ARDS机械通气策略的评估

1、ARDS机械通气策略的评估北京协和医院杜斌ARDS的回顾1967年Ashbaugh提出1985年病理生理研究1990年肺保护性通气策略1998年Amato2000年NHBLI的ARDSnet多中心研究1995年首次报道ARDS病死率降低内容什么是ARDS1如何选择潮气量2如何设定PEEP34是否需要肺复张内容如何选择潮气量2如何设定PEEP34是否需要肺复张什么是ARDS1什么是ALI / ARDSALI急性起病PaO2/FiO2 300CXR: 双侧浸润影PAWP 18 mmHgARDS急性起病PaO2/FiO2 200CXR: 双侧浸润影PAWP 18 mmHg什么是ARDSARF发病率(

2、1994)137.1例/100,000人口/年ALI发病率(1996 1999)22.4 64.2例/100,000人口/年Behrendt CE. Acute respiratory failure in the United States incidence and 31-day survival. Chest 2000; 118: 1100-5Goss CH, Brower RG, Hudson LD, et al. Incidence of Acute Lung Injury in the United States. Crit Care Med 31(6):1607-1611, 20

3、03ARDS在中国上海12所大学医院15个ICU2001 2002年间5320名患者收入ICU108名(2%)发生ARDSPaO2/FiO2111.3 40.3APACHE II17.3 8.0肺源性38% (41), 肺外源性62% (67)肺炎34.3%, 其他部位感染30.6%住院病死率68.5%Lu Y, Song Z, Zhou X, Huang S, Zhu D, Yang C, Bai X, Sun B, Spragg R; Shanghai ARDS Study Group. A 12-month clinical survey of incidence and outcome

4、 of acute respiratory distress syndrome in Shanghai intensive care units. Intensive Care Med. 2004 Dec; 30(12):2197-203什么是ARDSMoss M, Mannino DM. Race and gender differences in acute respiratory distress syndrome deaths in the United States: an analysis of multiple-cause mortality data (1979-1996).

5、Crit Care Med 2002; 30(8): 1679-1685什么是ARDSMoss M, Mannino DM. Race and gender differences in acute respiratory distress syndrome deaths in the United States: an analysis of multiple-cause mortality data (1979-1996). Crit Care Med 2002; 30(8): 1679-1685什么是ARDSHerridge M, Cheung AM, Tansey CM, et al.

6、 One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 2003; 348: 683-93.什么是ARDS3个月6个月12个月DLCO (%预期值)63 (54 77)70 (58 82)72 (61 82)6分钟行走距离(m)281 (55 454)396 (244 500)422 (277 510)6分钟行走时SaO2 88%的比例(%)1086SF-36中的physical role0 (0 0)0 (0 50)25 (0 100)Herridge M, Cheung

7、 AM, Tansey CM, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 2003; 348: 683-93.什么是ARDSARDS病死率40 60%病因学未知治疗支持性机械通气肺损伤如何对ARDS患者进行机械通气, 而不导致或加重肺损伤?内容什么是ARDS1如何选择潮气量2如何设定PEEP34是否需要肺复张如何选择潮气量充分的气体交换减少呼吸机相关性肺损伤的危险低容量: 周期性肺泡塌陷和复张高容量: 牵张/过度膨胀VALI 动物试验证据Dreyf

8、uss DP. AJRCCM 1988; 137:1159肺过度膨胀与肺炎克氏菌菌血症目的: 检验PIP和PEEP对菌血症发生的影响方法: 80只大鼠, 气道内植入肺炎克氏菌植入细菌22小时后进行机械通气3小时4种通气策略(13/3; 13/0;30/10;30/0)血培养Verbrugge, Lachmann Intens Care Med 1998;24:172-7VALI 临床试验证据ARDS潮气量的选择 临床试验作者患者数潮气量病死率小潮气量对照小潮气量对照小潮气量对照P值Amato29246.1 0.211.9 0.53871 0.001Stewart60607.2 0.810.6

9、0.250470.72Brochard58587.2 0.210.4 0.247380.38Brower26267.3 0.110.2 0.150460.60ARDSnet4324296.3 0.111.7 0.131400.007 measured body weight; ideal body weight = 25 x (height in meters)2; Dry weight measured weight minus estimated weight gain from salt and water retention; Predicted body weight 50 (for

10、 males) or 45.5 (for females) + 2.3 (height in inches) - 60ARDS潮气量的选择 临床试验组间潮气量差异大ARDSnet: 6.2 vs 11.8; Steward: 7.2 vs 10.8; Brochard: 7.1 vs 10.3大样本量(n= 861)足以检测组间的差异酸中毒的治疗与其他临床试验相比, 采用增加RR以及输注碳酸氢钠的方法纠正轻至中度酸中毒, 因此组间PaCO2和pH值差异较小ARDSnet: PaCO2: 41.5 vs 35.5; pH: 7.38 vs 7.41 (目标: 7.3 7.45); Steward

11、: 54.4 vs 45.7; 7.29 vs 7.34 (下限: 7.0); Brochard: 59.5 vs 41.3; 7.28 vs 7.4 (下限: 7.05)ARDS小潮气量临床试验的差异还有其他的原因吗?临床试验的差异性平台压的改变荟粹分析的提示2项阳性试验的对照组潮气量与临床情况存在差异, 因而不能确定试验组是否优于临床治疗大潮气量(12 ml/kg)组气道压高( 34 cm H2O), 患者预后差荟粹分析的提示3项阴性试验的对照组与临床情况非常接近只要气道压力介于28 32 cmH2O, 进一步降低潮气量(6 7 ml/kg), 患者不会额外受益荟粹分析的提示气道平台压力作

12、为主要指标一致的治疗指标与VALI密切相关Amato的研究还有哪些提示Study (reference)Died/Total (%)Died/Total (%)Low Vt/Open Lung GroupConventional GroupAmato, et al (1995)5/15 (33%)7/13 (54%)Amato, et al (1998)11/29 (38%)17/24 (71%)Interval (between 1995 1998)6/14 (43%)10/11 (91%)*P = 0.078 (7/13 vs. 10/11), Fishers exact testPars

13、huram C and Kavanagh B. Meta-analysis of tidal volumes in ARDS. Am J Respir Crit Care Med 2003; 167: 798ARDSNet研究中最初的潮气量ARDSNet研究中符合入选标准但未参与试验患者的生存率P = 0.002Krishnan JA, Hayden D, Schoenfeld D, Bernard G, Brower R. (for the NHLBI ARDSNetwork Investigators). Outcome of participants vs. eligible nonpa

14、rticipants in a clinical trial of critically ill patients Abstract. Am J Respir Crit Care Med 2000;161:A210有关机械通气的世界性调查结果1992年的情况超过1,000名受调查者45%表明会将潮气量限制在5 9 ml/kg(实际体重)96%表明潮气量的选择受到气道压力的影响Carmichael LC, Dorinsky PM, Higgins SB, Bernard GR, Dupont WD, Swindell B, Wheeler AP. Diagnosis and therapy of

15、 acute respiratory distress syndrome in adults: an international survey. J Crit Care 1996; 11: 9181994年的教科书Assuming that inflating the lungs to volumes above TLC is unsafe, it has become common practice to reduce VT to no more than 7 cm3/kg actual body weight in the management of ARDSHubmayr RD. Set

16、ting the ventilator. In: Tobin MJ, editor. Principles and practice of mechanical ventilation. New York: McGraw-Hill; 1994, p. 191206.NIH研究中6 ml/kg和12 ml/kg潮气量组患者病死率与第1天平台压的关系1.00.80.60.40.20Lowess smoother, bandwidth = .812 ml/kg group. Proportion discharge dead020263137.360Mean Pplat on day 11.00.8

17、0.60.40.20Lowess smoother, bandwidth = .86 ml/kg group. Proportion discharge dead020253260Mean Pplat on day 1NIH研究中6 ml/kg和12 ml/kg潮气量组患者病死率与第1天平台压的关系1.00.80.60.40.20020263137.360Mean Pplat on day 1Petrucci, Lacovelli. Meta-analysis Small Vt Cochrane Database 2003: 3所有5项研究, 共1,202名患者小潮气量组病死率降低216/60

18、5 (35.7%) vs. 249/597 (41.7%) p 0.05RR0.85 (CI 0.74 0.98)然而, 如果平台压 31 cmH2O, 小潮气量与大潮气量组患者间并无显著差异RR1.13 (CI 0.88 1.45)对ARDS病死率的影响Pplat 30 cmH2O, 无论潮气量如何, 病死率均降低Pplat越低, 预后越好与10 12 ml/kg相比, 5 8 ml/kg潮气量降低病死率?调整呼吸频率以纠正PaCO2 (只要没有内源性PEEP, 88%1可接受FiO2FiO2 0.602Brower RG, Lanken PN, MacIntyre N, et al. Hi

19、gher versus lower positive endexpiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004; 351:327336.Amato MBP, Barbas CSV, Medeiros DM, Magaldi RB, Schettino G, Lorenzi-Fihlo G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CRR. Effect

20、of protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338: 347-354最佳PEEP保证氧输送(DO2)达到最大值的PEEP水平Peter M Suter, et al. N Engl J Med 1975; 284超高PEEP: Qs/Qt 0.20PEEP up to 25 cmH2O well tolerated in healthy rhesus monkeys withIntermittent mandatory

21、 ventilationIntravascular volume expansionCareful cardiovascular monitoringKirby RR, Perry JC, Calderwood HW, Ruiz BC, Lederman DS. Cardiorespiratory effects of high positive end-expiratory pressure. Anesthesiology. 1975 Nov; 43(5):533-9.如何选择PEEPARDS肺形态学重力依赖区域的肺不张重力依赖区域的肺不张重力依赖区域的肺不张Control:VT 7; PE

22、EP 3MVHP:VT 15; PEEP 10MVZP:VT 15; PEEP 0HVZP:VT 40; PEEP 0Tremblay L. J Clin Invest 1997; 99:944PEEP 动物试验证据病死率的比较临床试验通气策略28天病死率PLV-TrialCMV治疗组年龄 65岁(n = 107)VT 9 ml/kg IBWPEEP 14 cmH2OEIP 28 cmH2O15.0%ARDSnet小潮气量组年龄 65岁(n = 350)VT 6 ml/kg IBWPEEP 9 cmH2OEIP 28 cmH2O19.7%Villar (待发表)RCT 严重ARDS P/F 2

23、00 mmHg高PEEP, 小潮气量 vs. 低PEEP, 中等潮气量对照组: Vt 9 11 ml/kg PBW, PEEP 5 cmH2O治疗组: Vt 5 8 ml/kg PBW, PEEP Pflex + 2 cmH2O目标: PCO2 35 50 mmHg, PO2 70 100 mmHg通过调整呼吸频率纠正PCO2治疗:氧合恶化 增加PEEP氧合改善 降低FiO2Villar (待发表) 第1天对照组治疗组P valueVt (ml/kg)10.2 1.27.3 0.9 0.001PEEP9.0 2.714.1 2.8 0.001Resp rate15.0 3.020.6 4.0

24、0.01Pplat32.6 6.230.6 6.0FiO20.70 0.200.60 0.15 0.05P/F124 54139 43PCO246.0 11.142.7 9.6pH7.35 0.077.35 0.09Villar (待发表)Day 3Day 6Vt (ml/kg)对照10.0 1.0*9.9 1.2*治疗7.1 0.97.1 0.9PEEP对照8.7 2.8*8.3 3.7治疗11.2 3.18.2 3.5FiO2对照0.67 0.19#0.61 0.22#治疗0.55 0.170.48 0.15Pplat对照32.5 7.5#32.4 8.0*治疗28.4 5.425.7 7

25、.2PaO2/FiO2对照134 57#163 93*治疗174 61208 72# p 0.01, * p 0.001Villar (待发表)对照组治疗组N = 50N = 53病死率54%病死率30%在最终的数据分析期间发现, 一个研究中心的随机分组存在问题, 因而需要删除该中心入选患者的相关数据N = 45N = 50病死率53.3%病死率32%P = 0.04 (0.017)Villar (待发表)次要预后指标对照组治疗组P值住院病死率55.5% (25)34% (17)0.04脱离呼吸机天数6.02 7.9510.9 9.450.008随机分组后器官衰竭数目1.71 1.341.10

26、 1.130.019高PEEP能否改善ARDS患者的预后?Amato NEJM 1998; 338: 347 (n = 53)Absolute mortality difference33%NNT3.03Villar, Kacmarek (待发表) (n = 95)Absolute mortality difference21.3%NNT4.7ARDSnet NEJM 2000; 342: 1305 (n = 861)Absolute mortality difference8.9%NNT11.2ALVEOLI试验 假设对于接受限制容量和压力的ALI/ARDS患者,更高的PEEP可能改善临床预

27、后NHLBI ARDS Clinical Trial Network. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. N Engl J Med 2004; 351: 327-36.ALVEOLI试验设计动脉氧合:SpO2 = 88 - 95% PaO2 = 55 - 80 mmHg NHLBI ARDS Clinical Trial Network. Higher versus Lower Positive End-E

28、xpiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. N Engl J Med 2004; 351: 327-36.Lower PEEP/ Higher FiO2PEEP558810121416 1820 24FiO2.3.4.4.5.5 .7.7.7 .9.91.0Higher PEEP/ Lower FiO2PEEP121414161618202224FiO2.3.3.4.4.5.5.5 .8.8 .91.0 ALVEOLI试验结果 PEEP*Low PEEPHigh PEEPPEEPcm

29、 H2O Study DayNHLBI ARDS Clinical Trial Network. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. N Engl J Med 2004; 351: 327-36.ALVEOLI试验 平台压*NHLBI ARDS Clinical Trial Network. Higher versus Lower Positive End-Expiratory Pressures in Pa

30、tients with the Acute Respiratory Distress Syndrome. N Engl J Med 2004; 351: 327-36.ALVEOLI试验 住院病死率P=0.56NHLBI ARDS Clinical Trial Network. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. N Engl J Med 2004; 351: 327-36.ALVEOLI试验 总结550名患

31、者试验中期结束无显著差异:病死率脱离呼吸机天数ICU以外住院日NHLBI ARDS Clinical Trial Network. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. N Engl J Med 2004; 351: 327-36.高PEEP对病死率的影响10% 0% 10%Favors Lower PEEP Favors Higher PEEPMortality DifferenceAdjusted Unad

32、justed (95% Confidence Intervals)NHLBI ARDS Clinical Trial Network. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. N Engl J Med 2004; 351: 327-36.ALVEOLI试验 高PEEP为何无效?高PEEP的有益作用被副作用抵消?需要进行肺复张?“低PEEP”足以防止低呼气末容积通气所导致的肺损伤?低潮气量和气道平台压力减少了低呼气

33、末容积通气所导致的肺损伤?NHLBI ARDS Clinical Trial Network. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. N Engl J Med 2004; 351: 327-36.为什么评价PEEP对ARDS患者预后影响的研究存在差异?设定PEEP的方法ARDSnet 采用PEEP/FiO2表Alveoli 采用PEEP/FiO2表Ranieri PV曲线Amato PV曲线Villar PV曲

34、线Kacmarek 至少13 cmH2O内容什么是ARDS1如何选择潮气量2如何设定PEEP34是否需要肺复张有关呼吸力学的假设和现实假设PEEP可以使塌陷的肺泡复张现实PEEP并不能使肺泡复张PEEP能够防止已经复张的肺泡再次塌陷PV曲线: 吸气支和呼气支呼气相肺泡塌陷与吸气相肺泡塌陷密切相关Crotti S, Mascheroni D, Caironi P, Pelosi P, Ronzoni G, Mondino M, Marini JJ, Gattinoni L. Recruitment and derecruitment during acute respiratory failur

35、e: a clinical study. Am J Respir Crit Care Med 2001: 164: 131-140.Decremental PEEP Associated With Best ComplianceHickling KG. Best compliance during a decremental, but not incremental, positive end- expiratory pressure trial is related to open-lung positive end- expiratory pressure. A mathematical

36、model of acute respiratory distress syndrome lungs. Am J Respir Crit Care Med 2001: 163: 69-78.02040608010005101520253035PEEP (cmH2O)Mean tidal PV slope (ml/cmH2O)Maximum PV slopeat PEEP 16Maximum PV slopeat PEEP 20Incremental PEEPDecremental PEEPHickling的数学模型The Pressure-Volume Curve Is Greatly Modified by Recruitment A Mathematica