Download - 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
9Am 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.
10Am 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 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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