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

Childrens Hospital of Michigan

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
Childrens Hospital of Michigan

A.K.A.
Adult Respiratory Distress Syndrome Da Nang Lung Transfusion Lung Post Perfusion Lung Shock Lung Traumatic Wet Lung

Childrens Hospital of Michigan

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
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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
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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
Childrens Hospital of Michigan

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

Childrens Hospital of Michigan

INCITING FACTORS
Shock Aspiration of gastric contents Trauma Infections Inhalation of toxic gases and fumes Drugs and poisons Miscellaneous
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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
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STAGES
Subacute, Proliferative phase: persistent hypoxemia development of hypercarbia fibrosing alveolitis further decrease in pulmonary compliance pulmonary hypertension

Childrens Hospital of Michigan

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
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MORTALITY
40-60% Deaths due to: multi-organ failure sepsis Mortality may be decreasing in recent years better ventilatory strategies earlier diagnosis and treatment
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PATHOGENESIS
Inciting event Inflammatory mediators Damage to microvascular endothelium Damage to alveolar epithelium Increased alveolar permeability results in alveolar edema fluid accumulation
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NORMAL ALVEOLUS
Type I cell Alveolar macrophage Endothelial Cell RBCs Type II cell Capillary

Childrens Hospital of Michigan

ACUTE PHASE OF ARDS

Type I cell Alveolar macrophage Endothelial Cell RBCs

Type II cell Capillary Neutrophils

Childrens Hospital of Michigan

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
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PATHOPHYSIOLOGY
Abnormalities of gas exchange Oxygen delivery and consumption Cardiopulmonary interactions Multiple organ involvement

Childrens Hospital of Michigan

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

Childrens Hospital of Michigan

OXYGEN EXTRACTION
Cell

O2
Arterial Inflow (Q)
O2 O2 O2 O2
capillary

O2 O2 O2

Venous Outflow (Q)

VO2 = Q x Hb X 13.4 X (SaO2 - SvO2)

(Adapted from the ICU Book by P. Marino)
Childrens Hospital of Michigan

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%
Childrens Hospital of Michigan

HEMODYNAMIC SUPPORT
Max O2 extraction Max O2 extraction

VO2
Critical DO2

VO2
Critical DO2

DO2

DO2

Normal
VO2 = DO2 X O2ER
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Septic Shock/ARDS
Abnormal Flow Dependency

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

Childrens Hospital of Michigan

CARDIOPULMONARY INTERACTIONS
A = Pulmonary hypertension resulting in increased RV afterload B = Application of high PEEP resulting in decreased preload A+B = Decreased cardiac output

Childrens Hospital of Michigan

RESPIRATORY SUPPORT
Conventional mechanical ventilation Newer modalities: High frequency ventilation ECMO Innovative strategies Nitric oxide Liquid ventilation Exogenous surfactant
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MANAGEMENT
Monitoring:

Respiratory Hemodynamic Metabolic Infections Fluids/electrolytes

Childrens Hospital of Michigan

MANAGEMENT
Optimize VO2/DO2 relationship DO2 hemoglobin mechanical ventilation oxygen/PEEP VO2 preload afterload contractility
Childrens Hospital of Michigan

CONVENTIONAL VENTILATION
Oxygen PEEP Inverse I:E ratio Lower tidal volume Ventilation in prone position

Childrens Hospital of Michigan

RESPIRATORY SUPPORT
Goal: maintain sufficient oxygenation and ventilation, minimize complications of ventilatory management Improve oxygenation: PEEP, MAP, Ti, O2 Improve ventilation: change in pressure

Childrens Hospital of Michigan

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

Childrens Hospital of Michigan

PEEP - Benefits
Increases transpulmonary distending pressure Displaces edema fluid into interstitium Decreases atelectasis Decrease in right to left shunt Improved compliance Improved oxygenation

Childrens Hospital of Michigan

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
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Everything hinges on the matter of evidence

Carl Sagan

Childrens Hospital of Michigan

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
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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
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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
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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
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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
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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
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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

Childrens Hospital of Michigan

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

Childrens Hospital of Michigan

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

Childrens Hospital of Michigan

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)

Childrens Hospital of Michigan

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.
Childrens Hospital of Michigan

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

Childrens Hospital of Michigan

New England Journal of Medicine

2000;342:1301-8

Childrens Hospital of Michigan

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

Childrens Hospital of Michigan

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

Childrens Hospital of Michigan

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
Childrens Hospital of Michigan

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
Childrens Hospital of Michigan

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
Childrens Hospital of Michigan

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

Childrens Hospital of Michigan

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

Childrens Hospital of Michigan

Inhaled Nitric Oxide (iNO)

Inhaled Nitric Oxide Study Group Dellinger RP et al. Crit Care Med 1998; 26:15-23 Prospective, randomized, placebo controlled, double blinded, multi-center study 177 adults with ARDS Improvement in oxygenation index No significant differences in mortality or days off ventilator
Childrens Hospital of Michigan

Inhaled Aerosolized Prostacyclin (IAP)

Potent selective pulmonary vasodilator Effective for pulmonary hypertension Short half-life (2-3 min) with rapid clearance Little or no hemodynamic effect Randomized clinical trials have not been done

Childrens Hospital of Michigan

Corticosteroids
Acute Phase Trials
Bernard GR et al. NEJM 1987;317:1565-70 99 patients prospectively randomized Methylprednisolone (30mg/kg q6h x 4) vs. placebo No differences in oxygenation, chest radiograph, infectious complications, or mortality

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Corticosteroids
Fibroproliferative Stage
Meduri GU et al. JAMA 1998;280:159-65 24 patients with severe ARDS and failure to improve by day 7 of treatment Placebo vs. methylprednisolone 2mg/kg/day for 32 days Steroid group showed improvement in lung injury score, improved oxygenation, reduced mortality No significant difference in infection rate
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PROGNOSIS
Underlying medical condition Presence of multiorgan failure Severity of illness

Childrens Hospital of Michigan

We are constantly misled by the ease with which our minds fall into the ruts of one or two experiences.
Sir William Osler

Childrens Hospital of Michigan