Effects of Methylprednisolone on Ventilator-Free Days in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome and COVID-19: A Retrospective Study.

Abstract

Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone is associated with increases in the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study. Setting: Intensive care unit. Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included. Interventions: None. Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) for the first 28 days. Defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional sub hazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg·kg−1 (IQR: 1–1.3 mg·kg−1) and median duration for 5 days (IQR: 5–7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6–20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6–16.7) in patients who did not receive methylprednisolone (difference, 4.61, 95% CI, 1.10–8.12, p = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95% CI: 0.02–0.45, p = 0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p = 0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR: 15–41 days] vs. 37 days [IQR: 23–52 days], p = 0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p = 0.052). However, 81% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.