Approaches to guiding oxygen therapy in adult intensive care patients with acute respiratory distress syndrome

Background

Acute respiratory distress syndrome (ARDS) is a very severe breathing problem with a high mortality rate (chance of dying). It has many potential causes, including viral infections such as COVID-19, and there are no specific treatments for it except for giving patients oxygen via a ventilator (artificial breathing machine) on an intensive care unit, often for long periods of time. However, large amounts of oxygen (either a high concentration of oxygen or oxygen administered for a long period of time) are associated with increased harm due to other illnesses (e.g. heart attack or stroke).

What did we want to find out?

We wanted to know whether patients with severe lung problems (ARDS) would do better (including less chance of dying) if they received higher or lower amounts of oxygen whilst they were on a ventilator in intensive care.

Methods

We searched major medical databases up to 15 May 2020 for clinical trials studying oxygen use in adult patients with ARDS in intensive care units. We only searched for studies with the sickest patients, that is those who needed help with their breathing through a breathing tube that was connected to an artificial breathing machine. We did not restrict the search by language of publication.

In addition to extracting and analysing the data from any studies that met these criteria, we also assessed the risk of bias (fairness) and the certainty (confidence) of the findings.

Results

We included only one study (205 participants) in the review. Patients with ARDS and receiving oxygen through a breathing tube in an intensive care unit may have a higher chance of death if they receive lower amounts of oxygen compared to receiving much higher amounts of oxygen, but the evidence is very uncertain.

Certainty of evidence

Our certainty (confidence) in these findings is very low as data were only available from one study that had only a small number of participants, and was stopped earlier than anticipated because of safety concerns. We are therefore unable to definitively say whether giving more or less oxygen to ARDS patients is helpful.

Authors' conclusions: 

We are very uncertain as to whether a higher or lower oxygen target is more beneficial in patients with ARDS and receiving mechanical ventilation in an intensive care setting. We identified only one RCT with a total of 205 participants exploring this question, and rated the risk of bias as high and the certainty of the findings as very low. Further well-conducted studies are urgently needed to increase the certainty of the findings reported here. This review should be updated when more evidence is available.

Read the full abstract...
Background: 

Supplemental oxygen is frequently administered to patients with acute respiratory distress syndrome (ARDS), including ARDS secondary to viral illness such as coronavirus disease 19 (COVID-19). An up-to-date understanding of how best to target this therapy (e.g. arterial partial pressure of oxygen (PaO2) or peripheral oxygen saturation (SpO2) aim) in these patients is urgently required.

Objectives: 

To address how oxygen therapy should be targeted in adults with ARDS (particularly ARDS secondary to COVID-19 or other respiratory viruses) and requiring mechanical ventilation in an intensive care unit, and the impact oxygen therapy has on mortality, days ventilated, days of catecholamine use, requirement for renal replacement therapy, and quality of life.

Search strategy: 

We searched the Cochrane COVID-19 Study Register, CENTRAL, MEDLINE, and Embase from inception to 15 May 2020 for ongoing or completed randomized controlled trials (RCTs).

Selection criteria: 

Two review authors independently assessed all records in accordance with standard Cochrane methodology for study selection.

We included RCTs comparing supplemental oxygen administration (i.e. different target PaO2 or SpO2 ranges) in adults with ARDS and receiving mechanical ventilation in an intensive care setting. We excluded studies exploring oxygen administration in patients with different underlying diagnoses or those receiving non-invasive ventilation, high-flow nasal oxygen, or oxygen via facemask.

Data collection and analysis: 

One review author performed data extraction, which a second review author checked. We assessed risk of bias in included studies using the Cochrane 'Risk of bias' tool. We used the GRADE approach to judge the certainty of the evidence for the following outcomes; mortality at longest follow-up, days ventilated, days of catecholamine use, and requirement for renal replacement therapy.

Main results: 

We identified one completed RCT evaluating oxygen targets in patients with ARDS receiving mechanical ventilation in an intensive care setting. The study randomized 205 mechanically ventilated patients with ARDS to either conservative (PaO2 55 to 70 mmHg, or SpO2 88% to 92%) or liberal (PaO2 90 to 105 mmHg, or SpO296%) oxygen therapy for seven days.

Overall risk of bias was high (due to lack of blinding, small numbers of participants, and the trial stopping prematurely), and we assessed the certainty of the evidence as very low. The available data suggested that mortality at 90 days may be higher in those participants receiving a lower oxygen target (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.03 to 3.27). There was no evidence of a difference between the lower and higher target groups in mean number of days ventilated (14.0, 95% CI 10.0 to 18.0 versus 14.5, 95% CI 11.8 to 17.1); number of days of catecholamine use (8.0, 95% CI 5.5 to 10.5 versus 7.2, 95% CI 5.9 to 8.4); or participants receiving renal replacement therapy (13.7%, 95% CI 5.8% to 21.6% versus 12.0%, 95% CI 5.0% to 19.1%). Quality of life was not reported.

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