Classifying ARDS Classifying ARDS Classifying ARDS Classifying ARDS The Role of EVLW The Role of EVLW Ch l Philli MD Charles Phillips MD Oregon Health and Science University Portland, Oregon USA
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Classifying ARDSClassifying ARDSClassifying ARDSClassifying ARDSThe Role of EVLWThe Role of EVLW
Ch l Philli MDCharles Phillips MDOregon Health and Science University Portland, Oregon USA
ARDS 2013• Incidence High
– 150,000 – 200,000 per year in US alone.
• Mortality persists at 30-45%
• Evidence that early detection of lung injury can• Evidence that early detection of lung injury can improve outcome
– More sensitive and specific markers of disease severity
ARDS Inflammatory ResponsePrecipitating
eventLeading to deterioration
f
S a ato y espo se
eventof patient’s condition
Increase inneutrophil
Impaired gasexchange and neutrophil
recruitmentexchange and
poor oxygenation
ProinflammatoryPulmonary Proinflammatoryeicosanoids and
free radicalsd d
Pulmonaryinflammation
with edema andt i ti producedvasoconstriction
Permission Paul Marik
Permeability injury
Thrombin TNF
Pulmonary capillary
Vessel Lumen
Cytokines
LPSTNF Reactive Oxygen/Nitrogen Species Stretch
Endothelium
Gap formationCell Activation
Endothelium
Epithelium
Alveoli
ALVEOLAREDEMA
Scanning EMEDEMA
ARDSARDS
EVLWEVLW
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 - 19941. Acute onset
2 Bilateral radiograph2. Bilateral radiograph3. PaO2/FiO2
4 No CHF4. No CHF
Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):818-24.
18 Years is a long timeBetter gBetter
Today1994
Today
Worse
1994 Today
SameSame
1994 Today1994 Today
18 Years is a long time18 Years is a long time
“After 18 years of applied research a number of issuesAfter 18 years of applied research, a number of issues regarding various criteria of the AECC definition have emerged”emerged– lack of explicit criteria for defining acute
– sensitivity of PaO2/FIO2 to different ventilator settings
– poor reliability of the chest radiograph criterionp y g p
– difficulties distinguishing hydrostatic edema
Chest radiogramsChest radiograms
# 22 3 4 6 13 15 19 11 20 1 14 7 16 18 21 5 23 24 8 17 2
T f ld diff b t d
% +
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 ALIwent from ARDS to ALI
within 6 hours of
applying PEEP
•21 pts with ARDS < 5 days
•67% moved from ARDS to ALI with
O2/F
iO2
67% moved from ARDS to ALI with ↑FiO2 0.5 to 1.0
PaO
orr)
PaO
2/FiO
2(T
o
FiO2
PaO /FiO poorly reflects disease severityPaO2/FiO2 poorly reflects disease severity
Parameter AUCEVLW 0 988 ±0 019EVLW 0.988 ±0.019
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 p gdiagnosis of ARDS stressing:a) Feasibility – can be applied widely
b) Reliability – Agreement on case identification
) V lidit fl t di itc) 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 centerstudies - 4 multicenter and 3 single-center prospective studies enrolled by AECC
a) studies collected data necessary to applya) studies collected data necessary to apply the draft Berlin Definition and the AECC definition
Variables testedVariables 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
CRS ≤ 40 ml/cm H2O Improved validity No effect PPV
VECORR ≥ 10L/min =minute ventilation X PaCO2/40)
Surrogate of Vd/VtImproved validity
No effect PPVventilation X PaCO2/40) Improved validity
Variable consideredVariable consideredC it i R ti l R t i l d dCriterion Rationale Reason not included
Vd/Vt Improved validity Not feasibleAss. Mortality
Plateau pressure Improved validityAss. Mortality
Not feasibley
EVLW Improved validityPPV - MortalitySensitive marker
Not feasible
Sensitive marker disease severity
Biologic markers Improved validity Not feasible, no standard
2012 Berlin Definition
1 Acute onset – 1 week1. Acute onset 1 week
2. Bilateral CXR opacities or CT radiograph ‐ samples
3 No CHF – clinician judgment verification (echo) if3. No CHF clinician judgment verification (echo) if no risk factors
4. NO ALI – those were the days4. NO ALI those were the days
5. ARDS PaO2/FiO2
Mild 201‐300 PEEP/CPAP≥5Mild 201 300 PEEP/CPAP≥5
Moderate 101‐200 PEEP≥5
Severe ≤ 100 PEEP≥5
• Unified definition of a disease– Epidemiologic studiesp g– Better examine therapy
Best practices– Best practices• Berlin
– Clarified acute– Conducting validation study kept definitionConducting validation study kept definition
simple
ARDSBerlin - 2012
1 Acute onset ≤ 7d1. Acute onset ≤ 7d
2. Bilateral radiograph or CT
3. PaO2/FiO2 – 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 hydrostatic edemag g y
New DefinitionsNew Definitions
• Will it facilitate recognition of the disease?
Time domain– 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/FiO2 is still too insensitive and too confounded 2
• Has poor PPV for outcome
• Ignored FiO effect• Ignored FiO2 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 p
– Missed treatment
– Inhomonogous treatment groups
• Cant have the syndrome unless receiving advanced medical care
• Hydrostatic edema
The Problem of Hydrostatic EdemaThe 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 aBerlin if you have risks factors for ARDS and a
high clinical suspicion you have ARDS
Edema
ARDS-CMARDS PERMEABILITY
CHFHydrostatic
65%Day 1 65%
29%
18%
Day 1
0-6hrs
06-hrs
60%
20%
46%
Day 1-3
?
12hrs 46%12hrs
EVLWEVLWIn order to better identify and properly classify ARDS we need a way to quantify both permeability and hydrostatic edema and determine their relative contribution toedema and determine their relative contribution to pathophysiology .
Extravascular lung water
ll h li id i h l i h l l l
Extravascular lung water
All the liquid in the lung not in the vascular or pleural space
Interstial, alveolar, lymph and airway “water”MucousS f t t} 20 25%SurfactantEdemaLymph
} 20-25%10%Lymph
Intercellular “water”PMN’s } 65%
10%
MacrophagesEndothelial and epithelial cells
} 65%
WET DRY
Injury ARDS Sepsis
WET DRY
Permeability ↑↑↑ ↑↑
Hydrostatic ↑↑ ↑↑
Oncotic Gradient ↑in ↑↑in
Alveolar clearance ↓↓↓ ↓↑EVLW
Lymph clearance ↑↑ ↑↑↑
Vascular dysfunction ↑↑ ↑↑↑
Transpulmonary ThermodilutionInjectThermodilutionTranspulmonary
Th dil ti
j
Thermodilution
Femoral Artery th i tthermister
EVLW goal directed Rx of ALIg
• Prospective randomized studyProspective, randomized study
• 48 subjects in ICU with SBP < 90 felt to require PAC
R ti EVLW d i t• Routine vs EVLW driven management
Subgroup: EVLW > 14, PAOP < 18 (ARDS)
– Mortality 33% (13/48) vs. 100% (35/48) (p<0.05)
EVLW PACEVLW PAC
• No correlation of EVLW and PAOP: r2 = 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•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 p p
Cutoff value of 16 ml/kg PBW
EVLW in patients at risk for ALIEVLW in patients at risk for ALI
2.6
LeTourneau, J, Phillips, CR CCM 2012
EVLWEVLW•Detected lung injury 2.6 days before meeting criteriabefore meeting criteria
•Discriminated those who got it vs those who didn’tvs. those who didn t
•Better predicted progression to ALIALI
LeTourneau, J; Phillips, CR
EVLW/PBV
EVLW indexed to central blood volume can discriminate hydrostatic edema from ARDSARDSPVPI ≥ 3 85%sensitivty, 100%specificity
The Case for EVLWThe Case for EVLWEVLW is at the center of the pathogenesis of ARDS
Targeting EVLW improves outcomeTargeting EVLW improves outcome
EVLW has good PPV for outcome
Progression to ARDS
Mortalityy
PVPI can be used to discriminate hydrostatic from permeability PEp y
Feasible?A box or a module available to plug into most bedside pt monitors
A central lineA t i l liAn arterial line
ConclusionConclusion• We need more sensitive and specific• We need more sensitive and specific
mechanistic criteria • Earlier and more sensitive detection
• Discriminate from other infiltrative lung processesDiscriminate from other infiltrative lung processes
• Discriminate type and etiology of lung injury so we may better classify severity and target diseasemay better classify severity and target disease processes
EVLW and PVPI can provide this and should beEVLW 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
Fl id I t L L h O tFluids Into Lung Lymph Out
• Subgroup: EVLW > 14, PAOP < 18 (ARDS)
– Mortality:
33% (13/48) 100% (35/48) ( <0 05)33% (13/48) vs. 100% (35/48) (p<0.05)
EVLW PAC
• No correlation of EVLW and PAOP: r2 = 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 didn’tgot t s t ose o d d t
•Better predicted progression to ALIprogression to ALI
LeTourneau, J; Phillips, CR, CCM 2012
f f• 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, COCVP, GEDI, SVV, Blood pressure, CXR, CO
• Asked to follow a protocol based on EVLW and record differencesrecord differences
Modified more than half ofModified more than half of therapeutic decisions
Of th 22 ith difi dOf the 22 with modified rx -it was effective in 18
13 i d d d fl id13 received reduced fluids or more diuretic - 12 of 13 improvedimproved
More negative fluid balance
CVP and GEDI was not useful in distinguishing groupsgroups
ARDS and Hydrostatic edemaARDS and Hydrostatic edema • # 1 cause of ARDS is sepsis
• Cardiac dysfunction in sepsis is characterized byy p y– ventricular dilatation– reduction in ejection fraction j– reduced contractility– can occur very early even during the ‘‘hyperdynamic’’can occur very early even during the hyperdynamic
phase
• Sepsis cardiomyopathy is commonSepsis cardiomyopathy is common
150 Pts on ventilators
EVLW as a preload metric
EVLW
CO
Large increase in EVLW
Small increase in CO
Preload
Determining EVLWDetermining EVLW
Temp-1
Time
∆ Down slope time
The Modern Era of ALI/ARDSThe Modern Era of ALI/ARDS• DaNang Lung Shock Lung Post Traumatic LungDaNang Lung, Shock Lung, Post Traumatic Lung
– WWII– Korea– Vietnam
• Acute Respiratory Distress in Adults , Ashbaugh, DG , Lancet 1967
C i f t t th– Cyanosis refractory to oxygen therapy– Pulmonary edema, atelectasis diffuse infiltrates on the chest radiograph – Vascular Congestion
Hyaline membranes– Hyaline membranes
• 1970 - 1980’s – increased vascular permeability studiesBrigham– Brigham
– Ohkuda– Fein
The Good1. 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 at riskEVLW predicts progression to ALI in patients at risk
EVLW driven protocols only approach shown to improve mortalitymortality
4. The promise of better outcomesGoal directed therapy
Better preload management
The BadThe BadSli htl ti t i l• Slightly over-estimates in normals
• Slightly under-estimates in disease• Low CI < 1.5 • AneurysmsAneurysms• Pulmonary Vascular obstruction
High PEEP– High PEEP – PE
A t i h t• Anatomic shunt• Focal injury
Critics SayCritics SayE l R i l ti• Early Recirculation– Occurs before thermal indicator fully distributes
• Heterogeneous perfusion of injured lungs– Deadspacep– Changes in pulmonary blood volume
• Heterogeneous downslope timesHeterogeneous downslope times– Central blood volume and extravascular lung
water are not single compartments and do not g pmonoexponentially empty
The UglyThe Ugly
• Not using it
ConclusionsThe foundation for clinical use of EVLW has been establishedbeen established
We should be measuring all goals of therapyWe should be measuring all goals of therapy in a tailored comprehensive approach
Fluids SV EVLWFluids – SV, EVLWVasoactive meds – MAP, SVRInotropes – SV, CO, contractilityInotropes SV, CO, contractility
Can do this simply, at the bedside with TPT for the ‘cost’ of an arterial catheterfor the cost of an arterial catheter
Berlin definitionBerlin definition
The Modern Era of ALI/ARDSThe Modern Era of ALI/ARDSU til 1990 li bl d• Up until 1990 – normalize blood gases– High oxygen concentrations – Large tidal volumesLarge 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 ofWhat s new in the Berlin definition of Acute Respiratory Distress Syndrome?Camporota L, Ranieri VM.
SVSV
Cardiac PreloadCardiac Preload
Related Documents
