感染、休克、创伤及烧伤等非心源性疾病过程中, 肺毛细血管内皮细胞和肺泡上皮细胞损伤造成弥漫性肺间质及肺泡水肿, 导致的急性低氧性呼吸功能不全或衰竭。以肺容积减少、肺顺应性降低、严重的通气/血流比例失调为病理生理特征, 临床表现为进行性低氧血症和呼吸窘迫, 肺部影像学表现为非均一性的渗出性病变。,ARDS 的关注要点,不是一个病，而是一

2、个综合征。 可以由一个原发病或诱因导致，也可以是多个诱因共同或序贯作用的结果。 ARDS的本质是SIRS，是SIRS的严重阶段；ARDS是MODS或MOF在肺部的表现。 “小肺”通气和严重的顽固性低氧血症是其最重要的特征。 ARDS的预防远比治疗更有意义. 辅助治疗：维持、维护肺脏功能，为原发病的治疗赢得时间。,ARDS的诊断标准,目前仍广泛沿用1994 年欧美联席会议提出的诊断标准: 急性起病; 氧合指数(PaO2/FiO2 ) 200mm Hg1mm Hg= 0.133 kPa, 不管呼气末正压(PEEP)水平; 正位X 线胸片显示双肺均有斑片状阴影; 肺动脉嵌顿压18 mm Hg, 或无

3、左心房压力增高的临床证据。如PaO 2/FiO 2300 mm Hg 且满足上述其他标准, 可诊断ALI。,ARDS的基本治疗策略,压力控制通气 气道峰压35cmH2O,平台压30cmH2O 小潮气量：4-6ml/kg PEEP 8-20cmH2O 允许性高碳酸血症(Permissive hypercapnia),严重ARDS的定义,当ARDS患者保护性肺通气策略失败,出现顽固性低氧血症和严重酸中毒,肺损伤评分3分时,可以认为患者存在严重ARDS,应考虑挽救性治疗措施(Rescue therapies).,Crit Care Med 2010 Vol. 38, No. 8,严重ARDS的定义,

4、肺损伤评分为以上所有项目评分之和,Crit Care Med 2010 Vol. 38, No. 8,严重ARDS的治疗策略-六步法,肺复张和高PEEP 俯卧位通气(PPV) 高频振荡通气(HFOV) 一氧化氮吸入(inhaled NO) 糖皮质激素glucocorticoid) 体外生命支持(ECLS),Crit Care Med 2010 Vol. 38, No. 8,六步法之一:肺复张和高PEEP,原理：Recruitment Maneuvers(复张手法）和高PEEP可以使陷闭和实变的部分或全部肺泡恢复通气,从而改善氧合,减少反复开放和关闭肺泡导致的肺损伤. 风险：肺泡液清除率下降、V

5、ALI和血流动力学障碍。 临床实施：RM结合高PEEP或单纯高PEEP，应考虑仅应用于危及生命的严重ARDS早期、有低氧血症且平台压30cmH2O者。休克、气胸或局限性病变的患者不建议使用使用RM。实施前需要充分容量复苏和镇静。最佳PEEP设置应高于RM前5-10 cmH2O，以维持肺开放。实施6-12小时内应反复评价氧合和顺应性是否得到改善，以决定后续治疗措施。,Crit Care Med 2010 Vol. 38, No. 8,常用的RMs,控制性肺膨胀(SI)法 PEEP递增法 压力控制(PCV)法,控制性肺膨胀(SI)法,如何实施RM?,设置FiO2=1.0； 等待10分钟； 适当镇静

6、； 可能需要多次RM。,RM必须终止的情况,MAP60mmHg或下降幅度20mmHg； SaPO288% HR130 or 60 per minute 新的心律失常；,PEEP递增法,PCV法,Pins=40cmH2O,40S,20cmH2O PEEP维持,方法一,方法二,Am J Respir Crit Care Med Vol 178. pp 11561163, 2008,Rationale: There are conflicting data regarding the safety and efficacy of recruitment maneuvers (RMs) in pati

7、ents with acute lung injury (ALI). Objectives: To summarize the physiologic effects and adverse events in adult patients with ALI receiving RMs. Methods: Systematic review of case series, observational studies, and RCTs with pooling of study-level data. Measurements and Main Results: Forty studies (

8、1,185 patients) met inclusion criteria. Oxygenation (31 studies; 636 patients) was significantly increased after an RM(PaO2: 106versus193mmHg, P50.001;and PaO2/FIO2 ratio: 139 versus 251mmHg, P,0.001). There were no persistent, clinically significant changes in hemodynamic parameters after an RM. Ve

9、ntilatory parameters (32 studies; 548 patients)were not significantly altered by an RM, except for higher PEEP post-RM (11 versus 16 cm H2O; P 5 0.02). Hypotension (12%) and desaturation (9%) were the most common adverse events (31 studies; 985 patients). Serious adverse events (e.g., barotrauma 1%

10、and arrhythmias 1%) were infrequent. Only 10 (1%) patients had their RMs terminated prematurely due to adverse events.,Conclusions: Adult patients with ALI receiving RMs experienced a significant increase in oxygenation, with few serious adverse events. Transient hypotension and desaturation during

11、RMs is common but is self-limited without serious short-term sequelae. Given the uncertain benefit of transient oxygenation improvements in patients with ALI and the lack of information on their influence on clinical outcomes, the routine use of RMs cannot be recommended or discouraged at this time.

12、 RMs should be considered for use on an individualized basis in patients with ALI who have life-threatening hypoxemia.,六步法之二：俯卧位通气,原理:促进肺膨胀不全区域复张。主要机制是通过减轻外部压力，改善肺通气/血流比例。 风险:局部并发症,如面部水肿、结膜出血、压疮；翻身导致管道脱落。 临床实施：俯卧位通气持续的时间：建议20小时。,Introduction: In patients with ALI and/or ARDS, recent randomised contr

13、olled trials (RCTs) showed a consistent trend of mortality reduction with prone ventilation. We updated a meta-analysis on this topic. Methods: RCTs that compared ventilation of adult patients with ALI/ARDS in prone versus supine position were included in this study-level meta-analysis. Analysis was

14、 made by a random-effects model. The effect size on ICU mortality was computed in the overall included studies and in two subgroups of studies:those that included all ALI or hypoxemic patients, and those that restricted inclusion to only ARDS patients.A relationship between studies effect size and d

15、aily prone duration was sought with meta-regression. We also computed the effects of prone positioning on major adverse airway complications.,Results: Seven RCTs (including 1,675 adult pts, of whom 862 were ventilated in the prone position) were included. The four most recent trials included only AR

16、DS patients, and also applied the longest proning durations and used lung-protective ventilation. The effects of prone positioning differed according to the type of study.Overall, prone ventilation did not reduce ICU mortality (odds ratio = 0.91, 95% confidence interval = 0.75 to 1.2;P = 0.39), but

17、it significantly reduced the ICU mortality in the four recent studies that enrolled only patients with ARDS (odds ratio = 0.71; 95% confidence interval = 0.5 to 0.99; P = 0.048; number needed to treat = 11). Meta regression on all studies disclosed only a trend to explain effect variation by prone d

18、uration (P = 0.06). Prone positioning was not associated with a statistical increase in major airway complications. Conclusions: Long duration of ventilation in prone position significantly reduces ICU mortality when only ARDS patients are considered.,六步法之三：高频振荡通气(HFOV),原理：使用高平均气道压，使肺泡复张并改善氧合；通气靠一个振

19、荡活塞在平均气道压上下建立高频率（180-900次/分）压力循环，产生小潮气量（1-2.5ML/KG). 风险：高压，可导致血流动力学恶化和气压伤；深度镇静和肌松影响气道分泌物的清除，可引起痰栓堵塞。 临床实施：在严重低氧血症和/或高气道平台压的ARDS患者早期应用；不建议用于休克、严重气道堵塞、颅内出血、难治疗性气压伤和严重酸中毒患者。,Crit Care Med 2010 Vol. 38, No. 8,BMJ 2010;340:c2327,Objective ：To determine clinical and physiological effects of HFOV compared

20、with conventional ventilation in patients with ALI/ARDS. Design： Systematic review and meta-analysis.Data sources Electronic databases to March 2010,conference proceedings, bibliographies, and primary investigators.Study selection Randomised controlled trials of high frequency oscillation compared w

21、ith conventional ventilation in adults or children with ALI/ARDS.Data selection Three authors independently extracted data on clinical, physiological, and safety outcomes according to a predefined protocol. We contacted investigators of all included studies to clarify methods and obtain additional d

22、ata. Analyses used random effects models,Characteristics of populations of patients and risk of bias40 in trials included in systematic review,Details of high frequency oscillation (HFO) and conventional mechanical ventilation (CMV) in trials included in systematic review,Additional interventions or

23、 rescue treatments and funding in trials of high frequency oscillation and conventional mechanical ventilation included in systematic review,Hospital or 30 day mortality in patients with acute lung injury/acute respiratory distress syndrome allocated to high frequency oscillation or conventional mec

24、hanical ventilation,Clinical outcomes and adverse events in trials of high frequency oscillation No of trials No of patients,Subgroup analyses based on age of patients, risk of bias, and use of lung protective ventilation in control groups,Results：8 RCTs (n=419patients) were included; almost all pat

25、ients had ARDS.Methodological quality was good. The ratio of partial pressure of oxygen to inspired fraction of oxygen at 24,48, and 72 hours was 16-24% higher in patients receiving high frequency oscillation. There were no significant differences in oxygenation index because mean airway pressure ro

26、se by 22-33% in patients receiving high frequency oscillation (P0.01). In patients randomised to high frequency oscillation, mortality was significantly reduced (risk ratio 0.77, 95% confidence interval 0.61 to 0.98, P=0.03; six trials, 365 patients, 160 deaths), and treatment failure (refractory hy

27、poxaemia, hypercapnoea,hypotension, or barotrauma) resulting in discontinuation of assigned therapy was less likely (0.67, 0.46 to 0.99,P=0.04; five trials, 337 patients, 73 events). Other risks were similar. There was substantial heterogeneity between trials for physiological (I2=21-95%) but not cl

28、inical (I2=0%) outcomes. Pooled results were based on few events for most clinical outcomes. Conclusion： HFO might improve survival and is unlikely to cause harm. As ongoing large multicentre trials will not be completed for several years,these data help clinicians who currently use or are consideri

29、ng this technique for patients with ARDS.,六步法之四：NO吸入,原理：吸入NO通气使部分肺组织血管舒张，血流重新分布，改善通气血流比例，从而改善氧合。 临床实施：用于前述措施治疗失败的严重低氧血症患者；吸入NO从1PPM开始，观察氧合改善情况，每30分钟滴定式增加剂量，最高至10PPM；无反应，应停止；有反应，应减量至维持氧合目标的最低剂量；使用时间4天。,Crit Care Med 2010 Vol. 38, No. 8,Background：Acute hypoxaemic respiratory failure (AHRF), defined a

30、s ALI and ARDS, are critical conditions. AHRF results from a number of systemic conditions and is associated with high mortality and morbidity in all ages. Inhaled nitric oxide (INO) has been used to improve oxygenation but its role remains controversial. Objectives：To systematically assess the bene

31、fits and harms of INO in critically ill patients with AHRF. Search strategy： RCTs were identified from electronic databases: the Cochrane Central Register of Controlled Trials(CENTRAL) (The Cochrane Library 2010, Issue 1); MEDLINE; EMBASE; Science Citation Index Expanded; International Web of Scienc

32、e; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 31st January 2010). We contacted trial authors,authors of previous reviews, and manufacturers in the field. Selection criteria：We included all RCTs, irrespective of blinding or language, that compared INO with no intervention o

33、r placebo in children or adults with AHRF. Data collection and analysis：Two authors independently abstracted data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as relative risks (RR) with 95%confidence intervals (CI).

34、Our primary outcome measure was all cause mortality.We performed subgroup and sensitivity analyses to assess the effect of INO in adults and children and on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of

35、 random error through trial sequential analysis.,Main results：We included 14 RCTs with a total of 1303 participants; 10 of these trials had a high risk of bias. INO showed no statistically significant effect on overall mortality (40.2%versus 38.6%) (RR 1.06, 95%CI 0.93 to 1.22; I2 = 0) and in severa

36、l subgroup and sensitivity analyses,indicating robust results. Limited data demonstrated a statistically insignificant effect of INO on duration of ventilation, ventilator free days, and length of stay in the intensive care unit and hospital. We found a statistically significant but transient improv

37、ement in oxygenation in the first 24 hours, expressed as the ratio of partial pressure of oxygen to fraction of inspired oxygen and the oxygenation index (MD 15.91, 95% CI 8.25 to 23.56; I2 = 25%). However, INO appears to increase the risk of renal impairment among adults (RR 1.59, 95% CI 1.17 to 2.

38、16; I2 = 0) but not the risk of bleeding or methaemoglobin or nitrogen dioxide formation. Authors conclusions：INO cannot be recommended for patients with AHRF. INO results in a transient improvement in oxygenation but does not reduce mortality and may be harmful.,六步法之五：糖皮质激素,原理：可以通过抑制中性粒细胞活化、成纤维细胞增殖

39、和胶原沉淀，阻止病情发展为严重和持续的ALI/ARDS。 临床实施：用于前述干预措施均失败的严重低氧血症患者；使用低剂量（1mg/kg.d）的甲强龙;3天后氧合指数、顺应性和PaCO2较基线水平无改善，则停用，有效则续用。,Crit Care Med 2010 Vol. 38, No. 8,Respir Care 2010;55(1):4352.,Probability of survival and the proportion of patients with persistent acute respiratory distress syndrome who became able to

40、 breathe without assistance during the first 180 days after randomization. (From Reference 12, with permission.),Major Findings and Assessment of Benefit or Harm for Key Outcomes and Physiologic Parameters in Patients With ARDS, Randomized to Methylprednisolone (vs Placebo) in the Corticosteroid for

41、 Late-Stage ARDS Clinical Trial (ARDS Network),Effect of steroids on mortality in acute respiratory distress syndrome (ARDS).,Major Findings and Assessment of Benefit or Harm for Key Outcome and Physiologic Parameters in Patients With ARDS Who Received Low-to-Moderate-Dose Corticosteroids (vs Placeb

42、o) in Prospective Cohort and Randomized Controlled Trials, in the Meta-analysis by Tang et al,ARDS发生的前1-14天，低中剂量的糖皮质激素使用在降低病死率和其他方面对患者是有利的； ARDS发生14天，糖皮质激素的作用不确定，不推荐使用；,六步法之六：体外生命支持ECLS,原理：用V-V生命支持回路，将患者血液导出并通过膜氧合替代肺进行气体交换。分两种类型：即高流量ECMO和低流量CO2清除回路。 临床实施：两种类型均可用于前述治疗措施无效的严重ARDS患者。但不用于有抗凝禁忌或高压机械通气1周患者。,Crit Care Med 2010 Vol. 38, No. 8,ECMO is widely accepte