Globally, oxygen is the most used drug in perioperative medicine; it is used in any surgery, patient or condition. Its perioperative use is so widespread that in many cases we forget that it is a drug and we use oxygen indiscriminately. Like any drug we use, we must know its effects on the organism, its indications and contraindications.1 the current target for perioperative use of oxygen is not uniformly standardised. Many anesthetists titrate inspiratory oxygen fraction (FiO2) to achieve a normal peripheral blood oxygen saturation (SpO2), whereas others give higher FiO2 to increase the arterial partial pressure of oxygen (PaO2) to supranormal levels (hyperoxia) in an attempt to protect vulnerable organs in high-risk patients or during high-risk procedures.2
One of the major sources of variability in the established use of Oxygen concentration in anaesthesia practice is related to the dual nature of this gas, with its beneficial profile in treating hypoxaemia and its deleterious effects producing reactive oxygen metabolites (ROMs) with hyperoxemia. the oxidative stress resulting from these ROMs is a primary cause of DNA damage, impairment of mitochondrial function and organ injuries affecting the brain and lung parenchyma primarily.2–4 In the last times, several systematic reviews and meta-analyses provide evidence of the risks/benefits of oxygen at different concentrations, but there are not clear-cut conclusions. This discrepancy in the scientific literature is mainly attributable to the multiple factors affecting perioperative care.3 Perioperative medicine is generally a very safe period with few serious complications in the immediate postoperative hours, so it therefore requires a much larger sample size to detect relevant differences in harm due to hyperoxia compared with critically ill patients.4 Research groups in emergency medicine and critical care have published several studies and meta-analyses showing significantly increased mortality attributed to liberal oxygen therapy,5 and they have even moved forward to establishing specific SpO2 targets for stopping and restarting oxygen if needed.
Perioperatively, pre-oxygenation is standard practice during induction of anesthesia. It produces hyperoxemia to increase time to obtain tracheal intubation.1 Delivering 100% oxygen substantially extends the time to arterial desaturation in the event of loss of airway patency following induction. If airway obstruction occurs in a patient breathing air, desaturation occurs in 1 min.6 With pre-oxygenation, this time is increased to 6 minutes.7 the use of high concentrations of oxygen further enhances ventilation defects by inducing airway closure and alveolar collapse. the kinetics of such oxygen-absorption atelectasis development is primarily determined by the alveolar concentration of oxygen and time of administration. Some previous studies involving the use of lung imaging techniques have established the existence of a threshold FiO2, provided at the induction of anaesthesia until no clinically significant areas of alveolar derecruitment remain. Exceeding the critical threshold of FIO2 of 80% leads to the rapid development of alveolar collapse.8 9 Also, Lung imaging studies have revealed that alveolar collapse persists despite the application of recruitment manoeuvres when a high concentration of oxygen is maintained during anaesthesia.9
An interesting confirmatory study summarizes these ideas,10 this study showed that during pre-oxygenation with 100% oxygen time to desaturation (SpO2<90%) extends to 6.5 min but it produces 5.6% of atelectasis. When 80% oxygen was used during pre-oxygenation time to desaturation extends to 5 min, but the production of atelectasis was almost four times lower 1.3%. These data provide compelling evidence that allowing patients to breathe air on induction of anesthesia is a high-risk strategy, but using 100% oxygen is also potentially harmful. Probably, pre-oxygenate with a FiO2 of 80% will be the best option to reduce atelectasis extending time to arterial desaturation during apnoea. 100% oxygen should be reserved for patients at particularly high risk. In these cases to apply CPAP during pre-oxygenation and after intubation, FiO2 reduction, recruitment manoeuvre and optimal PEEP should follow as soon as feasible.
In addition to these adverse pulmonary effects, anaesthetic management of age and COPD patients demands special attention; hyperoxia compromises the contractile function of the diaphragm in aged subjects.11 This disorder is related to hyperoxia-induced exacerbation of the generalized skeletal muscle destruction with age. Furthermore, in COPD patients even a modest increase in FiO2 (30%) for a short period (1h) leads to oxidative stress and airway inflammation. Both related to the pathogenesis of COPD.12 High FiO2 intraoperatively is related to a greater propensity to alveolar collapse (as described above), and High FiO2 after surgery suppresses hypoxic drive, which is crucial in maintaining alveolar ventilation in the presence of COPD. Thus, in the patients at high risk of hypercapnia, Oxygen should be carefully titrated in order to target Oxygen saturation between 88 and 92%.13
There is a general misbelief among clinicians that elevation of FiO2 results in increased oxygen transport capacity, thereby improving oxygenation at the level of the microcirculation. Blood oxygen content equation determines that when haemoglobin is fully saturated under physiological conditions, an increase in the arterial partial pressure of oxygen (PaO2) increases blood oxygen content only marginally.14 In contrast, High PaO2 concentration increases systemic vascular resistance; this leads to a decrease in cardiac output via both increased afterload and decreased preload.15 Due to these cardiovascular alterations, hyperoxygenation can reduce tissue perfusion and compromise oxygen transport. This effect is confirmed in studies where FiO2 of 100% compared with 30% reduces cardiac index by 4–6% in health ASA physical status I-II patients.16
In this line, a recent Cochrane review17 suggests that high concentration oxygen therapy may be harmful to patients with myocardial injury through mechanisms like reduced coronary arterial flow, reactive oxygen species, increased coronary and systemic vascular resistance, and reperfusion injury with oxidative stress and DNA damage. the adverse cardiovascular effects of giving high oxygen concentration have led to a change in resuscitation guidelines. the European Resuscitation Council Guidelines now recommend18 that patients should only be ventilated with 100% oxygen during cardiopulmonary resuscitation, but after return of spontaneous circulation, the inspired oxygen concentration should be titrated to achieve arterial oxygen saturation (SpO2) between 94 and 98%, or 88–92% if the patient is at risk of hypercapnic respiratory failure.
About the brain physiology, supplementing oxygen preoperatively leads to an increase in cerebral vascular resistance, with a subsequent decrease in cerebral blood flow, independently of the effect of CO2 on cerebral vasoreactivity.19 These effects on the cerebral vasculature have to be taken into account in routine clinical practice, where perioperative ventilation with high concentrations of oxygen is often performed arbitrarily in the context of traumatic brain injury or post-resuscitation. the frequently associated hypocapnia attributable to mechanical ventilation linked to the administration of high concentrations of oxygen can intensify cerebral vascular ischaemia.
Finally, since 2000 some articles reported that high perioperative FiO2 has a beneficial effect on surgical site infection (SSI) because adequate oxygen delivery to the wound facilitates bacterial killing by neutrophils and reduce SSI. the World Health Organization (WHO) published a comprehensive systematic review of SSI prevention in 2016 recommending 80% oxygen perioperatively.20 This meta-analysis of perioperative oxygen showed no overall significant benefit with hyperoxia on SSI. Only a subgroup analysis of trials where patients had oxygen therapy given through a tracheal tube resulted in significant benefit. Recently, WHO reviews perioperative hyperoxia comparing 80% vs 30% FiO2. In these meta-analyses21 22 they found no differences in the rates of atelectasis, cardiovascular events, ICU admission, and mortality. Although previous data suggest increased long-term mortality with perioperative 80% oxygen.23 the WHO founds small benefits on SSI with 80% FiO2 in intubated patients. a relative risk reduction (RRR) of 5%. Despite no overall benefit when including studies with oxygen therapy given through face masks. Against this, the World Federation of Societies of Anaesthesiologists (WFSA) recommends FiO230%–40% for general anaesthesia in intubated patients intraoperatively, and suggests using FiO2 to maintain a normal peripheral oxygen saturation, above 93%, postoperatively.24 Also, the latest Cochrane review to conclude that there is ‘insufficient evidence to support the routine use of high fraction of inspired oxygen beyond what is needed to maintain normal arterial oxygen saturation.25
As a conclusion, oxygen is a safe drug and using it to prevent hypoxemia is mandatory. All the problems described with oxygen, come from an overdose of oxygen, hyperoxia. the anesthesiologist must know the physiological effects produced by oxygen and the risks and benefits of hyperoxia. the objective is to use the most beneficial and safe oxygen concentration in each patient and each situation.
Ferrando C, Belda J, Soro M.. Perioperative hyperoxia: Myths and realities. Rev Esp Anestesiol Reanim 2018 Apr;65(4):183–187.
Meyhoff, Christian S. Perioperative hyperoxia: why guidelines, research and clinical practice collide. Br J Anaesth 2019 Mar;122(3):289–291.
Habre W, Peták F. Perioperative use of oxygen: variabilities across age. Br J Anaesth 2014 Dec;113Suppl 2:ii26–36.
Lumb A, Walton L. Perioperative Oxygen Toxicity. Anesthesiology Clin 2012;30(2012):591–605.
Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet 2018;391:1693–705.
Farmery AD, Roe PG. A model to describe the rate of oxyhaemoglobin desaturation during apnoea. Anaesthesia 1996;76:284–91.
Jense HG, Dubin SA, Silverstein PI, et al. Effect of obesity on safe duration of apnoea in anesthetized humans. Anesth Analg 1991;72:89–93.
Magnusson L, Spahn DR. New concepts of atelectasis during general anaesthesia. Br J Anaesth 2003;91:61–72.
Rothen HU, Sporre B, Engberg G, Wegenius G, Hogman M, Hedenstierna G. Influence of gas composition on recurrence of atelectasis after a reexpansion maneuver during general anesthesia. Anesthesiology 1995;82:832–42.
Edmark L, Kostova-Aherdan K, Enlund M, et al. Optimal oxygen concentration during induction of general anesthesia. Anesthesiology 2003;98:28–33.
Andrade PV, dos Santos JM, et al. Influence of hyperoxia and mechanical ventilation in lung inflammation and diaphragm function in aged versus adult rats. Inflammation 2014;37:486–94.
Carpagnano GE, Kharitonov SA, et al. Supplementary oxygen in healthy subjects and those with COPD increases oxidative stress and airway inflammation. Thorax 2004;59:1016–1019.
Decalmer S, O’Driscoll BR. Oxygen: friend or foe in peri-operative care? Anaesthesia 2013;68:8–12.
Lumb AB. Nunn’s Applied Respiratory Physiology. New York: Churchill Livingstone, 2010.
Park JH, Balmain S, Berry C, et al. Potentially detrimental cardiovascular effects of oxygen in patients with chronic left ventricular systolic dysfunction. Heart 2010; 96:533–8.
Anderson KJ, Harten JM, Booth MG, Kinsella J. the cardiovascular effects of inspired oxygen fraction in anaesthetized patients. Eur J Anaesthesiol 2005;22:420–5.
Cabello JB, Burls A, Emparanza JI, et al. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev 2010:CD007160.
Nolan JP, Soar J, Zideman DA, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 1: executive summary. Resuscitation 2010; 81:1219–1276.
Floyd TF, Clark JM, Gelfand R, et al. Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA. J Appl Physiol (1985) 2003;95:2453–61.
Allegranzi B, Zayed B, Bischoff P, et al. New WHO recommendations on intraoperative and postoperative measures for surgical site infection prevention: an evidence-based global perspective. Lancet Infect Dis 2016;16:e288–303.
de Jonge S, Egger M, Latif A, et al. Effectiveness of 80% vs 30–35% fraction of inspired oxygen in patients undergoing surgery: an updated systematic review and metaanalysis. Br J Anaesth 2019 Mar;122(3):325–334.
Mattishent K, Thavarajah M, Sinha A, et al. Safety of 80% vs 30–35% fraction of inspired oxygen in patients undergoing surgery: a systematic review and meta-analysis. Br J Anaesth 2019 Mar;122(3):311–324.
Meyhoff CS, Jorgensen LN, Wetterslev J, Christensen KB, Rasmussen LS. Increased long-term mortality after a high perioperative inspiratory oxygen fraction during abdominal surgery: follow-up of a randomized clinical trial. Anesth Analg 2012;115:849–54.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.