Perioperative oxygenation-what's the stress?

Abstract

Oxygen is the most used drug in anaesthesia. Despite such widespread use, optimal perioperative oxygen administration remains highly controversial because of concerns about the competing harms of both hyperoxia and hypoxia. Notwithstanding a Cochrane review concluding that routinely administering a fractional inspired oxygen concentration (FiO₂) >0.6 intraoperatively might increase postoperative morbidity and mortality, the World Health Organization (WHO) currently recommends all anaesthetised patients receive 0.8 FiO₂ during and immediately after surgery to reduce surgical site infections. Results from the largest trial available at the time of these two reviews (suggesting long-term survival may be worse with high FiO₂, particularly in patients with malignant disease) were considered 'biologically implausible' by the WHO's Guideline Development Group. In addition, the integrity of some perioperative oxygen studies has been challenged. Resolving these controversies is of fundamental importance to all perioperative clinicians. This narrative review is based on the inaugural BJA William Mapleson lecture delivered by the senior author (AC) at the 2023 annual meeting of the Royal College of Anaesthetists in Birmingham. We present the current evidence for perioperative oxygen administration and contrast this with how oxygen therapy is targeted in other specialties (e.g. intensive care medicine). We will explore whether anaesthetists follow the WHO recommendations and consider how oxygen administration affects the stress response to surgery. We reason that novel clinical trial designs in combination with targeted experimental medicine studies will be required to improve our understanding of how best to optimise individualised perioperative oxygenation-a cornerstone of anaesthesia.

Keywords: hyperoxia; hypoxia; oxidative stress; oxygen therapy; surgical site infections.

Fig 1

The 2018 recommendation for perioperative oxygenation from the World Health Organization's global guidelines for the prevention of surgical site infections. SSI, surgical site infection.

Fig 2

Timeline summarising some of the key events in more than two decades of research investigating the effect intraoperative oxygen administration has on surgical site infections (SSIs). After the first study exploring if ‘high’ (0.8) FiO₂ might reduce SSI rates compared with ‘low’ (0.3) FiO₂ reported in 2000, long-term follow-up of patients in the Danish PROXI trial suggested higher rates of adverse outcomes (including higher mortality) with 0.8 FiO₂. The World Health Organization (WHO) recommendations were first published in 2016 and reviewed again in 2018, shortly before several studies reported that anaesthetists often do not follow these recommendations internationally. More recent trials (e.g. the Australasian HOT-ROX) are now including a ‘usual care’ arm (i.e. FiO₂ around 0.5) and ‘high’ and ‘low’ groups.

Fig 3

Oxygen is fully reduced to water by gaining four electrons (blue arrows) in the mitochondrial respiratory chain (top line). Incomplete oxygen reduction results in the production of the reactive intermediates superoxide (O₂^•−), hydrogen peroxide (H₂O₂), and hydroxyl radicals (^•OH), respectively. These intermediates can go on to react with other cell constituents (red arrows) such as metal ions (e.g. Fe²⁺ in haemoproteins), thiols (e.g. glutathione) or compounds in the cell nucleus (e.g. DNA).