Relationship Between Corticosteroid use and Incidence of Ventilator-associated Pneumonia in COVID-19 Patients

A Retrospective Multicenter Study

Ouriel Saura; Anahita Rouzé; Ignacio Martin-Loeches; Pedro Povoa; Louis Kreitmann; Antoni Torres; Matthieu Metzelard; Damien Du Cheyron; Fabien Lambiotte; Fabienne Tamion; Marie Labruyere; Claire Boulle Geronimi; Charles-Edouard Luyt; Martine Nyunga; Olivier Pouly; Arnaud W. Thille; Bruno Megarbane; Anastasia Saade; Eleni Magira; Jean-François Llitjos; Iliana Ioannidou; Alexandre Pierre; Jean Reignier; Denis Garot; Jean-Luc Baudel; Guillaume Voiriot; Gaëtan Plantefeve; Elise Morawiec; Pierre Asfar; Alexandre Boyer; Armand Mekontso-Dessap; Fotini Bardaka; Emili Diaz; Christophe Vinsonneau; Pierre-Edouard Floch; Nicolas Weiss; Adrian Ceccato; Antonio Artigas; David Nora; Alain Duhamel; Julien Labreuche; Saad Nseir

Disclosures

Crit Care. 2022;26(292) 

In This Article

Abstract and Introduction

Abstract

Background: Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP.

Methods: Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox's proportional hazard models with adjustment on pre-specified confounders.

Results: Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17–1.31) at day 2, 0.95 (0.63–1.42) at day 7, 1.48 (1.01–2.16) at day 14 and 1.94 (1.09–3.46) at day 21.

Conclusions: No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.

Introduction

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to a severe respiratory tract infection (coronavirus disease 2019 (COVID-19)) and hit the world with multiple pandemic waves from December 2020. During the first surge of COVID-19, studies reported that around 80% of patients admitted to hospital for COVID-19 would require oxygen support[1,2] and a high rate of them an invasive mechanical ventilation (IMV) due to acute respiratory distress syndrome (ARDS) leading to high mortality rates.[3,4] IMV during ARDS exposes patients to severe complications, such as ventilator-associated pneumonia (VAP).

Several studies have recently described the high incidence of ventilator-associated lower respiratory tract infection (VA-LRTI) in COVID-19 patients ranging from 30 to 84%.[4–7] Previous studies demonstrated a significantly higher incidence of VA-LRTI and notably VAP in SARS-CoV-2 pneumonia patients versus non-SARS-CoV-2 pneumonia patients.[5,8–10] High rates of ARDS, alveolar inflammation, prolonged IMV, lung microbiota alteration, COVID-19-related specific lesions, neuromuscular blocking and immunosuppressive agent use could explain this high rate of VAP in SARS-CoV-2 pneumonia patients.[11,12]

The positive results of the randomized controlled multicenter trial RECOVERY[13] and its further confirmation in large meta-analysis[14] have placed dexamethasone as the first line agent for treating hospitalized COVID-19 patients with a significantly improved 28-day survival, especially in the subgroup of patients invasively ventilated. Yet, the impact of such treatment on the incidence of VAP in COVID-19 patients is still a matter for debate, as available data are scarce and conflicting.[3,15–19]

Hence, we sought to determine the relationship between adjuvant corticosteroid treatment and the incidence of VAP in a large cohort of COVID-19 patients invasively ventilated for more than 48 h, during the first surge of the SARS-CoV-2 pandemic. Our hypothesis was that VAP incidence would be higher in corticosteroid-treated versus non-treated COVID-19 patients.

The primary objective was to compare the incidence of VAP in patients receiving or not adjuvant corticosteroid treatment. Secondary objectives were to determine the relationship between adjuvant corticosteroid treatment and 28-day mortality, duration of mechanical ventilation and ICU length of stay, based on the occurrence of VAP. We also evaluated microbiology of VAP in both groups of patients.

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