Post on 31-May-2015
Children’s Hospital of Michigan
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 MedicineChildren’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 Shock Lung Traumatic Wet Lung
Children’s Hospital of Michigan
HISTORICAL PERSPECTIVES
Described by William Osler in the 1800’sAshbaugh, Bigelow and Petty, Lancet – 1967
12 patients pathology similar to hyaline membrane
disease in neonatesARDS is also observed in childrenNew criteria and definition
Children’s Hospital of Michigan
ORIGINAL DEFINITIONAcute respiratory distressCyanosis refractory to oxygen therapyDecreased lung complianceDiffuse infiltrates on chest radiograph
Difficulties: lacks specific criteria controversy over incidence and mortality
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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
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1994 CONSENSUSAcute onset
may follow catastrophic eventBilateral infiltrates on chest radiographPAWP < 18 mm HgTwo categories:
Acute Lung Injury - PaO2/FiO2 ratio < 300 ARDS - PaO2/FiO2 ratio < 200
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
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INCITING FACTORSShockAspiration of gastric contentsTraumaInfectionsInhalation of toxic gases and fumesDrugs and poisonsMiscellaneous
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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
Children’s Hospital of Michigan
STAGES
Subacute, Proliferative phase: persistent hypoxemia development of hypercarbia fibrosing alveolitis further decrease in pulmonary compliance pulmonary hypertension
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STAGESChronic 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 eventInflammatory 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
EndothelialCell
RBC’s
Capillary
Alveolarmacrophage
Type IIcell
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ACUTE PHASE OF ARDS
Type I cell
EndothelialCell
RBC’s
Capillary
Alveolarmacrophage
Type IIcell
Neutrophils
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PATHOGENESISTarget organ injury from host’s inflammatory response and
uncontrolled liberation of inflammatory mediatorsLocalized manifestation of SIRSNeutrophils and macrophages play major rolesComplement activationCytokines: TNF-, IL-1, IL-6Platelet activation factorEicosanoids: prostacyclin, leukotrienes, thromboxaneFree radicalsNitric oxide
Children’s Hospital of Michigan
PATHOPHYSIOLOGY
Abnormalities of gas exchangeOxygen delivery and consumptionCardiopulmonary interactionsMultiple 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
VO2 = Q x Hb X 13.4 X (SaO2 - SvO2)
ArterialInflow (Q) capillary
O2
O2
O2
O2 O2
O2
O2
VenousOutflow (Q)
Cell
O2
(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 contentNormal DO2: 520-570 ml/min/m2
Oxygen extraction ratio = (SaO2-SvO2/SaO2) X 100Normal O2ER = 20-30%
Children’s Hospital of Michigan
HEMODYNAMIC SUPPORT
Max O2
extraction
Critical DO2
VO2 = DO2 X O2ER
DO2
VO2
Normal
Max O2
extraction
Critical DO2
Abnormal Flow Dependency
DO2
VO2
Septic Shock/ARDS
Children’s Hospital of Michigan
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 ventilationNewer modalities:
High frequency ventilation ECMO
Innovative strategies Nitric oxide Liquid ventilation Exogenous surfactant
Children’s Hospital of Michigan
MANAGEMENT
Monitoring: Respiratory Hemodynamic Metabolic Infections Fluids/electrolytes
Children’s Hospital of Michigan
MANAGEMENT
Optimize VO2/DO2 relationshipDO2
hemoglobin mechanical ventilation oxygen/PEEP
VO2 preload afterload contractility
Children’s Hospital of Michigan
CONVENTIONAL VENTILATION
OxygenPEEPInverse I:E ratioLower tidal volumeVentilation in prone position
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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
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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 hingeson the matter ofevidence
Carl Sagan
Children’s Hospital of Michigan
Pressure-controlled Ventilation (PCV)
Time-cycled modeApproximate square waves of a preset pressure are
applied and released by means of a decelerating flowMore laminar flow at the end of inspirationMore even distribution of ventilation in patients with
marked different resistance values from one region of the lung to another
Children’s Hospital of Michigan
Pressure-controlled Inverse-ratio Ventilation
Conventional inspiratory-expiratory ratio is reversed(I:E 2:1 to 3:1)Longer time constantBreath starts before expiratory flow from prior breath
reaches baseline auto-PEEP with recruitment of alveoli
Lower inflating pressuresPotential 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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
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
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
Children’s Hospital of Michigan
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
Children’s Hospital of Michigan
High Frequency Oscillating Ventilator (HFOV)
Raise MAPRecruit lung volumeSmall changes in tidal volumeImpedes 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 sustainedSurvivors showed a decrease in OI and increase in PaO2/FiO2
twenty four hours after instituting HFV while non-survivors did notPre-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 outcome within 6 hours.
Children’s 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
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 exchangeMore uniform alveolar ventilationRecruitment of atelectasis in dorsal regionsImproved postural drainageRedistribution 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 RDSExosurf 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 areasNew approaches to delivery are under study, including
tracheal instillation and bronchoalveolar lavage
Children’s Hospital of Michigan
Inhaled Nitric Oxide (iNO)
Pulmonary vasodilatorSelectively improves perfusion of ventilated areasReduces intrapulmonary shuntingImproves arterial oxygenationT1/2 111 to 130 msecNo 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, multi-center 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 vasodilatorEffective for pulmonary hypertensionShort half-life (2-3 min) with rapid clearanceLittle or no hemodynamic effectRandomized clinical trials have not been done
Children’s Hospital of Michigan
CorticosteroidsAcute 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
Children’s Hospital of Michigan
CorticosteroidsFibroproliferative 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
Children’s Hospital of Michigan
PROGNOSIS
Underlying medical condition
Presence of multiorgan failure
Severity of illness
Children’s Hospital of Michigan
We are constantly misledby the ease with which ourminds fall into the ruts ofone or two experiences.
Sir William Osler