The Management of

Acute Respiratory
Distress Syndrome

Outlines

Introduction

Ventilator strategy

Adjunctive therapy

Case demonstration

 Definition

Acute onset

PaO2/FiO2 < 200 mmHg

CXR: bilateral infiltrates

PAWP < 18 mmHg,

no clinical evidence of LA HTN

Direct injury
Pneumonia
Gastric aspiration
Drowning
Fat and amniotic
fluid embolism
Pulmonary contusion
Alveolar hemorrhage
Toxic inhalation
Reperfusion

Indirect injury
Severe sepsis
Transfusions
Shock
Salicylate or narcotic
overdose
Pancreatitis

Differential Diagnosis

Left ventricular failure

Intravascular volume overload
Mitral stenosis
Veno-occlusive disease
Lymphangitic carcinoma
Interstitial and airway diseases

Hypersensitivity pneumonitis
Acute eosinophilic pneumonia
Bronchiolitis obliterans with organising pneumonia
Lancet 2007; 369:1553-65

Prognosis & Outcome

Predictive of death: advanced age, shock,

hepatic failure
Overall 28-day mortality: 20-40%
Lung function: returns to normal over 612 months
Common complications: neuropsychiatric
problems, neuromuscular weakness
Lancet 2007; 369:1553-65

Pathophysiology

Exudative phase
Cytokines inflammation surfactant
dysfunction atelectasis
Elastase epithelial barrier damage edema
Procoagulant tendency capillary thrombosis

Fibroproliferative phase
Chronic inflammation
Fibrosis
neovascularisation

Lancet 2007; 369:1553-65

NEJM 2000;342:1334-1349

NEJM 2000;342:1334-1349

NEJM 2000;342:1334-1349

Treatment

No specific treatment
Mainstay of treatment: supportive care
Avoid iatrogenic complications
Treat the underlying cause
Maintain adequate oxygenation

Supportive Care

Prevention of deep vein thrombosis,

gastrointestinal bleeding, and pressure
ulcers
Semi-recumbent position
Enteral nutrition
Infection control
Goal-directed sedation practice
Glucose control

Ventilator Strategy

Ventilator-induced Lung Injury

(VILI)

Barotrauma
Volutrauma
Atelectrauma
Biotrauma

Collapse

Over
Distension

Volutrauma

Increased alveolar
wall stress (stretch)
by high tidal volume
Parenchymal injury

Gross physical
disruption
Stretch-responsive
inflammatory
pathways

AJRCCM 1998; 157: 294-323

Atelectrauma

Cyclic closing and reopening of alveoli

Alveolar shear stress-related injury
Heterogeneous nature of lung aeration in
ALI/ARDS
Lung edema

PEEP

PEEP

PEEP

The PEEP Effect

NEJM 2006;354:1839-1841

Ventilator-induced Lung Injury

(VILI)

Upper
Deflection point

Lower
Inflection point

Lung-Protective Ventilation
ARDS Network, 2000: Multicenter, randomized 861 patients
Lung-protective
ventilation
Tidal Volume (ml/kg)
Pplateau
PEEP
Actual PEEP

Conventional
ventilation

12

<30

<50

Protocol
8.1

Protocol
9.1

Result (p<0.001)
31.0%
39.8%
Principle for FiO2 and PEEP Adjustment
FiO2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

PEEP

5-8

8-10

10

10-14

14

14-18

18-24

NEJM 2000; 342: 1301-1308

Lung-Protective Ventilation

Result:
Lower 22% mortality (31% vs 39.8%)
Increase ventilator-free days

NEJM 2000; 342: 1301-1308

Concerns when using lungprotective strategy

Heterogeneous distribution
Hypercapnia
Auto-PEEP
Sedation and paralysis
Patient-ventilator dyssynchrony
Increased intrathoracic pressure
Maintenance of PEEP

Other Ventilator Strategies

Lung recruitment maneuvers

Prone positioning
High-frequency oscillatory ventilation
(HFOV)

Lung Recruitment

To open the collapsed

alveoli
A sustained inflation
of the lungs to higher
airway pressure and
volumes

Ex.: PCV, Pi = 45
cmH2O, PEEP = 5
cmH2O, RR = 10 /min,
I : E = 1:1, for 2
minutes
NEJM 2007; 354: 1775-1786

Lung Recruitment

NEJM 2007; 354: 1775-1786

Lung Recruitment

NEJM 2007; 354: 1775-1786

Lung Recruitment

Potentially recruitable (PEEP 5 15 cmH2O)

Increase in PaO2:FiO2
Decrease in PaCO2
Increase in compliance

Sensitivity : 71%
Specificity : 59%

The effect of PEEP correlates with the

percentage of potentially recruitalbe lung
The percentage of recruitable lung correlates
with the overall severity of lung injury
NEJM 2007; 354: 1775-1786

Lung Recruitment

The percentage of potentially recruitable

lung:
Extremely variable,
Strongly associated with the response to
PEEP

Not routinely recommended

Prone Position

Prone Position

Mechanisms to
improve oxygenation:

Increase in endexpiratory lung volume

Better ventilationperfusion matching
More efficient drainage
of secretions

Prone Position

NEJM 2001;345:568-573

Prone Position

NEJM 2001;345:568-573

Prone Position

Improve oxygenation in about 2/3 of all

treated patients
No improvement on survival, time on
ventilation, or time in ICU
Might be useful to treat refractory
hypoxemia
Optimum timing or duration ?
Routine use is not recommended

High-Frequency Oscillatory
Ventilation (HFOV)

HFOV

Frequency: 180-600 breaths/min (3-10Hz)

Effect of HFOV on gas exchange in

ARDS patients

AJRCCM 2002; 166:801-8

Survival difference of ARDS patients

treated with HFOV or CMV
30-day: P=0.057
90-day: P=0.078

AJRCCM 2002; 166:801-8

HFOV

Complications:

Recognition of a
pneumothorax
Desiccation of secretions
Sedation and paralysis
Lack of expiratory filter

Failed to show a mortality

benefit
Combination with other
interventions ?
Chest 2007; 131:1907-1916

Adjunctive Therapy

Steroid treatment
Fluid management
Extracorporeal membrane oxygenation
(ECMO)
Nitric oxide
Others

Steroid therapy

NEJM 2006;354:1671-1684

Steroid therapy

Increase the number of ventilator-free and

shock-free days during the first 28 day
Improve oxygenation, compliance and blood
pressure
No increase in the rate of infectious
complications
Higher rate of neuromuscular weakness
Routine use of steroid is not supported
Starting steroid more than 14 days after the
onset of ARDS may increase mortality
NEJM 2006;354:1671-1684

Fluid Management

NEJM 2006;354:2564-2575

Fluid Management

NEJM 2006;354:2564-2575

Fluid Management

NEJM 2006;354:2213-24

Fluid Management

Conservative strategy improves lung

function and shortens the duration of
ventilator use and ICU stay
No significant mortality benefit
The use of pulmonary artery catheter not
routinely suggested

Extracorporeal Membrane
Oxygenation (ECMO)

No improvement on survival or time on

ventilation
Substantial risk of infection and bleeding
Not routinely recommended

Nitric Oxide

Vasodilator
Improve oxygenation and pulmonary
vascular resistance
No improvement on survival
Routine use is not recommended

Unproven Treatments

Ketoconazole
Pentoxyfilline and lisofylline
Nutritional modification
Antioxidants
Neutrophil elastase inhibition
Surfactant
Liquid ventilation
Lancet 2007; 369:1553-65

Conclusions

The only treatment that shows mortality

benefit:
lung-protective ventilation strategy
Low tidal volume (6ml/Kg), high PEEP,
adequate Pplat (<30 cmH2O)

Modalities to improve oxygenation:

Prone position, steroid, fluid treatment, steroid,

HFOV, NO

Combining other treatments:

Activated protein C, antibiotics, EGDTetc