What Is New in ARDS ?

Lluis Blanch MD PhDSenior Critical Care Center

Scientific Director Corporació Parc TaulíUniversitat Autónoma de Barcelona

Sabadell, Spain

11th Annual CongressTurkish Thoracic Society

Belek-Antalya. April 23 – 27, 2008

What Is New in ARDS ?

• Definition • Types • Therapy • Mechanical Ventilation• Practice & Organization

Aim of the talk: Aim of the talk: To reveal novel solutions for problems during mechanical ventilation and supportive therapy in ARDS.

What Is New in ARDS ?

• Definition

• Types

• Therapy

• Mechanical Ventilation

• Practice & Organization

Fan E, et al. JAMA 2005;294:2889-96Fan E, et al. JAMA 2005;294:2889-96

Diagnostic Criteria for ARDSDiagnostic Criteria for ARDS

The definitions of ARDS and ALI require the use of standard ventilator settings to ensure that patients with consistent levels of lung injury are properly classified as having ARDS or ALI

In 170 pts meeting ARDS criteria (PaO2/FiO2 < 200 mmHg) diferent combinations of FiO2 & PEEP at VT 7 ml/kg were obtained in Day 0 and in Day 1.

PaO2/FiO2

156 mmHg PaO2/FiO2

247 mmHg

PaO2/FiO2

370 mmHg

Nuckton TJ et al. N Engl J Med 2002; 346:1281.Nuckton TJ et al. N Engl J Med 2002; 346:1281.

Observed Mortality According to the Quintile of Observed Mortality According to the Quintile of Dead-Space Fraction in 179 Patients with ARDS Dead-Space Fraction in 179 Patients with ARDS

Mechanisms:Mechanisms:

1- Injury of pulmonary capillaries by thrombotic and inflammatory factors.

2- Obstruction of pulmonary blood flow in pulmonary circulation.

3- Lung areas with high V/Q ratio (impaired CO2 excretion)

Exhaled Volume

PCO2

Phase I

Phase II

Phase IIIPaCO2

PetCO2

EffectiveAlveolar Ventilation

D

S

adm 2 4h 48h

0,2

0,3

0,4

0,5

0,6

0,7

VAE/VT

* #

P = 0.013

Ns

0.2

0.4

0.5

0.6

0.7

0.3

Adm 48 h24 h

**

ns

p<0.05

VAE/VT SD

SS 73%SS 73%SP 93%SP 93%

What Is New in ARDS ?

• Definition

• Types

• Therapy

• Mechanical Ventilation

• Practice & Organization

Severe intra-alveolar infiltrates, deposition of hyaline membranes, vascular congestion and microthrombi.

Human ARDS

Matute-Bello G, et al. http://www.thoracic.orgMatute-Bello G, et al. http://www.thoracic.org

LPSinhaled

OAIi.v.

CLPsepsis

Models of ARDS

American–European Consensus Conference Definition and Sensitivity, Specificity, and Likelihood Ratios Assessed in Patients

Who Died in the Intensive Care UnitReference Standard: Diffuse Alveolar Damage at Autopsy

The accuracy of the American–European Consensus Conference definition of ARDS was only moderate. The definition was more accurate for patients

with extrapulmonary risk factors than for patients with pulmonary risk factors.

Mortality in Relation to the Percentage of Mortality in Relation to the Percentage of PPotentially otentially RRecruitable ecruitable LLungung

PRL: difference between non-aerated tissue between 5 and 45 cmH2O PEEP

DirectDirectIndirectIndirectPulmonaryPulmonaryExtrapulmonaryExtrapulmonaryMedicalMedicalSurgicalSurgicalPrimaryPrimarySecondarySecondary

Human ARDSHuman ARDS

??

What Is New in ARDS ?

• Definition

• Types

• Therapy

• Mechanical Ventilation

• Practice & Organization

Effects of NO on MortalityEffects of NO on Mortality

Effects of NO on PaO2/FiO2Effects of NO on PaO2/FiO2

Effects of NO onEffects of NO onRenal DysfunctionRenal Dysfunction

Day 28Day 28Ventilator-free daysVentilator-free daysMortality %Mortality %

CMVCMV13 13 9 9

1515

Low doseLow dosePLV groupPLV group

7 7 9* 9*2626

High doseHigh dosePLV groupPLV group

10 10 9* 9*1919

311 pts with ARDS311 pts with ARDSAt Randomization:At Randomization:VT 9 VT 9 ml/kgml/kg, PEEP 14 , PEEP 14 cmHcmH22OO

Pplat 30 Pplat 30 cmHcmH22OO

Rationale: Persistent ARDS is characterized by ongoing inflammation, parenchymal-cell proliferation and disordered deposition of collagen all of which may be responsive to corticosteroid therapy.

Main Outcome VariablesMain Outcome Variables

Prolonged methylprednisolone treatment of greater than 1 week’s duration after removing patients randomized after day

14.

Steroid Treatment in ARDS

Meduri GU Intensive Care Med 2008; 34:61-69

Correct use of prolonged glucocorticoid treatment is associatedwith a substantial and significant improvement in meaningfulpatient-centered outcome variables.Surveillance measures:1) intensive infection vigilance2) avoidance of paralytic agents3) avoidance of rebound inflammation with premature discontinuation

of treatment

Pulmonary Edema Formation in Congestive Heart Failure & ARDS

Piantadosi CA, Schwartz DA. Ann Intern Med 2004; 141:460-470.Piantadosi CA, Schwartz DA. Ann Intern Med 2004; 141:460-470.

B-agonists can can enhance alveolar fluid clearance through the up-regulation of sodium transport mechanisms located on the alveolar epithelial cells.

Objective & Methods: manipulation of alveolar fluid clearance with B-agonists can accelerate the resolution of alveolar edema.

40 pts.with ALI/ARDS were randomized to treatment with intravenous salbutamol (15 g kg-1 h-1) or placebo for 7 d.

Results: Patients in the salbutamol group had lower extravascular lung water, plateau pressure and LIS at day 7 compared with placebo group.

Main Outcome Variables

Prone Positioning in Critically Ill PatientsProne Positioning in Critically Ill Patients

Am J Resp Crit Care Med 2006;173:1233-39

ARDS patientsFiO2 0.85, VT 8 ml/kg, PEEP 12SAPS 38 – 42 & Diffuse InfiltratesEnrolled 48 hProne 20 h/day

A total of 718 turning procedures were done and PP was applied for a mean of 17 h/day. A total of 28

complications were reported, most rapidly reversible.

Probability

of

Survival

10 20 30 40 50 60

Days After Randomization

0

20

40

60

80

100

SUPINE

PRONE

p= 0.27

Spanish Trial: Kaplan-Meier Estimates of ICU Survival (up to 60 days)

25% ↓ Mortality in Prone

What Is New in ARDS ?

• Definition

• Types

• Therapy

• Mechanical Ventilation

• Practice & Organization

ARDSNet: VT 6 ml/kg & Pplat < 30 cm H2O

PaO2/FiO2 149±34 102±24 0,009

Pplat 25,5±0.528,9±0.

90,006

PEEP 9,3±2.312,6±2.

50,005

Days off MV

7±8 1±2 0,01

More Protected (n=20) Less Protected (n=10)

JAMA, Feb.13, 2008;209:646-55 JAMA, Feb.13, 2008;209:646-55

ALI pts. (n=767)Minimal Distension (n=382): - VT 6 ml/kg PBW - PEEP 5 – 9 cmH2OIncreased Recruitment (n=385) - VT 6 ml/kg PBW - PEEP to reach Pplat 28-30 cmH2O

Mortality: MD 31.2%, IR 27.8 %, p=.31Vent. Free Days: MD 3, IR 7, p=.04Organ Failure Free Days: MD 2, IR 6, p=.04IR assocaited with better PaO2, Crs, less adjunctive therapies and larger fluid requir.

JAMA, Feb.13, 2008;209:637-45 JAMA, Feb.13, 2008;209:637-45

ALI pts. & PaO2 < 250 mmHg (n=983)Control Ventilation (n=508): - VT 6 ml/kg PBW, Pplat < 30 cmH2O, - PEEP mean 9.8 cmH2O -Table-Lung Open Ventilation (n=475) - VT 6 ml/kg PBW, Pplat < 40 cmH2O - PEEP mean 14.6 cmH2O -Table- & RMs.

Mortality: CV 40.4%, LOV 36.4%, p=.19Refractory Hipoxemia: CV 10%, LOV 5% p=.01Rescue Therapies: CV 13%, LOV 8%, p=.05

RM associated with a complication in 22.1% of p.

What Is New in ARDS ?

• Definition

• Types

• Therapy

• Mechanical Ventilation

• Practice & Organization

Assessing practice changes

1998 (1.383 p.) 2004 (1.675 p.)

Thank Youlblanch@tauli.cat