Editorial article
New anesthetic considerations in thoracic surgery
Nuevas consideraciones anestésicas en cirugía torácica
Departamento de Anestesiología y Reanimación, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Sarrais Polo, A. Alonso Morenza, J. Rey Picazo, L. Álvarez Mercadal, R. Beltrao Sial, C. Aguilar Lloret" "autores" => array:6 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Sarrais Polo" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Alonso Morenza" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Rey Picazo" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Álvarez Mercadal" ] 4 => array:2 [ "nombre" => "R." "apellidos" => "Beltrao Sial" ] 5 => array:2 [ "nombre" => "C." "apellidos" => "Aguilar Lloret" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0034935617302256" "doi" => "10.1016/j.redar.2017.10.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0034935617302256?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341192918300027?idApp=UINPBA00004N" "url" => "/23411929/0000006500000003/v3_201803240409/S2341192918300027/v3_201803240409/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial article</span>" "titulo" => "New anesthetic considerations in thoracic surgery" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "125" "paginaFinal" => "128" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "F. de la Gala, I. Garutti" "autores" => array:2 [ 0 => array:4 [ "nombre" => "F." "apellidos" => "de la Gala" "email" => array:1 [ 0 => "galareyes@telefonica.net" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "I." "apellidos" => "Garutti" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Departamento de Anestesiología y Reanimación, Hospital General Universitario Gregorio Marañón, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nuevas consideraciones anestésicas en cirugía torácica" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">For more than 50 years we have known that perioperative surgical stress induces an endocrine-metabolic inflammatory response that is more intense in major surgery. However, the contribution of anaesthetic agents to this response has been much less studied, although they are known to have less impact on inflammation than surgical trauma. Moreover, anaesthetics are thought to have little or no effect the inflammatory response in healthy patients receiving anaesthesia for short surgical procedures. However, in immunocompromised patients (oncological, diabetic, advanced age, malnourished), anaesthetic agents may exert an important immunosuppressive effect.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Various clinical studies have previously linked the intensity of the perioperative inflammatory response with the postoperative prognosis.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">2,3</span></a> This is why the use of surgical and anaesthetic techniques aimed at attenuating the exaggerated postoperative proinflammatory response has become standard clinical practice, particularly in high-risk patients.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Regarding the anaesthetic technique, there is a broad consensus that regional anaesthesia attenuates the inflammatory response,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">6</span></a> while the most commonly used anaesthetic agents (morphine derivatives or hypnotics) impair this response to varying degrees. Most data available on the relationship between anaesthetic agents and inflammatory response comes from experimental studies.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">7,8</span></a> However, the results of these studies cannot be directly translated into clinical practice, as inflammation will be influenced by the intensity of the surgical stress, the preoperative status of the patient and their genetic predisposition to respond to surgery-induced immune system aggression. The number of studies analysing the effect of anaesthesia on the prognosis of cancer patients highlights the concern currently surrounding the issue of surgery-induced inflammatory response. Unfortunately, the findings of these studies are inconsistent and no clear evidence will be available until randomised clinical trials are conducted.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">There no clear consensus on the benefits and drawback of the hypnotic agents widely used in clinical practice (propofol versus halogenated agents), although some studies have suggested that in patients undergoing minor surgery, propofol has less effect on the postoperative inflammatory response than halogenated anaesthetics. However, studies in major surgery in major interventions, such as cardiothoracic surgery, have shown the opposite to be true, namely, that halogenated agents reduce the inflammatory response.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">2,11–13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Pulmonary resection surgery is a major intervention usually performed to remove a lung tumour. In addition to surgery-induced changes in the inflammatory response, this procedure is known to induce a certain degree of lung damage, particularly due to the use of single lung ventilation (OLV), during which alveolar concentrations of proinflammatory mediators increase and are released into the systemic circulation (decompartmentalisation).<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Various physiopathological explanations for the increase in pulmonary inflammatory response during OLV have been put forward,<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">15</span></a> and can be summarised thus:</p><p id="par0035" class="elsevierStylePara elsevierViewall">First, ventilator-induced lung injury, usually associated with low compliance, high airway pressures and a relatively high tidal volume, increase the susceptibility of the lung to volutrauma and atelectasis, despite the use of protective ventilation and “permissive” hypercapnia.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">16</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Inhalation anaesthetics and propofol are potent bronchodilators. In thoracic surgery patients, who frequently present a certain degree of bronchial hyperresponsiveness, these agents can facilitate the entry of air into the alveoli and reduce airway pressures. However, although the anticholinergic properties of both propofol and halogenated agents act indirectly on airway smooth muscle, halogenated agents directly relax the airway by reducing calcium concentrations and altering homeostasis, and therefore have a greater bronchodilator effect than propofol. In fact, inhalation anaesthetics, particularly sevoflurane, are first choice due to their protective effect against bronchial constriction.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">17</span></a> The greater bronchodilatory effect of halogenated agents reduces airway pressure during the delicate OLV period. Not all inhalation anaesthetics have the same beneficial effects on the airway. Differences have been observed between the two most commonly used today (sevoflurane and desflurane), insofar as several studies show that the bronchodilatory effects of desflurane disappear when the MAC is above 1, whereas the bronchodilatory effect of sevoflurane not dose-dependent, and the bronchodilatory effect is maintained at doses higher than 1 MAC.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">18</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Secondly, the operated lung is damaged by both surgical manipulation of the lung parenchyma and by ischaemia-reperfusion (IR).<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">16</span></a> IR injury occurs even though bronchial circulation is maintained without ventilation. The absence of ventilation in the operated lung triggers hypoxic pulmonary vasoconstriction (HPV) in that lung, which decreases the blood supply and causes a hypoxic environment in lung tissue. Subsequent pulmonary reventilation will cause a certain degree of IR injury, which has been associated with the post-OLV pulmonary inflammatory response.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">19</span></a> Anaesthetic agents can also play an important role in this injury. Inhalation anaesthetics, particularly sevoflurane, are known to cause a preconditioning phenomenon that protects the cells that will be affected by low oxygen levels and subsequent reperfusion injury when the blood supply is re-established.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">20</span></a> The mechanism of action of volatile anaesthetic-induced preconditioning (anaesthetic preconditioning) has been associated with the modulation of cytosolic calcium concentrations through potassium mitochondrial channels that favour early activation of protective enzymes and late induction of protein synthesis that protects against necrosis and cellular apoptosis.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">21,22</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">However, in spite of the differences between the aforementioned mechanisms behind the inflammatory response to OLV in each lung, a recent study in which we compared pulmonary inflammatory markers synthesised in each lung before and after OLV found that both lungs made a similar contribution to the pulmonary inflammatory response.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">23</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">To summarise the state of the knowledge, Sun et al. published a meta-analysis in which they show that inhalation anaesthetics with halogenated agents are associated with lower pulmonary inflammatory response in patients undergoing OLV.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">24</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Postoperative prognosis</span><p id="par0060" class="elsevierStylePara elsevierViewall">The next and most important issue is whether these benefits can be translated into clinical practice and affect postoperative results. This seems to be confirmed in cardiac surgery patients, in whom halogenated agents have been shown to be superior to propofol in decreasing morbidity, mortality, infarct size and the need for postoperative mechanical ventilation. Halogenated inhalation anaesthetics have been recommended by the European Society of Cardiothoracic Surgery in coronary artery bypass graft surgery (Level IB).<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">25</span></a> Cardiac surgery with cardiopulmonay bypass is similar to OLV interventions insofar as they both involve the full or partial absence of alveolar ventilation.</p><p id="par0065" class="elsevierStylePara elsevierViewall">In lung resection surgery, however, the few clinical studies that have investigated whether certain hypnotic agents can improve postoperative outcomes, have observed an incidence of up to 40% of postoperative pulmonary complications (PPC) in interventions using this type of anaesthesia. However, these results come from small clinical studies that were not designed specifically to answer this question. Two recent studies designed for this purpose have addressed this interesting phenomenon. In 2016, Beck-Schimmer et al.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">26</span></a> published the results of an interesting clinical study comparing the clinical outcomes of patients undergoing lung resection surgery and receiving either inhalation anaesthesia with desflurane or intravenous anaesthesia with propofol. Although they did not measure the perioperative inflammatory response, their main objective was to compare the incidence of major postoperative medical or surgical complications (according to the Clavien-Dindo classification). The authors found no difference in the incidence of major complications between the study groups during their postoperative hospital stay (16.5% in the propofol group vs 13% in the desflurane group). In parallel with this study, our group conducted another similar randomised controlled trial<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">27</span></a> to compare the effect of propofol and sevoflurane in this same type of patient. Our primary outcome measure was the incidence of PPC (defined in the ARISCAT study) during the first postoperative month. We found clear evidence that sevoflurane was superior to propofol in attentuating the pulmonary (level of pro-inflammatory cytokines in bronchoalveolar lavages) and systemic inflammatory response in the first 24 postoperative hours. In addition, during OLV, patients in the sevoflurane group showed lower peak pressure, plateau pressure and driving pressure values and better lung compliance than patients in the propofol group. Twenty-four hours after surgery, patients in the sevoflurane group showed better postoperative gas exchange and a lower incidence of PPC (14% vs 28%, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02). However, an analysis of major postoperative complications (Clavien-Dindo grade III, IV and V) showed no statistically significant differences between groups, a finding echoed in the Beck-Schimmer study. With regard to our secondary outcome measure, 1-year mortality, 2 patients in the sevoflurane group died vs 12 patients in the propofol group (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01). We cannot directly associate this finding with the PPCs observed, since many patients died due to tumour progression, a factor that clearly affects first-year outcomes in pulmonary oncological surgery.</p><p id="par0070" class="elsevierStylePara elsevierViewall">In conclusion, inhaled halogenated anaesthetic agents, particularly sevoflurane, attenuate the exaggerated postoperative inflammatory response and have bronchodilatory effects that reduce airway resistance during OLV. We believe it should be included among the lung protective ventilation strategies already used during lung resection surgery.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Postoperative prognosis" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: de la Gala F, Garutti I. Nuevas consideraciones anestésicas en cirugía torácica. Rev Esp Anestesiol Reanim. 2018;65:125–128.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:27 [ 0 => array:3 [ "identificador" => "bib0140" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anesthetics, immune cells, and immune responses" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. Kurosawa" 1 => "M. 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