Mechanical Ventilation

in Acute Respiratory Distress Syndrome

Case

Male / 65

Severe dyspnea, 3 days

High fever and purulent sputum

WBC: 23,000/mm3

2D-echo: EF 60%

Oxygenation under Mechanical ventilation

Mode: Controlled Mandatory Ventilation

FIO2: 80%

PEEP: 8 cmH2O

ABGA

pH 7.356

PaCO2 42.7 mmHg

PaO2 80.0 mmHg

HCO3- 29.7 mEq/L

SaO2 93.6%

Q1: Which of the following is a correct pathophysiology of hypoxemia

in this patient?

1. Decreased alveolar-capillary barrier permeability

2. Eosinophil dependent lung injury

3. A decrease in cytokines

4. Increased alveolar fluid removal

5. Heterogeneous acute lung inflammation

Summary of the Case

Acute onset of dyspnea, 3 days

Severe hypoxemia, PaO2/FIO2 = 80 / 0.8 = 100 mmHg

Bilateral opacities in a chest X-ray

Normal cardiac function

What Condition?

ARDS Acute Respiratory

Distress Syndrome

RECOMMENDED CRITERIA FOR ACUTE LUNG INJURY (ALI) AND

ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

Timing Oxygenation Chest Radiograph

Pulmonary Artery

Wedge Pressure

ALI criteria Acute onset PaO2/FIO2 300 mmHg

(regardless of

PEEP level)

Bilateral

infiltrates

seen on frontal

chest radiograph

18 mmHg when

measured or no

clinical evidence

of left atrial

hypertension

ARDS criteria Acute onset PaO2/FIO2 200 mmHg

(regardless of

PEEP level)

Bilateral

infiltrates

seen on frontal

chest radiograph

18 mmHg when

measured or no

clinical evidence

of left atrial

hypertension

www.wordle.net Bernard GR, et al. Am J Respir Crit Care Med 1994;149;818

Timing Within 1 week of a known clinical insult or new or worsening respiratory

symptoms

Chest

imaginga

Bilateral opacities—not fully explained by effusions, lobar/lung collapse,

or nodules

Origin

of edema

Respiratory failure not fully explained by cardiac failure or fluid overload

Need objective assessment (eg, echocardiography) to exclude hydrostatic

edema if no risk factor present

Oxygenationb

Mild 200 mmHg < PaO2/FIO2 300 mmHg with PEEP or CPAP 5 cmH2Oc

Moderate 100 mmHg < PaO2/FIO2 200 mmHg with PEEP 5 cmH2O

Severe PaO2/FIO2 100 mmHg with PEEP 5 cm H2O Abbreviations: CPAP, continuous positive airway pressure; FIO2, fraction of inspired oxygen; PaO2, partial pressure of arterial oxygen;

PEEP, positive end-expiratory pressure aChest radiograph or computed tomography scan. bIf altitude is higher than 1000 m, the correction factor should be calculated as follows: [PaO2/FIO2(barometric pressure/760)]. cThis may be delivered noninvasively in the mild acute respiratory distress syndrome group.

The New (Berlin) Definition of ARDS

ARDS Definition Task Force, et al. JAMA. 2012;;307:2526

Increased permeability of the alveolar-capillary barrier

Influx of protein-rich edema fluid into the air-space

Neutrophil dependent lung injury

Cytokines

Disrupt normal epithelial fluid transport, impairing the

removal of fluid

Abnormalities in the production, composition, and

function of surfactant

Abnormalities of the coagulation system

Ware LB, et al. N Engl J Med 2000;342:1334

Q1: Which of the following is a correct pathophysiology of hypoxemia

in this patient?

1. Decreased permeability of the alveolar-capillary barrier

2. Eosinophil dependent lung injury

3. Decrease in cytokines

4. Increased alveolar fluid removal

5. Heterogeneous acute lung inflammation

Expiration Inspiration

Mechanical Ventilation with traditional high tidal volume

and zero PEEP Physical stretch

Shearing force

Multiple Organ Dysfunction

Syndrome

1. Spillover

2. Translocation

Lung Protective Ventilation Strategies

Low Tidal Volume

6~8 mL/Kg of predicted body weight

Plateau Pr. < 30 cmH2O

High (adequate)

PEEP

Shearing force

Heterogeneity

Homogeneity

Prone Position Ventilation

Recruitment Maneuver

In a Narrow Sense

Lung protective ventilation strategy

Low tidal volume

High-PEEP

Prone position

Recruitment maneuver

In a Broad Sense

Q2: Which of the following mechanical ventilation strategies for ARDS

is a recommended therapy based on strong clinical evidence?

1. Low tidal volume

2. High-PEEP

3. Prone position

4. Recruitment maneuver

5. High frequency ventilation

A, recommended therapy based on strong clinical evidence from randomized clinical trials; B, recommended therapy based on

supportive but limited clinical data; C, indeterminate evidence: recommended only as alternative therapy; D, not recommended based

on clinical evidence against efficacy of therapy.

Low tidal

volume

High PEEP Prone position

ventilation

Recruitment

maneuvers

A

B

C

D

recommended therapy based on strong clinical

evidence from randomized clinical trials A

indeterminate evidence: recommended only

as alternative therapy C

Evidence based recommendations for LPV strategies

Q2: Which of the following mechanical ventilation strategies for ARDS

is a recommended therapy based on strong clinical evidence?

1. Low tidal volume

2. High-PEEP

3. Prone position

4. Recruitment maneuver

5. High frequency ventilation

Review of Evidence

Low Tidal Volume

Different ONLY in

Traditional

tidal volume

Lower

tidal volume

Tidal

volume 12 mL/Kg* 6 mL/Kg*

Plateau

pressure 50 cmH2O 30 cmH2O

*Kg of predicted body weight

ARDS Network Trial: Lower Tidal Volume vs. Traditional Tidal Volume

VARIABLE

GROUP

RECEIVING

LOWER TIDAL

VOLUMES

GROUP

RECEIVING

TRADITIONAL

TIDAL VOLUMES

P VALUE

DEATH before discharge home

and breathing without

assistance (%) 31.0 39.8 0.007

Breathing without assistance

by day 28 (%) 65.7 55.0 <0.001

No. of ventilator-free days,

days 1 to 28 1211 1011 0.007

No. of days without failure

of nonpulmonary organs

or systems*, days 1 to 28 1511 1211 0.006

Plasma interleukin-6** on day 3,

pg/mL 2.00.5 2.30.7 0.002 ** Interleukin-6, IL-6

: a representative

pro-inflammatory

cytokine

*without MODS

Main Outcomes of ARDS Network Trial

A, recommended therapy based on strong clinical evidence from randomized clinical trials; B, recommended therapy based on

supportive but limited clinical data; C, indeterminate evidence: recommended only as alternative therapy; D, not recommended based

on clinical evidence against efficacy of therapy.

Low tidal

volume

High PEEP Prone position

ventilation

Recruitment

maneuvers

A

B

C

D

recommended therapy based on strong clinical

evidence from randomized clinical trials A

Evidence based recommendations for LPV strategies

High PEEP

Clinical trials Mortality

p High PEEP Control

ALVEOLI ARDS network, USA

N Engl J Med 2004;351:327-36 27.5% 24.9% 0.48

Not

Significant

LOVS Canada, Australia,

and Saudi Arabia

JAMA 2008;299:637-45 36.4% 40.4% 0.19

EXPRESS France

JAMA 2008;299:646-55 27.8% 31.2% 0.31

Mortality in Large-scaled clinical trials

Oxygenation in Large-scaled clinical trials

Clinical trials PaO2/FIO2 at Day 7, mmHg

p High PEEP Control

ALVEOLI 218

> 181 <0.05

Significant LOVS 212.7 180.8 <0.001

EXPRESS 206 184 0.03

NO Effect on Mortality Gain

Only Improves Oxygenation

Prone Position Ventilation

Q3: Which is right among these descriptions

for prone position ventilation?

1. Increases heterogeneity of lung inflammation

2. Decreases mortality in all ARDS patients

3. Improves oxygenation

4. Decreases ventilation-perfusion match

5. Increases ventilator-induced lung injury

Supine

Changes from Supine to Prone Position

Prone

1

2

Homogeneity

End-expiratory lung

volume

Ventilation-perfusion

matching

Regional changes in

ventilation

Alterations in chest-wall

mechanics

Ventilator-induced

Lung Injury

Watanabe I, et al. Crit Care Med 2002;30:1799

Beuret P, et al. Intensive Care Med 2002;28:564

Guerin C, et al. JAMA 2004;292:2379

Curley MA, et al. JAMA 2005;294:229

Voggenreiter G, et al. J Trauma 2005;59:333

Papazian L, et al. Crit Care Med 2005;33:2162

Mancebo J, et al. Am J Respir Crit Care Med 2006;173:1233

Demory D, et al. Crit Care Med 2007;35:106

Chan MC, et al. J Formos Med Assoc 2007;106:708

Ibrahim TS, et al. J Med Sci 2007;7:390

Prone ventilation reduces mortality in patients with acute respiratory

failure and severe hypoxemia: sytematic review and meta-analysis

Sud S, et al. Intensive Care Med 2010;36:585

Systematic Review and Meta-analysis

Gattinoni L, et al.

N Engl J Med

2001;345:568

Taccone P, et al.

JAMA

2009;302:1977

Clinical Evidence

Oxygenation

Improves in

Prone Position

Prone Higher

Day 1

Day 2

Day 3

p=0.54

p=0.35

Mortalities in All Patients and PaO2/FIO2 100 mmHg subgroup

Not

Significant

p=0.01

Reduction

in Mortality

Mortality in Severe Hypoxemia, PaO2/FIO2 < 100 mmHg subgroup

Favors prone

Improves Oxygenation

Can reduce Mortality

in a severe subset of ARDS

by meta-analysis

1. Increases heterogeneity of lung inflammation

2. Decreases mortality in all ARDS patients

3. Improves oxygenation

4. Decreases ventilation-perfusion match

5. Increases ventilator-induced lung injury

Q3: Which is right among these descriptions

for prone position ventilation?

Recruitment Maneuver

CPAP

Extended Sigh

Recruitment maneuver

Similar with

Prone Position

Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006667

28 day mortality

ICU mortality

In hospital mortality

Not

Significant

Not

Significant

Not

Significant

A, recommended therapy based on strong clinical evidence from randomized clinical trials; B, recommended therapy based on

supportive but limited clinical data; C, indeterminate evidence: recommended only as alternative therapy; D, not recommended based

on clinical evidence against efficacy of therapy.

Low tidal

volume

High PEEP Prone position

ventilation

Recruitment

maneuvers

A

B

C

D

Evidence based recommendations for LPV strategies

indeterminate evidence: recommended only

as alternative therapy C

But, evidence is changing…..

A, recommended therapy based on strong clinical evidence from randomized clinical trials; B, recommended therapy based on

supportive but limited clinical data; C, indeterminate evidence: recommended only as alternative therapy; D, not recommended based

on clinical evidence against efficacy of therapy.

Low tidal

volume

High PEEP Prone position

ventilation

Recruitment

maneuvers

A

B

C

D

Insufficient Evidence

Recent

RCT Systematic

Review

Evidence is changing…..

Recent Feature Meta-analysis for High PEEP

Clinical trials

ALVEOLI ARDS network, USA

N Engl J Med 2004;351:327-36

LOVS Canada, Australia, and Saudi Arabia

JAMA 2008;299:637-45

EXPRESS France

JAMA 2008;299:646-55

Systematic Review

Meta-analysis

ALI non-ARDS

Hospital Mortality 0.049

ICU Mortality 0.001 <

Rescue Therapy < <

<.001

<.001

<

> 0.004

With ARDS

Days with

unassisted

breathing

Stratified by Presence of ARDS at Baseline

Can Improve Mortality

in Severe ARDS

Recent Feature Clinical Trial for Prone Position Ventilation

Prone Positioning in Severe Acute Respiratory Distress Syndrome

PROSEVA study

Guerin C, et al. N Engl J Med 2013;368:2159

Enroll Criteria Enroll Time

Very Severe ARDS

: a Pao2:Fio2 ratio of < 150 mmHg, with

an Fio2 of ≥ 60%

a PEEP of ≥ 5 cmH2O

Less than 36 hours

: earlier than in prior studies

Supine

Prone

At least

16 Hours/Day 28 days

Main Results : 28-day and 90-day mortalities

>

>

* *

* *

*

*

Significant

Significant

Main Results : Other outcomes

<

>

< <

*

*

* *

*

*

*

Significant

Significant

Significant

*

Reduces Mortality

in a Severe subset of ARDS

New evidence is emerging and

Clinical evidence grade of medical strategies are

continuously changing.

Conclusions

3 Always Keep Up With Changing Evidence

1 Essential MV strategy for

ARDS patients Low Tidal Volume

2 Should be considered in Selected

Clinical Conditions

esp. Severe ARDS patients

High PEEP

Prone Position Ventilation

Recruitment Maneuver

Thank You For Your Attention