How hyperoxia affects systemic redox state: insights from PULSE-Ox, a randomised double-blind mechanistic feasibility trial.

BACKGROUND

Oxygen therapy is ubiquitous in medical practise, but recommendations for administration during surgery are conflicting, and mechanisms of harm are ill-defined. The World Health Organization (WHO) recommends that all anaesthetised patients receive 80% oxygen intraoperatively to reduce surgical site infections. Whether such high oxygen concentrations cause oxidative stress remains uncertain.

METHODS

Adults undergoing major cancer surgery were randomly allocated to conservative (FiO2=0.3, n=8), typical (FiO2=0.55, n=10) or recommended (FiO2=0.8, n=10) oxygen throughout anaesthesia. The aims were to determine whether i) intraoperative oxygen at or below WHO-recommended levels affects whole-body redox state, and ii) redox profiling could distinguish between different oxygen concentrations. Peripheral oxygen saturation (SpO2) and oxygen reserve index were monitored (co)oximetrically. Paired arterial/central venous blood samples/gases were collected 2-hourly. Lipid peroxides, protein carbonyls, free thiols, antioxidants and nitroso species were quantified using Liquid Chromatography-Tandem Mass Spectrometry, Enzyme-Linked Immunosorbent Assay (ELISA), colourimetry and gas-phase chemiluminescence.

RESULTS

Double-blinded recruitment of 28 patients (median age 65.8 yr) to three different intraoperative oxygen concentrations was feasible and successful during the study period from September, 2018 to May 2021. While SpO2 remained unchanged, systemic oxygen utilisation paradoxically decreased with higher oxygen concentrations (P=0.0006). While free thiol levels rose moderately, nitrosation increased significantly (P=0.039/0.002/0.039 for FiO2=0.3/0.55/0.8). Administration of 80% oxygen was associated with diminished reductive power (P=0.012) and significant oxidative stress (P=0.004).

CONCLUSIONS

Cross-sectional redox profiling may allow early identification of patients at risk of postoperative complications, while longitudinal profiling may distinguish between oxygen intervention groups. High oxygen concentrations challenge the body's ability to maintain redox balance, potentially increasing vulnerability to other stressors. Our results lay the foundation for large clinical effectiveness studies evaluating oxygen therapy targets and suggest that 'redox scoring' could guide individualised oxygen administration.

TRIAL REGISTRATION NUMBER: NCT03552627 (Clinicaltrials.gov).