Perioperative hyperoxia: Myths and realities

Ferrando, C.; Belda, J.; Soro, M.
doi:10.1016/j.redare.2017.12.011
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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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