You are on page 1of 81

Chapter 7: Acute

Respiratory Distress
Syndrome
James D. Fortenberry, MD, FCCM, FAAP
Medical Director, Critical Care Medicine and
Pediatric/Adult ECMO
Childrens Healthcare of Atlanta at Egleston
ARDS: What Is It?
Term first introduced in 1967
Acute respiratory failure with non-cardiogenic
pulmonary edema, capillary leak after diverse insult
Adult RDS defined to differentiate from neonatal
surfactant deficiency
Problems with definition troubled literature
Murray score 1988: CXR, PEEP, Hypoxemia,
Compliance
Synonyms
Shock lung
Da Nang Lung
Traumatic wet lung

New and Improved
Adult Respiratory Distress
Syndrome


Acute Respiratory Distress
Syndrome
ARDS: New Definition
Criteria
Acute onset
Bilateral CXR infiltrates
PA pressure < 18 mm Hg
Classification
Acute lung injury - P
a
O
2
: F
1
O
2
< 300
Acute respiratory distress syndrome -
P
a
O
2
: F
1
O
2
< 200
- 1994 American - European
Consensus Conference
ARDS - Epidemiology
New criteria allow better estimate of
incidence
1994 criteria in Sweden: ALI
17.9/100,000; 13.5/100,000 ARDS
US: may be closer to 75/1000,000
Prospective data pending
Incidence in children appears similar
5-9% of PICU admissions
Clinical Disorders Associated with ARDS
Direct Lung Injury Indirect Lung Injury
Common causes Common Causes
Pneumonia Sepsis
Aspiration of gastric
contents
Severe trauma with shock ,
multiple transfusions
Less common causes Less common causes
Pulmonary contusion Cardiopulmonary bypass
Fat emboli Drug overdose
Near-Drowning Acute pancreatitis
Inhalational injury Transfusions of blood products
Reperfusion pulmonary
edema
The Problem: Lung Injury
Etiology In Children
Trauma 5%
Non-infectious Pneumonia
14%
Cardiac Arrest 12%
Septic Syndrome 32%
Infectious Pneumonia 28%
Davis et al., J Peds 1993;123:35
ARDS - Pathogenesis
Instigation
Endothelial injury: increased
permeability of alveolar - capillary
barrier
Epithelial injury : alveolar flood, loss
of surfactant, barrier vs. infection
Pro-inflammatory mechanisms
ARDS Pathogenesis: Resolution Phase
Equally important
Alveolar edema - resolved by active
sodium transport
Alveolar type II cells - re-
epithelialize
Neutrophil clearance needed
ARDS - Pathophysiology
Capillary leak:non-cardiogenic pulmonary
edema
Inflammatory mediators
Diminished surfactant activity and airway
collapse
Reduced lung volumes
Heterogeneous
Baby Lungs
Altered pulmonary hemodynamics

ARDS:CT Scan View
ARDS - Pathophysiology:
Diminished Surfactant Activity

Surfactant production and composition
altered in ARDS: low lecithin-sphingomyelin
ratio
Components of edema fluid may inactivate
surfactant
ARDS - Pathophysiology:
Diminished Surfactant Activity
Surfactant product of Type II pneumocytes
Importance of surfactant:
P = 2T/r (Laplace equation; P: trans-
pulmonary pressure, T: surface tension,
r: radius)
Surfactant proportions surface tension to
surface area: thus
ARDS - Pathophysiology: Lung
Volumes
Reduced lung volumes, primarily reduced FRC
FRC = ? Nl =
Low FRC-large intrapulmonary shunt, hypoxemia
Implies
lower compliance = flatter PV curve
marked hysteresis
PV curve concave above FRC and inflection point
at volume > FRC
closing volume in range of tidal volume
resistance increased primarily due to mechanical
unevenness (vs. airway R): high flow rates
helpful


ARDS - Pathophysiology: Lung
Volumes
FRC = Volume of gas in lungs at end of
normal tidal expiration; outward recoil of
chest wall = inward recoil of lungs

Normal FRC =
FRC decreased by 20-40% in ARDS
FRC decreased by 20-30% when supine:
elevate head!

ARDS - Pathophysiology:
Mediators
Massive literature
Mediators involved but extent of
cause/effect unknown
Cellular:
neutrophils-causative: depletion in models
can obliterate lesion; ARDS can occur in
neutropenic patient; direct endothelial
injury, release radicals, proteolytic
enzymes
macrophages-release cytokines


ARDS - Pathophysiology:
Mediators
Humoral:
Complement
Cytokines: TNF, IL-1
PAF, PGs, leukotrienes
NO
Coagulant pathways
ARDS -
Pathophysiology:Pulmonary Edema
Non-cardiogenic pulmonary edema-
Starling formula
What changes in ARDS?
Q = K(P
c
- P
is
) - (
pl
-
is
)
Q =
K =
Pc = ; Pis =
=
pl = ; is =

Phases of ARDS
Acute - exudative, inflammatory: capillary
congestion, neutrophil aggregation, capillary
endothelial swelling, epithelial injury; hyaline
membranes by 72 hours
(0 - 3 days)
Sub-acute - proliferative: proliferation of type II
pneumocytes (abnormal lamellar bodies with
decreased surfactant), fibroblasts-intra-alveolar,
widening of septae
(4 - 10 days)
Chronic - fibrosing alveolitis: remodeling by
collagenous tissue, arterial thickening, obliteration
of pre-capillary vessels; cystic lesions
( > 10 days)
ARDS - Outcomes
Most studies - mortality 40% to 60%;
similar for children/adults
Death is usually due to sepsis/MODS
rather than primary respiratory
Mortality may be decreasing
53/68 % 39/36 %
ARDS - Principles of Therapy
Provide adequate gas
exchange
Avoid secondary injury
Therapies for ARDS
Innovations:
NO
PLV
Proning
Surfactant
Anti-
Inflammatory
Mechanical
Ventilation Gentle ventilation:
Permissive
hypercapnia
Low tidal volume
Open-lung
HFOV
ECMO
IVOX
IV gas
exchange
AVCO
2
R
Total
Implantable
Artificial Lung
ARDS
Extrapulmonary Gas Exchange
The Dangers of Overdistention
Repetitive shear stress
Injury to normal alveoli
inflammatory response
air trapping
Phasic volume swings: volume trauma
compliance
intrapulmonary shunt
FiO
2

WOB
inflammatory response

The Dangers of Atelectasis
0
10
20
13 33 38
Airway Pressure (cmH
2
0)
L
u
n
g

V
o
l
u
m
e

(
m
l
/
k
g
)
Atelectasis
Sweet Spot
Overdistention
Lung Injury Zones
ARDS: George H. W. Bush Therapy
Kinder, gentler forms of
ventilation:
Low tidal volumes (6-8 vs.10-15
cc/kg)
Open lung: Higher PEEP, lower
PIP
Permissive hypercapnia: tolerate
higher pCO
2


Lower Tidal Volumes for ARDS
Multi-center trial, 861 adult ARDS
Randomized:
Tidal volume 12 cc/kg
Plateau pressure < 50 cm H2O
vs
Tidal volume 6 cc/kg
Plateau pressure < 30 cm H2O
ARDS Network,
NEJM, 342: 2000
Lower Tidal Volumes for ARDS
0
5
10
15
20
25
30
35
40
Percent
D
e
a
t
h
V
e
n
t

f
r
e
e
d
a
y
s
Traditional
Lower
*
*
* p < .001
ARDS Network,
NEJM, 342: 2000
Is turning the
ARDS patient
prone to be
helpful?
Prone Positioning in ARDS
Theory: let gravity improve matching
perfusion to better ventilated areas
Improvement immediate
Uncertain effect on outcome
Prone Positioning in Adult ARDS
Randomized trial
Standard therapy vs. standard +
prone positioning
Improved oxygenation
No difference in mortality, time on
ventilator, complications

Gattinoni et al., NEJM, 2001
Prone Positioning in Pediatric ARDS:
Longer May Be Better
Compared 6-10 hrs PP vs. 18-24 hrs
PP
Overall ARDS survival 79% in 40 pts.
Relvas et al., Chest 2003
Brief vs. Prolonged Prone Positioning
in Children
0
5
10
15
20
25
Pre-PP Brief PP Prolonged PP
O
x
y
g
e
n
a
t
i
o
n

I
n
d
e
x

(
O
I
)

- Relvas et al., Chest 2003
*
*
**
High Frequency
Oscillation:
A Whole Lotta
Shakin Goin On
- Reese Clark
Its not absolute pressure,
but volume or pressure
swings that promote lung
injury or atelectasis.
Rapid rate
Low tidal volume
Maintain open lung
Minimal volume swings
High Frequency Ventilation
High Frequency Oscillatory Ventilation
HFOV is the easiest way to
find the ventilation
sweet spot
HFOV: Benefits Vs. Conventional
Ventilation
HFOV vs. CMV in Pediatric
Respiratory Failure: Results
Greater survival without severe lung
disease
Greater crossover to HFOV and
improvement
Failure to respond to HFOV strong
predictor of death
Arnold et al, CCM, 1994
0
20
40
HFOV CV CV to
HFOV
HFOV to
CV
S
u
r
v
i
v
a
l

w
i
t
h

C
L
D
%
- Arnold et al, CCM, 1994
*
HFOV vs. CMV in Pediatric
Respiratory Failure
HFOV
Reduces need for ECMO, chronic lung
disease in neonates
Improves survival without CLD in
pediatric ARDS
HFOV: Outcomes of Randomized
Controlled Trials
Pediatric ECMO
Potential candidates
Neonate - 18 years
Reversible disease process
Severe respiratory/cardiac failure
< 10 days mechanical ventilation
Acute, life-threatening deterioration
Impact of ECMO on Survival in
Pediatric Respiratory Failure
Retrospective, multi-center cohort analysis
331 patients, 32 hospitals
Use of ECMO associated with survival (p <
.001)
53 diagnosis and risk-matched pairs:
ECMO decreased mortality (26% vs 47%,
p < .01)
-Green et al, CCM, 24:1996

Impact of ECMO on Survival in
Pediatric Respiratory Failure
0
10
20
30
40
50
60
70
80
90
Mortality %
< 25% 25 - 50
%
50 -
75%
> 75%
ECMO
Non-ECMO
*
p < .05 - Green et al., CCM, 1996
Pediatric Respiratory ECMO -
Childrens Healthcare of Atlanta
Diagnosis Number Survival % ELSO Survival
%
ARDS/ARF 38 71 51
Bacterial
Pneumonia
9 85 79
Viral
Pneumonia
24 86 53
Trauma 5 80 63
Burns 4 75 52
TOTAL 86 79% 62%
Other Cost Intensive Therapies

Therapy Cost/Patient

Pediatric ECLS $ 232, 941

Pediatric Liver Transplant $ 206, 375

Pediatric Heart Transplant $ 126,695

ECMO: Comparison to Other
Expensive Therapies
4.19
43.5
62.5
26.5
16.3
0
10
20
30
40
50
60
70
C
o
s
t
/
L
i
f
e

-

Y
e
a
r

(
T
h
o
u
s
a
n
d
s

o
f

D
o
l
l
a
r
s
)
ECLS Liver Bone
Marrow
Cardiac Renal
Vats et al., CCM, 1998
If you think about ECMO,
it is worth a call to consider
ECMO
Surfactant in ARDS
ARDS:
surfactant deficiency
surfactant present is dysfunctional
Surfactant replacement improves
physiologic function

Calfs Lung Surfactant Extract in
Acute Pediatric Respiratory Failure
Multi-center trial-uncontrolled,
observational
Calf lung surfactant (Infasurf) intra-
tracheal
Immediate improvement and weaning in
24/29 children with ARDS
14% mortality
-Willson et al,CCM, 24:1996
Surfactant in Pediatric ARDS
Current randomized multi-center
trial
Placebo vs calf lung surfactant
(Infasurf)
Childrens at Egleston is a
participating center-study closed,
await results
Steroids in ARDS
Theoretical anti-inflammatory, anti-
fibrotic benefit
Previous studies with acute use (1st 5
days)
No benefit
Increased 2 infection
Effects of Prolonged Steroids in
Unresolving ARDS
Randomized, double-blind, placebo-
controlled trial
Adult ARDS ventilated for > 7 days without
improvement
Randomized:
Placebo
Methylprednisolone 2 mg/kg/day x 4
days, tapered over 1 month
Meduri et al, JAMA 280:159, 1998
Steroids in Unresolving ARDS
By day 10, steroids improved:
PaO
2
/FiO
2
ratios
Lung injury/MOD scores
Static lung compliance
24 patients enrolled; study stopped
due to survival difference
Meduri et al, JAMA, 1998
Steroids in Unresolving ARDS
0
10
20
30
40
50
60
70
80
90
100
ICU
survival
Hospital
survival
Steroid
Placebo
*
*
p<.01
*
- Meduri et al., JAMA, 1998
Inhaled Nitric Oxide in
Respiratory Failure
Neonates
Beneficial in term neonates with PPHN
Decreased need for ECMO
Adults/Pediatrics
Benefits - lowers PA pressures,
improves gas exchange
Randomized trials: No difference in
mortality or days of ventilation
ECMO and NO in Neonates
ECMO improves survival in neonates
with PPHN (UK study)
NO decreases need for ECMO in
neonates with PPHN: 64% vs 38%
(Clark et al, NEJM, 2000)


Effects of Inhaled Nitric Oxide In
Children with AHRF
Randomized, controlled, blinded multi-
center trial
108 children with OI > 15
Randomized: Inhaled NO 10 ppm vs.
mechanical ventilation alone

Dobyns, Cornfield, Anas,
Fortenberry et al., J. Peds, 1999
Inhaled NO and HFOV In Pediatric
ARDS
58
53
58
71
0
10
20
30
40
50
60
70
80
S
u
r
v
i
v
a
l

%
C
M
V
C
M
V

+

N
O
H
F
O
V
H
F
O
V

+

N
O
Dobyns et al.,
J Peds, 2000
*
Partial Liquid Ventilation
Partial Liquid Ventilation
Mechanisms of action
oxygen reservoir
recruitment of lung volume
alveolar lavage
redistribution of blood flow
anti-inflammatory


Liquid Ventilation
Pediatric trials started in 1996
Partial: FRC (15 - 20
cc/kg)
Study halted 1999 due to
lack of benefit
Adult study (2001): no
effect on outcome

ARDS- Mechanical Therapies
Prone positioning - Unproven outcome
benefit
Low tidal volumes - Outcome benefit in
large study
Open-lung strategy - Outcome benefit in
small study
HFOV -Outcome benefit in
small study
ECMO - Proven in neonates
unproven in children
Pharmacologic Approaches to
ARDS: Randomized Trials
Glucocorticoids
- acute - no benefit
- fibrosing alveolitis - lowered mortality,
small study
Surfactant - possible benefit in
children
Inhaled NO - no benefit
Partial liquid ventilation - no benefit
We must discard the old approach
and continue to search for ways to
improve mechanical ventilation. In
the meantime, there is no substitute
for the clinician standing by the
ventilator
- Martin J. Tobin, MD

You might also like