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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