Respiratory Muscle Dysfunction: A Multicausal Entity in the Critically Ill Patient Undergoing Mechanical Ventilation

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Díaz, Gustavo A. Ospina-Tascón, Blanca C. Salazar C" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Magda C." "apellidos" => "Díaz" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 1 => array:3 [ "nombre" => "Gustavo A." "apellidos" => "Ospina-Tascón" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "Blanca C." "apellidos" => "Salazar C" "email" => array:1 [ 0 => "bsblasalaz@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad de Cuidados Intensivos, Fundación Valle del Lili, Cali, Colombia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Grupo de Investigación Biomédica de la Universidad ICESI, Cali, Colombia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Ciencias Fisiológicas, Facultad de Salud, Universidad del Valle, Cali, Colombia" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Disfunción muscular respiratoria: una entidad multicausal en el paciente críticamente enfermo sometido a ventilación mecánica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2401 "Ancho" => 3167 "Tamanyo" => 480540 ] ] "descripcion" => array:1 [ "en" => "Factors contributing to respiratory muscle dysfunction in the critically ill patient undergoing mechanical ventilation." ] ] ] "textoCompleto" => "IntroductionMechanical ventilation (MV) is one of the most common means of life support in intensive care units (ICU) and forms part of the standard treatment of acute respiratory failure. However, despite its advantages, MV can cause direct systemic and pulmonary complications<a class="elsevierStyleCrossRef" href="#bib0005">1</a> leading to longer hospital stays, increased costs, higher mortality and loss of quality of life.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> As such, it is essential that the duration of MV in a critically ill patient is kept as short as possible by judicious daily evaluation on the part of the clinician. It has been calculated that around 40% of the total time on MV in the ICU is dedicated to weaning respiratory support.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Some descriptive studies have shown that 69% of patients are easily weaned, while 15% require prolonged MV (PMV), with hospital stays of over 10 days.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>Difficulty in weaning from MV is a significant problem, since it increases complications like nosocomial infections and/or airways lesions and others. In addition to producing significant deterioration in quality of life, difficulty in weaning consumes up to 40% of all ICU resources.<a class="elsevierStyleCrossRefs" href="#bib0010">2,5</a> Respiratory muscle dysfunction, particularly of the diaphragm, may play a key role in the pathophysiological mechanisms that lead to difficulty in weaning patients from MV.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> The limited mobility of the diaphragm under MV promotes the early onset of respiratory muscle dysfunction,<a class="elsevierStyleCrossRefs" href="#bib0010">2,3</a> and this can be exacerbated by other factors, such as advanced age, long duration of MV, controlled ventilatory mode, malnutrition, sepsis and some medications, such as glucocorticoids and neuromuscular blocking agents (NMBA).<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Awareness of the pathophysiological mechanisms underlying these factors in respiratory muscle dysfunction<a class="elsevierStyleCrossRef" href="#bib0040">8</a> and their role in difficult weaning is on the increase.Two aspects are highlighted in this report. The first is that the factors primarily associated with respiratory muscle dysfunction occur frequently and often simultaneously in patients on MV. The second is that the common mechanism underlying the physiopathology of these factors is proteolysis and/or reduced muscle protein synthesis, which has also been shown on histology as atrophy.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>Factors Associated With Respiratory Muscle DysfunctionAgeIn two prospective multicentre studies in mechanically ventilated patients in intensive care units in more than 20 countries in America and Europe<a class="elsevierStyleCrossRef" href="#bib0050">10</a> and in Latin America,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> the average age of patients was 57 years, while that of patients on PMV was 72 years. Generally in humans, skeletal muscle strength, mass and structure change with age. At the age of 70 years, subjects have a reduction of muscle mass of between 20% and 30%, causing a loss of peripheral strength of between 20% and 40%.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> This diminished peripheral mass is the result of a fall in number and size of muscle fibres, principally the fast twitch type.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> Age-related changes may be different in the respiratory muscles and in the peripheral muscles, since respiratory activity is continuous, while peripheral muscle activity may not be. Although data in humans are limited, age-related respiratory muscle dysfunction has been demonstrated by a loss of strength, determined in subjects aged between 65 and 85 years as a yearly reduction in maximum inspiratory pressure (MIP) of 0.8–2.7cmH2O<a class="elsevierStyleCrossRef" href="#bib0070">14</a> and a 25% fall in transdiaphragmatic pressure in adults between 65 and 75 years of age.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> A mechanism that may explain these changes is the accumulative effect of oxygen-derived free radicals that may trigger proteolytic processes.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> It has also been suggested that with advancing age, remodelling occurs in the muscle fibres, with fast twitch myosin fibres being replaced by slow twitch isoforms.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>Duration and Mode of Mechanical VentilationIn reports on the progress of patients admitted to the ICU, 30% needed a mean duration of 5–8 days MV support and the most frequently used mode was assist-control (60%).<a class="elsevierStyleCrossRefs" href="#bib0050">10,11</a> Among MV patients, 30% had difficulty weaning and a significant proportion of these became what was defined as PMV. It seems that, in addition to MV duration, ventilatory mode is a determining factor for the development of diaphragmatic muscle dysfunction.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> This was first described in 1994 by Le Bourdelles et al.,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> who submitted rats to MV and showed that maximum muscle strength per unit cross-sectional area fell after 48hours of support. Interest in diaphragm muscle wastage has been growing in recent years.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Several studies performed in different animal species have shown that significant atrophy of the slow and fast twitch fibres of this muscle occurs after only 12–18hours (h) on MV.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> This occurs before the appearance of atrophy in the musculoskeletal system that has often been described in experimental animal models after 96h of MV.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Similar results were confirmed in humans after 18–69h of MV<a class="elsevierStyleCrossRef" href="#bib0045">9</a>: diaphragm atrophy was seen when biopsies from brain death patients (after undergoing controlled MV) were compared with controls undergoing chest surgery. One important finding was the reduction of the cross-sectional area in both type I and type II fibres in patients receiving ventilation for more than 48h. Some animal studies show that immobility from controlled MV also causes a loss of fibres from the locomotor skeletal muscles, a myofibrillar disorder of the diaphragm, and, furthermore, changes in the Z-line structure in both.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>The mechanism mainly associated with diaphragm atrophy in animal models<a class="elsevierStyleCrossRef" href="#bib0100">20</a> and in humans undergoing MV is the increase in proteolysis.<a class="elsevierStyleCrossRefs" href="#bib0045">9,21</a> In animals, a reduction in protein synthesis has also been observed.<a class="elsevierStyleCrossRefs" href="#bib0090">18,20</a> The contribution of calpain, caspase-3, and the lyosomal and the ubiquitin-proteasome systems has been discussed in recent studies.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Current research is directed towards the transduction pathways of these mechanisms, with the aim of identifying drugs or therapeutic interventions that would deviate these pathways towards the prevention of atrophy and respiratory muscle dysfunction. In this respect, alternatives, such as reducing the time of controlled mode MV, transcutaneous electric stimulation of the diaphragm, early mobilisation of patients<a class="elsevierStyleCrossRef" href="#bib0110">22</a> and the use of antioxidant drugs, have been proposed.Nutritional and Metabolic StatusBetween 30% and 60% of ICU patients have or will have some degree of malnutrition, due to metabolic changes causing a greater energy output and the nutritional deficit due to poor absorption or reduced availability of nutrients during critical disease.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> The increase in catabolic hormones (glucagon, adrenaline and cortisol) and cytokines<a class="elsevierStyleCrossRef" href="#bib0120">24</a> and the inhibition of anabolic hormones, such as insulin and testosterone, produces a situation of hypermetabolism. A hypermetabolic patient will suffer a loss of muscle mass and strength and immune response.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> Hormone imbalance has frequently been associated with the development of hyperglycaemia. Although this is a condition that adapts to critical disease, it remains a factor for negative prognosis in the short, mid and long-term.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Hyperglycaemia aids the storage of lipids in the form of triglycerides and low density lipoproteins.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> The unavailability of these substrates as energy sources leads to marked proteolysis, and as such, to a loss of muscle mass, an increase in severe infections, multiple organ failure and death, particularly in critically ill surgical patients.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> The weight of the diaphragm in a malnourished rat drops more than the weight of the muscles of the limbs, as a result of atrophy and remodelling of fast twitch fibres.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> In addition, hyperglycaemia causes oxidative stress, which has been associated with nerve fibre loss and atrophy, with the corresponding impact on muscular neurotransmission.ComorbiditiesCritically ill patients undergoing MV may present various comorbidities, the most common being sepsis, diabetes mellitus, hypertension and acute myocardial infarction. Complications such as barotrauma, sepsis, acute respiratory distress syndrome (ARDS), MV-related pneumonia, cardiogenic shock and polyneuropathy in critically ill patients may also occur.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> The effects of these diseases in the development of respiratory muscle dysfunction due to mechanisms mediated by changes in protein metabolism may be additive. For example, in both animals and humans, the systemic inflammatory response in sepsis induces an increase in proinflammatory cytokines (TNF-α, IL-6, IL-1) and free radicals,<a class="elsevierStyleCrossRef" href="#bib0145">29</a> which also promote greater activity of the proteolytic pathways,<a class="elsevierStyleCrossRef" href="#bib0150">30</a> as mentioned above. With regard to protein synthesis in the skeletal muscle of rats, it has been reported that other sepsis-induced inflammatory mediators, such as IL-1β, reduce eIF4G factor phosphorylation, thus altering the onset of translation of sarcoplasmic proteins, such as myofibrils, in muscles composed of fast twitch fibres.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> Mechanisms other than changes in protein metabolism regulation have been proposed in sepsis; mechanisms that are associated with changes in cell excitability, calcium homeostasis<a class="elsevierStyleCrossRef" href="#bib0150">30</a> and mitochondrial oxidative phosphorylation of the muscle.Pharmacological TreatmentGlucocorticoidsGlucocorticoids (GC) are used in the critically ill patient with sepsis, acute respiratory distress syndrome (ARDS) and refractory vasodilatory shock.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> High doses have been associated with neuromuscular disorders causing peripheral and respiratory muscle dysfunction. In patients on MV, GC have been seen to delay MV weaning and to increase the need for tracheostomy.<a class="elsevierStyleCrossRef" href="#bib0160">32</a>In humans and animals, GC-induced respiratory and peripheral muscle dysfunction is caused by inhibition of anabolism and by the catabolic effect of proteins.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> The anti-anabolic effect of the GCs inhibits protein synthesis by various mechanisms. One of these is the inhibition of amino acid transport within the muscles, limiting protein synthesis. Another mechanism that has been proposed is the inhibition of the stimulating effect of insulin and the insulin growth factor (IGF-1) on the phosphorylation of the eIF4-binding protein and ribosomal protein kinase S6, two key factors in mRNA translation.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> Finally, GCs inhibit myogenesis by the low regulation of myogenin, an essential transcription factor for the differentiation of satellite cells in muscle fibres.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> Stimulation of IGF-1 or the myostatin blockers constitute some of the more promising therapeutic targets for preventing GC-induced muscle atrophy. The catabolic action of GCs is mediated by the proteolytic ubiquitin-proteasome, lysosome and calpain-dependent systems<a class="elsevierStyleCrossRef" href="#bib0175">35</a> that primarily affect the myofibrillar proteins. In muscle wasting, intracellular mediators such as FOXO, GSK3b, C/EBPb, p300, REDD1 and ATF4 form part not only of the catabolic action but also of the inhibitory action of GC anabolism.<a class="elsevierStyleCrossRef" href="#bib0175">35</a>Neuromuscular Blocking AgentsNMBAs are used to improve synchrony in MV patients and to keep the ventilatory parameters high (PEEP>10cmH2O, FIO2>80%), when required. NMBAs are either depolarising or non-depolarising. In a study on rat diaphragm comparing the effects of these agents, non-depolarising NMBAs were found to be more potent.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> In humans, it has been reported that NMBAs did not cause ICU-acquired weakness compared to placebo.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> However, respiratory complications (prolonged desaturation, SatO2<90%) requiring re-intubation were reported in some publications.<a class="elsevierStyleCrossRef" href="#bib0190">38</a>Prolonged use of high-dose NMBAs together with steroids in the presence of prolonged immobilisation promotes muscle weakness in the critically ill patient and, in some cases, acute necrotising myopathy.<a class="elsevierStyleCrossRef" href="#bib0195">39</a> This condition progresses with generalised weakness of the peripheral and respiratory muscles, recovery is slow and patients are left with sequelae. In critically ill patients with sepsis or multiple organ failure, NMBA pharmacokinetics are altered due to changes in physical function, perfusion and the intracellular/extracellular fluid ratio.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> In the light of these findings, intermittent dosing with NMBAs that do not change kidney or liver function is recommended.Respiratory Muscular Dysfunction Synthesis in the Critically Ill Patient Undergoing Mechanical VentilationIn the schematic in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, the factors contributing to respiratory muscle dysfunction in the critically ill patient on MV are presented. The mechanisms involved in protein breakdown and/or the reduction of protein synthesis for each factor are listed.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>ConclusionAlthough respiratory muscle dysfunction in the critically ill patient undergoing MV has multicausal origins, the primary underlying mechanisms may be proteolysis and/or the reduction of protein synthesis, and in some cases, neurotransmission disturbances. Respiratory muscle dysfunction causes difficulty in weaning, PMV, and morbidity and mortality in the critically ill patient.Although the aim of this review was to focus on respiratory muscle dysfunction, the peripheral musculature is also affected in one way or another by the multicausal nature of this disorder and its associated mechanisms.RecommendationsEarly, integrated management of the multiple causes of respiratory muscle dysfunction may reduce hospital stay and associated morbidity and mortality, and could prevent the development and severity of the sometimes irreversible neuromuscular sequelae.It is important that research into the quantification and regulation of altered protein metabolism in these patients continues, with the aim of counteracting this metabolic tendency with a series of treatment prescriptions and diets more closely suited to the real conditions of the patient undergoing MV.FundingCall for Grants, Universidad del Valle, 2010.Framework AgreementFundación Valle del Lili and Universidad del Valle.Conflict of InterestsThere is no institutional or individual conflict of interests." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:2 [ "identificador" => "xres315526" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec298251" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres315527" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec298252" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Factors Associated With Respiratory Muscle Dysfunction" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Age" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Duration and Mode of Mechanical Ventilation" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Nutritional and Metabolic Status" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Comorbidities" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Pharmacological Treatment" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Glucocorticoids" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Neuromuscular Blocking Agents" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Respiratory Muscular Dysfunction Synthesis in the Critically Ill Patient Undergoing Mechanical Ventilation" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Recommendations" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0070" "titulo" => "Framework Agreement" ] 11 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflict of Interests" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-09-12" "fechaAceptado" => "2013-03-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec298251" "palabras" => array:7 [ 0 => "Respiratory muscle dysfunction" 1 => "Mechanical ventilation" 2 => "Weaning from mechanical ventilation" 3 => "Sepsis" 4 => "Critical patient" 5 => "Proteolysis" 6 => "Protein synthesis and malnutrition in the critically ill patient" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec298252" "palabras" => array:7 [ 0 => "Disfunción respiratoria" 1 => "Ventilación mecánica" 2 => "Destete de la ventilación mecánica" 3 => "Sepsis" 4 => "Paciente crítico" 5 => "Proteólisis" 6 => "Síntesis de proteínas y desnutrición en el paciente crítico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Respiratory muscle dysfunction, particularly of the diaphragm, may play a key role in the pathophysiological mechanisms that lead to difficulty in weaning patients from mechanical ventilation. The limited mobility of critically ill patients, and of the diaphragm in particular when prolonged mechanical ventilation support is required, promotes the early onset of respiratory muscle dysfunction, but this can also be caused or exacerbated by other factors that are common in these patients, such as sepsis, malnutrition, advanced age, duration and type of ventilation, and use of certain medications, such as steroids and neuromuscular blocking agents. In this review we will study in depth this multicausal origin, in which a common mechanism is altered protein metabolism, according to the findings reported in various models. The understanding of this multicausality produced by the same pathophysiological mechanism could facilitate the management and monitoring of patients undergoing mechanical ventilation." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Es probable que la disfunción de los músculos respiratorios, principalmente del diafragma, constituya una pieza clave dentro de los mecanismos fisiopatológicos que conducen a la dificultad del destete de la ventilación mecánica. La limitada movilidad del paciente crítico—y en especial del diafragma—cuando se requiere soporte prolongado con ventilación mecánica favorece el inicio temprano de la disfunción muscular respiratoria, la cual puede originarse también o hacerse mayor en presencia de factores frecuentes en el paciente críticamente enfermo, tales como sepsis, desnutrición, edad avanzada, duración y modo ventilatorio, uso de algunos medicamentos como glucocorticoides y bloqueadores neuromusculares. En esta revisión haremos énfasis en este origen multicausal, en el que la alteración del metabolismo de las proteínas es un mecanismo común involucrado, de acuerdo con los hallazgos reportados en diferentes modelos. El entendimiento de esta multicausalidad integrada por un mismo mecanismo fisiopatológico podría favorecer el manejo y la monitorización de los pacientes sometidos a ventilación mecánica." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Díaz MC, Ospina-Tascón GA, Salazar C BC. Disfunción muscular respiratoria: una entidad multicausal en el paciente críticamente enfermo sometido a ventilación mecánica. Arch Bronconeumol. 2014;50:73–77." ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2401 "Ancho" => 3167 "Tamanyo" => 480540 ] ] "descripcion" => array:1 [ "en" => "Factors contributing to respiratory muscle dysfunction in the critically ill patient undergoing mechanical ventilation." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ventilator-induced lung injury and recommendations for mechanical ventilation of patients with ARDS" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "W.L. Lee" 1 => "A. Slutsky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-2001-15784" "Revista" => array:6 [ "tituloSerie" => "Semin Respir Crit Care Med" "fecha" => "2001" "volumen" => "22" "paginaInicial" => "269" "paginaFinal" => "280" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16088679" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Legacy of intensive care unit-acquired weakness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.S. Herridge" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e3181b6f35c" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2009" "volumen" => "37" "paginaInicial" => "S457" "paginaFinal" => "S461" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20046135" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "What is the proper approach to liberating the weak from mechanical ventilation?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L. Brochard" 1 => "A.W. Thille" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e3181b6e28b" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2009" "volumen" => "37" "paginaInicial" => "S410" "paginaFinal" => "S415" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20046128" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Weaning from mechanical ventilation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Boles" 1 => "J. Bion" 2 => "A. Connors" 3 => "M. Herridge" 4 => "B. Marsh" 5 => "C. Melot" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00010206" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2007" "volumen" => "29" "paginaInicial" => "1033" "paginaFinal" => "1056" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17470624" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How is mechanical ventilation employed in the intensive care unit? An international utilization review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Esteban" 1 => "A. Anzueto" 2 => "I. Alía" 3 => "F. Gordo" 4 => "C. Apezteguía" 5 => "F. Pálizas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.161.5.9902018" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2000" "volumen" => "161" "paginaInicial" => "1450" "paginaFinal" => "1458" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10806138" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Determinants of weaning success in patients with prolonged mechanical ventilation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Carlucci" 1 => "P. Ceriana" 2 => "G. Prinianakis" 3 => "F. Fanfulla" 4 => "R. Colombo" 5 => "S. Nava" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc7927" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2009" "volumen" => "13" "paginaInicial" => "R97" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19549301" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intensive care unit-acquired weakness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. Griffiths" 1 => "J. Hall" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e3181cc4b53" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2010" "volumen" => "38" "paginaInicial" => "779" "paginaFinal" => "787" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20048676" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prolonged mechanical ventilation alters diaphragmatic structure and function" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.K. Powers" 1 => "A.N. Kavazis" 2 => "S. Levine" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e3181b6e760" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2009" "volumen" => "37" "paginaInicial" => "S347" "paginaFinal" => "S353" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20046120" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Levine" 1 => "T. Nguyen" 2 => "N. Taylor" 3 => "M.E. Friscia" 4 => "M.T. Budak" 5 => "P. Rothenberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa070447" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2008" "volumen" => "358" "paginaInicial" => "1327" "paginaFinal" => "1335" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18367735" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characteristics and outcomes in adult patients receiving mechanical ventilation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Esteban" 1 => "A. Anzueto" 2 => "F. Frutos" 3 => "I. Alía" 4 => "L. Brochard" 5 => "T.E. Stewart" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2002" "volumen" => "287" "paginaInicial" => "345" "paginaFinal" => "355" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11790214" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Características de los pacientes que reciben ventilación mecánica en unidades de cuidados intensivos: primer estudio multicéntrico chileno" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Tomicic" 1 => "M. Espinoza" 2 => "M. Andresen" 3 => "J. Molina" 4 => "M. Calvo" 5 => "H. Ugarte" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "/S0034-98872008000800001" "Revista" => array:6 [ "tituloSerie" => "Rev Med Chile" "fecha" => "2008" "volumen" => "136" "paginaInicial" => "959" "paginaFinal" => "967" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18949178" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Respiratory muscle fibres: Specialisation and plasticity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B. Polla" 1 => "G. d’Antona" 2 => "R. Bottinelli" 3 => "C. Reggiani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2003.009894" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2004" "volumen" => "59" "paginaInicial" => "808" "paginaFinal" => "817" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15333861" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Muscle strength and speed of movement in relation to age and muscle morphology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L. Larsson" 1 => "G. Grimby" 2 => "J. Karlsson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Appl Physiol" "fecha" => "1979" "volumen" => "46" "paginaInicial" => "451" "paginaFinal" => "456" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/438011" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Respiratory muscle strength in the elderly. Correlates and reference values. Cardiovascular Health Study Research Group" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P.L. Enright" 1 => "R.A. Kronmal" 2 => "T.A. Manolio" 3 => "M.B. Schenker" 4 => "R.E. Hyatt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.149.2.8306041" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1994" "volumen" => "149" "paginaInicial" => "430" "paginaFinal" => "438" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8306041" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of diaphragm strength between healthy adult elderly and young men" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K. Tolep" 1 => "N. Higgins" 2 => "S. Muza" 3 => "G. Criner" 4 => "S.G. Kelsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.152.2.7633725" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1995" "volumen" => "152" "paginaInicial" => "677" "paginaFinal" => "682" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7633725" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The contractile properties of the elderly human diaphragm" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.I. Polkey" 1 => "M.L. Harris" 2 => "P.D. Hughes" 3 => "C.H. Hamnegärd" 4 => "D. Lyons" 5 => "M. Green" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.155.5.9154857" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1997" "volumen" => "155" "paginaInicial" => "1560" "paginaFinal" => "1564" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9154857" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of mechanical ventilation on diaphragm function and biology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G. Gayan-Ramirez" 1 => "M. Decramer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2002" "volumen" => "20" "paginaInicial" => "1579" "paginaFinal" => "1586" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12503720" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of mechanical ventilation on diaphragmatic contractile properties in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Le Bourdelles" 1 => "N. Viires" 2 => "J. Boczkowski" 3 => "N. Seta" 4 => "D. Pavlovic" 5 => "M. Aubier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.149.6.8004310" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1994" "volumen" => "149" "paginaInicial" => "1539" "paginaFinal" => "1544" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8004310" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protein metabolism and beta-myosin heavy-chain mRNA in unweighted soleus muscle" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.B. Thomason" 1 => "R.B. Biggs" 2 => "F.W. Booth" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol" "fecha" => "1989" "volumen" => "257" "paginaInicial" => "R300" "paginaFinal" => "R305" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanical ventilation depresses protein synthesis in the rat diaphragm" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.A. Shanely" 1 => "D. van Gammeren" 2 => "K.C. DeRuisseau" 3 => "A.M. Zergeroglu" 4 => "M.J. McKenzie" 5 => "K.E. Yarasheski" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200304-575OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2004" "volumen" => "170" "paginaInicial" => "994" "paginaFinal" => "999" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15297271" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Jaber" 1 => "B.J. Petrof" 2 => "B. Jung" 3 => "G. Chanques" 4 => "J.P. Berthet" 5 => "C. Rabuel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201004-0670OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2011" "volumen" => "183" "paginaInicial" => "364" "paginaFinal" => "371" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20813887" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.D. Schweickert" 1 => "M.C. Pohlman" 2 => "A.S. Pohlman" 3 => "C. Nigos" 4 => "A.J. Pawlik" 5 => "C.L. Esbrook" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(09)60658-9" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2009" "volumen" => "373" "paginaInicial" => "1874" "paginaFinal" => "1882" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19446324" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Valoración del estado nutricional en el paciente grave" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Acosta Escribano" 1 => "V. Gómez-Tello" 2 => "S. Ruiz Santana" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Nutr Hosp" "fecha" => "2005" "volumen" => "20" "paginaInicial" => "5" "paginaFinal" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15981840" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Components of energy expenditure in patients with severe sepsis and major trauma: a basis for clinical care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Uehara" 1 => "L.D. Plank" 2 => "G.L. Hill" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "1999" "volumen" => "27" "paginaInicial" => "1295" "paginaFinal" => "1302" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10446823" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Insulin resistance in critically ill patients with acute renal failure" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Basi" 1 => "L.B. Pupim" 2 => "E.M. Simmons" 3 => "M.T. Sezer" 4 => "Y. Shyr" 5 => "S. Freedman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajprenal.00002.2005" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Renal Physiol" "fecha" => "2005" "volumen" => "289" "paginaInicial" => "F259" "paginaFinal" => "F264" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15840772" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changes in the concentration and composition of plasma lipoproteins during the acute phase response" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Y.A. Carpentier" 1 => "O. Scruel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Curr Opin Clin Nutr Metab Care" "fecha" => "2002" "volumen" => "5" "paginaInicial" => "153" "paginaFinal" => "158" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11844981" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intensive insulin therapy in critically ill patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Van den Berghe" 1 => "P. Wouters" 2 => "F. Weekers" 3 => "C. Verwaest" 4 => "F. Bruyninckx" 5 => "M. Schetz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa011300" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2001" "volumen" => "345" "paginaInicial" => "1359" "paginaFinal" => "1367" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11794168" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of nutritional deprivation on diaphragm contractility and muscle fiber size" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.I. Lewis" 1 => "G.C. Sieck" 2 => "M. Fournier" 3 => "M.J. Belman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Appl Physiol" "fecha" => "1986" "volumen" => "60" "paginaInicial" => "596" "paginaFinal" => "603" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3949661" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protein tyrosine nitration in the ventilatory muscles: role of nitric oxide synthases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E. Barreiro" 1 => "A.S. Comtois" 2 => "J. Gea" 3 => "V.E. Laubach" 4 => "S. Hussain" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1165/ajrcmb.26.4.4634" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Cell Mol Biol" "fecha" => "2002" "volumen" => "26" "paginaInicial" => "438" "paginaFinal" => "446" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11919080" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sepsis-induced myopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L.A. Callahan" 1 => "G.S. Supinski" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e3181b6e439" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2009" "volumen" => "37" "paginaInicial" => "S354" "paginaFinal" => "S367" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20046121" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sepsis-induced changes in protein synthesis: differential effects on fast- and slow-twitch muscles" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T.C. Vary" 1 => "S.R. Kimball" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Physiol Cell Physiol" "fecha" => "1992" "volumen" => "262" "paginaInicial" => "C1513" "paginaFinal" => "C1519" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Corticosteroids influence the mortality and morbidity of acute critical illness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Rady" 1 => "D. Johnson" 2 => "B. Patel" 3 => "J. Larson" 4 => "R. Helmers" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc4971" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2006" "volumen" => "10" "paginaInicial" => "R101" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16846529" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanisms of glucocorticoid-induced myopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "O. Schakman" 1 => "H. Gilson" 2 => "J.P. Thissen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1677/JOE-07-0606" "Revista" => array:6 [ "tituloSerie" => "J Endocrinol" "fecha" => "2008" "volumen" => "197" "paginaInicial" => "1" "paginaFinal" => "10" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18372227" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Messenger ribonucleic acid expression of the MyoD gene family in muscle tissue at slaughter in relation to selection for porcine growth rate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Te Pas" 1 => "F. Verburg" 2 => "C. Gerritsen" 3 => "K. de Greef" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Anim Sci" "fecha" => "2000" "volumen" => "78" "paginaInicial" => "69" "paginaFinal" => "77" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10682804" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of glucocorticoids in the molecular regulation of muscle wasting" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Menconi" 1 => "M. Fareed" 2 => "P. O’Neal" 3 => "V. Poylin" 4 => "W. Wei" 5 => "P.-O. Hasselgren" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.CCM.0000279194.11328.77" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2007" "volumen" => "35" "paginaInicial" => "S602" "paginaFinal" => "S608" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17713416" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased sensitivity to depolarizing and nondepolarizing neuromuscular blocking agents in young rat hemidiaphragms" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L.P. Fortier" 1 => "R. Robitaille" 2 => "F. Donati" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Anesthesiology" "fecha" => "2001" "volumen" => "95" "paginaInicial" => "478" "paginaFinal" => "484" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11506123" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neuromuscular blockers in early acute respiratory distress syndrome" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "ACURASYS Study Investigators" "etal" => true "autores" => array:6 [ 0 => "L. Papazian" 1 => "J. Forel" 2 => "A. Gacouin" 3 => "C. Penot-Ragon" 4 => "G. Perrin" 5 => "A. Loundou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1005372" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2010" "volumen" => "363" "paginaInicial" => "1107" "paginaFinal" => "1116" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20843245" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Grosse-Sundrup" 1 => "J.P. Henneman" 2 => "W.S. Sandberg" 3 => "B.T. Bateman" 4 => "J.V. Uribe" 5 => "N.T. Nguyen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "BMJ" "fecha" => "2012" "volumen" => "345" "paginaInicial" => "e6329" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23077290" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The use of neuromuscular blocking drugs in the intensive care unit: a US perspective" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Murray" 1 => "R. Strickland" 2 => "C. Weiler" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "1993" "volumen" => "19" "paginaInicial" => "S40" "paginaFinal" => "S44" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8106677" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacodynamics and pharmacokinetics of rocuronium in intensive care patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H. Sparr" 1 => "J. Wierda" 2 => "J. Proost" 3 => "C. Keller" 4 => "K. Khuenl-Brady" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Anaesth" "fecha" => "1997" "volumen" => "78" "paginaInicial" => "267" "paginaFinal" => "273" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9135303" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:3 [ "titulo" => "Acknowledgements" "texto" => "This study was made possible thanks to the institutional support provided by Universidad del Valle and Fundación Valle del Lili (FVL), Cali-Colombia. We would also like to thank Dr. Mónica P. Vargas, MD, Anaesthesiologist, Intensive Care Unit, FVL." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/15792129/0000005000000002/v1_201403040040/S1579212914000196/v1_201403040040/en/main.assets" "Apartado" => array:4 [ "identificador" => "14573" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Review article" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/15792129/0000005000000002/v1_201403040040/S1579212914000196/v1_201403040040/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212914000196?idApp=UINPBA00003Z"]

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Respiratory Muscle Dysfunction: A Multicausal Entity in the Critically Ill Patient Undergoing Mechanical Ventilation

Disfunción muscular respiratoria: una entidad multicausal en el paciente críticamente enfermo sometido a ventilación mecánica

Magda C. Díaza,c, Gustavo A. Ospina-Tascóna,b, Blanca C. Salazar Cc,

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bsblasalaz@gmail.com

Corresponding author.

a Unidad de Cuidados Intensivos, Fundación Valle del Lili, Cali, Colombia

b Grupo de Investigación Biomédica de la Universidad ICESI, Cali, Colombia

c Departamento de Ciencias Fisiológicas, Facultad de Salud, Universidad del Valle, Cali, Colombia

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Mechanical ventilation &#40;MV&#41; is one of the most common means of life support in intensive care units &#40;ICU&#41; and forms part of the standard treatment of acute respiratory failure&#46; However&#44; despite its advantages&#44; MV can cause direct systemic and pulmonary complications<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> leading to longer hospital stays&#44; increased costs&#44; higher mortality and loss of quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> As such&#44; it is essential that the duration of MV in a critically ill patient is kept as short as possible by judicious daily evaluation on the part of the clinician&#46; It has been calculated that around 40&#37; of the total time on MV in the ICU is dedicated to weaning respiratory support&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Some descriptive studies have shown that 69&#37; of patients are easily weaned&#44; while 15&#37; require prolonged MV &#40;PMV&#41;&#44; with hospital stays of over 10 days&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Difficulty in weaning from MV is a significant problem&#44; since it increases complications like nosocomial infections and&#47;or airways lesions and others&#46; In addition to producing significant deterioration in quality of life&#44; difficulty in weaning consumes up to 40&#37; of all ICU resources&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;5</span></a> Respiratory muscle dysfunction&#44; particularly of the diaphragm&#44; may play a key role in the pathophysiological mechanisms that lead to difficulty in weaning patients from MV&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The limited mobility of the diaphragm under MV promotes the early onset of respiratory muscle dysfunction&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> and this can be exacerbated by other factors&#44; such as advanced age&#44; long duration of MV&#44; controlled ventilatory mode&#44; malnutrition&#44; sepsis and some medications&#44; such as glucocorticoids and neuromuscular blocking agents &#40;NMBA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Awareness of the pathophysiological mechanisms underlying these factors in respiratory muscle dysfunction<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and their role in difficult weaning is on the increase&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Two aspects are highlighted in this report&#46; The first is that the factors primarily associated with respiratory muscle dysfunction occur frequently and often simultaneously in patients on MV&#46; The second is that the common mechanism underlying the physiopathology of these factors is proteolysis and&#47;or reduced muscle protein synthesis&#44; which has also been shown on histology as atrophy&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Factors Associated With Respiratory Muscle Dysfunction</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Age</span><p id="par0020" class="elsevierStylePara elsevierViewall">In two prospective multicentre studies in mechanically ventilated patients in intensive care units in more than 20 countries in America and Europe<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and in Latin America&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> the average age of patients was 57 years&#44; while that of patients on PMV was 72 years&#46; Generally in humans&#44; skeletal muscle strength&#44; mass and structure change with age&#46; At the age of 70 years&#44; subjects have a reduction of muscle mass of between 20&#37; and 30&#37;&#44; causing a loss of peripheral strength of between 20&#37; and 40&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> This diminished peripheral mass is the result of a fall in number and size of muscle fibres&#44; principally the fast twitch type&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Age-related changes may be different in the respiratory muscles and in the peripheral muscles&#44; since respiratory activity is continuous&#44; while peripheral muscle activity may not be&#46; Although data in humans are limited&#44; age-related respiratory muscle dysfunction has been demonstrated by a loss of strength&#44; determined in subjects aged between 65 and 85 years as a yearly reduction in maximum inspiratory pressure &#40;MIP&#41; of 0&#46;8&#8211;2&#46;7<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and a 25&#37; fall in transdiaphragmatic pressure in adults between 65 and 75 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> A mechanism that may explain these changes is the accumulative effect of oxygen-derived free radicals that may trigger proteolytic processes&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> It has also been suggested that with advancing age&#44; remodelling occurs in the muscle fibres&#44; with fast twitch myosin fibres being replaced by slow twitch isoforms&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Duration and Mode of Mechanical Ventilation</span><p id="par0025" class="elsevierStylePara elsevierViewall">In reports on the progress of patients admitted to the ICU&#44; 30&#37; needed a mean duration of 5&#8211;8 days MV support and the most frequently used mode was assist-control &#40;60&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> Among MV patients&#44; 30&#37; had difficulty weaning and a significant proportion of these became what was defined as PMV&#46; It seems that&#44; in addition to MV duration&#44; ventilatory mode is a determining factor for the development of diaphragmatic muscle dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> This was first described in 1994 by Le Bourdelles et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> who submitted rats to MV and showed that maximum muscle strength per unit cross-sectional area fell after 48<span class="elsevierStyleHsp" style=""></span>hours of support&#46; Interest in diaphragm muscle wastage has been growing in recent years&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Several studies performed in different animal species have shown that significant atrophy of the slow and fast twitch fibres of this muscle occurs after only 12&#8211;18<span class="elsevierStyleHsp" style=""></span>hours &#40;h&#41; on MV&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> This occurs before the appearance of atrophy in the musculoskeletal system that has often been described in experimental animal models after 96<span class="elsevierStyleHsp" style=""></span>h of MV&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Similar results were confirmed in humans after 18&#8211;69<span class="elsevierStyleHsp" style=""></span>h of MV<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#58; diaphragm atrophy was seen when biopsies from brain death patients &#40;after undergoing controlled MV&#41; were compared with controls undergoing chest surgery&#46; One important finding was the reduction of the cross-sectional area in both type I and type II fibres in patients receiving ventilation for more than 48<span class="elsevierStyleHsp" style=""></span>h&#46; Some animal studies show that immobility from controlled MV also causes a loss of fibres from the locomotor skeletal muscles&#44; a myofibrillar disorder of the diaphragm&#44; and&#44; furthermore&#44; changes in the Z-line structure in both&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The mechanism mainly associated with diaphragm atrophy in animal models<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and in humans undergoing MV is the increase in proteolysis&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;21</span></a> In animals&#44; a reduction in protein synthesis has also been observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;20</span></a> The contribution of calpain&#44; caspase-3&#44; and the lyosomal and the ubiquitin-proteasome systems has been discussed in recent studies&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Current research is directed towards the transduction pathways of these mechanisms&#44; with the aim of identifying drugs or therapeutic interventions that would deviate these pathways towards the prevention of atrophy and respiratory muscle dysfunction&#46; In this respect&#44; alternatives&#44; such as reducing the time of controlled mode MV&#44; transcutaneous electric stimulation of the diaphragm&#44; early mobilisation of patients<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and the use of antioxidant drugs&#44; have been proposed&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Nutritional and Metabolic Status</span><p id="par0035" class="elsevierStylePara elsevierViewall">Between 30&#37; and 60&#37; of ICU patients have or will have some degree of malnutrition&#44; due to metabolic changes causing a greater energy output and the nutritional deficit due to poor absorption or reduced availability of nutrients during critical disease&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> The increase in catabolic hormones &#40;glucagon&#44; adrenaline and cortisol&#41; and cytokines<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> and the inhibition of anabolic hormones&#44; such as insulin and testosterone&#44; produces a situation of hypermetabolism&#46; A hypermetabolic patient will suffer a loss of muscle mass and strength and immune response&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Hormone imbalance has frequently been associated with the development of hyperglycaemia&#46; Although this is a condition that adapts to critical disease&#44; it remains a factor for negative prognosis in the short&#44; mid and long-term&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Hyperglycaemia aids the storage of lipids in the form of triglycerides and low density lipoproteins&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> The unavailability of these substrates as energy sources leads to marked proteolysis&#44; and as such&#44; to a loss of muscle mass&#44; an increase in severe infections&#44; multiple organ failure and death&#44; particularly in critically ill surgical patients&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> The weight of the diaphragm in a malnourished rat drops more than the weight of the muscles of the limbs&#44; as a result of atrophy and remodelling of fast twitch fibres&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> In addition&#44; hyperglycaemia causes oxidative stress&#44; which has been associated with nerve fibre loss and atrophy&#44; with the corresponding impact on muscular neurotransmission&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Comorbidities</span><p id="par0040" class="elsevierStylePara elsevierViewall">Critically ill patients undergoing MV may present various comorbidities&#44; the most common being sepsis&#44; diabetes mellitus&#44; hypertension and acute myocardial infarction&#46; Complications such as barotrauma&#44; sepsis&#44; acute respiratory distress syndrome &#40;ARDS&#41;&#44; MV-related pneumonia&#44; cardiogenic shock and polyneuropathy in critically ill patients may also occur&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The effects of these diseases in the development of respiratory muscle dysfunction due to mechanisms mediated by changes in protein metabolism may be additive&#46; For example&#44; in both animals and humans&#44; the systemic inflammatory response in sepsis induces an increase in proinflammatory cytokines &#40;TNF-&#945;&#44; IL-6&#44; IL-1&#41; and free radicals&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> which also promote greater activity of the proteolytic pathways&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> as mentioned above&#46; With regard to protein synthesis in the skeletal muscle of rats&#44; it has been reported that other sepsis-induced inflammatory mediators&#44; such as IL-1&#946;&#44; reduce eIF4G factor phosphorylation&#44; thus altering the onset of translation of sarcoplasmic proteins&#44; such as myofibrils&#44; in muscles composed of fast twitch fibres&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Mechanisms other than changes in protein metabolism regulation have been proposed in sepsis&#59; mechanisms that are associated with changes in cell excitability&#44; calcium homeostasis<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> and mitochondrial oxidative phosphorylation of the muscle&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Pharmacological Treatment</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Glucocorticoids</span><p id="par0045" class="elsevierStylePara elsevierViewall">Glucocorticoids &#40;GC&#41; are used in the critically ill patient with sepsis&#44; acute respiratory distress syndrome &#40;ARDS&#41; and refractory vasodilatory shock&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> High doses have been associated with neuromuscular disorders causing peripheral and respiratory muscle dysfunction&#46; In patients on MV&#44; GC have been seen to delay MV weaning and to increase the need for tracheostomy&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In humans and animals&#44; GC-induced respiratory and peripheral muscle dysfunction is caused by inhibition of anabolism and by the catabolic effect of proteins&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The anti-anabolic effect of the GCs inhibits protein synthesis by various mechanisms&#46; One of these is the inhibition of amino acid transport within the muscles&#44; limiting protein synthesis&#46; Another mechanism that has been proposed is the inhibition of the stimulating effect of insulin and the insulin growth factor &#40;IGF-1&#41; on the phosphorylation of the eIF4-binding protein and ribosomal protein kinase S6&#44; two key factors in mRNA translation&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> Finally&#44; GCs inhibit myogenesis by the low regulation of myogenin&#44; an essential transcription factor for the differentiation of satellite cells in muscle fibres&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Stimulation of IGF-1 or the myostatin blockers constitute some of the more promising therapeutic targets for preventing GC-induced muscle atrophy&#46; The catabolic action of GCs is mediated by the proteolytic ubiquitin-proteasome&#44; lysosome and calpain-dependent systems<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> that primarily affect the myofibrillar proteins&#46; In muscle wasting&#44; intracellular mediators such as FOXO&#44; GSK3b&#44; <span class="elsevierStyleSmallCaps">C</span>&#47;EBPb&#44; p300&#44; REDD1 and ATF4 form part not only of the catabolic action but also of the inhibitory action of GC anabolism&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Neuromuscular Blocking Agents</span><p id="par0055" class="elsevierStylePara elsevierViewall">NMBAs are used to improve synchrony in MV patients and to keep the ventilatory parameters high &#40;PEEP&#62;10<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#44; FIO<span class="elsevierStyleInf">2</span>&#62;80&#37;&#41;&#44; when required&#46; NMBAs are either depolarising or non-depolarising&#46; In a study on rat diaphragm comparing the effects of these agents&#44; non-depolarising NMBAs were found to be more potent&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In humans&#44; it has been reported that NMBAs did not cause ICU-acquired weakness compared to placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> However&#44; respiratory complications &#40;prolonged desaturation&#44; SatO<span class="elsevierStyleInf">2</span>&#60;90&#37;&#41; requiring re-intubation were reported in some publications&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Prolonged use of high-dose NMBAs together with steroids in the presence of prolonged immobilisation promotes muscle weakness in the critically ill patient and&#44; in some cases&#44; acute necrotising myopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> This condition progresses with generalised weakness of the peripheral and respiratory muscles&#44; recovery is slow and patients are left with sequelae&#46; In critically ill patients with sepsis or multiple organ failure&#44; NMBA pharmacokinetics are altered due to changes in physical function&#44; perfusion and the intracellular&#47;extracellular fluid ratio&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> In the light of these findings&#44; intermittent dosing with NMBAs that do not change kidney or liver function is recommended&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Respiratory Muscular Dysfunction Synthesis in the Critically Ill Patient Undergoing Mechanical Ventilation</span><p id="par0065" class="elsevierStylePara elsevierViewall">In the schematic in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; the factors contributing to respiratory muscle dysfunction in the critically ill patient on MV are presented&#46; The mechanisms involved in protein breakdown and&#47;or the reduction of protein synthesis for each factor are listed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusion</span><p id="par0070" class="elsevierStylePara elsevierViewall">Although respiratory muscle dysfunction in the critically ill patient undergoing MV has multicausal origins&#44; the primary underlying mechanisms may be proteolysis and&#47;or the reduction of protein synthesis&#44; and in some cases&#44; neurotransmission disturbances&#46; Respiratory muscle dysfunction causes difficulty in weaning&#44; PMV&#44; and morbidity and mortality in the critically ill patient&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Although the aim of this review was to focus on respiratory muscle dysfunction&#44; the peripheral musculature is also affected in one way or another by the multicausal nature of this disorder and its associated mechanisms&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Recommendations</span><p id="par0080" class="elsevierStylePara elsevierViewall">Early&#44; integrated management of the multiple causes of respiratory muscle dysfunction may reduce hospital stay and associated morbidity and mortality&#44; and could prevent the development and severity of the sometimes irreversible neuromuscular sequelae&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">It is important that research into the quantification and regulation of altered protein metabolism in these patients continues&#44; with the aim of counteracting this metabolic tendency with a series of treatment prescriptions and diets more closely suited to the real conditions of the patient undergoing MV&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Funding</span><p id="par0090" class="elsevierStylePara elsevierViewall">Call for Grants&#44; Universidad del Valle&#44; 2010&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Framework Agreement</span><p id="par0095" class="elsevierStylePara elsevierViewall">Fundaci&#243;n Valle del Lili and Universidad del Valle&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of Interests</span><p id="par0100" class="elsevierStylePara elsevierViewall">There is no institutional or individual conflict of interests&#46;</p></span></span>"
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          "titulo" => "Abstract"
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          "titulo" => "Palabras clave"
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          "titulo" => "Introduction"
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          "titulo" => "Factors Associated With Respiratory Muscle Dysfunction"
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            0 => array:2 [
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              "titulo" => "Age"
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              "titulo" => "Duration and Mode of Mechanical Ventilation"
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              "titulo" => "Nutritional and Metabolic Status"
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              "titulo" => "Glucocorticoids"
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              "titulo" => "Neuromuscular Blocking Agents"
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            2 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Respiratory Muscular Dysfunction Synthesis in the Critically Ill Patient Undergoing Mechanical Ventilation"
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          "identificador" => "sec0055"
          "titulo" => "Conclusion"
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          "titulo" => "Recommendations"
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          "titulo" => "Funding"
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    "fechaRecibido" => "2012-09-12"
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            0 => "Respiratory muscle dysfunction"
            1 => "Mechanical ventilation"
            2 => "Weaning from mechanical ventilation"
            3 => "Sepsis"
            4 => "Critical patient"
            5 => "Proteolysis"
            6 => "Protein synthesis and malnutrition in the critically ill patient"
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          "palabras" => array:7 [
            0 => "Disfunci&#243;n respiratoria"
            1 => "Ventilaci&#243;n mec&#225;nica"
            2 => "Destete de la ventilaci&#243;n mec&#225;nica"
            3 => "Sepsis"
            4 => "Paciente cr&#237;tico"
            5 => "Prote&#243;lisis"
            6 => "S&#237;ntesis de prote&#237;nas y desnutrici&#243;n en el paciente cr&#237;tico"
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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Respiratory muscle dysfunction&#44; particularly of the diaphragm&#44; may play a key role in the pathophysiological mechanisms that lead to difficulty in weaning patients from mechanical ventilation&#46; The limited mobility of critically ill patients&#44; and of the diaphragm in particular when prolonged mechanical ventilation support is required&#44; promotes the early onset of respiratory muscle dysfunction&#44; but this can also be caused or exacerbated by other factors that are common in these patients&#44; such as sepsis&#44; malnutrition&#44; advanced age&#44; duration and type of ventilation&#44; and use of certain medications&#44; such as steroids and neuromuscular blocking agents&#46; In this review we will study in depth this multicausal origin&#44; in which a common mechanism is altered protein metabolism&#44; according to the findings reported in various models&#46; The understanding of this multicausality produced by the same pathophysiological mechanism could facilitate the management and monitoring of patients undergoing mechanical ventilation&#46;</p>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Es probable que la disfunci&#243;n de los m&#250;sculos respiratorios&#44; principalmente del diafragma&#44; constituya una pieza clave dentro de los mecanismos fisiopatol&#243;gicos que conducen a la dificultad del destete de la ventilaci&#243;n mec&#225;nica&#46; La limitada movilidad del paciente cr&#237;tico&#8212;y en especial del diafragma&#8212;cuando se requiere soporte prolongado con ventilaci&#243;n mec&#225;nica favorece el inicio temprano de la disfunci&#243;n muscular respiratoria&#44; la cual puede originarse tambi&#233;n o hacerse mayor en presencia de factores frecuentes en el paciente cr&#237;ticamente enfermo&#44; tales como sepsis&#44; desnutrici&#243;n&#44; edad avanzada&#44; duraci&#243;n y modo ventilatorio&#44; uso de algunos medicamentos como glucocorticoides y bloqueadores neuromusculares&#46; En esta revisi&#243;n haremos &#233;nfasis en este origen multicausal&#44; en el que la alteraci&#243;n del metabolismo de las prote&#237;nas es un mecanismo com&#250;n involucrado&#44; de acuerdo con los hallazgos reportados en diferentes modelos&#46; El entendimiento de esta multicausalidad integrada por un mismo mecanismo fisiopatol&#243;gico podr&#237;a favorecer el manejo y la monitorizaci&#243;n de los pacientes sometidos a ventilaci&#243;n mec&#225;nica&#46;</p>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; D&#237;az MC&#44; Ospina-Tasc&#243;n GA&#44; Salazar C BC&#46; Disfunci&#243;n muscular respiratoria&#58; una entidad multicausal en el paciente cr&#237;ticamente enfermo sometido a ventilaci&#243;n mec&#225;nica&#46; Arch Bronconeumol&#46; 2014&#59;50&#58;73&#8211;77&#46;</p>"
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              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ventilator-induced lung injury and recommendations for mechanical ventilation of patients with ARDS"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "W&#46;L&#46; Lee"
                            1 => "A&#46; Slutsky"
                          ]
                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1055/s-2001-15784"
                      "Revista" => array:6 [
                        "tituloSerie" => "Semin Respir Crit Care Med"
                        "fecha" => "2001"
                        "volumen" => "22"
                        "paginaInicial" => "269"
                        "paginaFinal" => "280"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16088679"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
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            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Legacy of intensive care unit-acquired weakness"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;S&#46; Herridge"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CCM.0b013e3181b6f35c"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2009"
                        "volumen" => "37"
                        "paginaInicial" => "S457"
                        "paginaFinal" => "S461"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20046135"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "What is the proper approach to liberating the weak from mechanical ventilation&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "L&#46; Brochard"
                            1 => "A&#46;W&#46; Thille"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CCM.0b013e3181b6e28b"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2009"
                        "volumen" => "37"
                        "paginaInicial" => "S410"
                        "paginaFinal" => "S415"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20046128"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Weaning from mechanical ventilation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Boles"
                            1 => "J&#46; Bion"
                            2 => "A&#46; Connors"
                            3 => "M&#46; Herridge"
                            4 => "B&#46; Marsh"
                            5 => "C&#46; Melot"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00010206"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2007"
                        "volumen" => "29"
                        "paginaInicial" => "1033"
                        "paginaFinal" => "1056"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17470624"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "How is mechanical ventilation employed in the intensive care unit&#63; An international utilization review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Esteban"
                            1 => "A&#46; Anzueto"
                            2 => "I&#46; Al&#237;a"
                            3 => "F&#46; Gordo"
                            4 => "C&#46; Apeztegu&#237;a"
                            5 => "F&#46; P&#225;lizas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.161.5.9902018"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2000"
                        "volumen" => "161"
                        "paginaInicial" => "1450"
                        "paginaFinal" => "1458"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10806138"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Determinants of weaning success in patients with prolonged mechanical ventilation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Carlucci"
                            1 => "P&#46; Ceriana"
                            2 => "G&#46; Prinianakis"
                            3 => "F&#46; Fanfulla"
                            4 => "R&#46; Colombo"
                            5 => "S&#46; Nava"
                          ]
                        ]
                      ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/cc7927"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2009"
                        "volumen" => "13"
                        "paginaInicial" => "R97"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19549301"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0035"
              "etiqueta" => "7"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intensive care unit-acquired weakness"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46; Griffiths"
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                    0 => array:2 [
                      "doi" => "10.1097/CCM.0b013e3181cc4b53"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2010"
                        "volumen" => "38"
                        "paginaInicial" => "779"
                        "paginaFinal" => "787"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20048676"
                            "web" => "Medline"
                          ]
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                      ]
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                ]
              ]
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              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prolonged mechanical ventilation alters diaphragmatic structure and function"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46;K&#46; Powers"
                            1 => "A&#46;N&#46; Kavazis"
                            2 => "S&#46; Levine"
                          ]
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                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CCM.0b013e3181b6e760"
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                        "tituloSerie" => "Crit Care Med"
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                        "volumen" => "37"
                        "paginaInicial" => "S347"
                        "paginaFinal" => "S353"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20046120"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Levine"
                            1 => "T&#46; Nguyen"
                            2 => "N&#46; Taylor"
                            3 => "M&#46;E&#46; Friscia"
                            4 => "M&#46;T&#46; Budak"
                            5 => "P&#46; Rothenberg"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa070447"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2008"
                        "volumen" => "358"
                        "paginaInicial" => "1327"
                        "paginaFinal" => "1335"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18367735"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characteristics and outcomes in adult patients receiving mechanical ventilation"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Esteban"
                            1 => "A&#46; Anzueto"
                            2 => "F&#46; Frutos"
                            3 => "I&#46; Al&#237;a"
                            4 => "L&#46; Brochard"
                            5 => "T&#46;E&#46; Stewart"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2002"
                        "volumen" => "287"
                        "paginaInicial" => "345"
                        "paginaFinal" => "355"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11790214"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Caracter&#237;sticas de los pacientes que reciben ventilaci&#243;n mec&#225;nica en unidades de cuidados intensivos&#58; primer estudio multic&#233;ntrico chileno"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46; Tomicic"
                            1 => "M&#46; Espinoza"
                            2 => "M&#46; Andresen"
                            3 => "J&#46; Molina"
                            4 => "M&#46; Calvo"
                            5 => "H&#46; Ugarte"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "/S0034-98872008000800001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Med Chile"
                        "fecha" => "2008"
                        "volumen" => "136"
                        "paginaInicial" => "959"
                        "paginaFinal" => "967"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18949178"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Respiratory muscle fibres&#58; Specialisation and plasticity"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "B&#46; Polla"
                            1 => "G&#46; d&#8217;Antona"
                            2 => "R&#46; Bottinelli"
                            3 => "C&#46; Reggiani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.2003.009894"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2004"
                        "volumen" => "59"
                        "paginaInicial" => "808"
                        "paginaFinal" => "817"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15333861"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Muscle strength and speed of movement in relation to age and muscle morphology"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46; Larsson"
                            1 => "G&#46; Grimby"
                            2 => "J&#46; Karlsson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Appl Physiol"
                        "fecha" => "1979"
                        "volumen" => "46"
                        "paginaInicial" => "451"
                        "paginaFinal" => "456"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/438011"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Respiratory muscle strength in the elderly&#46; Correlates and reference values&#46; Cardiovascular Health Study Research Group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46;L&#46; Enright"
                            1 => "R&#46;A&#46; Kronmal"
                            2 => "T&#46;A&#46; Manolio"
                            3 => "M&#46;B&#46; Schenker"
                            4 => "R&#46;E&#46; Hyatt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.149.2.8306041"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1994"
                        "volumen" => "149"
                        "paginaInicial" => "430"
                        "paginaFinal" => "438"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8306041"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of diaphragm strength between healthy adult elderly and young men"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "K&#46; Tolep"
                            1 => "N&#46; Higgins"
                            2 => "S&#46; Muza"
                            3 => "G&#46; Criner"
                            4 => "S&#46;G&#46; Kelsen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.152.2.7633725"
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                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1995"
                        "volumen" => "152"
                        "paginaInicial" => "677"
                        "paginaFinal" => "682"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7633725"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The contractile properties of the elderly human diaphragm"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;I&#46; Polkey"
                            1 => "M&#46;L&#46; Harris"
                            2 => "P&#46;D&#46; Hughes"
                            3 => "C&#46;H&#46; Hamneg&#228;rd"
                            4 => "D&#46; Lyons"
                            5 => "M&#46; Green"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.155.5.9154857"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1997"
                        "volumen" => "155"
                        "paginaInicial" => "1560"
                        "paginaFinal" => "1564"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9154857"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of mechanical ventilation on diaphragm function and biology"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46; Gayan-Ramirez"
                            1 => "M&#46; Decramer"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2002"
                        "volumen" => "20"
                        "paginaInicial" => "1579"
                        "paginaFinal" => "1586"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12503720"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of mechanical ventilation on diaphragmatic contractile properties in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G&#46; Le Bourdelles"
                            1 => "N&#46; Viires"
                            2 => "J&#46; Boczkowski"
                            3 => "N&#46; Seta"
                            4 => "D&#46; Pavlovic"
                            5 => "M&#46; Aubier"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.149.6.8004310"
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                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1994"
                        "volumen" => "149"
                        "paginaInicial" => "1539"
                        "paginaFinal" => "1544"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8004310"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protein metabolism and beta-myosin heavy-chain mRNA in unweighted soleus muscle"
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                          "etal" => false
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                            0 => "D&#46;B&#46; Thomason"
                            1 => "R&#46;B&#46; Biggs"
                            2 => "F&#46;W&#46; Booth"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol"
                        "fecha" => "1989"
                        "volumen" => "257"
                        "paginaInicial" => "R300"
                        "paginaFinal" => "R305"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanical ventilation depresses protein synthesis in the rat diaphragm"
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                          "autores" => array:6 [
                            0 => "R&#46;A&#46; Shanely"
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                            2 => "K&#46;C&#46; DeRuisseau"
                            3 => "A&#46;M&#46; Zergeroglu"
                            4 => "M&#46;J&#46; McKenzie"
                            5 => "K&#46;E&#46; Yarasheski"
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2004"
                        "volumen" => "170"
                        "paginaInicial" => "994"
                        "paginaFinal" => "999"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15297271"
                            "web" => "Medline"
                          ]
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                ]
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              "identificador" => "bib0105"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans"
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                            2 => "B&#46; Jung"
                            3 => "G&#46; Chanques"
                            4 => "J&#46;P&#46; Berthet"
                            5 => "C&#46; Rabuel"
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201004-0670OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2011"
                        "volumen" => "183"
                        "paginaInicial" => "364"
                        "paginaFinal" => "371"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20813887"
                            "web" => "Medline"
                          ]
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                    ]
                  ]
                ]
              ]
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            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Early physical and occupational therapy in mechanically ventilated&#44; critically ill patients&#58; a randomised controlled trial"
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                            1 => "M&#46;C&#46; Pohlman"
                            2 => "A&#46;S&#46; Pohlman"
                            3 => "C&#46; Nigos"
                            4 => "A&#46;J&#46; Pawlik"
                            5 => "C&#46;L&#46; Esbrook"
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                      ]
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "Lancet"
                        "fecha" => "2009"
                        "volumen" => "373"
                        "paginaInicial" => "1874"
                        "paginaFinal" => "1882"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19446324"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Valoraci&#243;n del estado nutricional en el paciente grave"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Acosta Escribano"
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                            2 => "S&#46; Ruiz Santana"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Nutr Hosp"
                        "fecha" => "2005"
                        "volumen" => "20"
                        "paginaInicial" => "5"
                        "paginaFinal" => "8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15981840"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Components of energy expenditure in patients with severe sepsis and major trauma&#58; a basis for clinical care"
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                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Uehara"
                            1 => "L&#46;D&#46; Plank"
                            2 => "G&#46;L&#46; Hill"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "1999"
                        "volumen" => "27"
                        "paginaInicial" => "1295"
                        "paginaFinal" => "1302"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10446823"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Insulin resistance in critically ill patients with acute renal failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Basi"
                            1 => "L&#46;B&#46; Pupim"
                            2 => "E&#46;M&#46; Simmons"
                            3 => "M&#46;T&#46; Sezer"
                            4 => "Y&#46; Shyr"
                            5 => "S&#46; Freedman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajprenal.00002.2005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Renal Physiol"
                        "fecha" => "2005"
                        "volumen" => "289"
                        "paginaInicial" => "F259"
                        "paginaFinal" => "F264"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15840772"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Changes in the concentration and composition of plasma lipoproteins during the acute phase response"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Y&#46;A&#46; Carpentier"
                            1 => "O&#46; Scruel"
                          ]
                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Clin Nutr Metab Care"
                        "fecha" => "2002"
                        "volumen" => "5"
                        "paginaInicial" => "153"
                        "paginaFinal" => "158"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11844981"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intensive insulin therapy in critically ill patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Van den Berghe"
                            1 => "P&#46; Wouters"
                            2 => "F&#46; Weekers"
                            3 => "C&#46; Verwaest"
                            4 => "F&#46; Bruyninckx"
                            5 => "M&#46; Schetz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa011300"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2001"
                        "volumen" => "345"
                        "paginaInicial" => "1359"
                        "paginaFinal" => "1367"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11794168"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of nutritional deprivation on diaphragm contractility and muscle fiber size"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;I&#46; Lewis"
                            1 => "G&#46;C&#46; Sieck"
                            2 => "M&#46; Fournier"
                            3 => "M&#46;J&#46; Belman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Appl Physiol"
                        "fecha" => "1986"
                        "volumen" => "60"
                        "paginaInicial" => "596"
                        "paginaFinal" => "603"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3949661"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protein tyrosine nitration in the ventilatory muscles&#58; role of nitric oxide synthases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Barreiro"
                            1 => "A&#46;S&#46; Comtois"
                            2 => "J&#46; Gea"
                            3 => "V&#46;E&#46; Laubach"
                            4 => "S&#46; Hussain"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/ajrcmb.26.4.4634"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2002"
                        "volumen" => "26"
                        "paginaInicial" => "438"
                        "paginaFinal" => "446"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11919080"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sepsis-induced myopathy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "L&#46;A&#46; Callahan"
                            1 => "G&#46;S&#46; Supinski"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CCM.0b013e3181b6e439"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2009"
                        "volumen" => "37"
                        "paginaInicial" => "S354"
                        "paginaFinal" => "S367"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20046121"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sepsis-induced changes in protein synthesis&#58; differential effects on fast- and slow-twitch muscles"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46;C&#46; Vary"
                            1 => "S&#46;R&#46; Kimball"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Physiol Cell Physiol"
                        "fecha" => "1992"
                        "volumen" => "262"
                        "paginaInicial" => "C1513"
                        "paginaFinal" => "C1519"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Corticosteroids influence the mortality and morbidity of acute critical illness"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Rady"
                            1 => "D&#46; Johnson"
                            2 => "B&#46; Patel"
                            3 => "J&#46; Larson"
                            4 => "R&#46; Helmers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/cc4971"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2006"
                        "volumen" => "10"
                        "paginaInicial" => "R101"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16846529"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanisms of glucocorticoid-induced myopathy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "O&#46; Schakman"
                            1 => "H&#46; Gilson"
                            2 => "J&#46;P&#46; Thissen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1677/JOE-07-0606"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Endocrinol"
                        "fecha" => "2008"
                        "volumen" => "197"
                        "paginaInicial" => "1"
                        "paginaFinal" => "10"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18372227"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Messenger ribonucleic acid expression of the MyoD gene family in muscle tissue at slaughter in relation to selection for porcine growth rate"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Te Pas"
                            1 => "F&#46; Verburg"
                            2 => "C&#46; Gerritsen"
                            3 => "K&#46; de Greef"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Anim Sci"
                        "fecha" => "2000"
                        "volumen" => "78"
                        "paginaInicial" => "69"
                        "paginaFinal" => "77"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10682804"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of glucocorticoids in the molecular regulation of muscle wasting"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Menconi"
                            1 => "M&#46; Fareed"
                            2 => "P&#46; O&#8217;Neal"
                            3 => "V&#46; Poylin"
                            4 => "W&#46; Wei"
                            5 => "P&#46;-O&#46; Hasselgren"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.CCM.0000279194.11328.77"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2007"
                        "volumen" => "35"
                        "paginaInicial" => "S602"
                        "paginaFinal" => "S608"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17713416"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased sensitivity to depolarizing and nondepolarizing neuromuscular blocking agents in young rat hemidiaphragms"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46;P&#46; Fortier"
                            1 => "R&#46; Robitaille"
                            2 => "F&#46; Donati"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesthesiology"
                        "fecha" => "2001"
                        "volumen" => "95"
                        "paginaInicial" => "478"
                        "paginaFinal" => "484"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11506123"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neuromuscular blockers in early acute respiratory distress syndrome"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "ACURASYS Study Investigators"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Papazian"
                            1 => "J&#46; Forel"
                            2 => "A&#46; Gacouin"
                            3 => "C&#46; Penot-Ragon"
                            4 => "G&#46; Perrin"
                            5 => "A&#46; Loundou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1005372"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2010"
                        "volumen" => "363"
                        "paginaInicial" => "1107"
                        "paginaFinal" => "1116"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20843245"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications&#58; prospective propensity score matched cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Grosse-Sundrup"
                            1 => "J&#46;P&#46; Henneman"
                            2 => "W&#46;S&#46; Sandberg"
                            3 => "B&#46;T&#46; Bateman"
                            4 => "J&#46;V&#46; Uribe"
                            5 => "N&#46;T&#46; Nguyen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "2012"
                        "volumen" => "345"
                        "paginaInicial" => "e6329"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23077290"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The use of neuromuscular blocking drugs in the intensive care unit&#58; a US perspective"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Murray"
                            1 => "R&#46; Strickland"
                            2 => "C&#46; Weiler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "1993"
                        "volumen" => "19"
                        "paginaInicial" => "S40"
                        "paginaFinal" => "S44"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8106677"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacodynamics and pharmacokinetics of rocuronium in intensive care patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "H&#46; Sparr"
                            1 => "J&#46; Wierda"
                            2 => "J&#46; Proost"
                            3 => "C&#46; Keller"
                            4 => "K&#46; Khuenl-Brady"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Anaesth"
                        "fecha" => "1997"
                        "volumen" => "78"
                        "paginaInicial" => "267"
                        "paginaFinal" => "273"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9135303"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
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        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0105" class="elsevierStylePara elsevierViewall">This study was made possible thanks to the institutional support provided by Universidad del Valle and Fundaci&#243;n Valle del Lili &#40;FVL&#41;&#44; Cali-Colombia&#46; We would also like to thank Dr&#46; M&#243;nica P&#46; Vargas&#44; MD&#44; Anaesthesiologist&#44; Intensive Care Unit&#44; FVL&#46;</p>"
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Article information

ISSN: 15792129
Original language: English

DOI:10.1016/j.arbr.2014.01.007

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2020 December	47	27	74
2020 November	71	15	86
2020 October	63	22	85
2020 September	56	35	91
2020 August	73	34	107
2020 July	62	37	99
2020 June	75	12	87
2020 May	99	26	125
2020 April	123	31	154
2020 March	65	25	90
2020 February	51	16	67
2020 January	55	25	80
2019 December	69	22	91
2019 November	62	16	78
2019 October	42	19	61
2019 September	54	22	76
2019 August	35	7	42
2019 July	48	21	69
2019 June	40	12	52
2019 May	53	13	66
2019 April	43	22	65
2019 March	56	33	89
2019 February	38	24	62
2019 January	44	21	65
2018 December	57	24	81
2018 November	132	25	157
2018 October	284	20	304
2018 September	130	17	147
2018 May	108	1	109
2018 April	99	9	108
2018 March	294	6	300
2018 February	42	8	50
2018 January	40	7	47
2017 December	45	5	50
2017 November	49	9	58
2017 October	48	12	60
2017 September	55	10	65
2017 August	50	15	65
2017 July	52	7	59
2017 June	82	8	90
2017 May	65	18	83
2017 April	66	8	74
2017 March	77	11	88
2017 February	49	4	53
2017 January	43	11	54
2016 December	54	5	59
2016 November	83	14	97
2016 October	104	22	126
2016 September	157	21	178
2016 August	53	15	68
2016 July	41	18	59
2016 March	3	0	3
2016 February	1	0	1
2015 December	3	0	3
2015 October	73	4	77
2015 September	51	13	64
2015 August	66	20	86
2015 July	63	19	82
2015 June	38	10	48
2015 May	78	19	97
2015 April	70	16	86
2015 March	66	14	80
2015 February	67	11	78
2015 January	60	17	77
2014 December	49	14	63
2014 November	64	17	81
2014 October	58	16	74
2014 September	63	15	78
2014 August	50	14	64
2014 July	72	14	86
2014 June	74	15	89
2014 May	40	25	65
2014 March	0	3	3

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