ards lecture

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


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 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


ORIGINAL DEFINITIONAcute respiratory distressCyanosis refractory to oxygen therapyDecreased lung complianceDiffuse 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 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


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 FACTORSShockAspiration of gastric contentsTraumaInfectionsInhalation of toxic gases and fumesDrugs and poisonsMiscellaneous


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


STAGESChronic 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 eventInflammatory mediators

Damage to microvascular endothelium Damage to alveolar epithelium Increased alveolar permeability results

in alveolar edema fluid accumulation


NORMAL ALVEOLUS

Type I cell

EndothelialCell

RBC’s

Capillary

Alveolarmacrophage

Type IIcell


ACUTE PHASE OF ARDS

Type I cell

EndothelialCell

RBC’s

Capillary

Alveolarmacrophage

Type IIcell

Neutrophils


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


PATHOPHYSIOLOGY

Abnormalities of gas exchangeOxygen delivery and consumptionCardiopulmonary interactionsMultiple 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 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)


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%


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


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 ventilationNewer 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 relationshipDO2

hemoglobin mechanical ventilation oxygen/PEEP

VO2 preload afterload contractility


CONVENTIONAL VENTILATION

OxygenPEEPInverse I:E ratioLower tidal volumeVentilation 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 hingeson the matter ofevidence

Carl Sagan


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


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


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 MAPRecruit lung volumeSmall changes in tidal volumeImpedes 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 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)


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 exchangeMore uniform alveolar ventilationRecruitment of atelectasis in dorsal regionsImproved postural drainageRedistribution 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 189±34

prone vs. 83±14 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 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


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


Inhaled Nitric Oxide (iNO)

Pulmonary vasodilatorSelectively improves perfusion of ventilated areasReduces intrapulmonary shuntingImproves arterial oxygenationT1/2 111 to 130 msecNo systemic hemodynamic effects


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


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


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


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


PROGNOSIS

Underlying medical condition

Presence of multiorgan failure

Severity of illness


We are constantly misledby the ease with which ourminds fall into the ruts ofone or two experiences.

Sir William Osler

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