CHEST. 2007;131(4): 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 PaO 2 to fraction of inspired oxygen (FIO 2 ) (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  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 H 2 O 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.