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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

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