Perioperative hyperoxia: Myths and realities | Revista Española de Anestesiología y Reanimación (English Edition)

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Ferrando, J. Belda, M. Soro" "autores" => array:3 [ 0 => array:4 [ "nombre" => "C." "apellidos" => "Ferrando" "email" => array:1 [ 0 => "cafeoranestesia@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Belda" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "M." 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Because it is so ubiquitous, and because in our minds it is not considered a drug, observational studies into intraoperatory respiratory management have shown that the adjusted “dose”, in other words, the fraction of inspired oxygen (FIO2), is usually based on the preferences of the anaesthesiologist and local customs instead of clinical evidence.<a class="elsevierStyleCrossRef" href="#bib0280">2</a>The aim of this article is to describe the physiological principles and current evidence that justifies the use of high FIO2 during the perioperative period—an issue that has been extensively, though inconclusively, studied over the past 20 years.Pre-oxygenationThe benefit of administering high FIO2 as a safety mechanism during anaesthetic induction is indisputable; high FIO2 increases body oxygen stores and thereby delays the onset of arterial haemoglobin desaturation during hypoventilation or apnoea.<a class="elsevierStyleCrossRef" href="#bib0285">3</a> Pre-oxygenation increases the fraction of alveolar oxygen (FAO2) and decreases the fraction of alveolar nitrogen (FAN2), which is why it is also called denitrogenation in the literature.<a class="elsevierStyleCrossRef" href="#bib0290">4</a>The efficiency and effectiveness of pre-oxygenation depend on a series of patient-related factors, such as young age, advanced age, obesity or pregnancy. These will not be discussed here, but need to be considered. It can also depend on approach to ventilation, which include techniques aimed at improving alveolar ventilation and residual functional capacity, such as positive continuous airway pressure (CPAP), non-invasive ventilation, and new techniques such as high-flow nasal cannula.<a class="elsevierStyleCrossRefs" href="#bib0295">5–7</a> These techniques have been shown to improve preoxygenation by delaying the onset of arterial haemoglobin desaturation during apnoea.<a class="elsevierStyleCrossRefs" href="#bib0295">5–7</a>The ultimate goal of pre-oxygenation is to achieve an end-tidal oxygen concentration of over 90%, which means around 2000ml of O2 in the lungs and an apnoea tolerance of between 8 and 10min for a normal consumption of O2.<a class="elsevierStyleCrossRef" href="#bib0310">8</a> For the best results (end-tidal oxygen concentration >90%), healthy adults should be pre-oxygenated for between 3 and 5min,<a class="elsevierStyleCrossRef" href="#bib0310">8</a> although this will depend on factors such as alveolar ventilation, functional residual capacity, oxygen consumption, cardiac output, blood oxygen levels, etc.The potential risks associated with preoxygenation are absorption atelectasis, the formation of radical oxygen species, and vasoconstriction. These will be discussed further on. Delayed diagnosis of oesophageal intubation has also been described as a potential complication due to the delay in onset of hypoxaemia.<a class="elsevierStyleCrossRef" href="#bib0290">4</a> However, the routine use of capnography has meant that diagnosis of this complication no longer relies on measuring SpO2 levels.<a class="elsevierStyleCrossRef" href="#bib0315">9</a>Intraoperative and postoperativeSurgical site infection (SSI) is among the potentially more serious postoperative complications. Incidence varies according to surgeries, but can be as high as 30% in patients undergoing colorectal surgery.<a class="elsevierStyleCrossRefs" href="#bib0320">10,11</a> SSI, which can also lead to other complications, such as surgical suture dehiscence, the need for reoperation, sepsis and septic shock,<a class="elsevierStyleCrossRef" href="#bib0330">12</a> has a negative impact on healthcare providers, since it prolongs the hospital stay, significantly increases healthcare costs, and delays the patient's return to their normal activity.<a class="elsevierStyleCrossRefs" href="#bib0320">10,11</a> This led to the launch in 2017 of the Quirúriga Zero Infection [Zero Surgical Infections] project, which was backed by numerous Scientific Societies and sponsored by the Spanish Ministry of Health, Social Services and Equality.<a class="elsevierStyleCrossRef" href="#bib0335">13</a>Anaesthesiologists can adopt a number of measure to prevent SSI, some of which are aimed at optimising the body's innate immunity against surgical pathogens. Neutrophil-mediated oxidative killing of pathogens has been known for some time to be the primary mechanism of defence against surgical pathogens.<a class="elsevierStyleCrossRefs" href="#bib0340">14,15</a> The mechanism is dependent on tissue oxygen pressure (PtO2), which in turn depends directly on arterial partial pressure of oxygen (PaO2).<a class="elsevierStyleCrossRefs" href="#bib0340">14,15</a> This is why measures to increase PtO2, such as increasing cardiac output and fluid therapy, normothermia, analgesic management or epidural anaesthesia, have been shown to reduce SSI.<a class="elsevierStyleCrossRefs" href="#bib0350">16–20</a>Oxygen transport depends directly on cardiac output and arterial oxygen content. With normal cardiac output, haemoglobin concentration >10g/dl, and arterial oxygen saturation >97%, PtO2 can only be increased by increasing PaO2. Tests have shown that, with adequate tissue oxygen perfusion, oxygen supplementation (increase in FIO2) will increase both PaO2 and PtO2.<a class="elsevierStyleCrossRef" href="#bib0375">21</a> This facilitates the oxidative action of neutrophils on the surgical pathogen and explains the improvement in SSI rates.<a class="elsevierStyleCrossRef" href="#bib0380">22</a> Based on this premise, many clinical studies in the last 20 years have compared the perioperative administration of different FIO2 levels and their capacity to reduce SSI. In physio-pathological terms, the potential benefit of increasing FIO2 (up to 80%) is clear. However, the impact of this on SSI is less evident, despite numerous clinical trials. The first trial conducted by Greif et al.<a class="elsevierStyleCrossRef" href="#bib0385">23</a> showed that high FIO2 in 500 patients undergoing colorectal surgery reduced SSI rates. It is important to note that this was the first and only trial to measure PtO2, and showed a significant increase in this parameter with respect to patients receiving low FIO2. These preliminary results were subsequently corroborated by other studies: Belda et al.<a class="elsevierStyleCrossRef" href="#bib0390">24</a> in 300 patients undergoing colorectal surgery, Bickel et al.<a class="elsevierStyleCrossRef" href="#bib0395">25</a> in 210 patients undergoing emergency appendectomy, and Schietroma et al.<a class="elsevierStyleCrossRef" href="#bib0400">26</a> in 171 patients undergoing gastrectomy. In all these cases, the use of high FIO2 was associated with a significant increase in PaO2. In addition to reducing SSI, some also observed a lower rate of suture dehiscence.In contrast, Meyhoff et al.,<a class="elsevierStyleCrossRef" href="#bib0405">27</a> in the largest study conducted so far (PROXI trial), found no differences in 1400 patients undergoing scheduled and urgent abdominal surgery (including appendectomy). Interestingly, in a substudy of the PROXI trial, the authors observed higher long-term mortality in the high FIO2 group, but only in patients undergoing cancer surgery.<a class="elsevierStyleCrossRef" href="#bib0410">28</a> A further study conducted by the same group was unable to corroborate these results, so new evidence is needed to establish a relationship between perioperative FIO2 and mortality.<a class="elsevierStyleCrossRef" href="#bib0415">29</a> Pryor et al.<a class="elsevierStyleCrossRef" href="#bib0420">30</a> not only showed no difference, but observed an increased risk of SSI in patients receiving high FIO2. This study was halted after the first interim analysis due to failure to reach the target sample size. It should be noted that PaO2 was not measured in these 2 trials, and therefore it is not possible to confirm the correlation between high FIO2 and increased PtO2. Kurz et al.<a class="elsevierStyleCrossRef" href="#bib0425">31</a> found no difference in SSI in 586 patients undergoing colorectal surgery. In contrast, they found that SSI was less prevalent among patients with high PaO2. These contrasting results could be due several factors, such as differences in the surgical procedures studied, differences in inclusion criteria (such as the ASA status), in the duration of administration of the different FIOs2 levels, differences in ventilatory management, or in factors that can directly affect SSI, such as glycaemic control, analgesia management, temperature, the transfusion strategy, fluid therapy and haemodynamic status in general, or the use of epidural anaesthesia.Despite the potential limitations of the foregoing studies, their findings have prompted various meta-analyses, reviews and editorials in recent years.<a class="elsevierStyleCrossRefs" href="#bib0430">32–36</a> Different meta-analyses have either shown a benefit in high FIO2 or no difference.<a class="elsevierStyleCrossRefs" href="#bib0430">32–34</a> In 2015, a Cochrane review concluded that there is insufficient evidence to recommend using high FIO2 as a preventive measure for SSI.<a class="elsevierStyleCrossRef" href="#bib0455">37</a> In contrast, in 2017 the World Health Organization,<a class="elsevierStyleCrossRef" href="#bib0460">38</a> the American Society of Surgeons<a class="elsevierStyleCrossRef" href="#bib0465">39</a> and the Centre for Disease Control<a class="elsevierStyleCrossRef" href="#bib0470">40</a> recommended the use of high FIO2 during surgery and the first postoperative hours to prevent SSI. These guidelines have been both criticised and praised in various editorials,<a class="elsevierStyleCrossRefs" href="#bib0450">36,41,42</a> with critics mainly basing their objections on the potential detrimental effects associated with FIO2.Potential risks of high FIO2Absorption atelectasisAbsorption atelectasis during anaesthesia is driven by 2 mechanisms. On the one hand, functional residual capacity is reduced almost to residual volume. The end-tidal volume may be less than the closing volume, leading to the collapse of small airways in the dependent parts of the lung. On the other hand, accumulation of gas causes compression atelectasis, which also compresses the airway. If the airway is closed, or partially closed, any gas that spreads outside the alveolus is lost, due to the capacity of O2 to penetrate the blood-air barrier (alveolar-capillary membrane). The same is not true of N2, however, which is therefore usually found in greater concentrations in the alveoli. It is important to consider 2 factors. First, limiting FIO2 to 80% does not significantly increase these atelectases, even when this percentage is maintained throughout the intervention and not only during induction and eduction.<a class="elsevierStyleCrossRef" href="#bib0485">43</a> Second, physiological studies using imaging techniques have shown that adequate airway pressurisation, either with CPAP or high-flow nasal cannula in spontaneous ventilation or PEEP in controlled ventilation, prevents the appearance of absorption atelectasis.<a class="elsevierStyleCrossRefs" href="#bib0295">5,7,43</a> To date, none of the studies comparing different concentrations of FIO2 have reported a higher incidence of postoperative atelectasis or higher postoperative oxygen requirements in the high FIO2 group.<a class="elsevierStyleCrossRefs" href="#bib0385">23–31</a>Hyperoxic acute lung injuryAlthough hyperoxic acute lung injury has been extensively studied in the literature, there is no evidence of it occurring in humans, and evidence of this entity is entirely based on the results of experimental studies which, due to their setting and methodology, cannot be extrapolated to surgical patients.<a class="elsevierStyleCrossRef" href="#bib0490">44</a> Hyerpoxia increases circulating levels of reactive oxygen species that can overwhelm the body's antioxidant defence system and destroy cellular structures. However, we have observed that hyperoxia reduces oxidative stress in colon and thoracic surgery<a class="elsevierStyleCrossRef" href="#bib0495">45</a> (unpublished results).Evidence shows that, in the absence of ventilator-induced lung injury, the risk of hyperoxic lung injury can be ruled out provided FIO2 is <70%, but problems can arise with FIO2 >80% administered for 24h or more.<a class="elsevierStyleCrossRef" href="#bib0490">44</a> This means that there is no evidence so far to correlate high perioperative FIO2 with acute lung injury. Moreover, a recent study in healthy volunteers that compared high and low FIO2 found no differences in various inflammatory markers of endothelial injury between study groups.<a class="elsevierStyleCrossRef" href="#bib0500">46</a>Regarding the appearance of postoperative pulmonary complications, a recent retrospective analysis of 3035 patients published in 2017 found an association between high intraoperative FIO2 and the appearance of postoperative pulmonary complications.<a class="elsevierStyleCrossRef" href="#bib0505">47</a> This, however, has not been corroborated in any of the randomised clinical trials that included postoperative pulmonary complications as secondary “outcome variables” or in an international prospective observational study in more than 29,000 patients, and also published in 2017.<a class="elsevierStyleCrossRefs" href="#bib0280">2,23–31</a>VasoconstrictionHuman physiological studies have shown that hyperoxia during spontaneous ventilation produces significant coronary vasoconstriction that reduces not only coronary blood flow, but also myocardial oxygen consumption. This is mainly caused by the inhibition of endothelial vasodilators, mainly nitric oxide. Another, albeit undocumented, mechanism that could favour vasoconstriction is the increase in circulating reactive oxygen species.<a class="elsevierStyleCrossRef" href="#bib0510">48</a> The clinical repercussions of hyperoxia-induced coronary vasoconstriction in surgical patients have not been documented. In a recent study in 57 patients, the authors compared the effects of hyperoxia with normoxia in patients undergoing coronary artery bypass surgery, and found no differences between groups in myocardial injury (primary outcome measure), tissue perfusion, oxidative stress and organ function.<a class="elsevierStyleCrossRef" href="#bib0515">49</a>A similar effect has been described in the brain. Various studies have shown that although hyperoxia favours vasoconstriction, it also reduces brain metabolism and cerebral O2 consumption by up to 20%. However, again, there is no evidence that this is clinically relevant in surgical patients.<a class="elsevierStyleCrossRef" href="#bib0520">50</a> A recent study in postoperative coronary artery bypass surgery patients who had received FIO2 of 90% reported clinically non-significant haemodynamic changes associated with high FIO2, but no changes in microcirculation or cerebral blood flow.<a class="elsevierStyleCrossRef" href="#bib0525">51</a>Future research linesThe concept of prehabilitation in surgical patients was introduced some years ago. This technique consists of a series of strategies aimed at optimising the patient's status before surgery in order to maximise postoperative recovery. One of the measures in this programme is physical exercise, which seems to improve tolerance to surgical stress, which many studies have assessed as maximum oxygen uptake (VO2max). Although not yet investigated in Spain, several international studies have analysed the effects of normobaric hyperoxia during physical exercise, which is equivalent to the stress of surgery. Overall, these studies conclude that the administration, however brief, of high FIO2, improves both performance and post-exercise recovery.<a class="elsevierStyleCrossRefs" href="#bib0530">52,53</a> This opens a new door to future studies comparing different FIO2 levels in the surgical patient.In summary, taking into consideration the evidence presented in this review and the recommendations made by different organisations and societies such as the World Health Organisation and the Centre for Disease Control, and awaiting the results of an ongoing study,<a class="elsevierStyleCrossRef" href="#bib0540">54</a> we recommend the use of high perioperative FIO2 in patients undergoing scheduled surgery with general anaesthesia." 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Rev Esp Anestesiol Reanim. 2018;65:183–187." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "This article is part of the Anaesthesiology and Resuscitation Continuing Medical Education Program. An evaluation of the questions on this article can be made through the Internet by accessing the Education Section of the following web page: <a class="elsevierStyleInterRef" target="_blank" id="intr0005" href="http://www.elsevier.es/redar">www.elsevier.es/redar</a>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:54 [ 0 => array:3 [ "identificador" => "bib0275" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An estimation of the global volume of surgery: a modelling strategy based on available data" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.G. Weiser" 1 => "S.E. 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Perioperative hyperoxia: Myths and realities

Hiperoxia perioperatoria: mitos y realidades

C. Ferrandoa,

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cafeoranestesia@gmail.com

Corresponding author.

, J. Beldaa,b, M. Soroa

a Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valencia, Valencia, Spain

b Departamento de Cirugía, Facultad de Medicina, Universidad de Valencia, Valencia, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Millions of patients undergo surgery each year&#44; many of them requiring general anaesthesia&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">1</span></a> All these patients receive the drug most widely used in any operating room&#8212;oxygen&#46; Because it is so ubiquitous&#44; and because in our minds it is not considered a drug&#44; observational studies into intraoperatory respiratory management have shown that the adjusted &#8220;dose&#8221;&#44; in other words&#44; the fraction of inspired oxygen &#40;FIO<span class="elsevierStyleInf">2</span>&#41;&#44; is usually based on the preferences of the anaesthesiologist and local customs instead of clinical evidence&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The aim of this article is to describe the physiological principles and current evidence that justifies the use of high FIO<span class="elsevierStyleInf">2</span> during the perioperative period&#8212;an issue that has been extensively&#44; though inconclusively&#44; studied over the past 20 years&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Pre-oxygenation</span><p id="par0015" class="elsevierStylePara elsevierViewall">The benefit of administering high FIO<span class="elsevierStyleInf">2</span> as a safety mechanism during anaesthetic induction is indisputable&#59; high FIO<span class="elsevierStyleInf">2</span> increases body oxygen stores and thereby delays the onset of arterial haemoglobin desaturation during hypoventilation or apnoea&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">3</span></a> Pre-oxygenation increases the fraction of alveolar oxygen &#40;FAO<span class="elsevierStyleInf">2</span>&#41; and decreases the fraction of alveolar nitrogen &#40;FAN<span class="elsevierStyleInf">2</span>&#41;&#44; which is why it is also called denitrogenation in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The efficiency and effectiveness of pre-oxygenation depend on a series of patient-related factors&#44; such as young age&#44; advanced age&#44; obesity or pregnancy&#46; These will not be discussed here&#44; but need to be considered&#46; It can also depend on approach to ventilation&#44; which include techniques aimed at improving alveolar ventilation and residual functional capacity&#44; such as positive continuous airway pressure &#40;CPAP&#41;&#44; non-invasive ventilation&#44; and new techniques such as high-flow nasal cannula&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#8211;7</span></a> These techniques have been shown to improve preoxygenation by delaying the onset of arterial haemoglobin desaturation during apnoea&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The ultimate goal of pre-oxygenation is to achieve an end-tidal oxygen concentration of over 90&#37;&#44; which means around 2000<span class="elsevierStyleHsp" style=""></span>ml of O<span class="elsevierStyleInf">2</span> in the lungs and an apnoea tolerance of between 8 and 10<span class="elsevierStyleHsp" style=""></span>min for a normal consumption of O<span class="elsevierStyleInf">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">8</span></a> For the best results &#40;end-tidal oxygen concentration &#62;90&#37;&#41;&#44; healthy adults should be pre-oxygenated for between 3 and 5<span class="elsevierStyleHsp" style=""></span>min&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">8</span></a> although this will depend on factors such as alveolar ventilation&#44; functional residual capacity&#44; oxygen consumption&#44; cardiac output&#44; blood oxygen levels&#44; etc&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The potential risks associated with preoxygenation are absorption atelectasis&#44; the formation of radical oxygen species&#44; and vasoconstriction&#46; These will be discussed further on&#46; Delayed diagnosis of oesophageal intubation has also been described as a potential complication due to the delay in onset of hypoxaemia&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">4</span></a> However&#44; the routine use of capnography has meant that diagnosis of this complication no longer relies on measuring SpO<span class="elsevierStyleInf">2</span> levels&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Intraoperative and postoperative</span><p id="par0035" class="elsevierStylePara elsevierViewall">Surgical site infection &#40;SSI&#41; is among the potentially more serious postoperative complications&#46; Incidence varies according to surgeries&#44; but can be as high as 30&#37; in patients undergoing colorectal surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">10&#44;11</span></a> SSI&#44; which can also lead to other complications&#44; such as surgical suture dehiscence&#44; the need for reoperation&#44; sepsis and septic shock&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">12</span></a> has a negative impact on healthcare providers&#44; since it prolongs the hospital stay&#44; significantly increases healthcare costs&#44; and delays the patient&#39;s return to their normal activity&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">10&#44;11</span></a> This led to the launch in 2017 of the <span class="elsevierStyleItalic">Quir&#250;riga Zero Infection</span> &#91;Zero Surgical Infections&#93; project&#44; which was backed by numerous Scientific Societies and sponsored by the Spanish Ministry of Health&#44; Social Services and Equality&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">13</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Anaesthesiologists can adopt a number of measure to prevent SSI&#44; some of which are aimed at optimising the body&#39;s innate immunity against surgical pathogens&#46; Neutrophil-mediated oxidative killing of pathogens has been known for some time to be the primary mechanism of defence against surgical pathogens&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">14&#44;15</span></a> The mechanism is dependent on tissue oxygen pressure &#40;PtO<span class="elsevierStyleInf">2</span>&#41;&#44; which in turn depends directly on arterial partial pressure of oxygen &#40;PaO<span class="elsevierStyleInf">2</span>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">14&#44;15</span></a> This is why measures to increase PtO<span class="elsevierStyleInf">2</span>&#44; such as increasing cardiac output and fluid therapy&#44; normothermia&#44; analgesic management or epidural anaesthesia&#44; have been shown to reduce SSI&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">16&#8211;20</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Oxygen transport depends directly on cardiac output and arterial oxygen content&#46; With normal cardiac output&#44; haemoglobin concentration &#62;10<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; and arterial oxygen saturation &#62;97&#37;&#44; PtO<span class="elsevierStyleInf">2</span> can only be increased by increasing PaO<span class="elsevierStyleInf">2</span>&#46; Tests have shown that&#44; with adequate tissue oxygen perfusion&#44; oxygen supplementation &#40;increase in FIO<span class="elsevierStyleInf">2</span>&#41; will increase both PaO<span class="elsevierStyleInf">2</span> and PtO<span class="elsevierStyleInf">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">21</span></a> This facilitates the oxidative action of neutrophils on the surgical pathogen and explains the improvement in SSI rates&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">22</span></a> Based on this premise&#44; many clinical studies in the last 20 years have compared the perioperative administration of different FIO<span class="elsevierStyleInf">2</span> levels and their capacity to reduce SSI&#46; In physio-pathological terms&#44; the potential benefit of increasing FIO<span class="elsevierStyleInf">2</span> &#40;up to 80&#37;&#41; is clear&#46; However&#44; the impact of this on SSI is less evident&#44; despite numerous clinical trials&#46; The first trial conducted by Greif et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">23</span></a> showed that high FIO<span class="elsevierStyleInf">2</span> in 500 patients undergoing colorectal surgery reduced SSI rates&#46; It is important to note that this was the first and only trial to measure PtO<span class="elsevierStyleInf">2</span>&#44; and showed a significant increase in this parameter with respect to patients receiving low FIO<span class="elsevierStyleInf">2</span>&#46; These preliminary results were subsequently corroborated by other studies&#58; Belda et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">24</span></a> in 300 patients undergoing colorectal surgery&#44; Bickel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">25</span></a> in 210 patients undergoing emergency appendectomy&#44; and Schietroma et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">26</span></a> in 171 patients undergoing gastrectomy&#46; In all these cases&#44; the use of high FIO<span class="elsevierStyleInf">2</span> was associated with a significant increase in PaO<span class="elsevierStyleInf">2</span>&#46; In addition to reducing SSI&#44; some also observed a lower rate of suture dehiscence&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In contrast&#44; Meyhoff et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">27</span></a> in the largest study conducted so far &#40;PROXI trial&#41;&#44; found no differences in 1400 patients undergoing scheduled and urgent abdominal surgery &#40;including appendectomy&#41;&#46; Interestingly&#44; in a substudy of the PROXI trial&#44; the authors observed higher long-term mortality in the high FIO<span class="elsevierStyleInf">2</span> group&#44; but only in patients undergoing cancer surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">28</span></a> A further study conducted by the same group was unable to corroborate these results&#44; so new evidence is needed to establish a relationship between perioperative FIO<span class="elsevierStyleInf">2</span> and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">29</span></a> Pryor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">30</span></a> not only showed no difference&#44; but observed an increased risk of SSI in patients receiving high FIO<span class="elsevierStyleInf">2</span>&#46; This study was halted after the first interim analysis due to failure to reach the target sample size&#46; It should be noted that PaO<span class="elsevierStyleInf">2</span> was not measured in these 2 trials&#44; and therefore it is not possible to confirm the correlation between high FIO<span class="elsevierStyleInf">2</span> and increased PtO<span class="elsevierStyleInf">2</span>&#46; Kurz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">31</span></a> found no difference in SSI in 586 patients undergoing colorectal surgery&#46; In contrast&#44; they found that SSI was less prevalent among patients with high PaO<span class="elsevierStyleInf">2</span>&#46; These contrasting results could be due several factors&#44; such as differences in the surgical procedures studied&#44; differences in inclusion criteria &#40;such as the ASA status&#41;&#44; in the duration of administration of the different FIOs<span class="elsevierStyleInf">2</span> levels&#44; differences in ventilatory management&#44; or in factors that can directly affect SSI&#44; such as glycaemic control&#44; analgesia management&#44; temperature&#44; the transfusion strategy&#44; fluid therapy and haemodynamic status in general&#44; or the use of epidural anaesthesia&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Despite the potential limitations of the foregoing studies&#44; their findings have prompted various meta-analyses&#44; reviews and editorials in recent years&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">32&#8211;36</span></a> Different meta-analyses have either shown a benefit in high FIO<span class="elsevierStyleInf">2</span> or no difference&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">32&#8211;34</span></a> In 2015&#44; a Cochrane review concluded that there is insufficient evidence to recommend using high FIO<span class="elsevierStyleInf">2</span> as a preventive measure for SSI&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">37</span></a> In contrast&#44; in 2017 the World Health Organization&#44;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">38</span></a> the American Society of Surgeons<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">39</span></a> and the Centre for Disease Control<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">40</span></a> recommended the use of high FIO<span class="elsevierStyleInf">2</span> during surgery and the first postoperative hours to prevent SSI&#46; These guidelines have been both criticised and praised in various editorials&#44;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">36&#44;41&#44;42</span></a> with critics mainly basing their objections on the potential detrimental effects associated with FIO<span class="elsevierStyleInf">2</span>&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Potential risks of high FIO<span class="elsevierStyleInf">2</span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Absorption atelectasis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Absorption atelectasis during anaesthesia is driven by 2 mechanisms&#46; On the one hand&#44; functional residual capacity is reduced almost to residual volume&#46; The end-tidal volume may be less than the closing volume&#44; leading to the collapse of small airways in the dependent parts of the lung&#46; On the other hand&#44; accumulation of gas causes compression atelectasis&#44; which also compresses the airway&#46; If the airway is closed&#44; or partially closed&#44; any gas that spreads outside the alveolus is lost&#44; due to the capacity of O<span class="elsevierStyleInf">2</span> to penetrate the blood-air barrier &#40;alveolar-capillary membrane&#41;&#46; The same is not true of N<span class="elsevierStyleInf">2</span>&#44; however&#44; which is therefore usually found in greater concentrations in the alveoli&#46; It is important to consider 2 factors&#46; First&#44; limiting FIO<span class="elsevierStyleInf">2</span> to 80&#37; does not significantly increase these atelectases&#44; even when this percentage is maintained throughout the intervention and not only during induction and eduction&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">43</span></a> Second&#44; physiological studies using imaging techniques have shown that adequate airway pressurisation&#44; either with CPAP or high-flow nasal cannula in spontaneous ventilation or PEEP in controlled ventilation&#44; prevents the appearance of absorption atelectasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#44;7&#44;43</span></a> To date&#44; none of the studies comparing different concentrations of FIO<span class="elsevierStyleInf">2</span> have reported a higher incidence of postoperative atelectasis or higher postoperative oxygen requirements in the high FIO<span class="elsevierStyleInf">2</span> group&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">23&#8211;31</span></a></p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Hyperoxic acute lung injury</span><p id="par0065" class="elsevierStylePara elsevierViewall">Although hyperoxic acute lung injury has been extensively studied in the literature&#44; there is no evidence of it occurring in humans&#44; and evidence of this entity is entirely based on the results of experimental studies which&#44; due to their setting and methodology&#44; cannot be extrapolated to surgical patients&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">44</span></a> Hyerpoxia increases circulating levels of reactive oxygen species that can overwhelm the body&#39;s antioxidant defence system and destroy cellular structures&#46; However&#44; we have observed that hyperoxia reduces oxidative stress in colon and thoracic surgery<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">45</span></a> &#40;unpublished results&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Evidence shows that&#44; in the absence of ventilator-induced lung injury&#44; the risk of hyperoxic lung injury can be ruled out provided FIO<span class="elsevierStyleInf">2</span> is &#60;70&#37;&#44; but problems can arise with FIO<span class="elsevierStyleInf">2</span> &#62;80&#37; administered for 24<span class="elsevierStyleHsp" style=""></span>h or more&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">44</span></a> This means that there is no evidence so far to correlate high perioperative FIO<span class="elsevierStyleInf">2</span> with acute lung injury&#46; Moreover&#44; a recent study in healthy volunteers that compared high and low FIO<span class="elsevierStyleInf">2</span> found no differences in various inflammatory markers of endothelial injury between study groups&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">46</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Regarding the appearance of postoperative pulmonary complications&#44; a recent retrospective analysis of 3035 patients published in 2017 found an association between high intraoperative FIO<span class="elsevierStyleInf">2</span> and the appearance of postoperative pulmonary complications&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">47</span></a> This&#44; however&#44; has not been corroborated in any of the randomised clinical trials that included postoperative pulmonary complications as secondary &#8220;outcome variables&#8221; or in an international prospective observational study in more than 29&#44;000 patients&#44; and also published in 2017&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">2&#44;23&#8211;31</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Vasoconstriction</span><p id="par0080" class="elsevierStylePara elsevierViewall">Human physiological studies have shown that hyperoxia during spontaneous ventilation produces significant coronary vasoconstriction that reduces not only coronary blood flow&#44; but also myocardial oxygen consumption&#46; This is mainly caused by the inhibition of endothelial vasodilators&#44; mainly nitric oxide&#46; Another&#44; albeit undocumented&#44; mechanism that could favour vasoconstriction is the increase in circulating reactive oxygen species&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">48</span></a> The clinical repercussions of hyperoxia-induced coronary vasoconstriction in surgical patients have not been documented&#46; In a recent study in 57 patients&#44; the authors compared the effects of hyperoxia with normoxia in patients undergoing coronary artery bypass surgery&#44; and found no differences between groups in myocardial injury &#40;primary outcome measure&#41;&#44; tissue perfusion&#44; oxidative stress and organ function&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">49</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">A similar effect has been described in the brain&#46; Various studies have shown that although hyperoxia favours vasoconstriction&#44; it also reduces brain metabolism and cerebral O<span class="elsevierStyleInf">2</span> consumption by up to 20&#37;&#46; However&#44; again&#44; there is no evidence that this is clinically relevant in surgical patients&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">50</span></a> A recent study in postoperative coronary artery bypass surgery patients who had received FIO<span class="elsevierStyleInf">2</span> of 90&#37; reported clinically non-significant haemodynamic changes associated with high FIO<span class="elsevierStyleInf">2</span>&#44; but no changes in microcirculation or cerebral blood flow&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">51</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Future research lines</span><p id="par0090" class="elsevierStylePara elsevierViewall">The concept of prehabilitation in surgical patients was introduced some years ago&#46; This technique consists of a series of strategies aimed at optimising the patient&#39;s status before surgery in order to maximise postoperative recovery&#46; One of the measures in this programme is physical exercise&#44; which seems to improve tolerance to surgical stress&#44; which many studies have assessed as maximum oxygen uptake &#40;VO<span class="elsevierStyleInf">2</span><span class="elsevierStyleSup">max</span>&#41;&#46; Although not yet investigated in Spain&#44; several international studies have analysed the effects of normobaric hyperoxia during physical exercise&#44; which is equivalent to the stress of surgery&#46; Overall&#44; these studies conclude that the administration&#44; however brief&#44; of high FIO<span class="elsevierStyleInf">2</span>&#44; improves both performance and post-exercise recovery&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">52&#44;53</span></a> This opens a new door to future studies comparing different FIO<span class="elsevierStyleInf">2</span> levels in the surgical patient&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In summary&#44; taking into consideration the evidence presented in this review and the recommendations made by different organisations and societies such as the World Health Organisation and the Centre for Disease Control&#44; and awaiting the results of an ongoing study&#44;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">54</span></a> we recommend the use of high perioperative FIO<span class="elsevierStyleInf">2</span> in patients undergoing scheduled surgery with general anaesthesia&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ferrando C&#44; Belda J&#44; Soro M&#46; Hiperoxia perioperatoria&#58; mitos y realidades&#46; Rev Esp Anestesiol Reanim&#46; 2018&#59;65&#58;183&#8211;187&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">This article is part of the Anaesthesiology and Resuscitation Continuing Medical Education Program&#46; An evaluation of the questions on this article can be made through the Internet by accessing the Education Section of the following web page&#58; <a class="elsevierStyleInterRef" target="_blank" id="intr0005" href="http://www.elsevier.es/redar">www&#46;elsevier&#46;es&#47;redar</a></p>"
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