ACUTE RESPIRATORY DISTRESS SYNDROME,Michael L. Fiore, MD Fellow in Critical Care Medicine Mary W. Lieh-Lai, MD, Director, ICU and Fellowship Program Division of Critical Care Medicine Childrens Hospital of Michigan/Wayne State University,A.K.A.,Adult Respiratory Distress Syndrome Da Nang Lung Transfusion Lung Post Perfusion Lung Shock Lung Traumatic Wet Lung,HISTORICAL PERSPECTIVES,Described by William Osler in the 1800s Ashbaugh, Bigelow and Petty, Lancet 1967 12 patients pathology similar to hyaline membrane disease in neonates ARDS is also observed in children New criteria and definition,ORIGINAL DEFINITION,Acute respiratory distress Cyanosis refractory to oxygen therapy Decreased lung compliance Diffuse infiltrates on chest radiograph Difficulties: lacks specific criteria controversy over incidence and mortality,REVISION OF DEFINITIONS,1988: four-point lung injury score Level of PEEP PaO2 / FiO2 ratio Static lung compliance Degree of chest infiltrates 1994: consensus conference simplified the definition,1994 CONSENSUS,Acute onset may follow catastrophic event Bilateral infiltrates on chest radiograph PAWP 18 mm Hg Two categories: Acute Lung Injury - PaO2/FiO2 ratio 300 ARDS - PaO2/FiO2 ratio 200,EPIDEMIOLOGY,Earlier numbers inadequate (vague definition) Using 1994 criteria: 17.9/100,000 for acute lung injury 13.5/100,000 for ARDS Current epidemiologic study underway In children: approximately 1% of all PICU admissions,INCITING FACTORS,Shock Aspiration of gastric contents Trauma Infections Inhalation of toxic gases and fumes Drugs and poisons Miscellaneous,STAGES,Acute, exudative phase rapid onset of respiratory failure after trigger diffuse alveolar damage with inflammatory cell infiltration hyaline membrane formation capillary injury protein-rich edema fluid in alveoli disruption of alveolar epithelium,STAGES,Subacute, Proliferative phase: persistent hypoxemia development of hypercarbia fibrosing alveolitis further decrease in pulmonary compliance pulmonary hypertension,STAGES,Chronic phase obliteration of alveolar and bronchiolar spaces and pulmonary capillaries Recovery phase gradual resolution of hypoxemia improved lung compliance resolution of radiographic abnormalities,MORTALITY,40-60% Deaths due to: multi-organ failure sepsis Mortality may be decreasing in recent years better ventilatory strategies earlier diagnosis and treatment,PATHOGENESIS,Inciting event Inflammatory mediators Damage to microvascular endothelium Damage to alveolar epithelium Increased alveolar permeability results in alveolar edema fluid accumulation,NORMAL ALVEOLUS,ACUTE PHASE OF ARDS,PATHOGENESIS,Target organ injury from hosts inflammatory response and uncontrolled liberation of inflammatory mediators Localized manifestation of SIRS Neutrophils and macrophages play major roles Complement activation Cytokines: TNF-a, IL-1b, IL-6 Platelet activation factor Eicosanoids: prostacyclin, leukotrienes, thromboxane Free radicals Nitric oxide,PATHOPHYSIOLOGY,Abnormalities of gas exchange Oxygen delivery and consumption Cardiopulmonary interactions Multiple organ involvement,ABNORMALITIES OF GAS EXCHANGE,Hypoxemia: HALLMARK of ARDS Increased capillary permeability Interstitial and alveolar exudate Surfactant damage Decreased FRC Diffusion defect and right to left shunt,OXYGEN DELIVERY,DO2 = Q X CaO2 DO2 = Q X (1.34 X Hb X SaO2) X 10,Q = cardiac output,CaO2 = arterial oxygen content Normal DO2: 520-570 ml/min/m2 Oxygen extraction ratio = (SaO2-SvO2/SaO2) X 100 Normal O2ER = 20-30%,HEMODYNAMIC SUPPORT,Max O2 extraction,Critical DO2,Abnormal Flow Dependency,DO2,VO2,Septic Shock/ARDS,OXYGEN DELIVERY & CONSUMPTION,Pathologic flow dependency Uncoupling of oxidative dependency Oxygen utilization by non-ATP producing oxidase systems Increased diffusion distance for O2 between capillary and alveolus,CARDIOPULMONARY INTERACTIONS,A = Pulmonary hypertension resulting in increased RV afterload B = Application of high PEEP resulting in decreased preload A+B = Decreased cardiac output,RESPIRATORY SUPPORT,Conventional mechanical ventilation Newer modalities: High frequency ventilation ECMO Innovative strategies Nitric oxide Liquid ventilation Exogenous surfactant,MANAGEMENT,Monitoring: Respiratory Hemodynamic Metabolic Infections Fluids/electrolytes,MANAGEMENT,Optimize VO2/DO2 relationship DO2 hemoglobin mechanical ventilation oxygen/PEEP VO2 preload afterload contractility,CONVENTIONAL VENTILATION,Oxygen PEEP Inverse I:E ratio Lower tidal volume Ventilation in prone position,RESPIRATORY SUPPORT,Goal: maintain sufficient oxygenation and ventilation, minimize complications of ventilatory management Improve oxygenation: PEEP, MAP, Ti, O2 Improve ventilation: change in pressure,Mechanical Ventilation Guidelines,American College of Chest Physicians Consensus Conference 1993 Guidelines for Mechanical Ventilation in ARDS When possible, plateau pressures 35 cm H2O Tidal volume should be decreased if necessary to achieve this, permitting increased pCO2,PEEP - Benefits,Increases transpulmonary distending pressure Displaces edema fluid into interstitium Decreases atelectasis Decrease in right to left shunt Improved compliance Improved oxygenation,No Benefit to Early Application of PEEP,Pepe PE et al. NEJM 1984;311:281-6. Prospective randomization of intubated patients at risk for ARDS Ventilated with no PEEP vs. PEEP 8+ for 72 hours No differences in development of ARDS, complications, duration of ventilation, time in hospital, duration of ICU stay, morbidity or mortality,Everything hinges on the matter of evidence Carl Sagan,Pressure-controlled Ventilation (PCV),Time-cycled mode Approximate square waves of a preset pressure are applied and released by means of a decelerating flow More laminar flow at the end of inspiration More even distribution of ventilation in patients with marked different resistance values from one region of the lung to another,Pressure-controlled Inverse-ratio Ventilation,Conventional inspiratory-expiratory ratio is reversed (I:E 2:1 to 3:1) Longer time constant Breath starts before expiratory flow from prior breath reaches baseline auto-PEEP with recruitment of alveoli Lower inflating pressures Potential for decrease in cardiac output due to increase in MAP,Extracorporeal Membrane Oxygenation (ECMO),Zapol WM et al. JAMA 1979;242(20):2193-6 Prospectively randomized 90 adult patients Multicenter trial Conventional mechanical ventilation vs. mechanical ventilation supplemented with partial venoarterial bypass No benefit,Partial Liquid Ventilation (PLV),Ventilating the lung with conventional ventilation after filling with perfluorocarbon Perflubron 20 times O2 and 3 times the CO2 solubility Heavier than water Higher spreading coefficient Studies in animal models suggest improved compliance and gas exchange,Partial Liquid Ventilation (PLV),CL Leach, et al. NEJM 1996;335:761-7. The LiquiVent Study Group 13 premature infants with severe RDS refractory to conventional treatment No adverse events Increased oxygenation and improved pulmonary compliance 8 of 10 survivors,Partial Liquid Ventilation (PLV),Hirschl et al JAMA 1996;275:383-389 10 adult patients on ECMO with ARDS Ann Surg 1998;228(5):692-700 9 adult patients with ARDS on conventional mechanical ventilation Improvements in gas exchange with few complications No randomized or case controlled trials,High-Frequency Jet Ventilation,Carlon GC et al. Chest 1983;84:551-59 Prospective randomization of 309 adult patients with ARDS to receive HFJV vs. Volume Cycled Ventilation VCV provided a higher PaO2 HFJV had slightly improved alveolar ventilation No difference in survival, ICU stay, or complications,High Frequency Oscillating Ventilator (HFOV),Raise MAP Recruit lung volume Small changes in tidal volume Impedes venous return necessitating intravascular volume expansion and/or pressors,Predicting outcome in children with severe acute respiratory failure treated with high-frequency ventilation,Sarnaik AP, Meert KL, Pappas MD, Simpson PM, Lieh-Lai MW, Heidemann SM,Crit Care Med 1996; 24:1396-1402,SUMMARY OF RESULTS,Significant improvement in pH, PaCO2, PaO2 and PaO2/FiO2 occurred within 6 hours after institution of HFV The improvement in gas exchange was sustained Survivors showed a decrease in OI and increase in PaO2/FiO2 twenty four hours after instituting HFV while non-survivors did not Pre-HFV OI 20 and failure to decrease OI by 20% at six hours predicted death with 88% (7/8) sensitivity and 83% (19/23) specificity, with an odds ratio of 33 (p= .0036, 95% confidence interval 3-365),STUDY CONCLUSIONS,In patients with potentially reversible underlying diseases resulting in severe acute respiratory failure that is unresponsive to conventional ventilation, high frequency ventilation improves gas exchange in a rapid and sustained fashion. The magnitude of impaired oxygenation and its improvement after high frequency ventilation can predict outcome within 6 hours.,High Frequency Oscillating Ventilation (HFOV) Pediatric ARDS,Arnold JH et al. Crit Care Med 1994; 22:1530-1539. Prospective, randomized clinical study with crossover of 70 patients HFOV had fewer patients requiring O2 at 30 days HFOV patients had increase survivor Survivors had less chronic lung disease,New England Journal of Medicine 2000;342:1301-8,STUDY CONCLUSION,In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use,Prone Position,Improved gas exchange More uniform alveolar ventilation Recruitment of atelectasis in dorsal regions Improved postural drainage Redistribution of perfusion away from edematous, dependent regions,Prone Position,Nakos G et al. Am J Respir Crit Care Med 2000;161:360-68 Observational study of 39 patients with ARDS in different stages Improved oxygenation in prone (PaO2/FiO2 18934 prone vs. 8314 supine) after 6 hours No improvement in patients with late ARDS or pulmonary fibrosis,Prone Position,NEJM 2001;345:568-73 Prone-Supine Study Group Multicenter randomized clinical trial 304 adult patients prospectively randomized to 10 days of supine vs. prone ventilation 6 hours/day Improved oxygenation in prone position No improvement in survival,Exogenous Surfactant,Success with infants with neonatal RDS Exosurf ARDS Sepsis Study. Anzueto et al. NEJM 1996;334:1417-21 Randomized control trial Multicenter study of 725 patients with sepsis induced ARDS No significant difference in oxygenation, duration of mechanical ventilation, hospital stay, or survival,Exogenous Surfactant,Aerosol delivery system only 4.5% of radiolabeled surfactant reached lungs Only reaches well ventilated, less severe areas New approaches to delivery are under study, including tracheal instillation and bronchoalveolar lavage,Inhaled Nitric Oxide (iNO),Pulmonary vasodilator Selectively improves perfusion of ventilated areas Reduces intrapulmonary shunting Improves arterial oxygenation T1/2 111 to 130 msec No systemic hemodynamic effects,Inhaled Nitric Oxide (iNO),Inhaled Nitric Oxide Study Group Dellinger RP et al. Crit Care Med 1998; 26:15-23