Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 26 December 2020 / Approved: 11 January 2021 / Online: 11 January 2021 (10:13:42 CET)

How to cite: Badr, M.; De Oliveira, B.; Abdallah, K.; Nadeem, A.; Varghese, Y.; Munde, D.; Salam, S.; Abduljawad, B.; Saleh, K.; Elkambergy, H.; Rida, A.; Bayrlee, A.; Wahla, A.; Dibu, J.; Haque, R.; Hamed, F.; Rahman, N.; Mallat, J. Effects of Methylprednisolone on Ventilator-Free Days in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome and COVID-19. Preprints 2021, 2021010177 (doi: 10.20944/preprints202101.0177.v1). Badr, M.; De Oliveira, B.; Abdallah, K.; Nadeem, A.; Varghese, Y.; Munde, D.; Salam, S.; Abduljawad, B.; Saleh, K.; Elkambergy, H.; Rida, A.; Bayrlee, A.; Wahla, A.; Dibu, J.; Haque, R.; Hamed, F.; Rahman, N.; Mallat, J. Effects of Methylprednisolone on Ventilator-Free Days in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome and COVID-19. Preprints 2021, 2021010177 (doi: 10.20944/preprints202101.0177.v1).

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 increases 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) during 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 subhazards 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 of 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, 91% 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.

Subject Areas

COVID-19; acute respiratory distress syndrome; methylprednisolone; mechanical ventilation; ventilator-free days; SARS-CoV-2 infection

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