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Meta-Analysis
. 2022 Jun 29;6(6):CD015077.
doi: 10.1002/14651858.CD015077.

Early spontaneous breathing for acute respiratory distress syndrome in individuals with COVID-19

Friedrich Hohmann  1 , Lisa Wedekind  1   2 , Felicitas Grundeis  1 , Steffen Dickel  3 , Johannes Frank  1 , Martin Golinski  3 , Mirko Griesel  1 , Clemens Grimm  3 , Cindy Herchenhahn  1 , Andre Kramer  1 , Maria-Inti Metzendorf  4 , Onnen Moerer  3 , Nancy Olbrich  1 , Volker Thieme  1 , Astrid Vieler  5 , Falk Fichtner  1 , Jacob Burns  6 , Sven Laudi  1
Affiliations
Meta-Analysis

Early spontaneous breathing for acute respiratory distress syndrome in individuals with COVID-19

Friedrich Hohmann et al. Cochrane Database Syst Rev. .

Abstract

Background: Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID-19 (caused by the SARS-CoV-2 virus), usually resulting in a prolonged stay in an intensive care unit (ICU) and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID-19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents (NMBA). This approach is potentially associated with both advantages (e.g. a preserved diaphragmatic motility and an optimised ventilation-perfusion ratio of the ventilated lung), as well as risks (e.g. a higher rate of ventilator-induced lung injury or a worsening of pulmonary oedema due to increases in transpulmonary pressure). As a consequence, spontaneous breathing in people with COVID-19-ARDS who are receiving IMV is subject to an ongoing debate amongst intensivists.

Objectives: To assess the benefits and harms of early spontaneous breathing activity in invasively ventilated people with COVID-19 with ARDS compared to ventilation strategies that avoid spontaneous breathing.

Search methods: We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, Clinical Trials.gov WHO ICTRP, and medRxiv) and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies from their inception to 2 March 2022.

Selection criteria: Eligible study designs comprised randomised controlled trials (RCTs) that evaluated spontaneous breathing in participants with COVID-19-related ARDS compared to ventilation strategies that avoided spontaneous breathing (e.g. using NMBA or deep sedation levels). Additionally, we considered controlled before-after studies, interrupted time series with comparison group, prospective cohort studies and retrospective cohort studies. For these non-RCT studies, we considered a minimum total number of 50 participants to be compared as necessary for inclusion. Prioritised outcomes were all-cause mortality, clinical improvement or worsening, quality of life, rate of (serious) adverse events and rate of pneumothorax. Additional outcomes were need for tracheostomy, duration of ICU length of stay and duration of hospitalisation.

Data collection and analysis: We followed the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently screened all studies at the title/abstract and full-text screening stage. We also planned to conduct data extraction and risk of bias assessment in duplicate. We planned to conduct meta-analysis for each prioritised outcome, as well as subgroup analyses of mortality regarding severity of oxygenation impairment and duration of ARDS. In addition, we planned to perform sensitivity analyses for studies at high risk of bias, studies using NMBA in addition to deep sedation level to avoid spontaneous breathing and a comparison of preprints versus peer-reviewed articles. We planned to assess the certainty of evidence using the GRADE approach.

Main results: We identified no eligible studies for this review.

Authors' conclusions: We found no direct evidence on whether early spontaneous breathing in SARS-CoV-2-induced ARDS is beneficial or detrimental to this particular group of patients. RCTs comparing early spontaneous breathing with ventilatory strategies not allowing for spontaneous breathing in SARS-CoV-2-induced ARDS are necessary to determine its value within the treatment of severely ill people with COVID-19. Additionally, studies should aim to clarify whether treatment effects differ between people with SARS-CoV-2-induced ARDS and people with non-SARS-CoV-2-induced ARDS.

Trial registration: ClinicalTrials.gov NCT04497454 NCT04922814 NCT05248243.

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Conflict of interest statement

FH: works as an Intensive Care Medicine physician and is member of the CEOsys project (no direct funding).

LW: is member of the CEOsys project funded by the Network of University Medicine (Nationales Forschungsnetzwerk der Universitätsmedizin (NUM)) by the Federal Ministry of Education and Research of Germany (Bundesministerium für Bildung und Forschung (BMBF)), grant number 01KX2021, paid to the institution.

FG: works as an Intensive Care Medicine physician and is a member of the CEOsys project funded by the Network of University Medicine (NUM) by the Federal Ministry of Education and Research of Germany (BMBF), grant number 01KX2021, paid to the institution.

DS: works as an Intensive Care Medicine physician and is member of the CEOsys project (no direct funding).

JF: works as an Intensive Care Medicine physician and is member of the CEOsys project funded by the Network of University Medicine (NUM) by the Federal Ministry of Education and Research of Germany (BMBF), grant number 01KX2021, paid to the institution.

MGo: works as an Intensive Care Medicine Consultant and is a member of the CEOsys project (no direct funding).

MGr: works as an Intensive Care Medicine physician and is a member of the CEOsys project funded by the Network of University Medicine (NUM) by the Federal Ministry of Education and Research of Germany (BMBF), grant number 01KX2021, paid to the institution.

CG: works as an Intensive Care Medicine physician and is a member of the CEOsys project (no direct funding).

CH: works as an Intensive Care Medicine physician and is a member of the CEOsys project funded by the Network of University Medicine (NUM) by the Federal Ministry of Education and Research of Germany (BMBF), grant number 01KX2021, paid to the institution.

AK: works as an Intensive Care Medicine physician and is a member of the CEOsys project funded by the Network of University Medicine (NUM) by the Federal Ministry of Education and Research of Germany (BMBF), grant number 01KX2021, paid to the institution.

MIM: is member of the CEOsys project funded by the Network of University Medicine (NUM) by the Federal Ministry of Education and Research of Germany (BMBF), grant number 01KX2021, paid to the institution.

OM: works as an Intensive Care Medicine Consultant and is a member of the CEOsys project (no direct funding).

NO: works as an Intensive Care Medicine physician and is member of the CEOsys project funded by the Network of University Medicine (NUM) by the Federal Ministry of Education and Research of Germany (BMBF), grant number 01KX2021, paid to the institution.

VT: works as an Intensive Care Medicine Consultant and is a member of the CEOsys project (no direct funding).

AV: works as Information Scientist and Librarian of the University of Leipzig Library (no direct funding).

FF: works as an Intensive Care Medicine Consultant and is a member of the CEOsys project (no direct funding).

JB: The Chair for Public Health and Health Services Research at the Institute for Medical Information Processing, Biometry and Epidemiology is part of the CEOsys project funded by the Network of University Medicine (NUM) by the Federal Ministry of Education and Research of Germany (BMBF), grant number 01KX2021, paid to the institution.

SL: works as an Intensive Care Medicine Consultant and is a member of the CEOsys project (no direct funding).

Figures

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Study flow diagram.
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References

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References to ongoing studies

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