Chapter 7: Acute Respiratory Distress Syndrome

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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

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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

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New and Improved

• Adult Respiratory Distress Syndrome
• Acute Respiratory Distress Syndrome

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ARDS New Definition

• Criteria
• Acute onset
• Bilateral CXR infiltrates
• PA pressure lt 18 mm Hg
• Classification
• Acute lung injury - PaO2 F1O2 lt 300
• Acute respiratory distress syndrome - PaO2 F1O2
  lt 200

- 1994 American - European Consensus
Conference
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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

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Clinical Disorders Associated with ARDS
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The Problem Lung Injury
Davis et al., J Peds 199312335
Non-infectious Pneumonia 14
Cardiac Arrest 12
Infectious Pneumonia 28
Hemorrhage 5
Trauma 5
Other 4
Septic Syndrome 32
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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
• Pro-inflammatory mechanisms

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ARDS Pathogenesis Resolution Phase

• Equally important
• Alveolar edema - resolved by active sodium
  transport
• Alveolar type II cells - re-epithelialize
• Neutrophil clearance needed

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ARDS - Pathophysiology

• Capillary leaknon-cardiogenic pulmonary edema
• Inflammatory mediators
• Diminished surfactant activity and airway
  collapse
• Reduced lung volumes
• Heterogeneous
• Baby Lungs
• Altered pulmonary hemodynamics

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ARDSCT Scan View
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ARDS - Pathophysiology Diminished Surfactant
Activity

• Surfactant production and composition altered in
  ARDS low lecithin-sphingomyelin ratio
• Components of edema fluid may inactivate
  surfactant

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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

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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 gt FRC
• closing volume in range of tidal volume
• resistance increased primarily due to mechanical
  unevenness (vs. airway R) high flow rates
  helpful

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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!

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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

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ARDS - Pathophysiology Mediators

• Humoral
• Complement
• Cytokines TNF, IL-1
• PAF, PGs, leukotrienes
• NO
• Coagulant pathways

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ARDS - PathophysiologyPulmonary Edema

• Non-cardiogenic pulmonary edema-Starling formula
• What changes in ARDS?
• Q K(Pc - Pis) - ? (?pl - ?is)
• Q
• K
• Pc Pis
• ?
• ?pl ?is

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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
• ( gt 10 days)

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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

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ARDS - Principles of Therapy

• Provide adequate gas exchange
• Avoid secondary injury

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Therapies for ARDS
Mechanical Ventilation
Innovations NO PLV Proning Surfactant Anti-Inflam
matory
Gentle ventilation Permissive hypercapnia Low
tidal volume Open-lung HFOV
ARDS
Extrapulmonary Gas Exchange
Total Implantable Artificial Lung
IVOX IV gas exchange
AVCO2R
ECMO
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The Dangers of Overdistention

• Repetitive shear stress
• Injury to normal alveoli
• inflammatory response
• air trapping
• Phasic volume swings volume trauma

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The Dangers of Atelectasis

• compliance
• intrapulmonary shunt
• FiO2
• WOB
• inflammatory response

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Lung Injury Zones
Overdistention
Sweet Spot
Atelectasis
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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 pCO2

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Lower Tidal Volumes for ARDS

• Multi-center trial, 861 adult ARDS
• Randomized
• Tidal volume 12 cc/kg
• Plateau pressure lt 50 cm H2O
• vs
• Tidal volume 6 cc/kg
• Plateau pressure lt 30 cm H2O

ARDS Network, NEJM, 342 2000
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Lower Tidal Volumes for ARDS
22 decrease


ARDS Network, NEJM, 342 2000
p lt .001
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Is turning the ARDS patient prone to be helpful?
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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 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

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Prone Positioning in Pediatric ARDSLonger 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


Oxygenation Index (OI)

- Relvas et al., Chest 2003
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High Frequency OscillationA Whole Lotta Shakin
Goin On
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Its not absolute pressure, but volume or
pressure swings that promote lung injury or
atelectasis.
- Reese Clark
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High Frequency Ventilation

• Rapid rate
• Low tidal volume
• Maintain open lung
• Minimal volume swings

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High Frequency Oscillatory Ventilation
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HFOV is the easiest way to find the
ventilation sweet spot
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HFOV Benefits Vs. Conventional Ventilation
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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
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HFOV vs. CMV in Pediatric Respiratory Failure

- Arnold et al, CCM, 1994
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HFOV Outcomes of Randomized Controlled Trials

• HFOV
• Reduces need for ECMO, chronic lung disease in
  neonates
• Improves survival without CLD in pediatric ARDS

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Pediatric ECMO

• Potential candidates
• Neonate - 18 years
• Reversible disease process
• Severe respiratory/cardiac failure
• lt 10 days mechanical ventilation
• Acute, life-threatening deterioration

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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 lt .001)
• 53 diagnosis and risk-matched pairs
• ECMO decreased mortality (26 vs 47, p
  lt .01)

-Green et al, CCM, 241996
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Pediatric Respiratory ECMO - Childrens
Healthcare of Atlanta
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Other Cost Intensive Therapies
Therapy Cost/Patient Pediatric ECLS
232, 941 Pediatric Liver Transplant
206, 375 Pediatric Heart Transplant
126,695
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ECMO Comparison to Other Expensive Therapies
Vats et al., CCM, 1998
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If you think about ECMO, it is worth a call to
consider ECMO
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Surfactant in ARDS

• ARDS
• surfactant deficiency
• surfactant present is dysfunctional
• Surfactant replacement improves physiologic
  function

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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, 241996
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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

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Steroids in ARDS

• Theoretical anti-inflammatory, anti-fibrotic
  benefit
• Previous studies with acute use (1st 5 days)
• No benefit
• Increased 2? infection

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Effects of Prolonged Steroids in Unresolving ARDS

• Randomized, double-blind, placebo-controlled
  trial
• Adult ARDS ventilated for gt 7 days without
  improvement
• Randomized
• Placebo
• Methylprednisolone 2 mg/kg/day x 4 days, tapered
  over 1 month

Meduri et al, JAMA 280159, 1998
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Steroids in Unresolving ARDS

• By day 10, steroids improved
• PaO2/FiO2 ratios
• Lung injury/MOD scores
• Static lung compliance
• 24 patients enrolled study stopped due to
  survival difference

Meduri et al, JAMA, 1998
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Steroids in Unresolving ARDS



plt.01
- Meduri et al., JAMA, 1998
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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

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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)

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Effects of Inhaled Nitric Oxide In Children with
AHRF

• Randomized, controlled, blinded multi-center
  trial
• 108 children with OI gt 15
• Randomized Inhaled NO 10 ppm vs. mechanical
  ventilation alone

Dobyns, Cornfield, Anas, Fortenberry et al., J.
Peds, 1999
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Inhaled NO and HFOV In Pediatric ARDS

Dobyns et al., J Peds, 2000
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Partial Liquid Ventilation
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Partial Liquid Ventilation

• Mechanisms of action
• oxygen reservoir
• recruitment of lung volume
• alveolar lavage
• redistribution of blood flow
• anti-inflammatory

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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

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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

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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
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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