Benefits and harms of perioperative high fraction inspired oxygen for surgical site infection prevention: a protocol for a systematic review and meta-analysis of individual patient data of randomised controlled trials.

INTRODUCTION: The use of high fraction of inspired oxygen (FiO2) intraoperatively for the prevention of surgical site infection (SSI) remains controversial. Promising results of early randomised controlled trials (RCT) have been replicated with varying success and subsequent meta-analysis are equivocal. Recent advancements in perioperative care, including the increased use of laparoscopic surgery and pneumoperitoneum and shifts in fluid and temperature management, can affect peripheral oxygen delivery and may explain the inconsistency in reproducibility. However, the published data provides insufficient detail on the participant level to test these hypotheses. The purpose of this individual participant data meta-analysis is to assess the described benefits and harms of intraoperative high FiO2compared with regular (0.21-0.40) FiO2 and its potential effect modifiers. METHODS AND ANALYSIS: Two reviewers will search medical databases and online trial registries, including MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and WHO regional databases, for randomised and quasi-RCT comparing the effect of intraoperative high FiO2 (0.60-1.00) to regular FiO2 (0.21-0.40) on SSI within 90 days after surgery in adult patients. Secondary outcome will be all-cause mortality within the longest available follow-up. Investigators of the identified trials will be invited to collaborate. Data will be analysed with the one-step approach using the generalised linear mixed model framework and the statistical model appropriate for the type of outcome being analysed (logistic and cox regression, respectively), with a random treatment effect term to account for the clustering of patients within studies. The bias will be assessed using the Cochrane risk-of-bias tool for randomised trials V.2 and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. Prespecified subgroup analyses include use of mechanical ventilation, nitrous oxide, preoperative antibiotic prophylaxis, temperature (<35°C), fluid supplementation (<15 mL/kg/hour) and procedure duration (>2.5 hour). ETHICS AND DISSEMINATION: Ethics approval is not required. Investigators will deidentify individual participant data before it is shared. The results will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42018090261.

The Effect of Hyperbaric Oxygen Therapy on Markers of Oxidative Stress and the Immune Response in Healthy Volunteers.

Hyperbaric oxygen therapy (HBOT) consists of breathing 100% oxygen under increased ambient pressure. There are indications that HBOT induces oxidative stress and activates immune pathways. However, previous research on immunological effects of HBOT has mainly been established in in vitro experiments and selected patient populations, limiting generalizability and increasing the chances of confounding by comorbidities and specific patient-related factors. More insight into the immunological effects of HBOT would aid investigation and comprehension of potentially novel treatment applications. Therefore, in this study, we investigated the effects of three 110-min HBOT-sessions with 24-h intervals on immunological parameters in healthy, young, male volunteers. Blood samples were obtained before and after the first and third HBOT sessions. We assessed neutrophilic reactive oxygen species (ROS) production, systemic oxidative stress [plasma malondialdehyde (MDA) concentrations] as well as neutrophil phagocytic activity, plasma concentrations of tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and IL-10, and production of TNF, IL-6, and IL-10 by leukocytes ex vivo stimulated with the Toll-like receptor (TLR) ligands lipopolysaccharide (TLR4) and Pam3Cys (TLR2). We observed decreased neutrophilic ROS production and phagocytosis following the second HBOT session, which persisted after the third session, but no alterations in MDA concentrations. Furthermore, plasma concentrations of the investigated cytokines were unaltered at all-time points, and ex vivo cytokine production was largely unaltered over time as well. These results indicate no induction of systemic oxidative stress or a systemic inflammatory response after repeated HBOT in healthy volunteers but may suggest exhaustion of ROS generation capacity and phagocytosis.

The Effects of Hyperbaric Oxygenation on Oxidative Stress, Inflammation and Angiogenesis.

Hyperbaric oxygen therapy (HBOT) is commonly used as treatment in several diseases, such as non-healing chronic wounds, late radiation injuries and carbon monoxide poisoning. Ongoing research into HBOT has shown that preconditioning for surgery is a potential new treatment application, which may reduce complication rates and hospital stay. In this review, the effect of HBOT on oxidative stress, inflammation and angiogenesis is investigated to better understand the potential mechanisms underlying preconditioning for surgery using HBOT. A systematic search was conducted to retrieve studies measuring markers of oxidative stress, inflammation, or angiogenesis in humans. Analysis of the included studies showed that HBOT-induced oxidative stress reduces the concentrations of pro-inflammatory acute phase proteins, interleukins and cytokines and increases growth factors and other pro-angiogenesis cytokines. Several articles only noted this surge after the first HBOT session or for a short duration after each session. The anti-inflammatory status following HBOT may be mediated by hyperoxia interfering with NF-κB and IκBα. Further research into the effect of HBOT on inflammation and angiogenesis is needed to determine the implications of these findings for clinical practice.