Spontaneous breathing activity in COVID-19-related lung failure

Is early spontaneous breathing beneficial in the treatment of lung failure in individuals with COVID-19?

People with severe COVID-19 can present with lung failure, which is called acute respiratory distress syndrome (ARDS). This requires invasive mechanical ventilation through a breathing tube. It is possible to allow breathing, triggered by the patient (called spontaneous breathing), whilst being on a ventilator. However, it is unclear whether this is beneficial for such individuals, especially in the early phase of ventilation.

Key messages

We found no evidence if spontaneous breathing is beneficial in the treatment of lung failure due to COVID-19.

What are the advantages of early spontaneous breathing in ARDS? 

The advantage of spontaneous breathing during mechanical ventilation is the preserved movement of the diaphragm (the major muscle for breathing located under the lungs). It leads to better distribution of the inhaled air, especially in the pulmonary alveoli (small air sacs within the lungs) close to the diaphragm. In general, ventilation procedures with possible spontaneous breathing require lower doses of sedatives (which slow down brain activity). Since these can cause low blood pressure, it can additionally reduce the administration of cardiovascular medicines.

Can early spontaneous breathing be harmful in the treatment of ARDS?

During spontaneous breathing under mechanical ventilation, increased pressure fluctuations in the lungs may occur. Increased pressure difference within the lung is the main cause of ventilator-associated lung injury.

What is the alternative to using early spontaneous breathing?

Spontaneous breathing may be suppressed by increased sedation or blockade of the nerves innervating muscles by medicines that allow for breathing (called neuromuscular blockade). The advantage of complete ventilator-based breathing is a lower oxygen consumption of the muscles and the reduced risk of self-inflicted lung injury.

What did we want to find out?

We wanted to evaluate the benefits and harms of early spontaneous breathing activity in ventilated people with COVID-19 with ARDS compared to ventilation strategies that avoid spontaneous breathing.

What did we do? 

We searched for studies that compared early spontaneous breathing during invasive mechanical ventilation with mandatory invasive ventilation and neuromuscular blockade in people with ARDS related to COVID-19. People could have been any age, sex or ethnicity. 

What did we find? 

After systematic search, we found no records that met the inclusion criteria.

Main results

We identified no eligible studies for this review.

What are the limitations of the evidence?

To date, there are no studies that have compared early spontaneous breathing during invasive mechanical ventilation to mandatory invasive ventilation without spontaneous breathing in people with ARDS related to COVID-19. 

How up-to-date is this evidence?

Our evidence is up-to-date to 2 March 2022.

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.

Read the full abstract...

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.


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 strategy: 

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.