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ARDS. Definition and Epidemiology. Vietnam war. ARDS. Ashbaugh et al. Acute respiratory distress in adults . Lancet 1967. ALI/ARDS. acute onset bilateral CXR infiltrates P/F ratio <200 (ALI <300) pulmonary artery occlusion pressure < 18 mm Hg

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slide2

ARDS

Definition and Epidemiology.

slide3

Vietnam war

ARDS

Ashbaughet al.

Acute respiratorydistress in adults.

Lancet 1967

.

slide4

ALI/ARDS

  • acute onset
  • bilateral CXR infiltrates
  • P/F ratio <200 (ALI <300)
  • pulmonary artery occlusion pressure < 18 mm Hg
  • or absence of clinical evidence of left atrial hypertension

AECC 1994

slide5

DEFINITION

Esteban A et al.

Ann Intern Med. 2004

In a series of autopsy patients, the accuracy of the American-European Consensus Conference definition of ARDS was only moderate.

slide8

incidence

ALI: 20 to 50 cases per 100,000

ARDS: 3 to 8 cases per 100,000

recent study

ARDS and ALI: 22 cases/100,000

Rubenfeld GD et al. NEJM 2005

slide13

ARDS

How can we improve the diagnosis and assess the risk of death.

slide14

This meta-analysis provides a unique ranking of plasma biomarkers according to their strength of association with ARDS diagnosis or mortality. The relative performance of biomarkers among studies shown in this ranking may help to improve acute respiratory distress syndrome diagnosis and outcome prediction

Critical Care Medicine 2014

ards diagnosis
ARDS: diagnosis

Critical Care Medicine 2014

ards prognosis
ARDS: prognosis

Critical Care Medicine 2014

slide17

Rationale: PaO₂/Fio₂ may increase when Fio2 is raised from moderate to high levels, suggesting that patients with similar PaO₂/Fio₂ ratios but different Fio₂ levels have different risks of mortality

Conclusions: the addition of baseline Fio2 to PaO₂/Fio₂ could be used to identify subsets of patients with low or high mortality

slide19

ARDS

How can we decrease mortality

slide20

ARDS

How can we decrease mortality:

New drugs

New management strategies

New ventilatory strategies

slide31

Pulmonary vascular leakage occurs early in acute respiratory distress syndrome (ARDS). Mortality is high (35-45%), but no effective pharmacotherapy exists. Production of anti-inflammatory adenosine by ecto-5'-nucleotidase (CD73) helps maintain endothelial barrier function. We tested whether interferon-beta-1a (IFN-beta-1a), which increases CD73 synthesis, can reduce vascular leakage and mortality in patients with ARDS.

slide34

Conclusions: FP-1201 up-regulates human lung CD73 expression, and is associated with a reduction in 28-day mortality in patients with ARDS. Our findings need to be substantiated in large, prospective randomised trials, but suggest that FP-1201 could be the first effective, mechanistically targeted, disease-specific pharmacotherapy for patients with ARDS

slide35

ARDS

How can we decrease mortality:

New drugs

New management strategies

New ventilatory strategies

New ventilatory options

slide39

ARDS

How can we decrease mortality:

New drugs

New management strategies

New ventilatory strategies

New ventilatory options

slide41

VILI: lung edema

RATS

Dreyfuss D et al. Am Rev RespirDis 1988

slide42

VILI: biotrauma

RATS

Tremblay L et al. JCI 1997

slide43

RABBITS

Low TV high PEEP=noninjurious

vs High TV low PEEP=injurious

slide45

Ventilator-induced lung injury

Imai Y. Crit Care Med 2005; 33:S129–S134

slide46

the search of a new “DOGMA”

HOW TO VENTILATE TO PREVENT VILI

slide48

861 PATIENTS WITH ALI/ARDS

* (p = 0.007)

12 ml/Kg 6 ml/Kg

NIH ARDS network, NEJM 2000; 342: 1301-1308

plasma cytokine levels
Plasma Cytokine Levels

Stuber F, Putensen C et al: Intensive Care Med 2003

slide50

Avoidrecruitment and derecruitment

Keeping VT low and PEEP high

slide52

time1

time2

time1

time2

Entry

Entry

Ranieri VM et al JAMA 1999 282: 54-61

slide53
PEEP

Briel M, et al. Jama 2010

slide57

High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome

Roberto Santa Cruz,*, Juan Ignacio Rojas, Rolando Nervi, Roberto Heredia, AgustínCiapponi

Authors' conclusions

Available evidence indicates that high levels of PEEP, as compared with low levels, did not reduce mortality before hospital discharge. The data also show that high levels of PEEP produced no significant difference in the risk of barotrauma, but rather improved participants' oxygenation to the first, third, and seventh days. This review indicates that the included studies were characterized by clinical heterogeneity.  

slide58

EI

Low VT and plateau <30 cmH20

CLUSTER # 1

Delta vol (ml)

120

60

EE

40

0

-1000

-900

-500

-100

-20

Hounsfield Units

Hyperinflated

Normally aerated

Poorly aerated

Not aerated

Terragni and coworkers: Am J Respir Crit Care Med, 2007

slide59

EI

Low VT and plateau <30 cmH20

Delta vol (ml)

CLUSTER # 2

120

80

EE

40

0

-1000

-900

-500

-100

-20

Hounsfield Units

Hyperinflated

Normally aerated

Poorly aerated

Not aerated

Terragni and coworkers: Am J Respir Crit Care Med, 2007

slide67

Ventilator Settings, Respiratory-System Mechanics, and Results of Arterial Blood Gas Measurements at the Time of Inclusion in the Study.

Guérin C et al. N Engl J Med 2013;368:2159-2168

slide68

Kaplan–Meier Plot of the Probability of Survival from Randomization to Day 90.

Guérin C et al. N Engl J Med 2013;368:2159-2168

slide69

WE MISS MANY OF THESE PATIENTS

N D Ferguson et al. Critical Care 2007

slide70

ECMO

ECCO2-R

HFO

iNO

Neuromuscular Blockade

Increasing Intensity of Intervention

Prone Positioning

Low – Moderate PEEP

Higher PEEP

NIV

Low Tidal Volume Ventilation

Increasing Severity of Lung Injury

Mild ARDS

Moderate ARDS

Severe ARDS

PaO2/FiO2

300

250

200

150

100

50

slide74

ARDS

How can we decrease mortality:

New drugs

New management strategies

New ventilatory strategies

New ventilatory options

slide78

OUTCOME

Peek GJ, et al. Lancet 2009

slide80

CO2 REMOVAL TO PREVENT VILI

  • ARDS patients are exposed to VILI despite low VT ventilation (1/3 of patients)
  • High PaCO2 and low pH may limit the application of low VT ventilation

combine CO2 removal to protective ventilation to:

  • protect the lung by further reducing VT
  • manage acidosis
  • minimal or no side effects
slide82

10 6

0

STRESS NO STRESS

slide84

“ARDSNet” 28≤PPLAT≤30

P = 0.001

P = 0.001

“ARDSNet” 25<PPLAT<28

IL-6 (pg/ml)

n.s.

n.s.

Entry

Entry

72 hrs

LOWER ARDSNet/CO2 removal

72 hrs ARDSNet

slide85
CONCLUSIONS I
  • ARDS is still associated wit a very high mortality rate
  • Predictors of poor prognosis are: high dead-space, high FiO2 requirements at baseline and an increase in specific plasmatic biomarkers
  • No drugs have been shown to influence the mortality rate. New treatments however are presently on the pipeline
  • No specific approach (i.e. conservative fluid management, invasive monitoring) is superior to others
slide86
CONCLUSIONS II
  • Invasive MV may induce VILI, including apoptosis that can be minimized by specific approach (i.e. low tidal volume and specific PEEP titration using the esophageal balloon)
  • A trial of NIV may be provided to the less hypoxic patients
  • Prone positioning may improve the chance of survival
  • ECMO and extracorporeal CO2 removal may be effective techniques for decreasing mortality in patients non-respondent to MV or reducing the risk of VILI, respectively.