Skip to main content
Top
Published in: Annals of Intensive Care 1/2022

Open Access 01-12-2022 | Pneumonia | Research

Association of early dexamethasone therapy with mortality in critically Ill COVID-19 patients: a French multicenter study

Authors: Matthieu Raymond, Aurélie Le Thuaut, Pierre Asfar, Cédric Darreau, Florian Reizine, Gwenhaël Colin, Charly Dano, Julien Lorber, Baptiste Hourmant, Agathe Delbove, Aurélien Frérou, Jean Morin, Pierre Yves Egreteau, Philippe Seguin, Jean Reignier, Jean-Baptiste Lascarrou, Emmanuel Canet

Published in: Annals of Intensive Care | Issue 1/2022

Login to get access

Abstract

Background

Dexamethasone is recommended for COVID-19 patients who require oxygen therapy. However, its effectiveness in reducing mortality and intubation, and its safety, remain debated. We aimed to investigate whether dexamethasone reduces day-28 mortality in unselected patients with critical COVID-19.

Methods

We performed an observational cohort study in consecutive COVID-19 patients admitted to any of 13 French intensive care units (ICUs) in 2020. The primary objective was to determine whether early dexamethasone therapy was associated with day-28 mortality and the secondary objectives were to assess whether early dexamethasone decreased intubation requirements and to collect adverse events.

Results

Of 1058 included patients, 611 (57.75%) received early dexamethasone (early dexamethasone group), 358 (33.83%) did not receive any steroids (no steroids group), and 89 (8.41%) received late dexamethasone or other steroids. Day-28 mortality was similar between the early dexamethasone and the no steroids groups (15.06% and 14.25%, respectively; P = 0.59). Factors associated with day-28 mortality were older age (adjusted hazard ratio [aHR], 1.06; 1.04–1.09; P < 0.001), worse SOFA score (aHR, 1.13; 1.06–1.20; P < 0.001), and immunocompromised status (aHR, 1.59; 1.01–2.50; P = 0.043). Early dexamethasone was associated with fewer intubations (48.55% vs. 61.49%, P < 0.001) and more ventilator-free days by day 28 (22 [2–28] vs. 17 [1–28] days, P = 0.003), compared to no steroids. Ventilator-associated pneumonia (VAP) was more common with early dexamethasone (HR, 1.29 [1.01–1.63], P = 0.04) than with no steroids, whereas no differences were noted for bloodstream infection, fungal infection, or gastrointestinal bleeding.

Conclusions

Early dexamethasone in critically ill COVID-19 patients was not associated with lower day-28 mortality. However, early dexamethasone was associated with lower intubation needs and more ventilator-free days by day 28. In patients treated with invasive mechanical ventilation, early dexamethasone was associated with a higher risk of VAP.
Appendix
Available only for authorised users
Literature
2.
go back to reference COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med. 2021;47:60–73.CrossRef COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med. 2021;47:60–73.CrossRef
6.
go back to reference Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA. 2020;324:1307–16.CrossRefPubMed Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA. 2020;324:1307–16.CrossRefPubMed
7.
go back to reference Dequin P-F, Heming N, Meziani F, Plantefève G, Voiriot G, Badié J, et al. Effect of hydrocortisone on 21-day mortality or respiratory support among critically Ill patients with COVID-19: a randomized clinical trial. JAMA. 2020;324:1298–306.CrossRefPubMed Dequin P-F, Heming N, Meziani F, Plantefève G, Voiriot G, Badié J, et al. Effect of hydrocortisone on 21-day mortality or respiratory support among critically Ill patients with COVID-19: a randomized clinical trial. JAMA. 2020;324:1298–306.CrossRefPubMed
11.
go back to reference WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. Association between administration of systemic corticosteroids and mortality among critically Ill patients with COVID-19: a meta-analysis. JAMA. 2020. https://doi.org/10.1001/jama.2020.17023.CrossRef WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. Association between administration of systemic corticosteroids and mortality among critically Ill patients with COVID-19: a meta-analysis. JAMA. 2020. https://​doi.​org/​10.​1001/​jama.​2020.​17023.CrossRef
12.
go back to reference Blonz G, Kouatchet A, Chudeau N, Pontis E, Lorber J, Lemeur A, et al. Epidemiology and microbiology of ventilator-associated pneumonia in COVID-19 patients: a multicenter retrospective study in 188 patients in an un-inundated French region. Crit Care Lond Engl. 2021;25:72.CrossRef Blonz G, Kouatchet A, Chudeau N, Pontis E, Lorber J, Lemeur A, et al. Epidemiology and microbiology of ventilator-associated pneumonia in COVID-19 patients: a multicenter retrospective study in 188 patients in an un-inundated French region. Crit Care Lond Engl. 2021;25:72.CrossRef
13.
go back to reference Razazi K, Arrestier R, Haudebourg AF, Benelli B, Carteaux G, Decousser J-W, et al. Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease. Crit Care Lond Engl. 2020;24:699.CrossRef Razazi K, Arrestier R, Haudebourg AF, Benelli B, Carteaux G, Decousser J-W, et al. Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease. Crit Care Lond Engl. 2020;24:699.CrossRef
14.
go back to reference Maes M, Higginson E, Pereira-Dias J, Curran MD, Parmar S, Khokhar F, et al. Ventilator-associated pneumonia in critically ill patients with COVID-19. Crit Care Lond Engl. 2021;25:25.CrossRef Maes M, Higginson E, Pereira-Dias J, Curran MD, Parmar S, Khokhar F, et al. Ventilator-associated pneumonia in critically ill patients with COVID-19. Crit Care Lond Engl. 2021;25:25.CrossRef
15.
go back to reference Buetti N, Ruckly S, de Montmollin E, Reignier J, Terzi N, Cohen Y, et al. COVID-19 increased the risk of ICU-acquired bloodstream infections: a case-cohort study from the multicentric OUTCOMEREA network. Intensive Care Med. 2021;47:180–7.CrossRefPubMedPubMedCentral Buetti N, Ruckly S, de Montmollin E, Reignier J, Terzi N, Cohen Y, et al. COVID-19 increased the risk of ICU-acquired bloodstream infections: a case-cohort study from the multicentric OUTCOMEREA network. Intensive Care Med. 2021;47:180–7.CrossRefPubMedPubMedCentral
16.
go back to reference Machado M, Valerio M, Álvarez-Uría A, Olmedo M, Veintimilla C, Padilla B, et al. Invasive pulmonary aspergillosis in the COVID-19 era: an expected new entity. Mycoses. 2021;64:132–43.CrossRefPubMed Machado M, Valerio M, Álvarez-Uría A, Olmedo M, Veintimilla C, Padilla B, et al. Invasive pulmonary aspergillosis in the COVID-19 era: an expected new entity. Mycoses. 2021;64:132–43.CrossRefPubMed
17.
go back to reference Koehler P, Bassetti M, Chakrabarti A, Chen SCA, Colombo AL, Hoenigl M, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis. 2021;21:e149–62.CrossRefPubMed Koehler P, Bassetti M, Chakrabarti A, Chen SCA, Colombo AL, Hoenigl M, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis. 2021;21:e149–62.CrossRefPubMed
18.
go back to reference von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet Lond Engl. 2007;370:1453–7.CrossRef von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet Lond Engl. 2007;370:1453–7.CrossRef
19.
go back to reference Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. 2015;34:3661–79.CrossRefPubMedPubMedCentral Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. 2015;34:3661–79.CrossRefPubMedPubMedCentral
20.
go back to reference Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788–800.CrossRefPubMed Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788–800.CrossRefPubMed
21.
go back to reference Angus DC, Clermont G, Linde-Zwirble WT, Musthafa AA, Dremsizov TT, Lidicker J, et al. Healthcare costs and long-term outcomes after acute respiratory distress syndrome: a phase III trial of inhaled nitric oxide. Crit Care Med. 2006;34:2883–90.CrossRefPubMed Angus DC, Clermont G, Linde-Zwirble WT, Musthafa AA, Dremsizov TT, Lidicker J, et al. Healthcare costs and long-term outcomes after acute respiratory distress syndrome: a phase III trial of inhaled nitric oxide. Crit Care Med. 2006;34:2883–90.CrossRefPubMed
22.
go back to reference Annane D, Pastores SM, Rochwerg B, Arlt W, Balk RA, Beishuizen A, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically Ill patients (part I): society of critical care medicine (sccm) and European society of intensive care medicine (ESICM) 2017. Crit Care Med. 2017;45:2078–88.CrossRefPubMed Annane D, Pastores SM, Rochwerg B, Arlt W, Balk RA, Beishuizen A, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically Ill patients (part I): society of critical care medicine (sccm) and European society of intensive care medicine (ESICM) 2017. Crit Care Med. 2017;45:2078–88.CrossRefPubMed
23.
go back to reference Moreno G, Rodríguez A, Reyes LF, Gomez J, Sole-Violan J, Díaz E, et al. Corticosteroid treatment in critically ill patients with severe influenza pneumonia: a propensity score matching study. Intensive Care Med. 2018;44:1470–82.CrossRefPubMedPubMedCentral Moreno G, Rodríguez A, Reyes LF, Gomez J, Sole-Violan J, Díaz E, et al. Corticosteroid treatment in critically ill patients with severe influenza pneumonia: a propensity score matching study. Intensive Care Med. 2018;44:1470–82.CrossRefPubMedPubMedCentral
24.
go back to reference Amado-Rodríguez L, Salgado Del Riego E, Gomez de Ona J, López Alonso I, Gil-Pena H, López-Martínez C, et al. Effects of IFIH1 rs1990760 variants on systemic inflammation and outcome in critically ill COVID-19 patients in an observational translational study. J eLife. 2022. https://doi.org/10.7554/eLife.73012.CrossRef Amado-Rodríguez L, Salgado Del Riego E, Gomez de Ona J, López Alonso I, Gil-Pena H, López-Martínez C, et al. Effects of IFIH1 rs1990760 variants on systemic inflammation and outcome in critically ill COVID-19 patients in an observational translational study. J eLife. 2022. https://​doi.​org/​10.​7554/​eLife.​73012.CrossRef
25.
go back to reference Sinha P, Furfaro D, Cummings MJ, Abrams D, Delucchi K, Maddali MV, et al. Latent class analysis reveals COVID-19-related acute respiratory distress syndrome subgroups with differential responses to corticosteroids. Am J Respir Crit Care Med. 2021;204:1274–85.CrossRefPubMedPubMedCentral Sinha P, Furfaro D, Cummings MJ, Abrams D, Delucchi K, Maddali MV, et al. Latent class analysis reveals COVID-19-related acute respiratory distress syndrome subgroups with differential responses to corticosteroids. Am J Respir Crit Care Med. 2021;204:1274–85.CrossRefPubMedPubMedCentral
26.
go back to reference Torres A, Motos A, Cillóniz C, Ceccato A, Fernández-Barat L, Gabarrús A, et al. Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study. Intensive Care Med. 2022;48:850–64.CrossRefPubMedPubMedCentral Torres A, Motos A, Cillóniz C, Ceccato A, Fernández-Barat L, Gabarrús A, et al. Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study. Intensive Care Med. 2022;48:850–64.CrossRefPubMedPubMedCentral
Metadata
Title
Association of early dexamethasone therapy with mortality in critically Ill COVID-19 patients: a French multicenter study
Authors
Matthieu Raymond
Aurélie Le Thuaut
Pierre Asfar
Cédric Darreau
Florian Reizine
Gwenhaël Colin
Charly Dano
Julien Lorber
Baptiste Hourmant
Agathe Delbove
Aurélien Frérou
Jean Morin
Pierre Yves Egreteau
Philippe Seguin
Jean Reignier
Jean-Baptiste Lascarrou
Emmanuel Canet
Publication date
01-12-2022
Publisher
Springer International Publishing
Published in
Annals of Intensive Care / Issue 1/2022
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-022-01074-w

Other articles of this Issue 1/2022

Annals of Intensive Care 1/2022 Go to the issue