What’s New In Pediatric ARDS Nancy G. Hoover, MD Medical Director, PICU Walter Reed AMC

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  • Whats New In Pediatric ARDS Nancy G. Hoover, MD Medical Director, PICU Walter Reed AMC
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  • New and Improved Acute Respiratory Distress Syndrome Ashbaugh, Lancet, 1967 Adult Respiratory Distress Syndrome To distinguish from neonatal HMD/RDS Acute Respiratory Distress Syndrome American-European Consensus conference, 1994
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  • ARDS: New Definition Criteria Acute onset Acute onset Bilateral CXR infiltrates Bilateral CXR infiltrates PA pressure < 18 mm Hg PA pressure < 18 mm Hg Classification Classification Acute lung injury - P a O 2 : F 1 O 2 < 300 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 Acute respiratory distress syndrome - P a O 2 : F 1 O 2 < 200 1994 American-European Consensus Conference
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  • Clinical Disorders Associated with ARDS Direct Injury Common Causes Common Causes Pneumonia Pneumonia Gastric aspiration Gastric aspiration Less Common Causes Less Common Causes Pulmonary contusion Pulmonary contusion Fat emboli Fat emboli Near drowning Near drowning Inhalational injury Inhalational injury Indirect Injury Common Causes Common Causes Sepsis Shock after severe trauma Less Common Causes Less Common Causes Cardiopulm. bypass Drug overdose Acute pancreatitis Massive blood transfusions
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  • The Problem: Lung Injury Other 4% Hemorrhage 5% Trauma 5% Noninfectious Pneumonia 14% Cardiac Arrest 12% Septic Syndrome 32% Infectious Pneumonia 28% Davis et al., J Peds 1993;123:35
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  • ARDS - Pathogenesis Instigation Endothelial injury: increased permeability of alveolar - capillary barrier Endothelial injury: increased permeability of alveolar - capillary barrier Epithelial injury : alveolar flood, loss of surfactant, barrier vs. infection Epithelial injury : alveolar flood, loss of surfactant, barrier vs. infection Proinflammatory mechanisms Proinflammatory mechanisms
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  • ARDS Pathogenesis Resolution Equally important Equally important Alveolar edema - resolved by active sodium transport Alveolar edema - resolved by active sodium transport Alveolar type II cells - re-epithelialize Alveolar type II cells - re-epithelialize Neutrophil clearance needed Neutrophil clearance needed
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  • ARDS - Pathophysiology Decreased compliance Decreased compliance Alveolar edema Alveolar edema Heterogenous Heterogenous Baby Lungs Baby Lungs
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  • Phases of ARDS Acute - exudative, inflammatory Acute - exudative, inflammatory (0 - 3 days) Subacute - proliferative Subacute - proliferative (4 - 10 days) Chronic - fibrosing alveolitis Chronic - fibrosing alveolitis ( > 10 days)
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  • Phases of ARDS
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  • ARDS - Outcomes Most studies - mortality 40% to 60% Most studies - mortality 40% to 60% Majority of deaths sepsis or MOD rather than primary respiratory Majority of deaths sepsis or MOD rather than primary respiratory Outcomes similar for adults and children Outcomes similar for adults and children Mortality may be decreasing 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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  • It would seem ironic that the very existence of humans is fully dependent on a gas that, in excess quantities, is toxic and lethal Lynn D. Martin
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  • Therapies for ARDS Innovations: iNO PLV Proning Surfactant Anti- Inflammatory Mechanical Ventilation Gentle ventilation: Permissive hypercapnia Low tidal volume Open-lung HFOV ARDS Extrapulmonary Gas Exchange
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  • The Dangers of Overdistention Repetitive shear stress Repetitive shear stress inflammatory response inflammatory response air trapping air trapping Phasic volume swings: volutrauma Phasic volume swings: volutrauma Injury to normal alveoli Injury to normal alveoli
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  • compliance compliance intrapulmonary shunt intrapulmonary shunt FiO 2 FiO 2 WOB WOB inflammatory response inflammatory response The Dangers of Atelectasis
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  • Atelectasis Sweet Spot Overdistention Lung Injury Zones
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  • Mechanical Therapies in ARDS Lower tidal volumes but avoidance of atelectasis with higher PEEP Lower tidal volumes but avoidance of atelectasis with higher PEEP Permissive hypercapnia Permissive hypercapnia HFOV HFOV Prone positioning Prone positioning
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  • Lower Tidal Volumes for ARDS Multi-center trial, 861 adult ARDS Multi-center trial, 861 adult ARDS Randomized: Randomized: Tidal volume 12 cc/kg Tidal volume 12 cc/kg Plateau pressure < 50 cm H2O Plateau pressure < 50 cm H2Ovs. Tidal volume 6 cc/kg Tidal volume 6 cc/kg Plateau pressure < 30 cm H2O Plateau pressure < 30 cm H2O ARDS Network, NEJM, 342: 2000
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  • Lower Tidal Volumes for ARDS * * * p
  • What about after first 28 days? NHLBI ARDS Clinical Trials Network, NEJM, 2006 NHLBI ARDS Clinical Trials Network, NEJM, 2006 180 adult patients with ARDS >7 days 180 adult patients with ARDS >7 days No difference in mortality with steroids No difference in mortality with steroids EXCEPT, if the patient was entered into the study after 14 days of ARDS EXCEPT, if the patient was entered into the study after 14 days of ARDS THEN, there was an increase in 60 and 180 day mortality THEN, there was an increase in 60 and 180 day mortality
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  • Inhaled Nitric Oxide in Respiratory Failure Neonates Beneficial in term neonates with PPHN Beneficial in term neonates with PPHN Decreased need for ECMO Decreased need for ECMOAdults/Pediatrics Benefits - lowers PA pressures, improves gas exchange Benefits - lowers PA pressures, improves gas exchange Randomized trials: No difference in mortality or days of ventilation 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) ECMO improves survival in neonates with PPHN (UK study) iNO decreases need for ECMO in neonates with PPHN: 64% vs 38% iNO 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 Randomized, controlled, blinded multi- center trial 108 children, median age 2.5 years 108 children, median age 2.5 years Entry: OI > 15 x 2 Entry: OI > 15 x 2 Randomized: Inhaled NO 10 ppm vs. mechanical ventilation alone Randomized: Inhaled NO 10 ppm vs. mechanical ventilation alone Dobyns, 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 Mechanisms of action oxygen reservoir oxygen reservoir recruitment of lung volume recruitment of lung volume alveolar lavage alveolar lavage redistribution of blood flow redistribution of blood flow anti-inflammatory anti-inflammatory
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  • Liquid Ventilation Pediatric trials started in 1996 Pediatric trials started in 1996 Partial: FRC (15 - 20 cc/kg) Partial: FRC (15 - 20 cc/kg) Study halted 1999 due to lack of benefit Study halted 1999 due to lack of benefit Adult study 2001 Adult study 2001 no effect on outcome no effect on outcome
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  • ARDS- Mechanical Therapies Low tidal volumes Outcome benefit in large study Prone positioningUnproven outcome benefit Open-lung strategyOutcome benefit in small study HFOVOutcome benefit in small study ECMOProven in neonates unproven in children
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  • Pharmacologic Approaches to ARDS: Randomized Trials Steroids - acuteno benefit - fibrosing alveolitislowered mortality, small study Surfactantpossible benefit in children Inhaled NOno benefit PLV 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
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  • If you think about ECMO, it is worth a call to consider ECMO
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  • Pediatric ECMO Potential candidates Potential candidates Neonate - 18 years Neonate - 18 years Reversible disease process Reversible disease process Severe respiratory/cardiac failure Severe respiratory/cardiac failure < 10 days mechanical ventilation < 10 days mechanical ventilation Acute, life-threatening deterioration Acute, life-threatening deterioration
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  • Impact of ECMO on Survival in Pediatric Respiratory Failure Retrospective, multicenter cohort analysis Retrospective, multicenter cohort analysis 331 patients, 32 hospitals 331 patients, 32 hospitals Use of ECMO associated with survival (p