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
Children’s Hospital of Michigan
A.K.A.
Adult
Respiratory
Distress
Syndrome
Da Nang Lung
Transfusion
Lung
Post Perfusion
Children’s Hospital of Michigan Lung
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
REVISION OF
DEFINITIONS
1988: four-point lung injury
score
Level of PEEP
PaO / FiO ratio
2 2
Static lung compliance
Degree of chest infiltrates
1994: consensus conference
simplified the definition
Children’s Hospital of Michigan
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
2 2
< 300
ARDS - PaO /FiO ratio < 200
2 2
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
INCITING FACTORS
Shock
Aspiration of gastric contents
Trauma
Infections
Inhalation of toxic gases and
fumes
Drugs and poisons
Miscellaneous
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
STAGES
Subacute, Proliferative phase:
persistent hypoxemia
development of hypercarbia
fibrosing alveolitis
further decrease in pulmonary
compliance
pulmonary hypertension
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
MORTALITY
40-60%
Deaths due to:
multi-organ failure
sepsis
Mortality may be decreasing in
recent years
better ventilatory strategies
earlier diagnosis and treatment
Children’s Hospital of Michigan
PATHOGENESIS
Inciting event
Inflammatory mediators
Damage to microvascular endothelium
Damage to alveolar epithelium
Increased alveolar permeability results in
alveolar edema fluid accumulation
Children’s Hospital of Michigan
NORMAL ALVEOLUS
Type I cell
Alveolar
macrophage
Endothelial
Cell
RBC’s Type II
cell
Capillary
Children’s Hospital of Michigan
ACUTE PHASE OF ARDS
Type I cell
Alveolar
macrophage
Endothelial
Cell
RBC’s Type II
cell
Capillary
Neutrophils
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
PATHOPHYSIOLOGY
Abnormalities of gas exchange
Oxygen delivery and consumption
Cardiopulmonary interactions
Multiple organ involvement
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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)
Children’s Hospital of Michigan
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%
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
CARDIOPULMONARY
INTERACTIONS
A = Pulmonary hypertension resulting
in increased RV afterload
B = Application of high PEEP resulting
in decreased preload
A+B = Decreased cardiac output
Children’s Hospital of Michigan
RESPIRATORY SUPPORT
Conventional mechanical
ventilation
Newer modalities:
High frequency ventilation
ECMO
Innovative strategies
Nitric oxide
Liquid ventilation
Exogenous surfactant
Children’s Hospital of Michigan
MANAGEMENT
Monitoring:
Respiratory
Hemodynamic
Metabolic
Infections
Fluids/electroly
tes
Children’s Hospital of Michigan
MANAGEMENT
Optimize VO2/DO2
relationship
DO2
hemoglobin
mechanical ventilation
oxygen/PEEP
VO2
preload
afterload
contractility
Children’s Hospital of Michigan
CONVENTIONAL
VENTILATION
Oxygen
PEEP
Inverse I:E ratio
Lower tidal volume
Ventilation in prone
position
Children’s Hospital of Michigan
RESPIRATORY SUPPORT
Goal: maintain sufficient
oxygenation and ventilation,
minimize complications of
ventilatory management
Improve oxygenation:
PEEP, MAP, Ti, O2
Improve ventilation:
change in pressure
Children’s Hospital of Michigan
Mechanical Ventilation
Guidelines
American College of Chest Physicians’
Consensus Conference 1993
Guidelines for Mechanical Ventilation
in ARDS
When possible, plateau pressures <
35 cm H2O
Tidal volume should be decreased if
necessary to achieve this, permitting
increased pCO2
Children’s Hospital of Michigan
PEEP - Benefits
Increases transpulmonary
distending pressure
Displaces edema fluid into
interstitium
Decreases atelectasis
Decrease in right to left shunt
Improved compliance
Improved oxygenation
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
Everything hinges
on the matter of
evidence
Carl Sagan
Children’s Hospital of Michigan
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
Children’sresistance
Hospital of Michigan values from one region of
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
Children’sdue to
Hospital of increase in MAP
Michigan
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
Children’s Hospital of Michigan
– No benefit
Partial Liquid
Ventilation (PLV)
Ventilating the lung with conventional
ventilation after filling with
perfluorocarbon
Perflubron
20 times O and 3 times the CO
2 2
solubility
Heavier than water
Higher spreading coefficient
Studies in animal models suggest
improved compliance and gas
Children’s Hospital of Michigan
exchange
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
Children’s Hospital of Michigan
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
Children’s Hospital trials
of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s 3-365)
Hospital of Michigan
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
Children’s Hospital of Michigan
outcome within 6 hours.
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
2
at 30 days
HFOV patients had increase survivor
Survivors had less chronic lung
disease
Children’s Hospital of Michigan
New England Journal of
Medicine 2000;342:1301-8
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
(PaO2/FiO2 189±34 prone vs. 83±14
supine) after 6 hours
No improvement in patients with late
ARDS or pulmonary fibrosis
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
Children’s Hospital significant difference in infection
of Michigan
rate
PROGNOSIS
Underlying medical condition
Presence of multiorgan failure
Severity of illness
Children’s Hospital of Michigan
We are constantly misled
by the ease with which our
minds fall into the ruts of
one or two experiences.
Sir William Osler
Children’s Hospital of Michigan
