Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.
OBJECTIVE
To determine the effects of low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS.


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
ICUs of five hospitals in Memphis.


METHODS
Ninety-one patients with severe early ARDS (</= 72 h), 66% with sepsis.


METHODS
Patients were randomized (2:1 fashion) to methylprednisolone infusion (1 mg/kg/d) vs placebo. The duration of treatment was up to 28 days. Infection surveillance and avoidance of paralysis were integral components of the protocol.


METHODS
The predefined primary end point was a 1-point reduction in lung injury score (LIS) or successful extubation by day 7.


RESULTS
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.
Meduri
G Umberto
GU
Division of Pulmonary, Critical Care, and Sleep Medicine, University of Tennessee Health Science Center, 956 Court Ave, Room H316, Memphis, TN 38163, USA. umeduri@utmem.edu
Golden
Emmel
E
Freire
Amado X
AX
Taylor
Edwin
E
Zaman
Muhammad
M
Carson
Stephanie J
SJ
Gibson
Mary
M
Umberger
Reba
R
D002097:C-Reactive Protein / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage*; D017052:Hospital Mortality; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D007902:Length of Stay; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D012121:Respiration, Artificial; D012124:Respiratory Care Units; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D002395:Catecholamines; D005938:Glucocorticoids; D002097:C-Reactive Protein; D006854:Hydrocortisone; D008775:Methylprednisolone