CHEST.  2007;131(4):954-963.

Methylprednisolone Infusion in Early Severe ARDS - Results of a Randomized Controlled Trial

The lung injury score (LIS) (1) levels of positive end-expiratory pressure (PEEP) (2) ratios of PaO2 to fraction of inspired oxygen (FIO2) (3) the static lung compliance (4) the degree of infiltration present on chest radiograph.

prolonged methylprednisolone administration (2 mg/kg/d) initiated in nonimprovers after 9 ± 3 days of ARDS

improvement in lung injury and multiple organ dysfunction syndrome (MODS) scores.

a significant reduction in levels of inflammatory markers and duration of mechanical ventilation.

prolonged administration of low-dose methylprednisolone (1 mg/kg/d)

initiated in early ARDS (within 72 h of diagnosis) (1)downregulates systemic inflammation (2) leads to earlier resolution of

pulmonary organ dysfunction (3) a reduction in duration of mechanical ventilation and ICU stay

Patients April 1997 and April 2002 in the medical and surgical ICUs l in Memphis,

TN. Adult intubated patients receiving mechanical ventilation, within 72 h of study entry, they met diagnostic criteria for ARDS by the American-European Consensus definition while receiving PEEP.

Testing of Adrenal Function short cosyntropin stimulation test Relative adrenal insufficiency was defined (1) cosyntropin-stimulated total cortisol increment < 9 µg/dL (2) in the absence of stimulation, by

a baseline cortisol level < 15

µg/dL.

Treatment Protocol (1) Methylprednisolone or normal saline solution in 240 mL of normal saline solution -> 10 mL/h oral dose when enteral intake was

restored (2) day 1~ day 14 1 mg/kg/d day 15~day21 0.5 mg/kg/d day 22~ day25 0.25 mg/kg/d day 26 ~ day 28 0.125 mg/kg/d (3) If the patient was extubated btween days 1

and 14, advanced to day 15 of drug therapy

Treatment Protocol (4) Ventilator management guidelines were initially designed to limit plateau pressure at ≤ 35 cm H2O and were later changed to conform with

the ARDS net findings (5) diagnostic fiberoptic bronchoscopy with bilateral BAL was performed prior to study entry, and then every 5 to 7 days

Treatment Protocol (6) If the patient failed to improve LIS

between study days 7 and 9, the patient left the treatment arm of the study to receive methylprednisolone therapy (2 mg/kg/d) for unresolving ARDS .

Statistical Analysis first 7 days, improvement in lung

function was defined as follows: (1) a reduction in LIS ≥ 1 point (2) a day 7 LIS ≤ 2.0 (for study entry

LIS ≤ 2.9) or ≤ 2.5 (for study entry LIS ≥

3.0).

This is the first randomized controlled trial investigating the efficacy and safety of low-dose prolonged methylprednisolone administration in early ARDS

The findings of this study support our original hypothesis that down-regulation of systemic inflammation with early introduction of prolonged glucocorticoid treatment hastens resolution of pulmonary organ dysfunction in ARDS.

study day 7( prolonged methylprednisolone infusion at a dosage of 1 mg/kg/d)

achieving the primary end point of a 1-point reduction in LIS and breathing without assistance.

reduction in C-reactive protein levels lower LIS and MODS score more ventilator- free days. reduction in duration of mechanical

ventilation and ICU length of stay

prolonged glucocorticoid treatment is failure to recognize infections in the presence of a blunted febrile response.

Among the 73 patients (including 10 control nonimprovers) who received methylprednisolone, 3 patients (4%) had prolonged neuromuscular weakness and delayed weaning. The percentage incidence is lower than that reported in the ARDSnet study[13] and is likely related to the lower dose of methylprednisolone and the limited use of neuromuscular blocking agents.

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.