Critical Appraisal Topics Outline
Title: There are still no adequate studies addressing the use of corticosteroids in adult respiratory distress
syndrome.
Clinical bottom line:
Methylprednisolone-induced down-regulation of systemic inflammation was associated
with significant improvement in pulmonary and extrapulmonary organ dysfunction and
reduction in duration of mechanical ventilation and ICU length of stay because
systemic inflammation-induced glucocorticoid receptor resistance and/or insensitivity is an acquired,
generalized process central to the pathogenesis of unresolving ARDS that is potentially reversed by
quantitatively adequate and prolonged glucocorticoid supplementation .
Citation/s: ARDS with steroid treatment is associated with a significant improvement in
pulmonary and extrapulmonary organ dysfunction and a reduction in duration of mechanical
ventilation and ICU length of stay
Lead author's name and fax:
G. Umberto Meduri, MD, FCCP,
Emmel Golden, MD,
Amado X. Freire, MD, MPH, FCCP,
Edwin Taylor, MD,
Muhammad Zaman, MD,
Stephanie J. Carson, RN,
Mary Gibson, RN, and
Reba Umberger, RN, MS
Three-part Clinical Question:
個案病歷號：1308XXX
情境重點簡述：patient happened cardiopulmonary distress s/p resuscitation and aspiration
pneumonia leading to ARDS(pulmonary sepsis) at the second day of admission
P:
ARDS (pulmonary sepsis)
I:
ARDS with steroid treatment
C: ARDS without steroid treatment
O: mortality
Type of question: Intervention
Search Terms & Strategy:
Database: Pubmed
Key words & Search strategy: ARDS(acute respiratory distress syndrome) and corticosteroid
and mortality
1.
2.
3.
4.
Pub med  MeSH ARDS(acute respiratory distress syndrome)narrow search  #1
Pub med  MeSH corticosteroidnarrow search  #5
Pub med  MeSH mortality narrow search  #7
#1 and #5 and #7- advanced searchMethylprednisolone infusion in early severe ARDS:
results of a randomized controlled trial.Meduri GU, Golden E, Freire AX, Taylor E, Zaman M, Carson
SJ, Gibson M, Umberger R.Chest. 2007 Apr;131(4):954-63.PMID: 17426195 [PubMed - indexed for MEDLINE]Related
articlesFree article
The Study:
Type: Randomized, double-blind, placebo-controlled trial
(A Randomized, double-blind, placebo-controlled trial was performed to determine the effects of
low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS.
Ninety-one patients with severe early ARDS (≤ 72 h), 66% with sepsis. Patients were randomized (2:1
fashion) to methylprednisolone infusion (1 mg/kg/d) vs placebo. The duration of treatment was up to 28
days.
Results: Treated patients had significant reduction in C-reactive protein levels, and by day 7 had lower
LIS and multiple organ dysfunction syndrome scores. Treatment was associated with a reduction in the
duration of mechanical ventilation, ICU stay, ICU mortality and lower rate of infections. )
Level of Evidence: 1b
The Evidence:
1. Compared with placebo, steroids were associated with significant improvement in pulmonary and
extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and ICU
length of stay.
2. Treatment with methylprednisolone significantly reduced mortality of ARDS.
Comments:
Methylprednisolone-induced down-regulation of systemic inflammation in ARDS was associated
with significant improvement in pulmonary and extrapulmonary organ dysfunction and reduction
in duration of mechanical ventilation and ICU length of stay.
No bias because patients were selected with randomized fashion (2:1 fashion) of ARDS patients
1. The choice of therapy for ARDS remains a controversial area, but in our opinion adjunctive
therapy with corticosteroids should only be considered in patients with sustained ARDS with
severe sepsis and ventilator support patients.
2. The efficacy of corticosteroids has not been adequately evaluated by RCT in the context of
such a ‘standard regimen’.
3. The renoprotective efficacy of the ‘standard regimen’ means that evaluation of any additional
intervention will require increasingly large and prolonged RCTs to prove benefit for additional
agents unless robust surrogate measures of outcome are developed to enable studies to be
scaled down without loss of power. Information from well-designed RCTs remains a pressing
priority if uncertainties in the treatment of corticosteroids are to be resolved.
In intention-to-treat analysis, the response of the two groups (63 treated and 28 control)
clearly diverged by day 7, with twice the proportion of treated patients achieving a 1-point
reduction in LIS (69.8% vs 35.7%; p _ 0.002) and breathing without assistance (53.9% vs 25.0%;
p _ 0.01). Treated patients had significant reduction in C-reactive protein levels, and by day 7
had lower LIS and multiple organ dysfunction syndrome scores. Treatment was associated with
a reduction in the duration of mechanical ventilation (p _ 0.002), ICU stay (p _ 0.007), and ICU
mortality (20.6% vs 42.9%; p _ 0.03). Treated patients had a lower rate of infections (p _ 0.0002),
and infection surveillance identified 56% of nosocomial infections in patients without fever.
Conclusions: Methylprednisolone-induced down-regulation of systemic inflammation was associated
with significant improvement in pulmonary and extrapulmonary organ dysfunction and
reduction in duration of mechanical ventilation and ICU length of stay.
References:
1. Meduri, GU, Yates, CR Systemic inflammation-associated glucocorticoid resistance and outcome of
ARDS. Ann N Y Acad Sci 2004;1024,24-53
2. Parsons, PE, Eisner, MD, Thompson, BT, et al Lower tidal volume ventilation and plasma cytokine
markers of inflammation in patients with acute lung injury. Crit Care Med 2005;33,1-6
3. Annane, D, Sebille, V, Bellissant, E Effect of low doses of corticosteroids in septic shock patients with
or without early acute respiratory distress syndrome. Crit Care Med 2006;34,22-30
Kill or Update By:
科部會議名稱
舉行日期時間
報告者: 姓名
指導臨床教師
: 彰化基督教醫院腎臟內科 EMB 個案報告會議
: 99 / 01 / 05 , 0730-0830
: 謝浩明 Code :141930
Email :141930@cch.org.tw
: 邱炳芳醫師