acute respiratory distress

7/29/2019 Acute Respiratory Distress

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CORTICOSTEROIDS INTREATMENT OF ACUTE

RESPIRATORY DISTRESS

SYNDROME

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CONTENT:

DEFINITION AND DIAGNOSIS

ETIOLOGY

PATHOGENESIS

TREATMENT

CONCLUSIONS

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DEFINITION AND DIAGNOSIS Bernard at al(The American-European Consensus

Conference on ARDS: definitions, mechanisms, relevantoutcomes,and clinical trial coordination.Am J Respir CritCare Med 1994)

A clinical syndrome:

Severe dyspnea of rapid onset.

Diffuse pulmonary infiltrate /Rx

Pulmonary-artery wedge pressure


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ETIOLOGY The NEJM 5/2000

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PATHOGENESIS

EXUDATIVE PROLIFERATIVE

DAY 0-7 14

FIBROTIC

21..

EDEMA

HYALINEMEMBRANES

INTERSTITIALSINFLAMMATION

INTERSTITIALFIBROSIS

FIBROSIS

The NEJ M 5/2000

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PATHOGENESIS(cont)The NEJ M 5/2000

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TREATMENT

General: ICU, prophylaxis VTE, GB, CVC, inf,nutrition.

Mechanical ventilation using relatively low VT.

Surfactant.

Extracorporeal techniques: Oxygenation(ECMO),

CO2 removal.

Antiinflammatory therapies : Corticosteroids,PG E1,

Neutrophil elastase inhibitors, Arachidonic acidInhibitors.

CORTICOSTEROIDS

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PATHOGENESIS Glucocorticoids regulate the host defense response

by

Inhibit the host defense response and inhibit the

transcription of TNF, IL-1, IL-2, and IL-6. Suppress the synthesis of phospholipase-a2,cox-2,

and nitric oxide synthase-1 genes,

Decreasing the production of prostanoids, platelet-

activating factor, and nitric oxide, three additionalkey molecules in the inflammatory pathway.

Inhibitory effect on fibrogenesis and the expression

of adhesion molecules.

8Am J Respir Crit Care Med Vol 160. pp 10791100, 1999


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PATHOGENESIS(cont) Fibroproliferation is a reaction reaprative and

replace the damaged cells by accumulation

products airspaces and walls of the intra-

acinar microvessels. Nonsurvivors of ARDS have higher initial plasma

and BAL levels of TNFa , IL-1b, IL-2, IL-4, IL-6,

and IL-8 compared with survivors.

Persistent elevation of plasma and BALcytokines TNFa , IL-1b, IL-6, and IL-8 is reported

in ARDS nonsurvivors



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PATHOGENESIS(cont) Medurri: The surviving patients treated with

corticosteroids had significant reductions in

plasma and BAL TNFa , IL-1b, IL-6, and IL-8.

The decreases in the cytokine levels after 5 to 14 d

of steroid treatment.

Meduri: significant decreases /plasma and BAL

PINP and PIIINP in patients treated with cortocoid,

whereas no changes in patients receiving placebo.

Decreases in plasma and BAL PINP and PIIINP

levels correlated with improvements in LIS and

PaO2/FIO2.



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EVIDENCE BASE

A number of trials have demonstrated that

patients with ARDS do not benefit from a

short course of large doses ofcorticosteroids administered early in the

disease.

There is evidence that corticosteroids maybe beneficial in the fibroproliferative phase,

or late phase of ARDS

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EVIDENCE BASE(cont)

Hooper and Kearl (Chest97:138143.) 26

patients who were treated with corticosteroids for

ARDS. Improve in respiratory parameters.

Survival 81% (21 of 26).

3 patients died of MOD

1 died of a cardiac arrhythmia,

and 1 died of systemic candidiasis

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EVIDENCE BASE(cont) Biffl and cs (Am. J. Surg. 170:591596) 6 patients

with persistent, severe ARDS failing CMV treated

with methylprednisolone 1-2 mg/kg every 6 h

(PaO2/FIO2) improved from 84 to 172 (p< 0.01) LIS decreased from 3.6 to 2.9 (p< 0.01) d7.

Overall survival was 83% (5 of 6).

The mean duration of corticosteroid therapy was

21.3 d

1 patient developed a S. aureus lung abscess and

2 patients had catheter-related sepsis.

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EVIDENCE BASE(cont) G. Umberto Meduri and ass. (JAMA. 1998;280:159-

165)4 ICU: 24 patients 1994 - 1996 RCT, double-blind

By Day 7 of treatment PaO2/FIO2 increased from 164 to 234 (p=0.0004)

LIS decreased from 3.0 to 2.1 (p= 0.001)

Overall survival rate was 72% (18 of 25).

ICU survival 87% (13 of 15) in rapid responders,83% (5 of 6) in delayed responders, and 25% (1 of4) in the nonresponders.

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EVIDENCE BASE(cont) G. Umberto Meduri and ass.(CHEST 2007;

131:954963RCT double-blind in 91 patients

Significant changes were observed for

Pa O2/FIO2 ratio 262 versus 148, p


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Rong-chang Chen and ass. (CHEST 2006;129:14411452)

Retrospective study: 401 of 1,278 SARS

cases treated in Guangzhou China between12/2002 and 6/2003.

Univariate analysis and adjustment for possible

confounders, treatment with corticosteroid wasshown contributing to lower overall mortality,

instant mortality, and shorter hospitalization

stay (p


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CONCLUSIONThere is no really specific therapy for ARDS.

There are more and more novel therapies for

the acute respiratory distress syndrome.Nowaday, the new points are based on

clinical evidences, we should give

corticosteroid in the fibroproliferative phase ofARDS, 7-14 days, without evidence ofinfection.

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REFERENCES1. Bernard GR et al. The American European Consensus Conference on

ARDS. Am J Respir Crit Care Med 1994; 149: 818 8242. Meduri et al. Corticosteroid rescue treatment of progressive

fibroproliferation in late ARDS. Patterns of response and predictors ofoutcome. Chest 1994; 105: 1516 1527

3. Meduri GU et al. Effect of prolonged methylprednisoloine therapy inunresolving acute respiratory distress syndrome. A randomized controlledtrial. JAMA 1998; 280: 159 165

4. Brun-Buisson C and Brochard L. Corticosteroid therapy in acuterespiratory distress syndrome. Better late than never? JAMA 1998; 280:182 183

5. New Management strategies in ARDS. Editor Levy MM. Critical CareClinics, January 2002

6. JAMA -- Abstract Improved survival of patients with acute respiratorydistress syndrome (ARDS) 1983-1993, January 25, 1995, Milberg et al_273 (4) 306_files

7. NEJM -- Efficacy and Safety of Corticosteroids for Persistent AcuteRespiratory Distress Syndrome_files8. Use of corticosteroids in acute lung injury and ac___[Crit Care Med_

2009] - PubMed Result_files9. Novel therapies for the acute respiratory distress syndrome -Author: Mark

D Siegel, MD Section Editor: Polly E Parsons, MD Deputy Editors:Kevin C Wilson, MD - Last literature review version 16.1: January2008 | This Topic Last Updated: May 8, 2007

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