Comparing restrictive versus liberal oxygen strategies for trauma patients-the TRAUMOX2 trial:protocol for a randomised clinical trial

INTRODUCTION: Supplemental oxygen is commonly used in trauma patients, although it may lead to hyperoxaemia that has been associated with pulmonary complications and increased mortality. The primary objective of this trial, TRAUMOX2, is to compare a restrictive versus liberal oxygen strategy the first 8 hours following trauma. METHODS AND ANALYSIS: TRAUMOX2 is an investigator-initiated, international, parallel-grouped, superiority, outcome assessor-blinded and analyst-blinded, randomised, controlled, clinical trial. Adult patients with suspected major trauma are randomised to eight hours of a restrictive or liberal oxygen strategy. The restrictive group receives the lowest dosage of oxygen (>21%) that ensures an SpO(2) of 94%. The liberal group receives 12–15 L O(2)/min or FiO(2)=0.6–1.0. The primary outcome is a composite of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome). With 710 participants in each arm, we will be able to detect a 33% risk reduction with a restrictive oxygen strategy if the incidence of our primary outcome is 15% in the liberal group. ETHICS AND DISSEMINATION: TRAUMOX2 is carried out in accordance with the Helsinki II Declaration. It has been approved by the Danish Committee on Health Research Ethics for the Capital Region (H-21018062) and The Danish Medicines Agency, as well as the Dutch Medical Research Ethics Committee Erasmus MS (NL79921.078.21 and MEC-2021-0932). A website (www.traumox2.org) is available for updates and study results will be published in an international peer-reviewed scientific journal. TRIAL REGISTRATION NUMBERS: EudraCT 2021-000556-19; NCT05146700

Determining a safe upper limit of oxygen supplementation for adult patients:A systematic review

Objective This systematic review aimed to describe the connection between the inspired oxygen fraction and pulmonary complications in adult patients, with the objective of determining a safe upper limit of oxygen supplementation.Methods MEDLINE and Embase were systematically searched in August 2019 (updated July 2020) for studies fulfilling the following criteria: intubated adult patients (Population); high fractions of oxygen (Intervention) versus low fractions of (Comparison); atelectasis, acute respiratory distress syndrome (ARDS), pneumonia and/or duration of mechanical ventilation (Outcome); original studies both observational and interventional (Studies). Screening, data extraction and risk of bias assessment was done by two independent reviewers.Results Out of 6120 records assessed for eligibility, 12 were included. Seven studies were conducted in the emergency setting, and five studies included patients undergoing elective surgery. Eight studies reported data on atelectasis, two on ARDS, four on pneumonia and two on duration of mechanical ventilation. There was a non-significant increased risk of atelectasis if an oxygen fraction of 0.8 or above was used, relative risk (RR): 1.37 (95% CI 0.95 to 1.96). One study showed an almost threefold higher risk of pneumonia in the high oxygen fraction group (RR: 2.83 (95% CI 2.25 to 3.56)). The two studies reporting ARDS and the two studies with data on mechanical ventilation showed no association with oxygen fraction. Four studies had a high risk of bias in one domain.Conclusions In this systematic review, we found inadequate evidence to identify a safe upper dosage of oxygen, but the identified studies suggest a benefit of keeping inspiratory oxygen fraction below 0.8 with regard to formation of atelectases.PROSPERO registration number CRD42020154242