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Acute Respiratory Distress

Syndrome (ARDS)

Dr. Khairiyadi, M.Kes., Sp.A


Departemen Ilmu Kesehatan Anak
RSUD Ulin Banjarmasin

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Acute Respiratory Distress Syndrome
(ARDS)
• ARDS continues to contribute significantly to the disease burden in
today’s arena of pediatric critical care medicine.
• ARDS is a very heterogeneous disease which makes it difucult to
study
• Many studies have been performed (mainly in adult) but only lung
protective ventilation have been accepted as standard therapy
and had mortality benefit
• ARDS : acute, diffuse, inflammatory lung injury caused by diverse
pulmonary and non-pulmonary etiologies.
• ARDS in infant = Hyalin membran disease
• ARDS in adult does not same with ARDS in pediatric.
• Pediatric is not small adult

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Pathophysiology
• ARDS follows cascade of events after direct
pulmonary or systemic insult resulting into the
disruption of alveolar-capillary unit.
• The pathophysiology of ARDS is complex and
multifaceted involving 3 distinct components:
1. nature of the stimulus
2. host response to the stimulus, and
3. the role of iatrogenic factors
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ARDS - Pathogenesis
Instigation
• Endothelial injury: increased permeability of
alveolar - capillary barrier
• Epithelial injury : alveolar flood, loss of
surfactant, barrier vs. infection
• Proinflammatory mechanisms
ARDS Pathogenesis
Resolution
• Equally important
• Alveolar edema - resolved by active sodium
transport
• Alveolar type II cells - re-epithelialize
• Neutrophil clearance needed
ARDS - Pathophysiology

• Decreased compliance
• Alveolar edema
• Heterogenous
• “Baby Lungs”
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Clinical Disorders Associated with ARDS

Direct Lung Injury Indirect Lung Injury

Common causes Common Causes


Pneumonia Sepsis
Aspiration of gastric Severe trauma with shock ,
contents 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
Davis et al., J Peds 1993;123:35

Noninfectious Pneumonia
14%
Cardiac Arrest 12%

Infectious Pneumonia 28%

Trauma 5%

Septic Syndrome 32%


Etiology In Children
Phases of ARDS
• Acute - exudative, inflammatory
(0 - 3 days)
• Subacute - proliferative
(4 - 10 days)
• Chronic - fibrosing alveolitis
( > 10 days)
ARDS: New Definition
Criteria
– Acute onset
– Bilateral CXR infiltrates
– PA pressure < 18 mm Hg
– Classification
• Acute lung injury - PaO2 : F1O2 < 300
• Acute respiratory distress syndrome - PaO2 :
F1O2 < 200

- 1994 American - European


Consensus Conference
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Therapies for ARDS
Innovations: Mechanical
NO Ventilation Gentle ventilation:
PLV Permissive
Proning hypercapnia
Surfactant Low tidal volume
Anti-Inflammatory Open-lung
HFOV
ARDS

Extrapulmonary Gas Exchange


Total
Implantable
IVOX Artificial Lung
ECMO IV gas AVCO2R
exchange
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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
The Dangers of Overdistention
• Repetitive shear stress
• Injury to normal alveoli
• inflammatory response
• air trapping
• Phasic volume swings: volutrauma
The Dangers of Atelectasis
• compliance

• intrapulmonary shunt

• FiO2

• WOB

• inflammatory response
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Lung Injury Zones
Overdistention
Lung Volume (ml/kg)

20 “Sweet Spot”

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Atelectasis

0
13 33 38
Airway Pressure (cmH20)
ARDS: George 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 pCO2
Lower Tidal Volumes for ARDS

40 Traditional
35 * Lower
30
25
Percent 20
15 *
10
5
0
ARDS Network,
Death

Vent free
days
NEJM, 342: 2000
* p < .001
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
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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
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Brief vs. Prolonged Prone Positioning in
Children
25

20
*
Oxygenation Index

15
**
*
(OI)

10

0
Pre-PP Brief PP Prolonged PP

- Relvas et al., Chest 2003


High Frequency
Oscillation:
A Whole Lotta
Shakin’’ Goin
Shakin Goin’’ On
It’s not absolute pressure, but
volume or pressure swings that
promote lung injury or atelectasis.
- Reese Clark
High Frequency Ventilation

• Rapid rate
• Low tidal volume
• Maintain open lung
• Minimal volume swings
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
40
Survival with CLD%

20

0
HFOV CV CV to HFOV to
HFOV CV
- Arnold et al, CCM, 1994
Surfactant in ARDS

• ARDS:
– surfactant deficiency
– surfactant present is dysfunctional
• Surfactant replacement improves physiologic
function
Surfactant in Pediatric ARDS
• Current randomized multi-center trial
• Placebo vs calf lung surfactant (Infasurf)
• Children’s at Egleston is a participating
center-study closed, await results
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


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Steroids in Unresolving ARDS
100
90
80
70 Steroid
60 Placebo
50 * *
40
30
20
10
0
ICU Hospital
survival survival

* p<.01
- Meduri et al., JAMA, 1998
Steroids in Unresolving ARDS
• Randomized, double-blind, placebo-controlled trial
• ARDSNetwork-180 adults
• Randomized:
– Placebo
– Methylprednisolone
– No mortality difference
– Decreased ventilator-free days but only if started
7-14 days

Steinberg, NEJM, 354:1671,2006


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
Inhaled NO and HFOV In Pediatric ARDS

80
70
*
Survival %

60 71
50 58 58
40
53
30
20
10
0 NO
V

Dobyns et al.,
V

NO

O
CM

HF

+
+

J Peds, 2000
V
V

O
CM

HF
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
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