Original article
Role of neuromuscular blocking agents in the development of polyneuropathy and myopathy in critically ill patients
Rol de los bloqueantes neuromusculares en el desarrollo de polineuropatía y miopatía del enfermo crítico
Fernando Armestara,b,
, Sara Vitoria Rubioa, Isabel Ojanguren Sabánc, Jaume Coll-Cantíd, Hipólito Perez Moltoa
Corresponding author
a Servicio de Medicina Intensiva, Hospital Universitario Germans Trias i Pujol, Barcelona, Spain
b Departamento de Medicina, Universidad Autónoma de Barcelona, Barcelona, Spain
c Servicio de Anatomía Patológica, Hospital Universitario Germans Trias i Pujol, Barcelona, Spain
d Unidad Patología Neuromuscular, Departamento Neurociencias, Hospital Universitario Germans Trias i Pujol, Barcelona, Spain
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"apellidos" => "Armestar" "email" => array:1 [ 0 => "farmestar.germanstrias@gencat.cat" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Sara" "apellidos" => "Vitoria Rubio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Isabel" "apellidos" => "Ojanguren Sabán" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Jaume" "apellidos" => "Coll-Cantí" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Hipólito" "apellidos" => "Perez Molto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Intensiva, Hospital Universitario Germans Trias i Pujol, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Medicina, Universidad Autónoma de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario Germans Trias i Pujol, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Unidad Patología Neuromuscular, Departamento Neurociencias, Hospital Universitario Germans Trias i Pujol, Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Rol de los bloqueantes neuromusculares en el desarrollo de polineuropatía y miopatía del enfermo crítico" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">ICU-acquired weakness (ICUAW) is a neuromuscular disease that occurs in intensive care patients and is the most common cause of neuromuscular weakness. It is an entity that encompasses 2 distinct conditions that often occur together: myopathy and polyneuropathy. Although with some differences, both result in generalised muscle weakness that becomes incapacitating and leads to difficulties in weaning from mechanical ventilation, prolonging the patient’s stay and increasing mortality.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> ICUAW is also important once the patient is discharged, as mobility restriction is a factor in prolonging recovery.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Several factors associated with ICUAW have been described: female sex, multi-organ dysfunction, patient severity, hyperglycaemia, mechanical ventilation, malnutrition, sepsis, drug administration (neuromuscular blocking agents, aminoglycosides and norepinephrine). Among the drugs, the association between neuromuscular blocking agents and weakness in critically ill patients is controversial.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A study<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> demonstrated that the electromyographic (EMG) detection of fibrillation and/or positive waves in the muscles studied corresponded to a selective loss of thick filaments (myosin) in the muscle pathology anatomy.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this study is to determine whether the use of neuromuscular blocking agents is a factor associated with ICU-acquired weakness.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">Prospective, observational study of patients consecutively admitted to the intensive care department of a high complexity hospital. Patient data were collected over a period of 5 years (2007–2011).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Inclusion criteria were: patients aged 18 years or older and a Sequential Organ Failure Assessment (SOFA) score of 4 or more at admission. Exclusion criteria were: previous neuromuscular disease and pregnant patients.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Identification and monitoring of ICUAW: was performed by electromyography, using a portable MEDELEC Synergy TM N2 2-channel device. A conventional coaxial needle study of the deltoid, quadriceps, tibialis anterior and calf muscles was performed to detect fibrillation potentials and/or presence of positive waves. The first study was performed during the first week of admission, then every 3 days for 3 weeks and, finally, every 7–10 days until discharge. With each electromyographic examination, a simultaneous physical examination was performed to assess the deep bicipital and patellar muscle reflexes, as well as muscle balance and strength level using the Medical Research Council score when the patient was awake and cooperative. The presence of ICUAW myopathy was identified in patients by the presence of fibrillation and/or positive waves on needle electromyography. The presence of ICUAW polyneuropathy was identified when radial and sural nerve sensory potentials disappeared.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Study variables: presence of acquired polyneuropathy or myopathy of the critically ill patient, age, sex, severity assessment within the first 24 hours of admission using the Acute Physiology and Chronic Health Evaluation<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> (APACHE II) score, organ dysfunction assessment using the SOFA<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> score, presence of sepsis, shock, administration of neuromuscular blocking agents after orotracheal intubation procedure, cumulative glucocorticoid dose, peak blood glucose values, peak creatine kinase values which were monitored daily in the first week and every 3–7 days thereafter, intensive care unit (ICU) stay and mechanical ventilation time.</p><p id="par0045" class="elsevierStylePara elsevierViewall">To standardise glucocorticoid doses, the equivalent amount in milligrams of hydrocortisone was calculated. The dose received was collected daily until the onset of spontaneous pathological activity on EMG or on day 11 in patients with normal EMG.</p><p id="par0050" class="elsevierStylePara elsevierViewall">With regard to muscle blockers, 3 were used: atracurium, rocuronium and vecuronium.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Definitions</span><p id="par0055" class="elsevierStylePara elsevierViewall">Myopathy: primary muscle involvement characterised by symmetrical and preferably proximal limb weakness, normal or diminished osteotendinous reflexes and preserved sensation. The electromyographic feature is fibrillation and/or positive waves in the study.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Polyneuropathy: primary, distal, symmetrical axonal degeneration of motor and sensory fibres. As a result, there is functional denervation of striated muscle leading to degeneration of muscle fibres. Limb weakness is the predominant finding. The electromyographic feature is the absence of sensory potentials in the sural and radial nerve.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,11</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0070" class="elsevierStylePara elsevierViewall">To describe the distribution of the variables, medians and maximum and minimum values were used for quantitative variables and percentages for each of the categories for qualitative variables. The univariate association between qualitative outcome variables and qualitative independent variables was assessed with the Chi-square test or Fisher’s exact test. The relative chance and its 95% confidence interval were used as a measure of the magnitude of the association. Student’s t-test or Mann-Whitney U-test was used to assess the association between a quantitative and a qualitative variable. A value of p < 0.05 was considered statistically significant.</p><p id="par0075" class="elsevierStylePara elsevierViewall">The statistical programme R software version 3.3.1 was used.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">A total of 103 patients were included; the median age was 64 [18–84]. Sixty-four per cent were male and 36% female. The median APACHE II score was 21 and the median SOFA score was 9. Neuromuscular blocking agents were administered to 68%. Sepsis was 74.8% and shock 72.8%. The median ICU stay was 22 days [5–119]. Mortality was 29%. Sixty-three patients developed CEDD. 60.2% developed myopathy only, 5.83% also developed polyneuropathy and only one patient developed neuropathy only. All patients were on mechanical ventilation at the time of inclusion in the study. The main causes of admission to the ICU were pneumonia (26.2%), abdominal sepsis (18.4%), sepsis from another source (30%), pancreatitis (6.7%), stroke (5.8%) and trauma (4.8%).</p><p id="par0085" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the analysis of variables according to the presence or absence of acquired critical patient weakness. The use of neuromuscular blocking drugs was more common in patients with ICUAW, and this difference was statistically significant. ICU stay was longer in patients with ICUAW.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">In the electromyographic study, the first change was the appearance of spontaneous pathological activity, which was detected in the majority of patients who developed ICUAW on median day 7.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–11</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">In this study we found an association between neuromuscular blocking agents and the development of ICU-acquired weakness, a result similar to some studies; however, other studies did not find such an association. The Papazian study, conducted in 340 critically ill patients with acute respiratory distress syndrome (ARDS), did not find an association with paralysis in critically ill patients, but it should be noted that the primary objective of this study was the use of cisatracurium only for 48 hours in the initial phase of ARDS.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In the same vein, Puthucheary, in an interesting review, argues that there is no causal relationship between paralysis in critically ill patients and the administration of neuromuscular blocking agents, based, among others, on the results of a study of patients with severe asthma under invasive mechanical ventilation.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> On the other hand, Nguyen's study, like ours, does find an association, but without specifying the days of administration.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Yang’s meta-analysis also found the same association.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> A possible explanation for these very different results may lie in the duration of administration of the blocking agent, such that prolonged use over 48 hours may be associated with ICU-acquired weakness, whereas short use may not. The suggested mechanisms of action are inhibition of mitogenesis and, from studies in animal models, reduced sodium channel activity leading to muscle hypoexcitability.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,16</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">It is striking that, contrary to other authors, we did not find an association with glycaemia.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,16</span></a> Just as there are discrepancies between studies in the case of the administration of neuromuscular blocking agents, this is not the case for hyperglycaemia. However, our glycaemia figures in both groups are similar and do not allow us to extract results. One possible explanation is that current protocols for the critically ill have ensured that we routinely maintain blood glucose levels that are not excessively high.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The administration of glucocorticoids is still controversial to this day. The postulated mechanism of action, following studies in animal models, is muscle fibre atrophy and selective loss of thick myofilaments of muscle fibres.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The use of glucocorticoids is widespread in critically ill patients, and animal model trials have observed changes similar to ICUAW in humans following glucocorticoid administration. However, while some studies find such an association, others do not. Notably, a meta-analysis of 14 studies involving 2,571 patients found no such association.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> Our study did not find this association either.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Consistent with the existing literature,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> both length of stay and time on mechanical ventilation were longer in the group that developed ICUAW, highlighting the importance of controlling factors associated with the development of this condition.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Our study has several limitations. It did not assess the number of days neuromuscular blocking agents were given; therefore, we did not analyse prolonged use of neuromuscular blocking agents. Nor did we quantify doses. The use of neuromuscular blocking agents in the field of intensive care medicine, after induction for orotracheal intubation, is limited to certain diseases and for a short period of time. Therefore, although the dose is very important, it is also valid to know whether their use without taking into account the dose is an associated factor, as described in other studies mentioned in an attempt to resolve the controversy of the involvement of neuromuscular blocking agents in ICUAW.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> On the other hand, the association with other drugs such as amikacin<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> could not be analysed, as the number of patients in whom it was used was very small. Although the study is based on data from 2007–2011, its validity relies on the fact that the type of patient and the management it focuses on are essentially the same today. As the admission criterion was a SOFA score of 4 or higher, we selected the most severe patients, so our results are only valid for this group of patients.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusion</span><p id="par0120" class="elsevierStylePara elsevierViewall">In critically ill patients, the use of neuromuscular blocking agents is a factor associated with the development of neuromuscular disease in the critically ill.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Ethical considerations</span><p id="par0125" class="elsevierStylePara elsevierViewall">The present study was conducted in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). It was approved by the Clinical Research Ethics Committee of the Germans Trias i Pujol University Hospital (EO-05-022) and written informed consent was obtained from each patient.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0130" class="elsevierStylePara elsevierViewall">The study is part of the “Paràlisi del Malalt Crític” project, which received funding from the <span class="elsevierStyleGrantSponsor" id="gs0005">Fundació- Marató.TV3</span> (Grant PI <span class="elsevierStyleGrantNumber" refid="gs0005">61510</span>).</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0135" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres2269434" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1892155" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2269433" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1892156" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Definitions" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Ethical considerations" ] 10 => array:2 [ "identificador" => "sec0045" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "xack780801" "titulo" => "Acknowledgements" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2024-02-26" "fechaAceptado" => "2024-04-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1892155" "palabras" => array:3 [ 0 => "Acquired weakness in critically ill patients" 1 => "Electromyography" 2 => "Critically ill patient" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1892156" "palabras" => array:3 [ 0 => "Debilidad adquirida del enfermo crítico" 1 => "Electromiografía" 2 => "Enfermo crítico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Acquired critical illness weakness (AWCIP) is the most frequent neuromuscular disease in intensive care medicine departments. Its importance is given by the prolongation of hospital stay and the delayed recovery it causes to patients after hospitalization.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The main objective of this study was to investigate the association between neuromuscular blocking agents and the development of acquired weakness in critically ill patients.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">We conducted a prospective study of 103 critically ill patients who were periodically monitored with electromyography.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Results</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The development of AWCIP was observed in 63 patients. The group of patients who developed AWCIP had a significantly higher utilization of neuromuscular blocking agents than the group who did not develop AWCIP [79.4% vs 50%, OR:3.85 (1.63–9.39), p < 0.02]; likewise, this group of patients had a longer ICU stay [32 days vs 14 days, OR: 1.11 (1.06–1.17), p < 0.001] and a longer mechanical ventilation time [24 days vs 9 days, OR:1.2 (1.11–1.32), p < 0.001].</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusion</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Neuromuscular blocking agents are a factor associated with the occurrence of AWCIP.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Antecedentes</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La debilidad adquirida del enfermo crítico (DAEC) es la enfermedad neuromuscular más frecuente en los servicios de medicina intensiva. La importancia de está dada por la la prolongación de la estancia hospitalaria y la tardía recuperación que ocasiona a los pacientes que después del hospitalaria. El objetivo principal de este estudio fue abordar la asociación entre bloqueantes neuromusculares y el desarrollo de debilidad adquirida del enfermo crítico.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material y métodos</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Realizamos un estudio prospectivo de 103 pacientes críticamente enfermos que fueron monitorizados periódicamente con electromiografía.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La aparición de DAEC se objetivó en el 63 pacientes. El grupo de pacientes que desarrollaron DAEC tuvieron una utilización de bloqueantes neuromusculares significativamente mayor que el grupo que no desarrolló DAEC [79,4% vs 50%, OR:3,85 (1,63-9,39), p < 0,02]; así mismo, este grupo de pacientes tuvo una estancia en UCI más prolongada [32 días vs 14 días, OR: 1,11 (1,06-1,17), p < 0.001] y una mayor tiempo de ventilación mecánica [24 días vs 9 días, OR:1,2 (1,11-1,32), p < 0.001].</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusión</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Los bloqueantes neuromusculares son un factor asociado a la aparición de DAEC.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">APACHE: <span class="elsevierStyleItalic">Acute Physiology and Chronic Health Evaluation</span>; CK: creatine kinase; ICUAW: ICU-acquired weakness; NS: not significant; OR: <span class="elsevierStyleItalic">odds ratio</span>; SOFA: <span class="elsevierStyleItalic">Sequential Organ Failure Assessment.</span></p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ICUAW(n = 63) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No ICUAW(n = 40) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">OR \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median age in years(minimum–maximum) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 (19–84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.5 (18–84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.02 (0.992–1.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex (%)-male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.59 (0.697–3.63) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median SOFA(minimum–maximum) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (4–17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (4–20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.11 (1–1.25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median APACHE II admission (min–max) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (9–50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (6–32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.07 (0.987–1.17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Percentage of neuromuscular blocking agent use \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.85 (1.63–9.39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median glucocorticoids in mg/dl (minimum–maximum) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 (0–1410) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">200 (0–1450) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.00 (1.00–1.00) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median blood glucose in mg/dl(minimum–maximum) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">126 (90–168) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">130.5 (98–222) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.992 (0.97–1.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median maximum CK in IU/l(minimum–maximum) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74(12–1198) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 (5–11057) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.999 (0.998–1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Day of evolution of maximum CK in IU/l (minimum–maximum) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (2–8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3(2–6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.68 (0.97–1.17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Percentage of patients with sepsis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.786 (0.301–1.95) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Percentage of patients with shock \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.833 (0.33–2.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median number of days in ICU (minimum–maximum) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (7–119) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (5–40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.11 (1.06–1.17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median number of days of mechanical ventilation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (4–111) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (0–30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2 (1.11–1.32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Percentage of deaths \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.71 (1.07–7.55) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3686279.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Analysis of variables according to the presence of ICU-acquired weakness.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Illness Weakness, Polyneuropathy and Myopathy: diagnosis, treatment, and long-term outcomes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. 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