Early versus late 2 mg/kg methylprednisolone therapy in ARDS

The fibroproliferative stage and persistent inflammation of acute respiratory distress syndrome (ARDS) are key factors leading to either the resolution of the syndrome or fibrosis. Previous studies suggest that a corticosteroid therapy promotes the evolution of ARDS toward an adapted repair process whereas others suggest that this therapy increases the risk of death if it starts more than 14 days after ARDS onset. Since the efficacy and safety of delayed 2 mg/kg methylprednisolone therapy in patients with ARDS is a matter of debate, we performed this observational multicentric retrospective study. We analysed the data of 392 patients with ARDS who received 2 mg/kg methylprednisolone therapy. The primary endpoint was mortality six months after 2 mg/kg methylprednisolone therapy was started. The secondary endpoints included mortality 60 days after the corticosteroid therapy initiation and the number of ventilator-free days (VFDs) and intensive care unit (ICU)-free days. We investigated the occurrence of complications such as ventilator-acquired pneumonia (VAP), septic shock and gastrointestinal bleeding arising after the start of the protocol. A total of 189 (48.2%) patients received 2 mg/kg methylprednisolone therapy within the first 14 days of ARDS onset. A total of 203 (51.8%) patients received it more than 14 days included post-ARDS-onset. The mortality rate six months after the initiation of 2 mg/kg methylprednisolone therapy was 51.9% in the early initiation group and 52.2% in the late initiation group (p = 0.942). The mortality rate 60 days after the initiation of 2 mg/kg methylprednisolone therapy was 47.1% in the early group and 47.3% in the late group (p = 0.968). There was no significant difference in the number of VFDs (p = 0.336) or ICU-free days (p = 0.175) 60 days after the start of the 2 mg/kg protocol. Initiating the protocol 14 days after the onset of ARDS seemed to be associated with more complications (p < 0.001). Late initiation was associated with greater occurrence of VAP (p = 0.018) or gastrointestinal bleeding (p = 0.012). These results suggest that an initiation of 2 mg/kg methylprednisolone therapy after 14 days from ARDS onset is not associated with an increased risk of death as compared with initiation prior to day 14. Delayed 2 mg/kg methylprednisolone therapy in patients with persistent ARDS should be considered.