Pediatric ARDS: Understanding It and Managing It James D. Fortenberry, MD Medical Director, Pediatric and Adult ECMO Medical Director, Critical Care Medicine Children’s Healthcare of Atlanta.
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Pediatric ARDS: Understanding It and Managing It James D. Fortenberry, MD Medical Director, Pediatric and Adult ECMO Medical Director, Critical Care Medicine Children’s Healthcare of Atlanta at Egleston 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 - PaO2 : F1O2 < 300 Acute respiratory distress syndrome PaO2 : F1O2 < 200 - 1994 American - European Consensus Conference Clinical Disorders Associated with ARDS Direct Lung Injury Indirect Lung Injury Common causes Common Causes Pneumonia Aspiration of gastric contents Sepsis Severe trauma with shock , multiple transfusions Less common causes Less common causes Pulmonary contusion Fat emboli Near-Drowning Inhalational injury Reperfusion pulmonary edema Cardiopulmonary bypass Drug overdose Acute pancreatitis Transfusions of blood products 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 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 - reepithelialize • Neutrophil clearance needed ARDS - Pathophysiology • Decreased compliance • Alveolar edema • Heterogenous • “Baby Lungs” ARDS:CT Scan View Phases of ARDS • Acute - exudative, inflammatory (0 - 3 days) • Subacute - proliferative (4 - 10 days) • Chronic - fibrosing alveolitis ( > 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 AntiInflammatory Mechanical Ventilation Gentle ventilation: Permissive hypercapnia Low tidal volume Open-lung HFOV ARDS Extrapulmonary Gas Exchange ECMO IVOX IV gas exchange AVCO2R Total Implantable Artificial Lung 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 Lung Injury Zones Lung Volume (ml/kg) Overdistention 20 10 “Sweet Spot” Atelectasis 0 13 33 Airway Pressure (cmH20) 38 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 Lower * 35 30 25 Percent 20 * 15 10 Vent free days * p < .001 Death 5 0 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 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 25 Oxygenation Index (OI) 20 * 15 ** * 10 5 0 Pre-PP Brief PP Prolonged PP - Relvas et al., Chest 2003 High Frequency Oscillation: A Whole Lotta 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 Survival with CLD% 40 20 * 0 HFOV CV CV to HFOV HFOV to 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, placebocontrolled 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 100 90 80 70 60 50 40 30 20 10 0 Steroid Placebo * ICU survival - Meduri et al., JAMA, 1998 * Hospital survival * p<.01 Steroids in Unresolving ARDS • Randomized, double-blind, placebocontrolled 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 * 71 60 50 58 58 53 40 30 20 10 NO V + V HF O + V CM HF O V NO 0 CM Survival % 70 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 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