Letter to the Editor
Flow-controlled ventilation may reduce mechanical power and increase ventilatory efficiency in severe coronavirus disease-19 acute respiratory distress syndrome
A. Grassettoa,#,
, T. Pettenuzzob,#, F. Badiia, R. Carlona, N. Sellab, P. Navalesib,c
Corresponding author
alberto.grassetto@aulss2.veneto.it
Corresponding author at: Anesthesia and Intensive Care, Vittorio Veneto Hospital, Via C. Forlanini 71, 31029, Vittorio Veneto, Italy.
Corresponding author at: Anesthesia and Intensive Care, Vittorio Veneto Hospital, Via C. Forlanini 71, 31029, Vittorio Veneto, Italy.
a Anesthesia and Intensive Care, Vittorio Veneto Hospital, Via C. Forlanini 71, 31029 Vittorio Veneto, Italy
b Institute of Anesthesiology and Intensive Care, Padua University Hospital, Padua, Via V. Gallucci 13, 35121 Padua, Italy
c Department of Medicine, University of Padua, Via Giustiniani 2, 35128 Padua, Italy
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A Mann-Whitney test was used to compare responses between vaccines at the 2-week and 7–9-month timepoints.</p> <p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Dots represent individual test points and columns represent median responses within the test cohort. Not all subjects had specimens collected at all timepoints.</p> <p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Ag, antigen tube; IU, international units; m: months; ns: non-significant; wk, weeks.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "F. Stieber, N. Allen, K. Carpenter, P. Hu, R. Alagna, S. Rao, D. Manissero, J. Howard, V. Nikolayevskyy" "autores" => array:9 [ 0 => array:2 [ "nombre" => "F." "apellidos" => "Stieber" ] 1 => array:2 [ "nombre" => "N." "apellidos" => "Allen" ] 2 => array:2 [ "nombre" => "K." "apellidos" => "Carpenter" ] 3 => array:2 [ "nombre" => "P." "apellidos" => "Hu" ] 4 => array:2 [ "nombre" => "R." 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"apellidos" => "Grassetto" "email" => array:1 [ 0 => "alberto.grassetto@aulss2.veneto.it" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">#</span>" "identificador" => "fn1" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0001" ] ] ] 1 => array:3 [ "nombre" => "T." "apellidos" => "Pettenuzzo" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0002" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">#</span>" "identificador" => "fn1" ] ] ] 2 => array:3 [ "nombre" => "F." "apellidos" => "Badii" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0001" ] ] ] 3 => array:3 [ "nombre" => "R." "apellidos" => "Carlon" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0001" ] ] ] 4 => array:3 [ "nombre" => "N." "apellidos" => "Sella" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0002" ] ] ] 5 => array:3 [ "nombre" => "P." "apellidos" => "Navalesi" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0002" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0003" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Anesthesia and Intensive Care, Vittorio Veneto Hospital, Via C. Forlanini 71, 31029 Vittorio Veneto, Italy" "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:3 [ "entidad" => "Institute of Anesthesiology and Intensive Care, Padua University Hospital, Padua, Via V. Gallucci 13, 35121 Padua, Italy" "etiqueta" => "b" "identificador" => "aff0002" ] 2 => array:3 [ "entidad" => "Department of Medicine, University of Padua, Via Giustiniani 2, 35128 Padua, Italy" "etiqueta" => "c" "identificador" => "aff0003" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0001" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at: Anesthesia and Intensive Care, Vittorio Veneto Hospital, Via C. Forlanini 71, 31029, Vittorio Veneto, Italy." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="para0004" class="elsevierStylePara elsevierViewall">The prevention of ventilator-induced lung injury (VILI) is the mainstay of the management of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS).<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> Official guidelines have focused on tidal volume, plateau pressure (Pplat), positive end-expiratory pressure (PEEP), and driving pressure (DP), i.e., the difference between Pplat and PEEP, to identify lung-protective ventilation strategies.<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> However, even values of tidal volumes and Pplat that are normally considered safe may result in injurious ventilation.<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a></p><p id="para0005" class="elsevierStylePara elsevierViewall">Mechanical power (MP) represents the total energy transferred from the mechanical ventilator to the lungs during inflation and includes dynamic variables such as inspiratory flow rate and breathing frequency.<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> Some studies suggest that MP may predict mortality in ARDS patients<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> and that higher inspiratory flow rates increase the risk of VILI in patients with mild to moderate ARDS.<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p><p id="para0006" class="elsevierStylePara elsevierViewall">The lungs of patients with coronavirus disease (COVID)-19 related ARDS are characterized by parenchymal heterogeneity, leading to regional differences in pulmonary mechanical properties.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> Consequently, higher velocities of lung inflation may drive a greater fraction of tidal volume to alveolar units with shorter time constant and unevenly amplify lung stress in some regions.<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> Therefore, reducing flow rates might be beneficial.</p><p id="para0007" class="elsevierStylePara elsevierViewall">Flow-controlled ventilation (FCV) (Evone®, Ventinova Medical, Eindhoven, The Netherlands) is a ventilatory mode where both inspiratory and expiratory flow rates are maintained constant and < 20 L/min throughout the respiratory cycle by regulating tracheal pressure, as measured through a dedicated lumen opening at the distal end of the endotracheal tube.<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> During FCV, the inspiratory flow rate, inspiratory to expiratory ratio, peak inspiratory pressure (Ppeak), end-expiratory pressure (EEP), and the inspiratory concentration of oxygen are pre-set, whereas tidal volume and respiratory rate vary depending on ventilator settings and the patient's respiratory mechanics.<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> Some studies observed improved lung recruitment, more homogeneous lung aeration,<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> better gas exchange,<a class="elsevierStyleCrossRefs" href="#bib0008"><span class="elsevierStyleSup">8-12</span></a> and attenuated experimental lung injury with FCV,<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">,</span> compared to volume-targeted mechanical ventilation (conventional mechanical ventilation, CMV). We hypothesize that FCV would reduce MP and ventilatory ratio (VR) in COVID-19 patients developing refractory hypoxemia despite optimization of CMV and prone positioning.</p><p id="para0008" class="elsevierStylePara elsevierViewall">This pilot study was performed in 10 sedated and paralyzed COVID-19 ARDS patients admitted to the intensive care unit with arterial partial pressure of oxygen to inspired oxygen fraction ratio (PaO2/FiO2) < 150 mmHg during CMV while in prone position for at least 12 consecutive hours.<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> Inspiratory and expiratory flow rates were initially set at 15 L/min with inspiratory to expiratory ratio 1:1, while EEP was equal to PEEP and Ppeak to Pplat during CMV, thereby maintaining approximately the same DP and consequently similar tidal volumes. All measurements were obtained in CMV prior to switching to FCV (CMV1), after 4 hours of FCV, and then again after 4 hours of CMV (CMV2). All variables are reported as median (interquartile range) and compared using the Friedman test, followed by pairwise comparison with Wilcoxon signed-rank test and <span class="elsevierStyleItalic">post-hoc</span> Bonferroni correction. All statistical tests were two-tailed and statistical significance was defined as p<0.05.</p><p id="para0009" class="elsevierStylePara elsevierViewall">Patient age was 59 (55-57) years and the predicted body weight 65 (59-68) kg. Nine (90%) patients survived the hospital stay. As reported in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>, during FCV inspiratory flow rate, respiratory rate, and minute ventilation were all decreased, compared to both CMV1 and CMV2. During FCV the MP was 10.8 (9.9-13.4) J/min, as opposed to CMV1 [22.7 (20.3-25.6) J/min (p=0.006)] and CMV2 [20.1 (19.0-24.0) J/min (p=0.006)], and VR was 1.40 (1.28-1.44), as compared with CMV1 [2.22 (1.90-2.56) (p=0.006)] and CMV2 [2.20 (1.79-2.57) (p=0.006)]. Arterial partial pressure of carbon dioxide, pH, and PaO2/FiO2 were not significantly different among the three conditions.</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0010" class="elsevierStylePara elsevierViewall">Our study evaluating a series of 10 consecutive patients affected by COVID-19 with refractory hypoxemia, despite prone positioning while receiving CMV, suggests that FCV may be associated with some advantages. First, the application of FCV resulted in decreased MP, as a consequence of lower inspiratory flow rates and breathing frequencies, potentially reducing the dissipated energy.<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> Indeed, FCV was shown to reduce MP<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> and attenuate VILI through this mechanism in porcine models.<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> Second, our results are in keeping with preclinical<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> and clinical studies,<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span> demonstrating higher ventilatory efficiency, probably related to improved intrapulmonary distribution of ventilation with FCV. Third, although we did not observe any significant improvement in gas exchange with FCV, previous studies reported better oxygenation and carbon dioxide elimination with this mode.<a class="elsevierStyleCrossRefs" href="#bib0008"><span class="elsevierStyleSup">8-12</span></a><span class="elsevierStyleSup">,</span> Therefore, our study extends to the critical illness setting the current evidence, mainly limited to preclinical studies and small clinical studies performed in the operating room, suggesting that FCV might reduce VILI, while maintaining adequate gas exchanges.</p><p id="para0011" class="elsevierStylePara elsevierViewall">Our study has important limitations. First, the small sample size makes our findings exploratory and hypothesis-generating. Larger prospective studies are necessary to confirm these results and support clinical studies ascertaining the impact of FCV on clinical outcomes. Second, the external validity and the generalizability of our findings to patients with acute respiratory failure of different etiology need to be assessed. Furthermore, we cannot rule out that different dead space of the ventilator apparatus may have contributed to the improvement of VR with FCV. However, this is unlikely because we always used an active humidifier before the Y-piece of the respiratory circuit during CMV.</p><p id="para0012" class="elsevierStylePara elsevierViewall">In conclusion, FCV reduced MP and VR in a small cohort of severely hypoxemic COVID-19 patients receiving CMV and prone positioning.</p><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Authors' contributions</span><p id="para0013" class="elsevierStylePara elsevierViewall">Conception and design of the study: AG, TP. Acquisition of the data: AG, FB, RC. Analysis of the data: AG, TP, NS. Interpretation of the data: all authors. Drafting of the manuscript: AG, TP, NS, PN. Critical revision of the manuscript for important intellectual content: All authors. Final approval of the version to be submitted: all authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0001" "titulo" => "Authors' contributions" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-04-11" "fechaAceptado" => "2022-05-20" "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "#" "nota" => "<p class="elsevierStyleNotepara" id="notep0001">Equal contribution.</p>" "identificador" => "fn1" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: CMV, conventional mechanical ventilation; FCV, flow-controlled ventilation; PBW, predicted body weight; PEEP, positive end-expiratory pressure; PaCO<span class="elsevierStyleInf">2</span>, arterial partial pressure of carbon dioxide; PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>, arterial partial pressure of oxygen to fraction of inspired oxygen ratio; Crs, compliance of the respiratory system.</p><p id="spara004" class="elsevierStyleSimplePara elsevierViewall">All measurement were obtained in CMV prior to switching to FCV (CMV1), after 4 hours of FCV, and then again after 4 hours of CMV (CMV2). During CMV, plateau pressure (Pplat) and total PEEP were measured at the points of zero flow during an end-inspiratory and end-expiratory pause, respectively, while during FCV Pplat is displayed every 10 cycles after an automatic pressure drop in the pressure curve. Driving pressure was computed as the difference between Pplat and total PEEP, during CMV, and the difference between peak pressure (Ppeak) and end-expiratory pressure, during FCV. Crs was calculated as the ratio between tidal volume and driving pressure. Inspiratory flow during CMV was calculated as the ratio between tidal volumes and inspiratory time, while inspiratory flow during FCV is set on the ventilator.</p><p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Ventilatory ratio was calculated as the ratio between the product of measured minute ventilation (mL/min) and measured PaCO2 and the product between predicted minute ventilation (PBW*100 mL/min) and expected PaCO2 (37.5 mmHg) (10.1164/rccm.201804-0692OC). Mechanical power was calculated as follows: 0.098*respiratory rate*tidal volume*[Ppeak-1/2*(Pplat-PEEP)] (10.1186/s13054-020-03116-w).</p><p id="spara006" class="elsevierStyleSimplePara elsevierViewall">Variables are reported as median (interquartile range) and were compared using the Friedman two-way analysis of variance, followed by pairwise comparison with Wilcoxon signed-rank test and <span class="elsevierStyleItalic">post-hoc</span> Bonferroni correction, when indicated. The Kendall's W value is the effect size estimate for Friedman test and ranges from 0.1-0.3 (small effect) to >0.5 (large effect).</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">CMV1 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">FCV \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">CMV2 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">p-value<a class="elsevierStyleCrossRef" href="#tb1fn1"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Kendall's W \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0007"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="6" align="left" valign="top">Ventilatory settings</td></tr><tr title="table-row"><a name="en0008"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Respiratory rate (breaths/min) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0009"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26 (24-28) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">17 (16-18)<a class="elsevierStyleCrossRef" href="#tb1fn2"><span class="elsevierStyleSup">b</span></a><a class="elsevierStyleCrossRef" href="#tb1fn3"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25 (22-26) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0013"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.930 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0014"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Tidal volume (mL/kg PBW) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">6.9 (6.8-7.3) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">6.8 (6.5-7.3) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">6.8 (6.5-7.2) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.968 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0020"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Minute ventilation (L/min) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">11.8 (10.2-12.8) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7.7 (7.1-8.2)<a class="elsevierStyleCrossRef" href="#tb1fn4"><span class="elsevierStyleSup">d</span></a><a class="elsevierStyleCrossRef" href="#tb1fn5"><span class="elsevierStyleSup">e</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10.8 (9.6-12.1) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.830 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0026"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Peak pressure (cmH<span class="elsevierStyleInf">2</span>O) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">27 (25-28) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">23 (20-25)<a class="elsevierStyleCrossRef" href="#tb1fn2"><span class="elsevierStyleSup">b</span></a><a class="elsevierStyleCrossRef" href="#tb1fn3"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26 (25-28) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.810 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0032"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Plateau pressure (cmH<span class="elsevierStyleInf">2</span>O) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 (20-23) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 (19-23) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22 (21-23) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.015 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.420 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0038"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">PEEP (cmH<span class="elsevierStyleInf">2</span>O) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">9 (8-10) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">9 (7-10) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">9 (8-10) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.772 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.030 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0044"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Inspiratory flow (L/min) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26 (23-26) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15 (14-15)<a class="elsevierStyleCrossRef" href="#tb1fn4"><span class="elsevierStyleSup">d</span></a><a class="elsevierStyleCrossRef" href="#tb1fn5"><span class="elsevierStyleSup">e</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22 (22-26) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.800 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0050"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="6" align="left" valign="top">Gas exchanges</td></tr><tr title="table-row"><a name="en0051"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">pH \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7.37 (7.30-7.42) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7.39 (7.36-7.42) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7.34 (7.27-7.42) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.280 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.130 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0057"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">PaCO<span class="elsevierStyleInf">2</span> (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">49 (43-51) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">45 (42-48) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">51 (45-56) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.275 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.130 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0063"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">128 (116-134) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">136 (115-147) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">134 (106-152) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.275 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.150 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0069"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Ventilatory ratio \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2.22 (1.90-2.56) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.40 (1.28-1.44)<a class="elsevierStyleCrossRef" href="#tb1fn4"><span class="elsevierStyleSup">d</span></a><a class="elsevierStyleCrossRef" href="#tb1fn5"><span class="elsevierStyleSup">e</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2.20 (1.79-2.57) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.770 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0075"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="6" align="left" valign="top">Mechanical properties of the respiratory system</td></tr><tr title="table-row"><a name="en0076"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Crs (mL/cmH<span class="elsevierStyleInf">2</span>O) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">36 (34-38) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">35 (34-40) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">36 (33-39) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.704 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.040 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0082"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Driving pressure (cmH<span class="elsevierStyleInf">2</span>O) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13 (12-13) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12 (11-13) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13 (12-14) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.331 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.110 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0088"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Mechanical power (J/min) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22.7 (20.3-25.6) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10.8 (9.9-13.4)<a class="elsevierStyleCrossRef" href="#tb1fn4"><span class="elsevierStyleSup">d</span></a><a class="elsevierStyleCrossRef" href="#tb1fn5"><span class="elsevierStyleSup">e</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20.1 (19.0-24.0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.760 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:5 [ 0 => array:3 [ "identificador" => "tb1fn1" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="notep0007">p-value from the Friedman two-way analysis of variance.</p>" ] 1 => array:3 [ "identificador" => "tb1fn2" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="notep0008">p<0.05 between FCV and CMV1 after <span class="elsevierStyleItalic">post-hoc</span> Bonferroni correction.</p>" ] 2 => array:3 [ "identificador" => "tb1fn3" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="notep0009">p<0.05 between FCV and CMV2 after <span class="elsevierStyleItalic">post-hoc</span> Bonferroni correction.</p>" ] 3 => array:3 [ "identificador" => "tb1fn4" "etiqueta" => "d" "nota" => "<p class="elsevierStyleNotepara" id="notep0010">p<0.01 between FCV and CMV1 after <span class="elsevierStyleItalic">post-hoc</span> Bonferroni correction.</p>" ] 4 => array:3 [ "identificador" => "tb1fn5" "etiqueta" => "e" "nota" => "<p class="elsevierStyleNotepara" id="notep0011">p<0.01 between FCV and CMV2 after <span class="elsevierStyleItalic">post-hoc</span> Bonferroni correction.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Ventilatory settings, mechanical properties of the respiratory system, and outcome variables</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:13 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ventilator-induced lung injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "AS Slutsky" 1 => "VM. 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| Year/Month | Html | Total | |
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| 2024 November | 33 | 9 | 42 |
| 2024 October | 172 | 49 | 221 |
| 2024 September | 128 | 45 | 173 |
| 2024 August | 136 | 45 | 181 |
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| 2024 May | 118 | 66 | 184 |
| 2024 April | 82 | 36 | 118 |
| 2024 March | 102 | 31 | 133 |
| 2024 February | 83 | 29 | 112 |
| 2024 January | 88 | 35 | 123 |
| 2023 December | 64 | 39 | 103 |
| 2023 November | 75 | 62 | 137 |
| 2023 October | 107 | 59 | 166 |
| 2023 September | 73 | 37 | 110 |
| 2023 August | 56 | 33 | 89 |
| 2023 July | 40 | 25 | 65 |
| 2023 June | 67 | 34 | 101 |
| 2023 May | 89 | 59 | 148 |
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| 2022 November | 102 | 62 | 164 |
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