Acute Respiratory Distress Syndrome

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Acute Respiratory Distress Syndrome

• Allen H. Roberts II, M.D.
• Associate Professor of Medicine
• Georgetown University HospitalMarch 2009

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Case 1

• 66 yo male admitted to ICU with dyspnea, O2
  desaturation. Has unilateral ureteral
  obstruction and bacteremia. CXR shows patchy
  bilateral infiltrates
• After removal of a ureteral stone and institution
  of antibiotics, his oxygenation improved and the
  infiltrates resolved.

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Case 2

• 55 yo male admitted to SICU ESLD secondary to
  EtOH presented with LLL pneumonia 3 days prior.
  Developed hypoxemic respiratory failure requiring
  mechanical ventilation. Progressive airway
  pressure elevation and refractory hypoxemia on AC
  mode.
• Transitioned to APRV
• Progressive hypotension
• Barotrauma
• Multisystem failure
• Death

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Acute Lung Injury/ARDS

• Definitions
• Clinical settings / Presentation
• Pathophysiology / Natural History
• Ventilator Strategies Problems
• Non-Ventilator Management

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Acute Lung Injury/ARDS Definitions

• Acute Lung Injury acute lung inflammation with
  increased vascular permeability- - bilateral
  widespread infiltrates - PaO2/FiO2 lt 300 mmHg -
  PAWP lt 18 mmHg (if measured)
• ARDS - PaO2/FiO2 lt 200 mmHgBernard et al
  AJRCCM 1994 American-European Consensus
  Conference on ARDS

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ARDS Incidence

• Age adjusted incidence 86 per
  100,000 person-years
• In-hospital mortality 38.5 - (60 in patients
  gt 85 y.o.)
• 191,000 annual cases in US
• 
  Rubenfeld et al NEJM 2005 3531685-93

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ARDS Clinical Settings
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ARDS Clinical Features

• Pts at risk
• Onset of dyspnea, gas exchange abnormality within
  12-48 h of inciting event
• S/S of underlying disorder may predominate early
• Course can be variable not all require vent
• Generally resp failure is HYPOXEMIC

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ARDS in ICU

• Patient at risk
• Several days into unit stay primary process
  may be resolving
• Increasing FiO2 requirementShunt physiology
• Need to add PEEP to oxygenate or to down-titrate
  FiO2
• CXR evolving diffuse infiltrates

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ARDS Radiographic

• Early, CXR may be normal transient!
• Patchy or homogeneous diffuse, bilateral
  infiltrates
• Patchy areas may coalesce white out
• Diffuse alveolar infiltrates may clear somewhat
  leaving interstitial, then fibrotic
  patternor..CXR will clear with minimal
  residual
• Findings of barotrauma pneumothorax,
  pneumomediastinum, etc.

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ARDS CXR - Differential Diagnosis

• Acute Lung Injury
• Diffuse pneumonia (eg pneumococcal, Legionella)
• Acute interstitial pneumonia (AIP)
• Acute eosinophilic pneumonia
• Cardiogenic Pulmonary edema
• Diffuse alveolar hemorrhage
• ARDS can coexist with other processes!

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ARDS Pathophysiology

• Insult! Cytokines!!
• PMN infiltration predominate in BAL
  profilePathology Exudative
  Fibroproliferative
  Fibrotic
• Type II Pneumocyte damage decreased surfactant
  atelectasis
• Loss of compliance
• Shunt, VQ mismatch, Diffusion abnormality
  HYPOXEMIA

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Piantadosi, Annals of Int Med 2004,141460-470
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Piantadosi, Annals Int Med 2004 141460-470
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Piantadosi, Annals of Int Med 2004,141460-470
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ARDS Cytokines

• ProinflammatoryTNF, IL-1, Il-6, IL-8 -
  elevated in plasma and BAL fluid of pts at risk
  for and with ARDS - predictive of mortality
  (ARDSNET) Frank et al
  Chest 2006 1301906-1914

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Cytokines in ALI/ARDS

• 44 patients randomized to - control
  (traditional) vent targeted to normalize PaCO2
  vs - study (lung protective) low Tidal
  Volume VT titrated based on pressure volume
  curve with strategy to minimize overinflation
  high airway pressures
• 
  Ranieri et al JAMA 282(1) July 1999

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Cytokines in ALI/ARDS

• ControlVT 11.1 cc/kgPEEP 6.5
• StudyVT 7.6 cc/kgPEEP 14.8
• 
  Ranieri et al JAMA 282(1) July 1999

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Cytokines, continued

• In study group (low VT, lung protective), lower
  levels of TNF, IL1, IL6 were found in BAL (plt.05)

• Mechanical ventilation induces a cytokine
  response which is minimized by lung protective
  strategies. Ranieri et al JAMA
  282(1) July 1999

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ARDS Off to the Unit

• Impaired Gas Exchange initially, respiratory
  alkalosis with widened A-a gradientinvariably
  progresses to frank hypoxemia.
• Shunt, diffusion, and VQ mismatch physiology
• Decreased Lung Compliance edema surfactant
  loss, atelectasishyaline membranes increased
  work of breathing
• Pulmonary Hypertension hypoxic vasoconstriction
  (early)diffuse lung remodeling (late)

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Ventilation General Approach

• Can attempt noninvasive (dont count on it)
• Intubate early if the clinical trajectory is
  clear
• Prepare for hemodynamic consequences of
  intubation positive pressure ventilation
• Goal Adequate Oxygenation with Avoidance of
  Complications

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ARDS The Old Days

• Start with Volume Cycled, Assist Control
• As compliance decreases and airway pressures
  rise, - transition to Pressure Control set a
  maximum airway pressure tidal volume
  dependent variable minute ventilation (VE)
  not stable extremely uncomfortable for
  patient heavy sedation, neuromuscular
  blockade

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Mechanical Ventilation in ARDSCurrent Theory

• Closed lung strategy - ARDSNET protocol low
  tidal volume, lung protective
  vs
• Open lung strategy - Airway Pressure Release
  Ventilation (APRV)
• - AC with recruiting maneuvers

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Volume-Cycled Ventilation Assist Control
(ACCMV)

• Conventional, familiar start with this
• Set Vt, rate (Vt x rate Ve)therefore
  guaranteed Ve ( minute ventilation)
• Problem non-compliant lung set Vt gives high
  airway pressures barotrauma

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ARDSNET

• 831 patients randomized to conventional VT 12
  cc/kg vs study VT 6cc/kg
• Enrollment stopped because of mid-study analysis
  showing improved survival in lower VT
  group(mortality 40 vs 31)ARDSNET, NEJM
  3421301-1308, 2000

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NEJM 3421301-1308, 2000 The ARDSNET Study
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What about patients without ARDS?

• Retrospective review of 332 patients without ARDS
  at admission to ICU
• 80 developed ARDS
• Multivariate analysis ARDS associated with -
  large VT (OR 1.3 for each cc/kg above 6) - blood
  products - acidemia - h/o restrictive lung
  diseaseGajic et al Critical Care Medicine
  200432(9)1817-1824

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• Gajic et al Critical Care Medicine
  200432(9)1817-1824

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Piantadosi Annals 2004
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PEEP

• ARDSNET Patients
• Randomized 549 pts to receive low PEEP
  (8.9/-3.5 cm) vshigh PEEP (14.7 /-
  3.5 cm)ARDSNET NEJM 351(4) 327-336 2004

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ARDSNET PEEP NEJM 2004, 351(4)327-36
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ARDSNET Published Conclusions 2000-2006

• Low VT associated with improved survival
• Optimal PEEP not definedhigher PEEP had no
  survival advantage

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Steroids for ARDS?

• Meduri et al, early 1990s subgroup of patients
  with ARDS had clinical radiographic improvement
  on 1-2 mg/kg methylprednisolone during the
  fibroproliferative phase.
• Infection sought pretreatment with BAL, some OLBx

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Steroids ARDSNET

• 180 pts randomized to methylprednisolone vs
  placebo
• Primary endpoint - 60 day mortality
• Secondary endpoints vent-free
  organ-failure-free days complications
• NEJM 2006 3541671-84

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Steroids ARDSNET

• 60 day mortality - 28.6 (placebo) vs 29.2
  (ns) - higher mortality with steroids if
  enrolled gt14 days after ARDS onset
• Greater incidence of neuromuscular weakness
• No increase in rate of infectious complications
  NEJM
  2006 3541671-84

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ARDSNET 2006 354(16) 1671-1684
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ARDSNET 2006354(16) 1671-83
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ARDSNET Published Conclusions 2000-2006

• Low VT associated with improved survival
• Optimal PEEP not definedhigher PEEP had no
  survival advantage
• Steroid treatment showed no benefit and some
  potential adverse effects - in general NOT
  recommended

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Steroids, continued

• 91 patients w/ARDS randomized to continuous
  low-dose methylprednisolone vs placebo
• Treated patients had - earlier reduction in
  lung injury score - reduced time on vent p.002
  - reduced ICU stay p .007 - reduced ICU
  mortality (21 vs 43) p.03 - lower rate of ICU
  infections p .0002
• Attributed to steroid-induced down-regulation of
  systemic inflammation
• Meduri et al Chest 2007 131954
  - 963

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No Survival Advantage

• Prone position
• Nitric oxide
• Liquid ventilation with fluorocarbons
• Intratracheal instillation of recombinant
  surfactant
• Use of Pulmonary Artery Catheter to help guide
  treatment

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Alternatives to ARDSNET

• Pressure control- inverse ratio
  ventilation(PC-IRV)
• Airway pressure release ventilation (APRV)
• High frequency oscillatory ventilationAll modes
  may improve oxygenation because of sustained
  recruitment, but to date none is known to offer a
  survival advantage.

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APRV
Habashi, N. CCM 33(3)S228-240, 2005
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ARDS Outcome

• Mortality 60 down to 30 1983 1996.Felt
  largely due to improved CCM capabilities rather
  than ARDS-specific therapy.
• Survivors have pulmonary restriction early after
  dischargeimproved PFTs plateau by 1 year.Many
  return to nl spirometry /- reduced DLCO.
• Significant neuropsychiatric issues may persist

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Rubenfeld et al NEJM 2005 353(16)1685-93
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ARDS- Survival Follow-up

• One year post discharge, 49 of survivors had
  returned to work, most to prior positions
• Those not returning - persistent weakness
  fatigue - job stress - poor mobility - poor
  functional statusHerridge et al NEJM 2003
  348(8)683-93

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Herridge et al NEJM 2003, 348(8) 683-93
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ARDS Conclusion

• Index of suspicion in pts at risk who develop
  resp sx or infiltrates
• Intubate early when it appears inevitable
• Low tidal volume
• Titrate FiO2 and PEEP
• Transition to APRV as rescue
• Steroids party line vs bottom line