CORTICOSTEROIDS IN TREATMENT OF ACUTE RESPIRATORY DISTRESS SYNDROME

CONTENT:
DEFINITION AND DIAGNOSIS
ETIOLOGY PATHOGENESIS TREATMENT CONCLUSIONS

DEFINITION AND DIAGNOSIS

Bernard at al (The American-European Consensus

Conference on ARDS: definitions, mechanisms, relevant outcomes,and clinical trial coordination. Am J Respir Crit Care Med 1994)

A clinical syndrome:
Severe Diffuse

dyspnea of rapid onset. pulmonary infiltrate /Rx

Pulmonary-artery

wedge pressure <18mmHg or the absence of clinical evidence of left atrial hypertension FiO2 < 300 ALI FiO2 < 200 ARDS
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PaO2/ PaO2/

ETIOLOGY The NEJM 5/2000

PATHOGENESIS
EXUDATIVE PROLIFERATIVE FIBROTIC

EDEMA HYALINE MEMBRANES

INTERSTITIALS INFLAMMATION INTERSTITIAL FIBROSIS

FIBROSIS

DAY

0-7
The NEJM 5/2000

14

21..

PATHOGENESIS(cont)
The NEJM 5/2000

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 acid Inhibitors.

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, plateletactivating factor, and nitric oxide, three additional key molecules in the inflammatory pathway. Inhibitory effect on fibrogenesis and the expression of adhesion molecules.
Am 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 intraacinar 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 BAL cytokines TNFa , IL-1b, IL-6, and IL-8 is reported in ARDS nonsurvivors
Am J Respir Crit Care Med Vol 160. pp 10791100, 1999
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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.
Am J Respir Crit Care Med Vol 160. pp 10791100, 1999
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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 of corticosteroids administered early in the disease. There is evidence that corticosteroids may be beneficial in the fibroproliferative phase, or late phase of ARDS
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EVIDENCE BASE(cont)
Hooper and Kearl (Chest 97:138143.) 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, doubleblind 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 of 4) in the nonresponders.
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EVIDENCE BASE(cont)
G. Umberto Meduri and ass. (CHEST 2007; 131:954963 RCT double-blind in 91 patients Significant changes were observed for
Pa O2/FIO2 ratio 262 versus 148, p<0.001 LIS 1.7 versus 3.0, p<0.001 mean pulmonary arterypressure 22.5 versus

30.0 mm Hg, p< 0.01 MODS score 0.7 versus 1.8, p<0.001 in the corticosteroid-treated group versus the placebo group.
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EVIDENCE BASE(cont)
Rong-chang Chen and ass. (CHEST 2006;

129:14411452) Retrospective study: 401 of 1,278 SARS cases treated in Guangzhou China between 12/2002 and 6/2003. Univariate analysis and adjustment for possible confounders, treatment with corticosteroid was shown contributing to lower overall mortality, instant mortality, and shorter hospitalization stay (p<0.05).
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CONCLUSION
There 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 of ARDS, 7-14 days, without evidence of infection.
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REFERENCES
1. 2. 3. 4. 5. 6. 7. 8. 9.

Bernard GR et al. The American European Consensus Conference on ARDS. Am J Respir Crit Care Med 1994; 149: 818 824 Meduri et al. Corticosteroid rescue treatment of progressive fibroproliferation in late ARDS. Patterns of response and predictors of outcome. Chest 1994; 105: 1516 1527 Meduri GU et al. Effect of prolonged methylprednisoloine therapy in unresolving acute respiratory distress syndrome. A randomized controlled trial. JAMA 1998; 280: 159 165 Brun-Buisson C and Brochard L. Corticosteroid therapy in acute respiratory distress syndrome. Better late than never? JAMA 1998; 280: 182 183 New Management strategies in ARDS. Editor Levy MM. Critical Care Clinics, January 2002 JAMA -- Abstract Improved survival of patients with acute respiratory distress syndrome (ARDS) 1983-1993, January 25, 1995, Milberg et al_ 273 (4) 306_files NEJM -- Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome_files Use of corticosteroids in acute lung injury and ac___[Crit Care Med_ 2009] - PubMed Result_files 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: January 2008 | This Topic Last Updated: May 8, 2007
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THANK YOU VERY MUCH FOR YOUR ATTENTION AND LISTENING!!!

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