Journal meeting. 時間 : Aug 4, 2014 地點 : ICU 討論室報告者 : 陳信宏主治醫師 : 楊俊杰醫師

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1 Journal meeting 時間 : Aug 4, 2014 地點 : ICU 討論室報告者 : 陳信宏主治醫師 : 楊俊杰醫師 本檔僅供內部教學使用檔案內所使用之照片之版權仍屬於原期刊公開使用時, 須獲得原期刊之同意授權

2 What is the future of ARDS after the Berlin definition? Carmen S.V. Barbas, Alexandre M. I sola, and Eliana B. Caser

3 Volume 20 Number 1 February 2014 Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited

4 Purpose of review Refining ARDS 2012 New Berlin definition Emphasizing the implications of the new findings for clinical practice or future research.

5 INTRODUCTION The diagnosis of ARDS now reclassified: PaO2/FIO2: mild (.300~ 200) moderate (.200~ 100) severe ARDS(.100~)

6 1. Importance of a new subcategory of severity: acute respiratory distress syndrome patients with right ventricular dysfunction and pulmonary hypertension 2. Impact of adding the analysis of thoracic tomography to improve the diagnosis and management of acute respiratory distress syndrome patients 3. Relationship among extravascular lung water index, pulmonary vascular permeability index and the new Berlin definition acute respiratory distress syndrome subcategories 4. Relationship between the finding of diffuse alveolar damage at autopsy and the new Berlin definition of subcategories of acute respiratory distress syndrome patients 5. New evidence that acute respiratory distress syndrome development after sepsis is a serious complication of sepsis and is associated with the most significant morbidity and mortality 6. Importance of new modified risk factors assessment after Berlin definition and prevention of acute respiratory distress syndrome 7. Pitfalls of using PaO2/FIO2 as acute respiratory distress syndrome diagnostic criterion 8. Importance of future better predictive mortality accuracy of acute respiratory distress syndrome definition 9. Are the Berlin definition thresholds of mild, moderate and severe the best ones to define new treatment strategies for acute respiratory distress syndrome?

7 1. Importance of a new subcategory of severity: ARDS patients with right ventricular dysfunction and pulmonary hypertension

8 Boissier et al. France, 226 in ICU, M-to-S, first 3 days TEE 49(22%), Cor pulmonale Mortality(28d) P<0.01 Cor pulmonale & sepsis right ventricular dysfunction

9 ARDS net Fluids and Catheter Therapy Trial: 475 ARDS, PA catheter TPG >12mmHg (pulmonary vascular dysfunction R pul HTN) significantly greater mortality Ventilatory (prone position, low driving pressures, titrated PEEP levels) ; pharmacologic therapy (pulmonary artery vasodilators) prognosis

10 2. Impact of adding the analysis of thoracic tomography to improve the diagnosis and management of ARDS patients

11 New ARDS thoracic CT Characteristics: infiltrate atelectasis & lung weight severity of the syndrome D/D lung recruitment maneuver (PEEP) lung recruitment maneuver (PEEP) minimal collapse(nonaerated), oxygenation,avoid potential ventilatorinduced lung injury (VILI).

12 Characteristics

13 New ARDS thoracic CT Meta-analysis of 4188 patients with ARDS. Early exudative phase detected by HRCT (X) Pulmonary fibro-proliferation assessed by HRCT: predicts increased mortality with an increased susceptibility to MOF, along with ventilator dependency

14 ARDS 3 phase ARDS is traditionally divided into three phases: exudative, proliferative and fibrotic (fig 1). The initial exudative phase involves the leakage of proteinaceous fluid and the migration of cells, in particular neutrophils, from the circulation into the interstitium and alveolar space following diffuse damage to the endothelial and epithelial surfaces. The proliferation of fibroblasts and type II pneumocytes characterises the second phase during which activated fibroblasts secrete a number of extracellular matrix proteins within the interstitium but also migrate into the alveolar space where they form attachments to damaged basement membranes7 and contribute to the intraalveolar fibrosis which can predominate in some cases. Unabated, this process leads to established fibrosis and the obliteration of alveolar spaces with a dense irregular matrix.4 The lung collagen content more than doubles in patients with ARDS who survive more than two weeks.3qualitatively, the fibrillar collagens (types I and III) predominate but their relative contribution is unclear. Some reports suggest that type III collagen predominates in the early proliferative stage, whereas type I collagen comprised of thicker more cross-linked fibrils is more prevalent in the fibrotic stage.4 8Other studies report the converse9 but differences in patient characteristics, stage of disease, lung sampling technique, and the biochemical analyses performed could account for these discrepancies. The composition and degree of cross-linking of matrix proteins deposited is an important issue as this influences its susceptibility to degradation which, in turn, could determine the degree to which established fibrosis might be reversible in ARDS.

15 Figure 1The classical model for the pathogenesis of ARDS suggests that damage to the endothelial and epithelial surfaces leads to exudation and inflammation. Fibroproliferation then ensues which, if excessive and unabated, results in established fibrosis. There is now mounting evidence to suggest that fibroproliferation is an early event in the pathogenesis of ARDS and we propose that this process occurs in parallel with exudative and inflammatory events. Thus, therapies preventing the progression to established fibrosis (with its devastating influence on mortality) will need to impact upon both proinflammatory and profibrotic mechanisms.

16 4. Relationship among: # (Extra-vascular lung water index, EVLWi & pulmonary vascular permeability index PVPi) # new Berlin definition ARDS subcategories

17 Extra-vascular lung water index & Pulmonary vascular permeability index Physiopathology transpulmonary thermodilution method #Evaluate severity:(evlwi >=10ml/kg) &(PVPi) EVLWi (m16.1;m17.2; S19.1; P<0.05) PVPi (m2.7;m3.0; S3.2; P<0.05) #In minimal PaO2/FIO2 ratio(berlin), 28-d mortality OR: M/m : S/m: #(EVLWi &PVPi)v.s.PaO2/FIO2 raito:(p<0.001,r<0)

18 5. Relationship between the finding of Diffuse alveolar damage(dad) at autopsy The new Berlin definition of subcategories of ARDS pts

19 Diffuse alveolar damage (DAD) by Autopsy 20 yrs, ARDS (Berlin) medical charts Microscopic analysis every lobe. 356 clinical criteria / 712 autopsies Sensitivity 89% & specificity 63% m14%(49), M40%(141) S46%(166). DAD159/ 356(45%)(m12%, M40%, S58% ) histopathological findings (DAD) were correlated to severity of ARDS.

20 New evidence that ARDS development after sepsis is a serious complication of sepsis and is associated with the most significant morbidity and mortality

21 Mikkelsen et al. 778 severe sepsis from ED Ventilation in first 5 days incidence of ARDS was 6.2% (48) ARDS :0.9% ED, 1.4% ward, 8.9% ICU median of 1-2 day after admission 4X higher risk mortality P< risk factor of ARDS, significant: 1) Lac >or =4 ; 2) LIPS ; 3)microbiologically proven infection

22 6. Importance of new modified risk factors assessment prevention of ARDS

23 lung injury prediction score (LIPS) # Improve: early diagnosis and prompt therapeutic intervention in ARDS. # avoid secondary hospital exposures, lower the incidence of ARDS # The median days 1or 2 prevention Serpa Neto et al. (in pts without ARDS in ventilator) lung protective ventilation strategy : lower TV prevention of ARDS

24 7. Pitfalls using PaO2/FIO2 as ARDS diagnostic criterion

25 The core PaO2/FIO2 ratio (Berlin) Ventilator parameters: FIO2, PEEP, T V, inspiratory pressure, RR, recruitment maneuvers, position #PEEP:10cmH20, FIO2 > 50% (within 24h) #PaO2/FIO2 ratio (first 24 h)& compliance (0.4ml/cmH2O /kg) (IBW) standard setting classify ARDS (m,m.s)

26 8. Importance of future better predictive mortality accuracy of ARDS definition

27 Predictive hospital mortality Mild, moderate and severe Higher hospital mortality 1.receiver operating 2.higher number of organ failures 3.oliguric-renal failure 4.septic shock 5.unknown-/multiple-site infection 6.higher APACHE score 7.older age The Berlin definition > AECC definition for predictive mortality

28 9. Are the Berlin definition thresholds of mild, moderate and severe the best ones to define new treatment strategies for ARDS?

29 Camporota and Ranieri: best-evidence Subgroups: adjunctive interventions, prognostication, resource allocation severity :PaO2/FIO2 ratio. The thresholds proposed by the Berlin: prone position in patients with PaO2/FIO2 below 150, better outcome?

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32 CONCLUSION The recent Berlin definition of ARDS was a decisive step forward in refining the diagnosis of ARDS now reclassified as mild, moderate or severe ARDS. The degree of ARDS severity according to this new classification correlated well with extravascular lung water index, PVPI and the finding of DAD on autopsy. The new possibility of bedside echocardiographic evaluation of biventricular cardiac function is indicating the necessity of including a subgroup of severity of patients with right ventricular dysfunction. HRCT evaluation showed that signs of pulmonary fibroproliferation in early ARDS predict increased ventilator dependency, multiple organ failure and mortality. The median development of ARDS 1 or 2 days after hospital admission emphasizes the need for ARDS intrahospital prevention especially protective ventilation in non- ARDS patients (Table 1). The better outcome with the use of prone position in patients with PaO2/FIO2 below 150 recently observed questioned the Berlin definition thresholds to decide the future best treatment strategies according to the proposed degree of severity of the syndrome. The impact of the new Berlin definition of ARDS on the incidence, better treatment stratification and mortality ratio of ARDS is still to be determined