Oxygen is one of the most common and overused interventions in hospitals. It is a crucial component of atmospheric air, comprising approximately 21%, and is vital to numerous bodily functions and processes. While once reserved to treat and support patients with various life-threatening lung diseases, it has increasingly been routinely employed to prevent hypoxemia, particularly in the perioperative setting. In the OR, much of patient care revolves around oxygen. This includes everything from preoxygenation, to providing adequate oxygenation during the case, to oxygen uptake and delivery to vital organs, to preventing hypoxemia to reduce mortality in scenarios such as traumatic brain injury, and finally to providing sufficient oxygenation to prevent postoperative respiratory insufficiency on emergence. While oxygen is vital to life and an important element of patient care, many providers fail to recognize the harms of over-oxygenation, notwithstanding normal oxygen levels in most patients. Even though oxygen delivery in the hospital setting is an important topic, guidance on a justifiable intraoperative fraction of inspired oxygen (FiO2) is lacking.
We recognize a normal partial pressure of arterial oxygen (PaO2) of ~75-100 mmHg and a normal alveolar oxygen tension (PAO2) of ~110 mmHg at sea level. At altitude, however, this alveolar oxygen tension drops and can be as low as ~85 mmHg in cities such as Salt Lake City, Utah. This is the equivalent of breathing ~18% FiO2 (BMJ 1998;317:1063-6; Am J Respir Crit Care Med 1999;160:1525-31). Insightful studies from atop Mt. Everest further help us to appreciate the low level of PaO2 necessary for mitochondrial function (N Engl J Med 2009;360:140-9; J Physiol 2016;594:1137-49). It is also interesting to note the variation in oxygen tension between organs. It has been suggested that kidney function has evolved by including a preglomerular arteriovenous shunt to protect the tissue from hyperoxia (Physiol Rev 2019;99:161-234). In the setting of this intriguing research, guidelines for the minimization of intraoperative oxygen therapy would appear relevant and necessary.
The World Health Organization recommends providing >80% FiO2 during general anesthesia to decrease the incidence of surgical site infections (asamonitor.pub/43AYgSG). This recommendation remains somewhat contentious as several potential adverse effects are associated with hyperoxemia (defined as a PaO2 >100 mmHg) (Rev Med Interne 2019;40:670-6). For example, hyperoxemia may cause ventilation/perfusion (V/Q) mismatch and oxygen-induced hypercapnia by inhibiting hypoxic pulmonary vasoconstriction, thereby increasing blood flow to poorly ventilated alveoli (Rev Med Interne 2019;40:670-6; Thorax 2017;72:ii1-ii90). Oxygen-induced hypercapnia is particularly harmful in patients with COPD and obesity hypoventilation syndrome. It abolishes the central nervous system’s hypoxic respiratory drive, releases CO2 from hemoglobin (Haldane effect), and increases dead-space ventilation (Rev Med Interne 2019;40:670-6). Furthermore, exposure to high oxygen concentration (i.e., FiO2 >0.6 for ≥24 h) expedites the formation of reactive oxygen species (ROS), leading to oxidative stress, which triggers the activation of innate immune responses that cause cell damage and apoptosis (Rev Med Interne 2019;40:670-6). The lungs are especially susceptible to damage from ROS, inducing alveolar damage and destruction of the epithelium of the tracheobronchial tree. This may manifest as retrosternal burning or tightness, chest pain, and dyspnea (Rev Med Interne 2019;40:670-6; BJA Educ 2019;19:176-82). High oxygen concentrations in the perioperative setting may delay the recognition and treatment of postoperative respiratory insufficiency and may also lead to absorption atelectasis, resulting in an unnecessary postoperative pulmonary complication (Rev Med Interne 2019;40:670-6; BJA Educ 2019;19:176-82). It may also exacerbate lung injury by upregulating pro-inflammatory cytokines and activating alveolar capillary endothelial cells, both triggering and worsening pulmonary conditions such as ARDS (Crit Care Med 2004;32:2496-2501; Am J Respir Cell Mol Biol 2006;34:453-63). Additionally, the benefit of oxygen therapy in ischemic diseases, such as myocardial infarction and stroke, has been questioned due to a lack of demonstrated improved outcomes and increased morbidity (Rev Med Interne 2019;40:670-6; BMJ 1976;1:1121-3).
While most of our surgical patients are not critically ill or suffering from life-threatening pathologies exacerbated by hyperoxemia, the side effect profile of high oxygen concentration should certainly not be considered innocuous. Chu et al. performed a meta-analysis of studies that revealed hyperoxemia is toxic at high FiO2 concentrations and may increase patient mortality (Rev Med Interne 2019;40:670-6; Lancet 2018;391:1693-1705). It is unsurprising that lung-protective ventilatory strategies adopted by intensivists dictate the provision of a modest amount of oxygen to maintain SpO2 >88% in patients with acute or chronic pulmonary pathology and ARDS. Additionally, there are significant circadian variations in oxygen saturation, particularly in the elderly and patients with obstructive sleep apnea; thus, it is reasonable to target an SpO2 of 88%-92% (Chest 1996;110:1489-92). Lung-protective ventilatory strategies have increasingly been adopted in the perioperative arena, and there has been an associated decrease in postoperative pulmonary complications (BMJ 2015;351:h3646). Unfortunately, there remains a paucity of literature regarding recommendations for FiO2 administration in the operative setting.
Thus, we ask whether we are causing more injury than we realize because most of our patients seemingly tolerate the administration of supratherapeutic oxygen levels. If there are a myriad of adverse effects but a small handful of beneficial effects, how do we weigh the risks and benefits? For now, it is imperative to recognize that oxygen is not risk-free, and administration should be tailored to each patient while factoring in the risk-benefit ratio. The goal should be to achieve optimal tissue oxygenation, not maximal oxygenation (BMJ 2002;324:1406-7). As more research on oxygen administration is being conducted, we can generally adhere to the following recommendations: Oxygen should not be administered until SpO2 falls below 90%-92%; in patients at risk of oxygen-induced hypercapnia, this threshold should be lowered to 88%; oxygen administration should be carefully monitored for adverse effects and titrated to a target SpO2 of 93%-96% (Rev Med Interne 2019;40:670-6; Thorax 2017;72:ii1-ii90; Lancet 2018;391:1693-1705; Respirology 2015;20:1182-91; BMJ 2018;363:k4169). It is paramount to recognize that too much of a good thing may not be so good.