Editorial
Positive end-expiratory pressure, or the perennial conundrum surrounding lung recruitment
Presión positiva al final de la espiración o el perenne enigma que rodea el reclutamiento pulmonar
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Systematic review and meta-analysis with meta-regression" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "516" "paginaFinal" => "531" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estrategia OLA para el SDRA: su efecto en la mortalidad depende del reclutamiento alcanzado (PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>) y la potencia mecánica. Revisión sistemática y metaanálisis con metarregresión" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1300 "Ancho" => 2175 "Tamanyo" => 398202 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">(A) Forest plot of comparison: OLA strategy vs. control ventilation, outcome: 28–30th day mortality. Includes risk of bias summary for each included study. (B) Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "V. Modesto i Alapont, A. Medina Villanueva, P. del Villar Guerra, C. Camilo, S. Fernández-Ureña, F. Gordo-Vidal, R. Khemani" "autores" => array:7 [ 0 => array:2 [ "nombre" => "V." "apellidos" => "Modesto i Alapont" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Medina Villanueva" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "del Villar Guerra" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Camilo" ] 4 => array:2 [ "nombre" => "S." "apellidos" => "Fernández-Ureña" ] 5 => array:2 [ "nombre" => "F." "apellidos" => "Gordo-Vidal" ] 6 => array:2 [ "nombre" => "R." "apellidos" => "Khemani" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569121000759?idApp=WMIE" "url" => "/02105691/0000004500000009/v1_202111260648/S0210569121000759/v1_202111260648/en/main.assets" ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Positive end-expiratory pressure, or the perennial conundrum surrounding lung recruitment" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "513" "paginaFinal" => "515" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "P.D. Wendel-Garcia, F. Roche-Campo, J. Mancebo" "autores" => array:3 [ 0 => array:3 [ "nombre" => "P.D." "apellidos" => "Wendel-Garcia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "F." "apellidos" => "Roche-Campo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "J." "apellidos" => "Mancebo" "email" => array:1 [ 0 => "JMancebo@santpau.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Institute of Intensive Care Medicine, University Hospital of Zurich, Zurich, Switzerland" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Intensive Care Dept, Hospital de Tortosa Verge de la Cinta, Tortosa, Tarragona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Intensive Care Dept, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Presión positiva al final de la espiración o el perenne enigma que rodea el reclutamiento pulmonar" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Six decades have passed since Ashbaugh and colleagues described the use of positive end-expiratory pressure (PEEP) to counteract alveolar collapse in adult (acute) respiratory distress syndrome, leading to the conception of the <span class="elsevierStyleItalic">open lung</span><span class="elsevierStyleItalic">approach</span>.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> Elevating the static alveolar distending pressure and reducing cyclic alveolar distension, were proposed as the optimal strategy to reduce the three mechanical components of ventilator-induced lung injury (VILI), namely baro-, volu- and atelectrauma.</p><p id="par0010" class="elsevierStylePara elsevierViewall">While today we have robust evidence that the use of high tidal volumes (<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>) is accompanied by a significant increase in mortality risk,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">2</span></a> the role of PEEP setting has remained controversial. For three decades randomized controlled trials attempting to prove the benefits of higher PEEP strategies (∼15<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O versus ∼8<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O) have been following up to each other, but compelling evidence has been lacking ever since. Even the implementation of more sophisticated PEEP titration strategies, such as oesophageal manometry<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a> and the use of staircase recruitment manoeuvres<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">4,5</span></a> have only added to the list of negative trials.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In the current issue of the <span class="elsevierStyleItalic">Journal</span>, Alapont and colleagues attempted to compile the current available evidence by pursuing a systematic review and meta-analysis of all randomized trials having investigated high PEEP strategies published to date.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">6</span></a> Not surprisingly, the heterogeneity of the meta-analysis was moderate to substantial, reflecting the high clinical and methodological variability in these studies. The pooled relative risk for mortality was indicative (0.90, 95% Confidence Interval 0.78–1.03), albeit inconclusively, of a protective effect of the <span class="elsevierStyleItalic">open lung approach</span> and presented a low GRADE quality of evidence. Similar results have been observed in a recently published large network meta-analysis,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a> which indicated an inconclusive protective effect for a low <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> – high PEEP strategy (defined in said study as <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>8<span class="elsevierStyleHsp" style=""></span>ml/kg and PEEP<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O).</p><p id="par0020" class="elsevierStylePara elsevierViewall">This brings us to the perennial question as to why high PEEP resists conclusive proof as opposed to low <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>? Conceptually we may break this apparent paradox down into the two opposite effects that <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> and PEEP exert on the total energy delivered to the lung. This energy and the response of the lung's parenchyma to it can be expressed through the mechanical power.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> Consequently, in contrast to the obvious reduction in mechanical power achieved by lowering <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>, a high PEEP setting will mostly be associated with an increase in delivered pulmonary energy. As recently shown in an animal model, VILI is directly dependent on the delivered mechanical power.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">9</span></a> Interestingly, the sensitivity analysis performed by Alapont and colleagues does indicate exactly towards this relationship. Studies in which a high PEEP setting induced a higher mechanical power relative to the control group were associated with a disappearing protective effect of high PEEP.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The high collinearity between the mechanical power and the driving pressure shown by the sensitivity analyses of Alapont et al. illustrates that the main mediator between PEEP increase and mechanical power reduction is a decreasing respiratory system elastance. In other words, only when an increase in PEEP leads to an effective distension of alveoli does it reduce the applied mechanical power. However, as Gattinoni et al. showed in their landmark paper, lung recruitability is highly heterogeneous, and less than 40% of patients seem to actively recruit a significant proportion of lung tissue during a recruitment manoeuvre.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a> Most strikingly, the authors observed that up to 24% of the total lung tissue cannot be recruited at end-inspiratory plateau airway pressures of 45<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a> Hence, one can speculate that more than half of the patients included in PEEP trials did not experience any alveolar recruitment and in the worst-case scenario experienced alveolar overdistension due to excessive PEEP settings. This possibly induced VILI, increasing mortality in the intervention group and drastically reducing statistical power. Ideally, we should fine tune <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> according to elastance, and PEEP according to lung recruitability.</p><p id="par0030" class="elsevierStylePara elsevierViewall">But how do we recognize recruitable patients? Performing two CT studies at different PEEP levels, might be a very elegant option and the current gold standard,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a> but is impractical at the bedside. On the other hand, recruitment assessment methods based on lung mechanics are generally limited in discerning between actual atelectatic tissue recruitment and overdistension of the baby lung. The recently proposed recruitment-to-inflation ratio might provide guidance in balancing the risk of atelectrauma against the risk of overdistension during recruitment.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">11</span></a> Another emergent technique, thoracic electric impedance tomography, can enable to discern alveolar recruitment from overdistension in a more visual approach, whilst concomitantly allowing assessment of regional pulmonary perfusion.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">12,13</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In a further sensitivity analysis, Alapont et al. illustrate that patients with a P<span class="elsevierStyleInf">a</span>O<span class="elsevierStyleInf">2</span>/F<span class="elsevierStyleInf">i</span>O<span class="elsevierStyleInf">2</span> ratio below 160<span class="elsevierStyleHsp" style=""></span>mmHg profit from high PEEP as opposed to patients with higher P<span class="elsevierStyleInf">a</span>O<span class="elsevierStyleInf">2</span>/F<span class="elsevierStyleInf">i</span>O<span class="elsevierStyleInf">2</span> ratios. Briel et al. showed a similar P<span class="elsevierStyleInf">a</span>O<span class="elsevierStyleInf">2</span>/F<span class="elsevierStyleInf">i</span>O<span class="elsevierStyleInf">2</span> ratio dependant protective effect for high PEEP in their individual data meta-analysis.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a> Indeed, the fraction of pulmonary recruitable patients increases with decreasing P<span class="elsevierStyleInf">a</span>O<span class="elsevierStyleInf">2</span>/F<span class="elsevierStyleInf">i</span>O<span class="elsevierStyleInf">2</span> ratio,<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">10,15</span></a> a property that has already successfully been implemented to enrich ARDS trials targeting pulmonary recruitment by means of prone position.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a> However, and as the ART,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> EPVent-2<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">3</span></a> and PHARLAP<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a> trials have exemplified, simple enrichment of PEEP trials with a P<span class="elsevierStyleInf">a</span>O<span class="elsevierStyleInf">2</span>/F<span class="elsevierStyleInf">i</span>O<span class="elsevierStyleInf">2</span> ratio below 200<span class="elsevierStyleHsp" style=""></span>mmHg does not suffice.</p><p id="par0040" class="elsevierStylePara elsevierViewall">How do we proceed from here? As exemplified by this meta-analysis, pursuing larger and more complex trials attempting to show the benefit of high PEEP in heterogeneous ARDS populations is a futile enterprise. Instead, it is time to step back to mechanistic research and reassess how to best characterize the mechanical properties of the lung and best recognize patients with recruitable lungs. It will be the task of phenotyping and <span class="elsevierStyleItalic">individualized</span> medicine to pave the way towards a successful implementation of the <span class="elsevierStyleItalic">open lung approach</span>. If this will be achieved through biological and inflammatory phenotypes,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a> by a more lung centred characterization of pulmonary morphology and mechanical properties<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">15</span></a> or if advanced pulmonary imaging tools are the key,<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a> remains unknown. However, it all points to an exciting future, full of research possibilities, ahead of us.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Up until then, we suggest a do no harm approach. From a pragmatic point of view, PEEP settings of 8–12<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O will likely provide for a balanced choice, while we employ a simple and proven lifesaving intervention in ARDS: low <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> and prone position.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:18 [ 0 => array:3 [ "identificador" => "bib0095" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous positive-pressure breathing (CPPB) in adult respiratory distress syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.G. Ashbaugh" 1 => "T.L. Petty" 2 => "D.B. Bigelow" 3 => "T.M. Harris" 4 => "W.R. 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| año/Mes | Html | Total | |
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