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.

Comparative efficacy of tocilizumab and baricitinib in COVID-19 treatment: a retrospective cohort study

“…Biological drugs are a risk factor for serious infection in rheumatoid arthritis [14]. Although the COVID-19 trials showed no difference in the incidence of infections in either TCZ or BRT groups, compared to that in the placebo [4,8], one retrospective study showed that concomitant use of TCZ and methylprednisolone is a risk factor for bacteremia [15]. Besides, whether there is a difference in the risk of developing infections between TCZ and BRT has not been evaluated earlier.…”

The roles of methylprednisolone treatment in patients with COVID-19: A systematic review and meta-analysis

“…After reviewing, 47 articles were removed for the following reasons: intervention group involved other agents (n = 16), non-comparative studies (n = 13), data cannot be extracted (n = 11), comparison between different glucocorticoids (n = 4), and duplicate data (n = 3). Finally, 5 RCTs [14] , [16] , [26] , [36] , [37] and 28 non-RCTs [13] , [15] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] met the criteria for inclusion in the meta-analysis. A flow diagram that describes the search process is shown in Fig.…”

“…In our analysis, there were 29 studies [13] , [14] , [15] , [16] , [17] , [19] , [20] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [42] , [43] , [45] providing the information regarding short-term mortality. After pooling data, short-term mortality was seen in 468 (21.8 %) of 2146 patients receiving methylprednisolone and 496 (24.8 %) of 1996 receiving no glucocorticoids treatment.…”

“…It is well established that the preferred glucocorticoid for the treatment of ARDS in ICU is methylprednisolone rather than dexamethasone. Since the outbreak of epidemic, there have been many studies on methylprednisolone treatment in patients with COVID-19 [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , but the results are inconsistent.…”

A Comparative Study on the Outcomes of Mechanically Ventilated COVID-19 vs Non-COVID-19 Patients with Acute Hypoxemic Respiratory Failure

“…In our study, mean ventilator days and ventilator-free days in COVID-19 patients were 10.54 and 3.92days, respectively which was similar to the published literature. 18 When compared to their non-COVID-19 counterpart, these durations were much longer, reflecting a much larger resource utilization of COVID-19 patients. This trend also reflects not only increased duration of ventilation in the COVID-19 group but also prolonged post-ventilation ICU stay in this group.…”