Oxidative Stress and Postoperative Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses

Oxidative stress (OS) is a key biological mechanism influencing surgical recovery, contributing to impaired healing, infectious complications, cardiovascular events, and mortality. This umbrella review aimed to synthesize evidence from systematic reviews and meta-analyses exclusively focused on the relationship between validated oxidative stress biomarkers and postoperative outcomes. Narrative and non-systematic reviews were excluded.

A comprehensive search of PubMed, Scopus, and Web of Science was conducted on 15 March 2024 and updated on 12 December 2024 to identify systematic reviews and meta-analyses including adult surgical patients, validated oxidative stress biomarkers, and clinical outcomes. Methodological quality was evaluated with AMSTAR 2 and ROBIS. The SANRA checklist was used only to verify that narrative or bibliometric reviews did not meet the inclusion criteria. These non-systematic reviews were excluded from the synthesis and cited solely as contextual references.

From 527 records, ten systematic reviews of moderate to high methodological quality were included, encompassing approximately 230 primary studies. The most frequently reported biomarkers were total antioxidant capacity (TAC), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Lower TAC, GSH, and SOD levels were consistently associated with poor recovery and multiorgan dysfunction, whereas elevated MDA and 8-OHdG levels correlated with infectious complications, delayed healing, cardiovascular events, persistent pain, and mortality. Antioxidant-based interventions such as vitamin C, N-acetylcysteine, and propofol showed heterogeneous but promising effects, particularly in high-risk surgical populations. The main limitations were the heterogeneity of biomarkers, variability in perioperative protocols, and partial overlap of primary evidence across reviews.

The findings were organized into three main clinical domains: (1) infectious complications and impaired healing; (2) cardiovascular and systemic complications; and (3) predictive and prognostic value of OS biomarkers for perioperative risk assessment. This thematic synthesis integrates evidence across different surgical specialties, highlighting consistent mechanistic patterns and key research gaps to inform future investigations and clinical decision-making.