1. ACUTE RESPIRATORY DISTRESS
SYNDROME
Michael L. Fiore, MD – Fellow in Critical Care Medicine
Mary W. Lieh-Lai, MD, Director, ICU and Fellowship Program
Division of Critical Care Medicine
Children’s Hospital of Michigan/Wayne State University
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2. A.K.A.
 Adult Respiratory
Distress Syndrome
 Da Nang Lung
 Transfusion Lung
 Post Perfusion Lung
 Shock Lung
 Traumatic Wet Lung
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3. HISTORICAL PERSPECTIVES
 Described by William Osler in the 1800’s
 Ashbaugh, Bigelow and Petty, Lancet – 1967
12 patients

 pathology similar to hyaline membrane
disease in neonates
 ARDS is also observed in children
 New criteria and definition
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4. ORIGINAL DEFINITION
 Acute respiratory distress
 Cyanosis refractory to oxygen therapy
 Decreased lung compliance
 Diffuse infiltrates on chest radiograph
 Difficulties:
 lacks specific criteria
 controversy over incidence and mortality
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5. REVISION OF DEFINITIONS
 1988: four-point lung injury score
 Level of PEEP
 PaO2 / FiO2 ratio
Static lung compliance

 Degree of chest infiltrates
 1994: consensus conference
simplified the definition
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6. 1994 CONSENSUS
 Acute onset
 may follow catastrophic event
 Bilateral infiltrates on chest radiograph
 PAWP < 18 mm Hg
 Two categories:
 Acute Lung Injury - PaO /FiO ratio < 300
2 2
 ARDS - PaO2/FiO2 ratio < 200
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7. EPIDEMIOLOGY
 Earlier numbers inadequate (vague definition)
 Using 1994 criteria:
 17.9/100,000 for acute lung injury
 13.5/100,000 for ARDS
 Current epidemiologic study underway
 In children: approximately 1% of all PICU admissions
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8. INCITING FACTORS
 Shock
 Aspiration of gastric contents
 Trauma
 Infections
 Inhalation of toxic gases and fumes
 Drugs and poisons
 Miscellaneous
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9. STAGES
 Acute, exudative phase
 rapid onset of respiratory failure after trigger
 diffuse alveolar damage with inflammatory cell
infiltration
 hyaline membrane formation
 capillary injury
 protein-rich edema fluid in alveoli
 disruption of alveolar epithelium
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10. STAGES
 Subacute, Proliferative phase:
 persistent hypoxemia
 development of hypercarbia
 fibrosing alveolitis
 further decrease in pulmonary
compliance
 pulmonary hypertension
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11. STAGES
 Chronic phase
 obliteration of alveolar and bronchiolar
spaces and pulmonary capillaries
 Recovery phase
 gradual resolution of hypoxemia
 improved lung compliance
 resolution of radiographic
abnormalities
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12. MORTALITY
 40-60%
 Deaths due to:
multi-organ failure

 sepsis
 Mortality may be decreasing in recent years
 better ventilatory strategies
 earlier diagnosis and treatment
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13. PATHOGENESIS
 Inciting event
 Inflammatory mediators
 Damage to microvascular endothelium
 Damage to alveolar epithelium
 Increased alveolar permeability results
in alveolar edema fluid accumulation
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14. NORMAL ALVEOLUS
Type I cell
Alveolar
macrophage
Endothelial
Cell
RBC’s Type II
cell
Capillary
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15. ACUTE PHASE OF ARDS
Type I cell
Alveolar
macrophage
Endothelial
Cell
RBC’s Type II
cell
Capillary
Neutrophils
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16. PATHOGENESIS
 Target organ injury from host’s inflammatory response and
uncontrolled liberation of inflammatory mediators
 Localized manifestation of SIRS
 Neutrophils and macrophages play major roles
 Complement activation
 Cytokines: TNF-α, IL-1β, IL-6
 Platelet activation factor
 Eicosanoids: prostacyclin, leukotrienes, thromboxane
 Free radicals
 Nitric oxide
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17. PATHOPHYSIOLOGY
 Abnormalities of gas exchange
 Oxygen delivery and consumption
 Cardiopulmonary interactions
 Multiple organ involvement
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18. ABNORMALITIES OF GAS EXCHANGE
 Hypoxemia: HALLMARK of ARDS
 Increased capillary permeability
 Interstitial and alveolar exudate
 Surfactant damage
 Decreased FRC
 Diffusion defect and right to left shunt
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19. OXYGEN EXTRACTION
Cell
O2
Arterial O2 O2
Venous
O2
Inflow Outflow
O2 O2 O2 O2
(Q) capillary (Q)
VO2 = Q x Hb X 13.4 X (SaO2 - SvO2)
(Adapted from the ICU Book by P. Marino)
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20. OXYGEN DELIVERY
DO2 = Q X CaO2
DO2 = Q X (1.34 X Hb X SaO2) X 10
Q = cardiac output
CaO2 = arterial oxygen content
Normal DO2: 520-570 ml/min/m2
Oxygen extraction ratio = (SaO2-SvO2/SaO2) X 100
Normal O2ER = 20-30%
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21. HEMODYNAMIC SUPPORT
Max O2 Max O2
extraction extraction
VO2 VO2
Critical DO2 Critical DO2
DO2 DO2
Normal Septic Shock/ARDS
VO2 = DO2 X O2ER Abnormal Flow Dependency
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22. OXYGEN DELIVERY & CONSUMPTION
 Pathologic flow dependency
 Uncoupling of oxidative dependency
 Oxygen utilization by non-ATP producing
oxidase systems
 Increased diffusion distance for O2 between
capillary and alveolus
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23. CARDIOPULMONARY INTERACTIONS
 A = Pulmonary hypertension resulting in
increased RV afterload
 B = Application of high PEEP resulting
in decreased preload
 A+B = Decreased cardiac output
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24. RESPIRATORY SUPPORT
 Conventional mechanical ventilation
 Newer modalities:
High frequency ventilation

 ECMO
 Innovative strategies
 Nitric oxide
 Liquid ventilation
 Exogenous surfactant
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25. MANAGEMENT
 Monitoring:
 Respiratory
 Hemodynamic
 Metabolic
 Infections
 Fluids/electrolytes
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26. MANAGEMENT
 Optimize VO2/DO2 relationship
 DO2
 hemoglobin
 mechanical ventilation
 oxygen/PEEP
 VO2
 preload
 afterload
 contractility
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27. CONVENTIONAL VENTILATION
 Oxygen
 PEEP
 Inverse I:E ratio
 Lower tidal volume
 Ventilation in prone position
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28. RESPIRATORY SUPPORT
 Goal: maintain sufficient oxygenation
and ventilation, minimize complications
of ventilatory management
 Improve oxygenation: PEEP, MAP,
Ti, O2
 Improve ventilation: change in
pressure
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29. Mechanical Ventilation Guidelines
 American College of Chest Physicians’ Consensus
Conference 1993
 Guidelines for Mechanical Ventilation in ARDS
 When possible, plateau pressures < 35 cm H O
2
 Tidal volume should be decreased if necessary to
achieve this, permitting increased pCO2
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30. PEEP - Benefits
 Increases transpulmonary distending pressure
 Displaces edema fluid into interstitium
 Decreases atelectasis
 Decrease in right to left shunt
 Improved compliance
 Improved oxygenation
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31. No Benefit to Early Application of
PEEP
 Pepe PE et al. NEJM 1984;311:281-6.
 Prospective randomization of intubated patients at
risk for ARDS
 Ventilated with no PEEP vs. PEEP 8+ for 72 hours
 No differences in development of ARDS,
complications, duration of ventilation, time in
hospital, duration of ICU stay, morbidity or mortality
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32. Everything hinges
on the matter of
evidence
Carl Sagan
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33. Pressure-controlled Ventilation
(PCV)
 Time-cycled mode
 Approximate square waves of a preset pressure are
applied and released by means of a decelerating flow
 More laminar flow at the end of inspiration
 More even distribution of ventilation in patients with
marked different resistance values from one region of
the lung to another
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34. Pressure-controlled Inverse-ratio
Ventilation
 Conventional inspiratory-expiratory ratio is reversed
 (I:E 2:1 to 3:1)
 Longer time constant
 Breath starts before expiratory flow from prior breath
reaches baseline → auto-PEEP with recruitment of
alveoli
 Lower inflating pressures
 Potential for decrease in cardiac output due to increase
in MAP
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35. Extracorporeal Membrane Oxygenation
(ECMO)
 Zapol WM et al. JAMA 1979;242(20):2193-6
 Prospectively randomized 90 adult patients
 Multicenter trial
– Conventional mechanical ventilation vs.
mechanical ventilation supplemented with partial
venoarterial bypass
– No benefit
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36. Partial Liquid Ventilation (PLV)
 Ventilating the lung with conventional ventilation after
filling with perfluorocarbon
 Perflubron
 20 times O and 3 times the CO solubility
2 2
 Heavier than water
 Higher spreading coefficient
 Studies in animal models suggest improved
compliance and gas exchange
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37. Partial Liquid Ventilation (PLV)
 CL Leach, et al. NEJM 1996;335:761-7. The LiquiVent
Study Group
 13 premature infants with severe RDS refractory to
conventional treatment
 No adverse events
 Increased oxygenation and improved pulmonary
compliance
 8 of 10 survivors
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38. Partial Liquid Ventilation (PLV)
 Hirschl et al
 JAMA 1996;275:383-389
• 10 adult patients on ECMO with ARDS
 Ann Surg 1998;228(5):692-700
• 9 adult patients with ARDS on conventional
mechanical ventilation
 Improvements in gas exchange with few
complications
 No randomized or case controlled trials
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39. High-Frequency Jet Ventilation
 Carlon GC et al. Chest 1983;84:551-59
 Prospective randomization of 309 adult patients with
ARDS to receive HFJV vs. Volume Cycled
Ventilation
 VCV provided a higher PaO
2
 HFJV had slightly improved alveolar ventilation
 No difference in survival, ICU stay, or complications
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40. High Frequency Oscillating Ventilator
(HFOV)
 Raise MAP
 Recruit lung volume
 Small changes in tidal volume
 Impedes venous return necessitating intravascular
volume expansion and/or pressors
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41. Predicting outcome in children with severe acute
respiratory failure treated with high-frequency
ventilation
Sarnaik AP, Meert KL, Pappas MD, Simpson PM, Lieh-Lai
MW, Heidemann SM
Crit Care Med 1996; 24:1396-1402
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42. SUMMARY OF RESULTS
 Significant improvement in pH, PaCO2, PaO2 and PaO2/FiO2
occurred within 6 hours after institution of HFV
 The improvement in gas exchange was sustained
 Survivors showed a decrease in OI and increase in PaO2/FiO2
twenty four hours after instituting HFV while non-survivors did not
 Pre-HFV OI > 20 and failure to decrease OI by > 20% at six hours
predicted death with 88% (7/8) sensitivity and 83% (19/23)
specificity, with an odds ratio of 33 (p= .0036, 95% confidence
interval 3-365)
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43. STUDY CONCLUSIONS
 In patients with potentially reversible underlying
diseases resulting in severe acute respiratory failure
that is unresponsive to conventional ventilation, high
frequency ventilation improves gas exchange in a rapid
and sustained fashion.
 The magnitude of impaired oxygenation and its
improvement after high frequency ventilation can predict
outcome within 6 hours.
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44. High Frequency Oscillating Ventilation
(HFOV) – Pediatric ARDS
 Arnold JH et al. Crit Care Med 1994; 22:1530-1539.
 Prospective, randomized clinical study with
crossover of 70 patients
 HFOV had fewer patients requiring O at 30 days
2
 HFOV patients had increase survivor
 Survivors had less chronic lung disease
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45. New England Journal of Medicine
2000;342:1301-8
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46. STUDY CONCLUSION
 In patients with acute lung injury and the acute
respiratory distress syndrome, mechanical ventilation
with a lower tidal volume than is traditionally used
results in decreased mortality and increases the number
of days without ventilator use
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47. Prone Position
 Improved gas exchange
 More uniform alveolar ventilation
 Recruitment of atelectasis in dorsal regions
 Improved postural drainage
 Redistribution of perfusion away from edematous,
dependent regions
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48. Prone Position
 Nakos G et al. Am J Respir Crit Care Med
2000;161:360-68
 Observational study of 39 patients with ARDS in
different stages
 Improved oxygenation in prone (PaO /FiO 189±34
2 2
prone vs. 83±14 supine) after 6 hours
 No improvement in patients with late ARDS or
pulmonary fibrosis
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49. Prone Position
 NEJM 2001;345:568-73
 Prone-Supine Study Group
 Multicenter randomized clinical trial
 304 adult patients prospectively randomized to 10
days of supine vs. prone ventilation 6 hours/day
 Improved oxygenation in prone position
 No improvement in survival
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50. Exogenous Surfactant
 Success with infants with neonatal RDS
 Exosurf ARDS Sepsis Study. Anzueto et al. NEJM
1996;334:1417-21
 Randomized control trial
 Multicenter study of 725 patients with sepsis induced
ARDS
 No significant difference in oxygenation, duration of
mechanical ventilation, hospital stay, or survival
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51. Exogenous Surfactant
 Aerosol delivery system – only 4.5% of radiolabeled
surfactant reached lungs
 Only reaches well ventilated, less severe areas
 New approaches to delivery are under study, including
tracheal instillation and bronchoalveolar lavage
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52. Inhaled Nitric Oxide (iNO)
 Pulmonary vasodilator
 Selectively improves perfusion of ventilated areas
 Reduces intrapulmonary shunting
 Improves arterial oxygenation
 T1/2 111 to 130 msec
 No systemic hemodynamic effects
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53. Inhaled Nitric Oxide (iNO)
 Inhaled Nitric Oxide Study Group
 Dellinger RP et al. Crit Care Med 1998; 26:15-23
 Prospective, randomized, placebo controlled, double
blinded, multi-center study
 177 adults with ARDS
 Improvement in oxygenation index
 No significant differences in mortality or days off
ventilator
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54. Inhaled Aerosolized Prostacyclin
(IAP)
 Potent selective pulmonary vasodilator
 Effective for pulmonary hypertension
 Short half-life (2-3 min) with rapid clearance
 Little or no hemodynamic effect
 Randomized clinical trials have not been done
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55. Corticosteroids
Acute Phase Trials
 Bernard GR et al. NEJM 1987;317:1565-70
 99 patients prospectively randomized
 Methylprednisolone (30mg/kg q6h x 4) vs. placebo
 No differences in oxygenation, chest radiograph,
infectious complications, or mortality
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56. Corticosteroids
Fibroproliferative Stage
 Meduri GU et al. JAMA 1998;280:159-65
 24 patients with severe ARDS and failure to improve
by day 7 of treatment
 Placebo vs. methylprednisolone 2mg/kg/day for 32
days
 Steroid group showed improvement in lung injury
score, improved oxygenation, reduced mortality
 No significant difference in infection rate
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57. PROGNOSIS
 Underlying medical condition
 Presence of multiorgan failure
 Severity of illness
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58. We are constantly misled
by the ease with which our
minds fall into the ruts of
one or two experiences.
Sir William Osler
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