ARDS for the ED ARDS for the ED PhysicianPhysician

Rafi Israeli, MDRafi Israeli, MDAssistant Professor of MedicineAssistant Professor of MedicineEmergency services InstituteEmergency services InstituteCleveland Clinic FoundationCleveland Clinic Foundation

Cleveland, OhCleveland, Oh

Conflicts of InterestConflicts of Interest

NoneNone

ARDS for the ED ARDS for the ED PhysicianPhysician

HistoryHistory Clinical CourseClinical Course PathophysiologyPathophysiology CausesCauses IncidenceIncidence TherapyTherapy

1967: Ashbaugh, et al. described 1967: Ashbaugh, et al. described Adult Adult Respiratory Distress SyndromeRespiratory Distress Syndrome

Respiratory DistressRespiratory Distress CyanosisCyanosis Hypoxemia despite oxygenHypoxemia despite oxygen Diffuse infiltrates on Chest XrayDiffuse infiltrates on Chest Xray

Drawback: No specific CriteriaDrawback: No specific Criteria

1988: Murray, et al. expanded the definition of 1988: Murray, et al. expanded the definition of ARDS using a 4- point scale, based on:ARDS using a 4- point scale, based on:

Extent of Chest Xray abnormalitiesExtent of Chest Xray abnormalities Severity of Hypoxia : Severity of Hypoxia : PaO2/FiO2PaO2/FiO2 Amount of PEEPAmount of PEEP Search for cause of ARDSSearch for cause of ARDS

Drawback: Does not predict OutcomeDrawback: Does not predict Outcome

Does not exclude Cardiogenic Pulm EdemaDoes not exclude Cardiogenic Pulm Edema

1994:Ameican- European Consensus 1994:Ameican- European Consensus Conference CommitteeConference Committee

Renamed Renamed Acute Resp Distress Acute Resp Distress SyndromeSyndrome

Described ARDS as Described ARDS as ““syndrome of syndrome of inflammation and permeabilityinflammation and permeability””

Coined the term ALI as a precursor Coined the term ALI as a precursor to ARDSto ARDS

1994:Ameican- European Consensus 1994:Ameican- European Consensus Conference Committee Conference Committee CriteriaCriteria::

Acute OnsetAcute Onset Bilateral infiltratesBilateral infiltrates PAWP≤ 18PAWP≤ 18 ALI: ALI: PaO2/FiO2 ≤ 300PaO2/FiO2 ≤ 300 ARDS: ARDS: PaO2/FiO2 ≤ 200PaO2/FiO2 ≤ 200

Drawback: Does not specify causeDrawback: Does not specify cause

Rapid OnsetRapid Onset ExudatesExudates ConsolidationsConsolidations Respiratory failureRespiratory failure Hypoxemia refractory to O2Hypoxemia refractory to O2 Inflammation (even in non-edematous Inflammation (even in non-edematous

lung)lung)

IL-1,6,8,10, CytokinesIL-1,6,8,10, Cytokines Diminished Lung complianceDiminished Lung compliance

Patchy infiltrates CoalescePatchy infiltrates Coalesce Air BronchogramsAir Bronchograms Pulmonary HypertensionPulmonary Hypertension Intrapulmonary ShuntingIntrapulmonary Shunting Endogenous VasoconstrictorsEndogenous Vasoconstrictors Hyperadrenergic StateHyperadrenergic State

Persistent HypoxiaPersistent Hypoxia Pulmonary FibrosisPulmonary Fibrosis Worsening ComplianceWorsening Compliance NeovascularizationNeovascularization Pulmonary HypertensionPulmonary Hypertension Macrophages clear neutrophilsMacrophages clear neutrophils Chronic InflammationChronic Inflammation

Active transport of Na into Active transport of Na into interstitiuminterstitium

Endocytosis of ProteinEndocytosis of Protein Transcytosis of ProteinTranscytosis of Protein Alveolar Epithelial type II cells Alveolar Epithelial type II cells

proliferateproliferate Apoptosis of remaining neutrophils?Apoptosis of remaining neutrophils?

Ware L and Matthay M. N Engl J Med 2000;342:1334-1349

The Normal Alveolus (Left-Hand Side) and the Injured Alveolus in the Acute Phase of Acute Lung Injury and the Acute Respiratory Distress Syndrome (Right-Hand Side)

Alveolar Epithelial Basement Alveolar Epithelial Basement Membrane BreakdownMembrane Breakdown

Damage to Vascular EndotheliumDamage to Vascular Endothelium Third Spacing of Protein-Rich fluidThird Spacing of Protein-Rich fluid Flooding of AlveoliFlooding of Alveoli ShockShock Type II cells damaged:Type II cells damaged:

Less SurfactantLess SurfactantDiminished fluid removalDiminished fluid removal

Platelet AggregationPlatelet Aggregation Microthrombi → ShuntingMicrothrombi → Shunting Fibrosis from disorganized repair of Fibrosis from disorganized repair of

intersitiumintersitium

DIRECT LUNG INJURYDIRECT LUNG INJURY INDIRECT LUNG INJURYINDIRECT LUNG INJURY

AspirationAspiration PneumoniaPneumonia Pulmonary Pulmonary

ContusionContusion Toxic InhalationToxic Inhalation Near-DrowningNear-Drowning

SepsisSepsis ShockShock Extrathoracic TraumaExtrathoracic Trauma Multiple FracturesMultiple Fractures BurnsBurns EclampsiaEclampsia PancreatitisPancreatitis DICDIC

20-75 per 100,00020-75 per 100,000 30% mortality30% mortality Recovery may take 6-12 monthsRecovery may take 6-12 months Residual: RestrictionResidual: Restriction

ObstructionObstruction

Gas- Exchange Gas- Exchange AbnormalitiesAbnormalities

Reduced Quality of LifeReduced Quality of Life

Treat Underlying CauseTreat Underlying Cause AntibioticsAntibiotics SurgerySurgery

Enteral FeedingsEnteral Feedings PeyerPeyer’’s Patchess Patches Less Catheter SepsisLess Catheter Sepsis

Supportive: ARDS Network Supportive: ARDS Network (ARDSNet)(ARDSNet)

The Problem: Ventilator- Induced Lung The Problem: Ventilator- Induced Lung InjuryInjury

High volumes and pressures: Stress High volumes and pressures: Stress Overdistension & Alveolar CrackingOverdistension & Alveolar Cracking Cyclic Opening and closing of Cyclic Opening and closing of

atelectatic alveoliatelectatic alveoli

Cause increased permeability and Cause increased permeability and alveolar damagealveolar damage

The Problem: Oxygen ToxicityThe Problem: Oxygen Toxicity Free RadicalsFree Radicals Oxygen Washout and De-Oxygen Washout and De-

RecruitmentRecruitment

High FiO2 can lead to further alveolar High FiO2 can lead to further alveolar damagedamage

Intubation almost always necessaryIntubation almost always necessary In past, goal was to normalize pH, In past, goal was to normalize pH,

PaCO2, PaO2PaCO2, PaO2 High volumes and pressures were High volumes and pressures were

usedused Worse outcomesWorse outcomes

AmatoAmato et al. 1998, Effects of a protective- et al. 1998, Effects of a protective- ventilation strategy on mortality in the acute ventilation strategy on mortality in the acute respiratory distress syndrome. respiratory distress syndrome. N. Engl. J. Med. N. Engl. J. Med. 338:347-54338:347-54

53 pts with early ARDS53 pts with early ARDS Compared Compared ““conventionalconventional”” ventilation of 12ml/kg ventilation of 12ml/kg

to to ““protectiveprotective”” 6ml/kg 6ml/kg Low PEEP. PaCO2 35-38Low PEEP. PaCO2 35-38 Improved survival at 28 daysImproved survival at 28 days Higher percentage of ventilator weaningHigher percentage of ventilator weaning Less barotraumaLess barotrauma

The Acute Respiratory Distress NetworkThe Acute Respiratory Distress Network. 2000. . 2000. Ventilation with lower tidal volumes as compared with Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. acute respiratory distress syndrome. N. Engl. J. Med. N. Engl. J. Med. 342:1301-8 342:1301-8

Larger Trial. 861 patientsLarger Trial. 861 patients Compared 12 ml/kg Compared 12 ml/kg vsvs. 6ml/kg ventilation.. 6ml/kg ventilation. Plateau pressures 50 cm H2O Plateau pressures 50 cm H2O vs. vs. 30 cm H2O.30 cm H2O. Trial ended early:Trial ended early:

39.8% mortality 39.8% mortality vs. vs. 31% mortality31% mortality

THIS HAS CHANGED CLINICAL PRACTICETHIS HAS CHANGED CLINICAL PRACTICE

PEEPPEEP

http://content.nejm.org/content/vol354/issue17/images/data/1839/DC1/NEJM_Slutsky_1839v1.swf

Minute Ventilation=RR x Tidal VolumeMinute Ventilation=RR x Tidal Volume High PEEP Levels (12-15cm H2O)High PEEP Levels (12-15cm H2O) Low Tidal Volumes and Peak and Plateau Low Tidal Volumes and Peak and Plateau

Pressures result in HypercapneaPressures result in Hypercapnea Carvalho et al.(1997) found the followingCarvalho et al.(1997) found the following

Increased HRIncreased HR Increased PA pressuresIncreased PA pressures Increased Cardiac OutputIncreased Cardiac Output Respiratory AcidosisRespiratory Acidosis But no adverse OutcomesBut no adverse Outcomes

GattinoniGattinoni et al. 2006.Lung Recruitment in Patients et al. 2006.Lung Recruitment in Patients with ARDS. with ARDS. N. Engl. J. Med. N. Engl. J. Med. 354:1775-86.354:1775-86.

What is optimal PEEP in What is optimal PEEP in individual individual PatientPatient??

PEEP in non-recruitable lung causes PEEP in non-recruitable lung causes overdistension: barotrauma and overdistension: barotrauma and alveolar stressalveolar stress

Study measured %age of recruitable Study measured %age of recruitable lung using CTlung using CT

GattinoniGattinoni et al. 2006.Lung Recruitment in et al. 2006.Lung Recruitment in Patients with ARDS. Patients with ARDS. N. Engl. J. Med. N. Engl. J. Med. 354:1775-86354:1775-86

Inclusion CriteriaInclusion Criteria PaO2:FiO2 < 300PaO2:FiO2 < 300 Bilateral pulmonary infiltratesBilateral pulmonary infiltrates PACWP < 18PACWP < 18

PEEP TrialPEEP Trial Prior to CT, high airway Prior to CT, high airway pressures and PEEP were applied. pressures and PEEP were applied.

Lung weight measured by CTLung weight measured by CT

Gattinoni L et al. N Engl J Med 2006;354:1775-1786

Frequency Distribution of Patients According to the Percentage of Potentially Recruitable Lung (Panel A) and CT Images at Airway Pressures of 5 and 45 cm of Water from Patients with a Lower

Percentage of Potentially Recruitable Lung (Panel B) and Those with a Higher Percentage of Potentially Recruitable Lung (Panel C)

GattinoniGattinoni et al. 2006.Lung Recruitment in et al. 2006.Lung Recruitment in Patients with ARDS. Patients with ARDS. N. Engl. J. Med. N. Engl. J. Med. 354:1775-86354:1775-86

ResultsResults In patients where higher %age of In patients where higher %age of

recruitable lung, mortality higher, worse recruitable lung, mortality higher, worse gas exchange.gas exchange.

Use of PEEP in patients with lower %age of Use of PEEP in patients with lower %age of recruitable lung was harmful.recruitable lung was harmful.

Results were variableResults were variable

Increase the Peep and Plateau Increase the Peep and Plateau pressure constant= recruitment.pressure constant= recruitment.

If increase in plateau pressure is If increase in plateau pressure is proportional to PEEP increase= proportional to PEEP increase= overdistensionoverdistension

Bedside Peep AdjustmentBedside Peep Adjustment

ProsPros Inflammatory Inflammatory

nature of diseasenature of disease Treatment of Treatment of

Fibrosing Fibrosing alveolitisalveolitis

ConsCons Historically, no Historically, no

benefit shown benefit shown with high dose with high dose steroidssteroids

Increased Increased infection infection

TangTang, et al.2009. Use of corticosteroids in acute , et al.2009. Use of corticosteroids in acute lung injury and acute respiratory distress lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis. syndrome: A systematic review and meta-analysis. Crit Care Med Crit Care Med 37;5:1594-160237;5:1594-1602

Systematic review of studies with Systematic review of studies with low-low-dosedose steroids steroids

Primary outcome: Hospital mortalityPrimary outcome: Hospital mortality Secondary outcomes: length of Secondary outcomes: length of

ventilation, ICU LOS, Lung injury ventilation, ICU LOS, Lung injury score, PaO2:FiO2.score, PaO2:FiO2.

TangTang, et al.2009. Use of corticosteroids in acute , et al.2009. Use of corticosteroids in acute lung injury and acute respiratory distress lung injury and acute respiratory distress syndrome: A systematic review and meta-syndrome: A systematic review and meta-analysis. analysis. Crit Care Med Crit Care Med 37;5:1594-160237;5:1594-1602

ResultsResults 9 studies reviewed (4 RCT, 5 cohort)9 studies reviewed (4 RCT, 5 cohort) 648 total subjects, mean age 51648 total subjects, mean age 51 40-250mg/d Methylprednisolone40-250mg/d Methylprednisolone 7-32 days7-32 days

TangTang, et al.2009. Use of corticosteroids in acute lung injury , et al.2009. Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: A systematic and acute respiratory distress syndrome: A systematic review and meta-analysis. review and meta-analysis. Crit Care Med Crit Care Med 37;5:1594-160237;5:1594-1602

Mortality: Mortality: Trend toward reduction. Trend toward reduction. RTC: P=0.08. Cohort: P=0.06. RTC: P=0.08. Cohort: P=0.06. Combined: P=0.01Combined: P=0.01

Morbidity:Morbidity: Reduced ventilation: 4 days Reduced ventilation: 4 days Reduced ICU stay: 4 daysReduced ICU stay: 4 daysImproved Disease Severity ScoresImproved Disease Severity ScoresImproved PaO2:FiO2Improved PaO2:FiO2

TangTang, et al.2009. Use of corticosteroids in acute , et al.2009. Use of corticosteroids in acute lung injury and acute respiratory distress lung injury and acute respiratory distress syndrome: A systematic review and meta-syndrome: A systematic review and meta-analysis. analysis. Crit Care Med Crit Care Med 37;5:1594-160237;5:1594-1602

Adverse Effects: Adverse Effects: No difference in No difference in infection, musculoskeletal infection, musculoskeletal complications, GI bleeding, major complications, GI bleeding, major organ failure.organ failure.

Can diuresis or fluid restriction minimize Can diuresis or fluid restriction minimize alveolar edema?alveolar edema?

ARDSNet 2006. Comparison of Two-Fluid Management ARDSNet 2006. Comparison of Two-Fluid Management Strategies in Acute Lung Injury. Strategies in Acute Lung Injury. N. Engl. J. Med. N. Engl. J. Med. 354;24 354;24 2564-752564-75

Prospective, RCT comparing liberal fluid use vs. Prospective, RCT comparing liberal fluid use vs. conservative (more Lasix, less boluses).conservative (more Lasix, less boluses).

More positive fluid balances in liberal vs. More positive fluid balances in liberal vs. conservative .conservative .

Subjects were intubated, PaO2:FiO2< 300Subjects were intubated, PaO2:FiO2< 300 Protocol initiated ~ 43 h post ICU admission.Protocol initiated ~ 43 h post ICU admission.

ARDSNet 2006. Comparison of Two-Fluid ARDSNet 2006. Comparison of Two-Fluid Management Strategies in Acute Lung Injury. Management Strategies in Acute Lung Injury. N. N. Engl. J. Med. Engl. J. Med. 354;24 2564-75354;24 2564-75

Hemodynamics: Lower intravascular Hemodynamics: Lower intravascular pressures in conservative grouppressures in conservative group

Lung Function: Lower PEEP, plateau Lung Function: Lower PEEP, plateau pressures, shortened ventilation time in pressures, shortened ventilation time in conservative groupconservative group

Metabolic: Higher creatinine values in Metabolic: Higher creatinine values in conservative.conservative.

Mortality: No difference in 60 day mortalityMortality: No difference in 60 day mortality

1994 American- European criteria 1994 American- European criteria require the absence of LA require the absence of LA hypertensionhypertension

PAC information often ambiguousPAC information often ambiguous Practitioners often misinterpret PAC Practitioners often misinterpret PAC

infoinfo Associated RisksAssociated Risks

The Acute Respiratory Distress Network. The Acute Respiratory Distress Network. 2006. 2006. PAC versus CVC to Guide Treatment of Acute Lung PAC versus CVC to Guide Treatment of Acute Lung Injury.Injury. N. Engl. J. Med. 354;21. N. Engl. J. Med. 354;21. 2213-24 2213-24

Included: intubated pts with Included: intubated pts with PaO2:FiO2<300.PaO2:FiO2<300.

Bilateral infiltratesBilateral infiltrates Excluded: ALI > 48 Hours, dialysis, Excluded: ALI > 48 Hours, dialysis,

irreversible conditionsirreversible conditions All pts were ventilated with low tidal All pts were ventilated with low tidal

volumesvolumes

The Acute Respiratory Distress Network. The Acute Respiratory Distress Network. 2006.PAC versus CVC to Guide Treatment of 2006.PAC versus CVC to Guide Treatment of Acute Lung Injury.Acute Lung Injury. N. Engl. J. Med. 354;21. N. Engl. J. Med. 354;21. 2213-242213-24

Death within 60 days was similar Death within 60 days was similar Ventilator- Free days similarVentilator- Free days similar No difference if patients were in No difference if patients were in

shockshock More Arrhythmias in PAC groupMore Arrhythmias in PAC group

Bajwa et al. 2008. Bajwa et al. 2008. Crit. Care. MedCrit. Care. Med.. Found Found that BNP Levels are elevated in ARDS.that BNP Levels are elevated in ARDS.

Levitt et al 2008. Levitt et al 2008. Crit CareCrit Care found that found that BNP levels do not distinguish CHF from BNP levels do not distinguish CHF from ARDS.ARDS.

ReasonsReasons Myocardial Dysfunction in sepsisMyocardial Dysfunction in sepsis Direct inflammation on myocytesDirect inflammation on myocytes RA and RV stretch in ARDSRA and RV stretch in ARDS

DiagnosisDiagnosisProcalcitoninProcalcitonin

Marker that indicates likelihood of Marker that indicates likelihood of having a systemic response to a having a systemic response to a bacterial infectionbacterial infection

One study found it to be a Marker One study found it to be a Marker for mortality in ARDSfor mortality in ARDS

DiagnosisDiagnosisUltrasoundUltrasound

Copetti et al. Copetti et al. Cardiovascular Cardiovascular UltrasoundUltrasound 2008, 2008, 66:16 :16 

NIVPPVNIVPPV

Zhan, et al.Zhan, et al. 2011. 2011. Early use of Early use of noninvasivenoninvasive positive pressure positive pressure ventilationventilation for acute lung for acute lung injury: A multicenter randomized controlled injury: A multicenter randomized controlled trial. trial. Crit Care MedCrit Care Med

RTCRTC

40 patients randomized to high flow oxygen vs. NIVPPV40 patients randomized to high flow oxygen vs. NIVPPV

Less intubations in NIVPPV (P <0.04)Less intubations in NIVPPV (P <0.04)

Total organ system failure less in NIVPPV group (P<0.001)Total organ system failure less in NIVPPV group (P<0.001)

NIVPPVNIVPPV

No good studies assesing NIVPPV as a No good studies assesing NIVPPV as a means to prevent intubation in means to prevent intubation in ARDS.ARDS.

Prognosis primarily depends on Prognosis primarily depends on underlying cause of lung injuryunderlying cause of lung injury

Sepsis has worst prognosisSepsis has worst prognosis Pneumonia has intermediate Pneumonia has intermediate

prognosisprognosis Trauma has best prognosisTrauma has best prognosis

Surviving Sepsis Surviving Sepsis GuidelinesGuidelines

6 cc/ kg Tidal Volume6 cc/ kg Tidal Volume End- inspiratory plateau pressures < End- inspiratory plateau pressures <

3030 Hypercapnea is acceptableHypercapnea is acceptable