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 Children’s Hospital of Michigan/Wayne State University
Children’s Hospital of Michigan

A.K.A.
Adult Respiratory Distress Syndrome  Da Nang Lung  Transfusion Lung  Post Perfusion Lung

Children’s Hospital of Michigan

HISTORICAL PERSPECTIVES
Described by William Osler in the 1800’s 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

Children’s Hospital of Michigan

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

Children’s Hospital of Michigan

REVISION OF DEFINITIONS
1988: four-point lung injury score  Level of PEEP  PaO / FiO ratio 2 2 Static lung compliance  Degree of chest infiltrates 1994: consensus conference simplified the definition

Children’s Hospital of Michigan

1994 CONSENSUS Acute onset
may follow catastrophic event Bilateral infiltrates on chest radiograph PAWP < 18 mm Hg Two categories:  Acute Lung Injury - PaO /FiO ratio 2 2 < 300  ARDS - PaO /FiO ratio < 200 2 2

Children’s 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

Children’s Hospital of Michigan

INCITING FACTORS
Shock Aspiration of gastric contents Trauma Infections Inhalation of toxic gases and fumes Drugs and poisons Miscellaneous
Children’s Hospital of Michigan

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
Children’s Hospital of Michigan

STAGES
Subacute, Proliferative phase:  persistent hypoxemia  development of hypercarbia  fibrosing alveolitis  further decrease in pulmonary compliance  pulmonary hypertension

Children’s 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
Children’s Hospital of Michigan

MORTALITY
40-60% Deaths due to:  multi-organ failure  sepsis Mortality may be decreasing in recent years  better ventilatory strategies  earlier diagnosis and treatment
Children’s Hospital of Michigan

PATHOGENESIS
Inciting event Inflammatory mediators  Damage to microvascular endothelium  Damage to alveolar epithelium  Increased alveolar permeability results in alveolar edema fluid accumulation

Children’s Hospital of Michigan

NORMAL ALVEOLUS
Type I cell Alveolar macrophage Endothelial Cell RBC’s Type II cell Capillary

Children’s Hospital of Michigan

ACUTE PHASE OF ARDS
Type I cell Alveolar macrophage Endothelial Cell RBC’s Type II cell Capillary Neutrophils

Children’s Hospital of Michigan

PATHOGENESIS
 Target organ injury from host’s inflammatory response and uncontrolled liberation of inflammatory mediators  Localized manifestation of SIRS  Neutrophils and macrophages play major roles  Complement activation  Cytokines: TNF-α , IL-1β , IL-6  Platelet activation factor  Eicosanoids: prostacyclin, leukotrienes, thromboxane  Free radicals  Nitric oxide
Children’s Hospital of Michigan

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

Children’s 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

Children’s Hospital of Michigan

OXYGEN EXTRACTION
Cell

O2
Arterial Inflow (Q)
O2 O2
capillary

O2 O2 O2

O2 O2

Venous Outflow (Q)

VO2 = Q x Hb X 13.4 X (SaO2 - SvO2)
(Adapted from the ICU Book by P. Marino)
Children’s 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%
Children’s Hospital of Michigan

HEMODYNAMIC SUPPORT
Max O2 extraction Max O2 extraction

VO2
Critical DO2

VO2
Critical DO2

DO2

DO2

Normal
VO2 = DO2 X O2ER
Children’s Hospital of Michigan

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
Children’s 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

Children’s Hospital of Michigan

RESPIRATORY SUPPORT
Conventional mechanical ventilation Newer modalities:  High frequency ventilation  ECMO Innovative strategies  Nitric oxide  Liquid ventilation  Children’s Hospital of MichiganExogenous surfactant

MANAGEMENT
Monitoring:
    

Respiratory Hemodynamic Metabolic Infections Fluids/electroly tes

Children’s Hospital of Michigan

MANAGEMENT
Optimize VO2/DO2 relationship DO2  hemoglobin  mechanical ventilation  oxygen/PEEP VO2  preload  afterload  contractility Children’s Hospital of Michigan

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

Children’s 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
Children’s 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 Children’s Hospital of Michigan

Everything hinges on the matter of evidence
Carl Sagan

Children’s 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 Children’sresistance values from one region of Hospital of Michigan

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 Children’sdue of Michigan Hospital to increase in MAP

Pressure-controlled Inverse-ratio Ventilation

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 Children’s Hospital of Michigan – No benefit

Partial Liquid Ventilation (PLV)
Ventilating the lung with conventional ventilation after filling with perfluorocarbon Perflubron  20 times O and 3 times the CO 2 2 solubility  Heavier than water  Higher spreading coefficient  Studies in animal models suggest improved compliance and gas Children’s Hospital of Michigan 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
Children’s Hospital of Michigan

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 Children’s Hospital trials of Michigan

Partial Liquid Ventilation (PLV)

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 PaO 2  HFJV had slightly improved alveolar ventilation  No difference in survival, ICU stay, or complications
Children’s 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
Children’s 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

Children’s 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) Children’s 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 Children’s Hospital of Michigan 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 O 2 at 30 days  HFOV patients had increase survivor  Survivors had less chronic lung disease Children’s Hospital of Michigan

New England Journal of Medicine 2000;342:1301-8

Children’s 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
Children’s 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
Children’s 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 189±34 prone vs. 83±14 supine) after 6 hours  No improvement in patients with late ARDS or pulmonary fibrosis
Children’s 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
Children’s 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
Children’s 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

Children’s 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
Children’s 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, multicenter study  177 adults with ARDS  Improvement in oxygenation index  No significant differences in mortality or days off ventilator

Children’s 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 Children’s Hospital of Michigan been done

Corticosteroids
Acute Phase Trials
Bernard GR et al. NEJM 1987;317:156570  99 patients prospectively randomized  Methylprednisolone (30mg/kg q6h x 4) vs. placebo  No differences in oxygenation, chest radiograph, infectious complications, or mortality
Children’s Hospital of Michigan

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 Children’s Hospital of Michigan rate

PROGNOSIS
Underlying medical condition Presence of multiorgan failure Severity of illness

Children’s 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

Children’s Hospital of Michigan

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