Classifying ARDS The Role of EVLW Ch l Philli MD Charles Phillips MD Oregon Health and Science University Portland, Oregon USA
Incidence High ARDS 2013 150,000 200,000 per year in US alone. Mortality persists at 30-45% Evidence that early detection of lung injury can improve outcome More sensitive and specific markers of disease severity
ARDS Inflammatory ato Response se Leading to deterioration of patient s condition Precipitating event Impaired gas exchange and poor oxygenation Increase in neutrophil recruitment Pulmonary inflammation with edema and vasoconstriction ti ti Proinflammatory eicosanoids and free radicals produced d Permission Paul Marik
Permeability injury Vessel Lumen Endothelium Epithelium Pulmonary capillary LPS Thrombin TNF Reactive Oxygen/Nitrogen Species Stretch Cytokines Gap formation Cell Activation Alveoli Scanning EM ALVEOLAR EDEMA
ARDS
EVLW Calfee, C. S. et al. Chest 2007;131:913-920
The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. NAECC - 1994 1. Acute onset 2. Bilateral radiograph 3. PaO 2 /FiO 2 4. No CHF Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):818-24.
18 Years is a long time Better 1994 Today
Worse 1994 Today
Same 1994 Today
18 Years is a long time
After 18 years of applied research, a number of issues regarding various criteria of the AECC definition have emerged lack of explicit criteria for defining acute sensitivity of PaO2/FIO2 to different ventilator settings poor reliability of the chest radiograph criterion difficulties distinguishing hydrostatic edema
Chest radiograms # 22 3 4 6 13 15 19 11 20 1 14 7 16 18 21 5 23 24 8 17 2 % + 36 43 43 46 46 46 46 57 57 57 61 61 61 64 64 68 68 68 71 71 71 Two-fold difference between readers К of 0.55 moderate agreement Full agreement < half Lower lung zones consolidation Atelectasis Small lung volumes Pleural effusions
One half of patients went from ARDS to ALI within 6 hours of applying PEEP
PaO 2 /FiO 2 21 pts with ARDS < 5 days 67% moved from ARDS to ALI with FiO 2 0.5 to 1.0 orr) PaO 2 /FiO 2 (To FiO 2
PaO 2 /FiO 2 poorly reflects disease severity Parameter AUC EVLW 0.988 ±0.019019 Vd/Vt 0.869 ±0.112 PaO2/FiO2 0.643 ±0.137 Phillips, CR, Smith SM CCM Vol 1 2008
1. Met in Berlin came up with a working diagnosis of ARDS stressing: a) Feasibility can be applied widely b) Reliability Agreement on case identification c) Validity - reflects disease severity, predicts outcome, identifies those who look like they have ARDS, captures all relevant aspects of syndrome 2. Formally evaluated using large cohort from 7 studies - 4 multicenter and 3 single-center prospective studies enrolled by AECC a) studies collected data necessary to apply a) studies collected data necessary to apply the draft Berlin Definition and the AECC definition
Variables tested Criterion Rationale Reason not included More quadrants on CXR Improved validity Poor reliability, no effect PPV PEEP 10 mmhg Improved validity No effect PPV C RS 40 ml/cm H 2 O Improved validity No effect PPV VE CORR 10L/min =minute ventilation X PaCO2/40) Surrogate of Vd/Vt Improved validity No effect PPV
Variable considered Cit Criterioni Rationale Reason not included d Vd/Vt Improved validity Not feasible Ass. Mortality Plateau pressure Improved validity Not feasible Ass. Mortality EVLW Improved validity Not feasible PPV - Mortality Sensitive marker disease severity Biologic markers Improved validity Not feasible, no standard
2012 Berlin Definition 1. Acute onset 1 week 2. Bilateral CXR opacities or CT radiograph samples 3. No CHF clinician judgment verification (echo) if no risk factors 4. NO ALI those were the days 5. ARDS PaO 2 /FiO 2 Mild 201 300 PEEP/CPAP 5 Moderate 101 200 PEEP 5 Severe 100 PEEP 5
Unified definition of a disease Epidemiologic studies Better examine therapy Best practices Berlin Clarified acute Conducting validation study kept definition simple
ARDS Berlin - 2012 1. Acute onset 7d 2. Bilateral radiograph or CT 3. PaO 2 /FiO 2 min PEEP - Mild, moderate, severe ARDS 4. No CHF echo to confirm lack of explicit criteria for defining acute sensitivity of PaO2/FIO2 to different ventilator settings poor reliability of the chest radiograph criterion difficulties distinguishing g hydrostatic edema
New Definitions Will it facilitate recognition of the disease? Time domain Epidemiologically Will it help to improve underlying pathophysiology? Will it improve prognostic ability? Will it change therapy?
What s Wrong? The radiological criteria are still not sufficiently sensitive or specific Pao2/FiO 2 is still too insensitive and too confounded Has poor PPV for outcome Ignored FiO 2 effect Min PEEP Ignored effect of PEEP on severity classification Ignored APRV, Bi-level, HFOV The disease does not exist unless it is being treated (min - PEEP)
The Problems Insensitive non-specific criteria Missed treatment Inhomonogous treatment groups Cant have the syndrome unless receiving advanced medical care Hydrostatic edema
The Problem of Hydrostatic Edema AECC excluded ARDS if you had CHF Berlin no risks factors must confirm normal heart function ECHO, CO Berlin if you have risks factors for ARDS and a high clinical suspicion you have ARDS
Edema ARDS PERMEABILITY ARDS-CM CHF Hydrostatic
Day 1 65% 0-6hrs 06-hrs Day 1-3? 29% 18% 60% 20% 12hrs 46%
EVLW In order to better identify and properly classify ARDS we need a way to quantify both permeability and hydrostatic edema and determine their relative contribution to pathophysiology.
Extravascular lung water All the liquid id in the lung not in the vascular or pleural l space Interstial, alveolar, lymph and airway water Mucous Surfactant Edema Lymph 10% t} } S f t 20-25% 25% Intercellular water 65% } PMN s Macrophages Endothelial and epithelial cells} 65%
WET DRY Injury ARDS Sepsis Permeability Hydrostatic Oncotic Gradient in in Alveolar clearance Lymph clearance Vascular dysfunction EVLW
Transpulmonary Inject Thermodilution Transpulmonary Thermodilution Femoral Artery thermister
EVLW goal directed Rx of ALI Prospective, randomized study 48 subjects in ICU with SBP < 90 felt to require PAC Routine vs EVLW driven management Subgroup: EVLW > 14, PAOP < 18 (ARDS) Mortality 33% (13/48) vs. 100% (35/48) (p<0.05) EVLW PAC No correlation of EVLW and PAOP: r 2 = 0.026, n = 290 Poor correlation of x ray reads with EVLW Eisenberg et al, Am Rev Respir Dis 1987;136
Retrospective 373 pts Sepsis ARDS Severe head trauma Intracranial hemorrhage Hemorrhagic shock EVLW 14.3ml/kg vs. 10.2ml/kg
AUC EVLW 0.988 ±0.019 Vd/Vt 0.869 ±0.112 PaO2/FiO2 0.643 ±0.137 EVLW > 16 near 100% mortality Phillips, CR, Smith SM CCM Vol 1 2008
44 pts with ARDS 34% septic PBW Improved predictive value Cutoff value of 16 ml/kg PBW
EVLW in patients at risk for ALI 2.6 LeTourneau, J, Phillips, CR CCM 2012
EVLW Detected lung injury 2.6 days before meeting criteria Discriminated those who got it vs. those who didn t Better predicted progression to ALI LeTourneau, J; Phillips, CR
EVLW/PBV EVLW indexed to central blood volume can discriminate hydrostatic edema from ARDS PVPI 3 85%sensitivty, 100%specificity
The Case for EVLW EVLW is at the center of the pathogenesis of ARDS Targeting EVLW improves outcome EVLW has good PPV for outcome Progression to ARDS Mortality PVPI can be used to discriminate hydrostatic from permeability PE
Feasible? A box or a module available to plug into most bedside pt monitors A central line An arterial line
Conclusion We need more sensitive and specific mechanistic criteria Earlier and more sensitive detection Discriminate from other infiltrative lung processes Discriminate type and etiology of lung injury so we may better classify severity and target disease processes EVLW and PVPI can provide this and should be EVLW and PVPI can provide this and should be incorporated into a definition of ARDS
Extravascular lung water Dynamic balance Fluid and cells in Fluid and cells out WET DRY Fluids Into Lung Lymph Out
Subgroup: EVLW > 14, PAOP < 18 (ARDS) Mortality: 33% (13/48) vs. 100% (35/48) (p<0.05) 05) EVLW PAC No correlation of EVLW and PAOP: r 2 = 0.026, n = 290 Poor correlation of x ray reads with EVLW Eisenberg et al, Am Rev Respir Dis 1987;13
EVLW Detected lung injury 2.6 days before meeting criteria Discriminated those who got it vs. those who dd didn t Better predicted progression to ALI LeTourneau, J; Phillips, CR, CCM 2012
Analyzed modifications in fluid and vasoactive drug therapy when including EVLW 42 pts with hypotension or hypoxemia, felt to be euvolemic Initial decisions based on CVP, GEDI, SVV, Blood pressure, CXR, CO Asked to follow a protocol based on EVLW and record differences
Modified more than half of therapeutic decisions Of the 22 with modified d rx - it was effective in 18 13 received reduced d fluids or more diuretic - 12 of 13 improved More negative fluid balance CVP and GEDI was not useful in distinguishing groups
ARDS and Hydrostatic edema # 1 cause of ARDS is sepsis Cardiac dysfunction in sepsis is characterized by ventricular dilatation reduction in ejection fraction reduced contractility can occur very early even during the hyperdynamic phase Sepsis cardiomyopathy is common
150 Pts on ventilators
EVLW as a preload metric EVLW CO Large increase in EVLW Small increase in CO Preload
Determining EVLW Temp -1 Time Down slope time
The Modern Era of ALI/ARDS DaNang Lung, Shock Lung, Post Traumatic Lung WWII Korea Vietnam Acute Respiratory Distress in Adults, Ashbaugh, DG, Lancet 1967 Cyanosis refractory to oxygen therapy Pulmonary edema, atelectasis diffuse infiltrates on the chest radiograph Vascular Congestion Hyaline membranes 1970-1980 s increased vascular permeability studies Brigham Ohkuda Fein
The Good 1. Can drown with only 200 300 ml extra lung water 2. No good surrogate markers of EVLW 3. EVLW Predicts mortality in ARDS EVLW predicts progression to ALI in patients atrisk EVLW driven protocols only approach shown to improve mortality 4. The promise of better outcomes Goal directed therapy Better preload management
The Bad Slightly over-estimates t in normals Slightly under-estimates in disease Low CI < 1.5 Aneurysms Pulmonary Vascular obstruction High PEEP PE Anatomic shunt Focal injury
Early Recirculation Critics Say Occurs before thermal indicator fully distributes Heterogeneous perfusion of injured lungs Deadspace Changes in pulmonary blood volume Heterogeneous downslope times Central blood volume and extravascular lung water are not single compartments and do not monoexponentially empty
Not using it The Ugly
Conclusions The foundation for clinical use of EVLW has been established We should be measuring all goals of therapy in a tailored comprehensive approach Fluids SV, EVLW Vasoactive meds MAP, SVR Inotropes SV, CO, contractility Can do this simply, at the bedside with TPT for the cost of an arterial catheter
Berlin definition
The Modern Era of ALI/ARDS Up until 1990 normalize blood gases High oxygen concentrations Large tidal volumes High pressures
44 pts with ARDS 34% septic PBW Improved predictive value Cutoff value of 16 ml/kg PBW
The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):818-24.
1. Plateau pressure rejected as not feasible 2.
Minerva Anestesiol. 2012 Aug 3. [Epub ahead of print] What's new in the'berlin' definition of What s new in the Berlin definition of Acute Respiratory Distress Syndrome? Camporota L, Ranieri VM.
SV Cardiac Preload