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The Role of Steroids in ARDSA review of the evidence
Alex Yartsev 11/2010
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Briefly, on the definition of ARDS• Acute severe hypoxic
respiratory failure with bilateral diffuse alveolar damage
• Lots of different criteria: 1994 AECC consensus, the LIS
score, the Delphi definition…
- It has to be acute- PaO2 to FiO2 ratio of <200 - PEEP > 10- bilaterality
• ABSENCE of left ventricular failure
Bersen A.D, the Acute Respiratory Distress Syndrome (ARDS) Ch 29 in Ohs Intensive Care Manual, 6th ed.
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Briefly, on the pathology of ARDSThere is diffuse alveolar damage;• Alveolar-capillary barrier is damaged
– Thus, there is pulmonary oedema
• There is a complex inflammatory infiltrate– Neutrophils play some role? a major role?...– but neutropenic patients gets ARDS as well…
• There is surfactant dysfunction– Surfactant keep alveoli from collapsing
• Sequence of events depends on what is causing the ARDS: is the cause pulmonary or extrapulmonary?
Bersen A.D, the Acute Respiratory Distress Syndrome (ARDS) Ch 29 in Ohs Intensive Care Manual, 6th ed.
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Briefly, on the pathogenesis of ARDS- The lung is a filter for the whole body’s blood- Circulating or local inflammatory mediators- Either way, something damages the endothelium first- The endothelium becomes leaky when it is inflamed- The endothelium expresses adhesion molecules, attracts neutrophils- Neutrophils / macrophages amplify lung damage- They also secrete mediators which cause pulmonary vasoconstriction
and thus worsening hypoxia
- Leaky inflamed endothelium ceases to produce surfactant, and surfactant is also lost because the leak through the capillary wall is bi-directional
Orfanos SE et al, Pulmonary endothelium in acute lung injury: from basic science to the critically ill Applied Physiology in Intensive Care Medicine 2009, Part 2, 215-227,
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Resolution of ARDS• Pulmonary oedema resolves (type 2 cells
pump Na+ back into the vessels)• About 5 days after onset, some repair takes
place• There is a balance between repair and fibrosis• Occasionally, fibrosis dominates• This is fibrosing alveolitis
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In summary• The causes of ARDS are inflammatory • The immune system does most of the damage• Recovery of alveolar function is impaired by the
inappropriate fibrosis process
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Why would steroids work?– Inhibit the extravasation of leucocytes
(inhibit leucocyte adhesion molecules from interacting with endothelial cell adhesion molecules; this raises the WCC )
– Increase the migration of lymphocytes to the lymphoid tissues (and out of the bloodstream)
– Inhibit the function of macrophages and antigen-presenting cells
– Inhibit phagocytosis by macrophages– Inhibit production of TNF-alpha and interleukin-1– Inhibit expression of cyclooxygenase-2: Thus, inhibit
the synthesis of prostaglandins– Inhibit synthesis of antibodies (in large doses)
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What harm could they do?
• More risk of neuromuscular weakness• When yoused together with neuromuscular blocking
agents, LOTS more risk of neuromuscular weakness• Blunted febrile response = iatrogenic sepsis goes
unrecognised
Meduri GU, (1998) Effect of prolonged methylprednisolone therapy in unresolvingacute respiratory distress syndrome. A randomized controlled trial. JAMA 280:159–165Meduri GU, (2007) Methylprednisolone infusion in early severe ARDS: results of a randomizedcontrolled trial. Chest 131:954–963Steinberg KP, (2006) Efficacy and safety of corticosteroids for persistent acute respiratorydistress syndrome. N Engl J Med 354:1671–1684
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Evidence for steroids in ARDS
• Meduri et al published a meta-analysis (2008)– n = 518; all trials retrieved from
Cochrane– Reduction in RR of death: 0.84
(0.78 if treated before day 14)- Reduced length of ICU stay and
decreased number of ventilated days
Meduri G.U et al Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature 2008 Intensive Care Medicine Volume 34, Number 1, 61-69
Gianfranco Umberto Meduri
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ARDS network trial
Steinberg KP, (2006) Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 354:1671–1684
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Evidence for benefit
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Evidence for minimal benefit
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And even if there was some benefit…
• When would you administer the steroids?• How long is an effective course?• Is there a difference in pulmonary vs
extrapulmonary causes of ARDS?• Is there an improvement in long term lung
function?
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And even if there was some benefit…
• When would you administer the steroids?• How long is an effective course?• Is there a difference in pulmonary vs
extrapulmonary causes of ARDS?• Is there an improvement in long term lung
function?
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No Further Questions, Please
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References• Bersen A.D, the Acute Respiratory Distress Syndrome (ARDS) Ch 29 in Ohs Intensive Care Manual, 6th ed.• Orfanos SE et al, Pulmonary endothelium in acute lung injury: from basic science to the critically ill
Applied Physiology in Intensive Care Medicine 2009, Part 2, 215-227, • Meduri G.U et al Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the
recent literature 2008 Intensive Care Medicine Volume 34, Number 1, 61-69• Steinberg KP, (2006) Efficacy and safety of corticosteroids for persistent acute respiratory distress
syndrome. N Engl J Med 354:1671–1684
•