Influence of rate of administration on the mechanism behind propofol induced loss of consciousness | Revista Española de Anestesiología y Reanimación (English Edition)

array:23 ["pii" => "S2341192921000810" "issn" => "23411929" "doi" => "10.1016/j.redare.2020.05.025" "estado" => "S300" "fechaPublicacion" => "2021-05-01" "aid" => "1236" "copyright" => "Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Revista Española de Anestesiología y Reanimación (English Version). 2021;68:245-51" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0034935620302590" "issn" => "00349356" "doi" => "10.1016/j.redar.2020.05.024" "estado" => "S300" "fechaPublicacion" => "2021-05-01" "aid" => "1236" "copyright" => "Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Esp Anestesiol Reanim. 2021;68:245-51" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:14 [ "idiomaDefecto" => true "cabecera" => "Original" "titulo" => "Influencia de la tasa de administración en el mecanismo subyacente a la pérdida de consciencia inducida por propofol" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:3 [ 0 => "es" 1 => "es" 2 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "245" "paginaFinal" => "251" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Influence of rate of administration on the mechanism behind propofol induced loss of consciousness" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1176 "Ancho" => 2083 "Tamanyo" => 156151 ] ] "descripcion" => array:1 [ "es" => "Curva de supervivencia de la pérdida de consciencia (probabilidad de permanecer consciente en el tiempo)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P. Sepúlveda, I. Acosta, A. Hoppe, F.A. Lobo, E. Carrasco" "autores" => array:5 [ 0 => array:2 [ "nombre" => "P." "apellidos" => "Sepúlveda" ] 1 => array:2 [ "nombre" => "I." "apellidos" => "Acosta" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Hoppe" ] 3 => array:2 [ "nombre" => "F.A." "apellidos" => "Lobo" ] 4 => array:2 [ "nombre" => "E." "apellidos" => "Carrasco" ] ] ] ] "resumen" => array:1 [ 0 => array:2 [ "clase" => "author-highlights" "resumen" => "Puntos clave<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Dependiendo de la tasa de infusión, los modelos del sitio de efecto del propofol calcularon concentraciones diferentes en el momento de pérdida de consciencia.</li><li class="elsevierStyleListItem" id="lsti0010">•La inducción rápida produce inconsciencia que realza el efecto en las estructuras del tronco encefálico.</li><li class="elsevierStyleListItem" id="lsti0015">•La inducción lenta produce inconsciencia con efecto predominante en las estructuras corticales.</li><li class="elsevierStyleListItem" id="lsti0020">•Los modelos farmacológicos de propofol podrían ser la fuente de datos de confusión a utilizar para guiar el estado de anestesia general en las inducciones rápidas.</li></ul>" ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2341192921000810" "doi" => "10.1016/j.redare.2020.05.025" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341192921000810?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0034935620302590?idApp=UINPBA00004N" "url" => "/00349356/0000006800000005/v3_202110060547/S0034935620302590/v3_202110060547/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2341192921000822" "issn" => "23411929" "doi" => "10.1016/j.redare.2020.11.003" "estado" => "S300" "fechaPublicacion" => "2021-05-01" "aid" => "1259" "copyright" => "Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Revista Española de Anestesiología y Reanimación (English Version). 2021;68:252-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Incidence of electrocardiographic alterations in the preoperative period of non-cardiac surgery" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "252" "paginaFinal" => "257" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Incidencia de alteraciones electrocardiográficas en el preoperatorio de cirugía no cardiaca" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. Gutiérrez Martínez, C. Jiménez-Méndez, R. Méndez Hernández, A. Hernández-Aceituno, A. Planas Roca, R.J. Aguilar Torres" "autores" => array:6 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Gutiérrez Martínez" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Jiménez-Méndez" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Méndez Hernández" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Hernández-Aceituno" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Planas Roca" ] 5 => array:2 [ "nombre" => "R.J." "apellidos" => "Aguilar Torres" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0034935620303157" "doi" => "10.1016/j.redar.2020.11.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0034935620303157?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341192921000822?idApp=UINPBA00004N" "url" => "/23411929/0000006800000005/v1_202106150624/S2341192921000822/v1_202106150624/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Influence of rate of administration on the mechanism behind propofol induced loss of consciousness" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "245" "paginaFinal" => "251" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "P. Sepúlveda, I. Acosta, A. Hoppe, F.A. Lobo, E. Carrasco" "autores" => array:5 [ 0 => array:4 [ "nombre" => "P." "apellidos" => "Sepúlveda" "email" => array:1 [ 0 => "pasevou@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "I." "apellidos" => "Acosta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Hoppe" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "F.A." "apellidos" => "Lobo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "E." "apellidos" => "Carrasco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Anestesiología y Dolor, Hospital Base San José Osorno, Osorno, Chile" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Neurología, Clínica Alemana Santiago, Vitacura, Santiago, Chile" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Centro Hospitalar do Porto, Hospital Geral de Santo António, Porto, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Universidad del Desarrollo, Facultad de Medicina Clínica Alemana" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Influencia de la tasa de administración en el mecanismo subyacente a la pérdida de consciencia inducida por propofol" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1176 "Ancho" => 2083 "Tamanyo" => 158363 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Loss of consciousness curve (probability of remaining conscious over time)." ] ] ] "textoCompleto" => "IntroductionThe mechanisms involved in propofol-induced loss of unconsciousness (LOC) are not yet fully understood.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> The concept of depth of anaesthesia has been used when processing electroencephalogram (EEG) signals, and is based on the assumption that there is an inverse linear relationship between propofol concentration and cerebral depression on EEG. From a pharmacological and neurobiological perspective, there are several inconsistencies, inaccuracies and limitations in the current notion of depth of anaesthesia as a simplifying mechanism, even when it is accompanied by the “effect-site” concept.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> For example, the recently observed concentration-effect hysteresis loop has been attributed solely to the equilibration delay between plasma and effect-site concentration, and other possible explanations such as slow activation/disassociation of receptors and neural pathways, changes in pharmacodynamics over time, or an indirect drug action mechanism<a class="elsevierStyleCrossRef" href="#bib0015">3</a> have been ignored.At the same time, the mechanisms of anaesthesia-induced LOC are more likely related to specific episodes of localized disconnection and lack of information processing, rather than global central nervous system depression.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>In current pharmacological models of propofol, the time course of the effect of the drug is described on the basis of the interaction between pharmacokinetic and pharmacodynamic parameters with an effect-site rate constant (ke0). The rate constant ke0, a component of target controlled infusion (TCI) devices, allows clinicians to calculate the effect site concentration (CeCALC) for any particular administration.Glen and Engbers<a class="elsevierStyleCrossRef" href="#bib0025">5</a> recently highlighted the advantages of effect-site TCI systems over plasma concentration-based TCI systems. CeCALC models are still widely debated.<a class="elsevierStyleCrossRefs" href="#bib0030">6–9</a>Design differences (for example, the different electroencephalographic processing methods used to quantify the hypnotic effect, the parameters used to determine the moment of LOC, the rate and route [arterial or venous] of drug administration) have led the development of very different models that can cause confusion in clinical practice – an issue that is widely discussed in the literature.Although the effect-site approach assumes that LOC is induced by a simple mechanism, and is followed by a stable state of unconsciousness, there is evidence to suggest the existence of predominately cortical or brainstem mechanisms due to the rate of drug administration and the effect-site concentration.We hypothesised that LOC can be achieved through different mechanisms, depending on the rate of induction: slow administration of propofol during induction would be associated with preservation of brainstem function at the time of LOC, while rapid administration would supress these functions during LOC. The existence of different mechanisms, and hence different effect-sites, could produce different states of neurological depression in LOC.In this study, therefore, we investigate whether the CeCALC of propofol resulting from different rates of administration may represent a unique neurological condition called “effect site”.MethodsDesignThis was a single-centre, blinded, randomized trial approved by the Ethics Committee of the Clínica Alemana de Santiago.Inclusion and exclusionAll patients signed an informed consent form prior to randomization and other study procedures. Inclusion criteria were: age 18–65 years of age, scheduled for hip arthroscopy, ASA I-II, no previous medication, no history of neurological disease, and normal neurological evaluation. Patients with a history of substance or alcohol abuse, documented adverse reactions to propofol, and those who had received neurotropic drugs within the 48 h preceding the procedure were excluded.InterventionThe study coordinator used the random number generator SPLUS (TIBCO Software Inc., Palo Alto, CA, USA) to assign subjects evenly to either the rapid induction (RI) or slow induction (SI) group. Subjects assigned to the RI group received propofol using the TCI Marsh model (ke0 1.21 min−1) for a calculated target infusion of 5.4 µg/mL (loading dose of 1.9 mg/kg EC95 of propofol for LOC), and those assigned to the SI group received propofol at a rate of 10 mg/kg/h.<a class="elsevierStyleCrossRefs" href="#bib0050">10,11</a> The Primea Orchestra (Fresenius-Kabi, Brezins, France) infusion pump was used in both groups, and we obtained effect site concentration (Ce) data at the time of LOC from the infusion pump. Once the SI group had achieved LOC, the infusion mode was changed to TCI, using the effect site concentration at loss of consciousness (CeLOC) value as a target. Infusion was maintained for 10 min in both groups to allow us to conduct spectrogram analysis.Systematic neurological evaluation: Full Outline of UnResponsiveness (FOUR) scoreThe FOUR score was used to assess neurological changes during induction of LOC.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> The clinical outcome assessments were performed by a single neurologist (IA) blinded to group assignment. The FOUR score is a coma scale that evaluates four components: ocular response (E), motor response (M), stem-brain reflexes (B), and respiration pattern (D). Each component has a maximum score of 4. The motor component combines the withdrawal reflex and decorticate rigidity responses; the position of the hands (thumb up, fist and peace sign) is a valid and reliable method to assess alertness. The three reflexes tested (photomotor, corneal and cough) in the B component assess the integrity of the mesencephalon, the pontine tegmentum and the medulla in different combinations. The respiration pattern component shows bi-hemispheric or lower brainstem dysfunction, where a score of 0 could indicate brain death. The FOUR score, together with other coma scales, gives a rapid, reproducible clinical assessment of brainstem reflexes.We did not perform serial cough reflex evaluations, as this involves the use of an endotracheal tube in all evaluations. The FOUR score uses this reflex to detect lack of medullary response as evidence of brain death. Our aim was to evaluate the activity of the brainstem nuclei involved in generating unconsciousness, mainly the midbrain-pontine structures, so we did not measure “absent pupil, corneal and cough reflexes” (B0), and instead measured only “absent pupil and corneal reflexes” (B1) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), and took this as B0.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Endpoints and resultsThe primary endpoint is the suppression of brainstem function in LOC, which was defined as the absolute absence of eye opening (E = 0) and the absence of response to verbal and painful stimuli (M = 0). Suppression of brainstem function was defined as the absence of brainstem reflexes (pupil, cornea, and cough: B = 0) and respiration pattern score (breaths at ventilator rate or apnoea: D = 0).A neurologist (IA) blinded to the induction technique performed the neurological evaluation using the FOUR score every 30 s from the start of propofol infusion to LOC. The Patient State Index (PSI) calculated using the Sedline monitor® (Masimo, Irvine, CA, USA) and the propofol CeCALC were recorded from the start of induction.Following this, based on drug volume and infusion time, we used the Anestfusor Series II Pro (Faculty of Medicine, University of Chile, available at <a href="http://www.smb.cl">www.smb.cl</a>) and Tivatrainer (GuttaBV, Aerdenhout, The Netherlands, available at <a href="https://www.eurosiva.eu/tivatrainer/TTweb/TTinfo.html">https://www.eurosiva.eu/tivatrainer/TTweb/TTinfo.html</a>) software to simulate the respective behaviour and CeCALC of propofol at the time of LOC of 3 other Pk/Pd models: the original Marsh model (ke0 0.2 min−1), the modified Marsh model (ke0 1.21 min−1), the Schnider model (ke0 0.45 min−1) and the Eleved model (ke0 0.26 min−1).<a class="elsevierStyleCrossRefs" href="#bib0050">10,13–15</a>Statistical analysisWith an estimated 10% loss of brainstem function in slow induction and 90% in rapid induction, we needed to recruit at least 8 patients in each group to detect a difference with a significance of 5% and a statistical power of 80%.We used Fisher's exact test to analyse the primary endpoint (presence of brainstem reflex), and time to LOC was described using the Kaplan–Meyer estimator compared with the Log-rank test. We used a 2-sample t-test to analyse the differences in CeCALC and PSI between study groups.ResultsInternal analysisThere were no significant differences in demographic data between groups (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The probabilities of remaining conscious (awake) over time in both arms are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>We observed statistically significant differences in the presence or absence of brainstem reflexes at the time of LOC (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>All subjects undergoing slow induction scored 4 points on FOUR B and R (pupil and corneal reflexes present and regular breathing pattern), 7 subjects in the RI group scored 0 on both FOUR B and R (pupil and corneal reflexes absent, apnoea), and 1 subject scored 4 on both B and R (pupil and corneal reflexes present and regular breathing pattern). Fisher's exact test (p = 0.001) showed significant differences in terms of brainstem reflexes at the time of LOC) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).Drug volume, mean time to LOC, SEF95, and SEDline PSI™ at the time of LOC are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>. This table also shows the mean CeCALC values at the time of LOC using the 4 different propofol effect-site models.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>DiscussionThe results of this study show that propofol-induced LOC is accompanied by different responses during suppression of brainstem function that are determined by the rate of administration and shown by different effect-site concentrations.Rapid infusion mainly affected the subcortical mechanism, whereas slow propofol infusion until LOC was not associated with the loss of brainstem reflexes, suggesting a predominantly cortical of loss of consciousness mechanism. These findings support the hypothesis that anaesthesia-induced LOC occurs through mechanisms, and these are not consistent with the theoretical CeCALC predicted by conventional Pk/Pd models created to show the varying time course of the effect.In a previous study evaluating rapid and intermediate rates of propofol administration using the Cerebral State Index monitor, Sepúlveda et al. found different CeCALCs at the time of LOC. Inconsistencies and differences in CeCALC at LOC between groups are related to the design of the effect-site model.<a class="elsevierStyleCrossRefs" href="#bib0080">16,17</a> The time course described by the rate constant ke0 is proportional to the concentration gradient between the central volume and the empirical and theoretical effect-site concept, and the correlation between ke0 and the rate of administration differs among authors.<a class="elsevierStyleCrossRefs" href="#bib0035">7,16,18</a>Effect site modelling is greatly affected by inaccuracies during the first 5 min of the mixing phase.<a class="elsevierStyleCrossRefs" href="#bib0095">19,20</a> Recently, Glen and Engbers<a class="elsevierStyleCrossRef" href="#bib0025">5</a> conducted a simulation study to clarify these discrepancies, and found that they could be due to various pharmacokinetic misinterpretations.The results of our study help explain the discrepancies in another way. The mechanisms underlying the generation of anaesthesia-induced LOC (predominantly cortical vs. brainstem) are different pharmacodynamic and neurological phenomena, although both lead to clinical LOC. Therefore, the effect should be shown using different effect-site models for each mode of induction.The effect-site model is based on different methods of processing EEG activity during drug administration, and shows a linear reduction in cortical neuroelectric activity described as anaesthesia depth. These parameters, however, are derived from pharmacokinetic models of neural correlates of consciousness based on incorrect descriptions of the mixing phase and an EEG processing index with low specificity and no sensitivity.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> Therefore, the concept of a unique, extended effect-site correlated with clinical anaesthesia-induced LOC is incorrect, and warrant a different approach that includes the different neural correlates of consciousness.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>The effects after rapid administration of a bolus of propofol are difficult to model, showing problems with frontal kinetics. This highly concentrated but unstable bolus ascends through the cerebral arterial circulation and rapidly reaches the GABAergic neurons of the pontine-medullary respiratory circuits and the pontine and mesencephalic structures of the reticular formation, together with their thalamic and hypothalamic projections, and ultimately blocks input from stimuli. All of this has been described as part of the bottom-up mechanism of LOC.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>In the SI group, we observed various clinical signs suggestive of a top-down phenomenon in which LOC occurs with preserved brainstem function and is probably associated with the breakdown of frontoparietal connectivity.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> Subjects consistently showed a loss of pursuit eye movement, suggesting impairment of the medial temporal cortical and lateral parietal networks involved in the potentials that determine the speed and direction of tracking eye movement.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> These data suggest that the phenomenon of cortical detachment associated with slow induction of LOC would be sufficient to generate a state of unconsciousness similar to NREM sleep and avoid the creation and activation of episodes of wakefulness.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>The correlation between speed of induction and the mechanisms of unconsciousness has potential relevance for anaesthesia in clinical practice, especially when calculating the Ce required for LOC in an individual patient, and avoid unnecessary overdose of anaesthesia agents. We believe slow, progressive, gradual induction is more accurate, since the Pk/Pd prediction models for slow infusions have shown better performance.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>The use of anaesthesia induction targets based on mean population values, or “statistics”, leads not only to the familiar haemodynamic effects of overdose, but also prevents clinicians from calculating anaesthesia requirements individually, bearing in mind that modern EEG-based monitors for measuring depth of anaesthesia do not reflect the complexity of the LOC processes that occur during anaesthesia.<a class="elsevierStyleCrossRefs" href="#bib0125">25,26</a>Although slow infusion through cortical circuits prolongs time to LOC, it is more predictable in terms of plasma mixture concentration and establishment of LOC, which is less influenced by brainstem structures.Differences found in CeCALC using the Marsh and Schnider models can be explained in various ways. The time to maximum effect in the Schnider model was obtained on the basis of rapid manual boluses (1.6 min), which contradicts his own Emax pharmacodynamic model obtained by slow infusions, showing an EC50 of 2.35 μg ml−1 for LOC in subjects aged 25 years. The CeLOC values in our study were quite high in the rapid infusion group. As such, they were not appropriate as anaesthesia maintenance targets and would have led to an overdose.The original Marsh model, meanwhile, shows less CeCALC mismatch between groups; however, this model (which cannot be used in effect-site TCI systems) shows a similar CeCALC for different neurological conditions revealed by the FOUR score and different PSI values (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).The modified Marsh model (available on modern infusion pumps) has a time to peak effect (TTPE) of 1.6 min, and has the same problem as Schnider's model. The ke0 in this model was derived from a TTPE following rapid bolus administration and is similar (2 mg/kg) to that of Schnider, though slightly slower (1200 ml/h).We used the FOUR score to evaluate our study subjects because it has been validated for clinical use, and estimates alertness (awakening) as well as mesencephalic (pontine) and medullary (respiratory) reflexes.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> The FOUR was also quick to administer and reproducible in the clinical setting. This allowed us to perform serial evaluations at short intervals (less than 30 s) during anaesthesia induction and to compare reactive (E and M) against reflective (B and D) components of the FOUR score as a function of time.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>In our study, LOC was also defined as the absence of motor response, and was evaluated using both physical and auditory stimuli. We believe this criterion is more specific and consistent with the LOC level required under anaesthetic conditions.The limitations of this study concern the characteristics of the clinical evaluation used – the FOUR score – which does not provide any information on superior functions. However, this instrument is highly effective in assessing the brainstem and cortical components of anaesthesia induction, even though it was designed and validated in very different clinical contexts from that used in this study. Another limitation is that we were only able to use surrogate parameters to build the effect-site PD models. Future research will make it possible to progress from effect modelling to managing general anaesthesia based on actual pharmacodynamics.Despite the small size of our cohort, it was large enough to shown the vast difference in clinical status between the two types of induction strategies.Although our results are probably not new to many clinicians, the inconsistency of current effect site models has not hitherto been discussed in depth. Our findings allow us to suggest that rapid anaesthesia induction produces a type of "bottom-up" LOC that predominantly affects brainstem structures, while slow induction produces a "top-down" LOC that predominantly affects cortical structures and their connections. Pharmacological descriptions based on models that do not distinguish between these two LOC mechanisms and assume the existence of a single effect site, together with the difficulties in modelling the kinetics of the first minutes of rapid administration, would explain the frequent discrepancies found between effect-time prediction models. More importantly, this impacts the way we use these models to assess (individualize needs) and adjust drug delivery.<a class="elsevierStyleCrossRef" href="#bib0140">28</a>AuthorshipP. Sepúlveda: designed the protocol, performed the study techniques, and drafted the manuscript.I. Acosta: designed the protocol, performed the study techniques, analysed the data, wrote the manuscript and organised the logistics.E. Carrasco: designed the protocol, performed the study techniques.A. Hoppe: designed the protocol and drafted the manuscript.F.A. Lobo: performed a critical review and drafted the manuscript.Conflict of interestsThe authors have no conflict of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1526130" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methodology" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1383581" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1526131" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Metodología" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1383580" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Inclusion and exclusion" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Intervention" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Systematic neurological evaluation: Full Outline of UnResponsiveness (FOUR) score" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Endpoints and results" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Internal analysis" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Authorship" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-01-31" "fechaAceptado" => "2020-05-26" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1383581" "palabras" => array:4 [ 0 => "Propofol" 1 => "Effect-site" 2 => "Pharmacodynamics" 3 => "Infusion rate" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1383580" "palabras" => array:4 [ 0 => "Propofol" 1 => "Sitio de efecto" 2 => "Farmacodinámica" 3 => "Tasa de infusión" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundPropofol effect-site time course models included in TCI systems have been under discussion.We hypothesized that the rate of administration is a major contributor affecting the construction of a useful effect-site model: yielding different plasmatic concentrations, loss of consciousness may occur by different mechanisms more complex than the pharmacological effect-site. MethodologyASA III patients were randomized in two groups: rapid induction (RI) received TCI of propofol effect-site (CeCALC) 5.4 μg/mL (modified Marsh model), and slow induction (SI) propofol infusion of 10 mg/kg/hour. A neurologist, blinded to induction method, performed neurological assessments using the FOUR score until the loss of consciousness (LOC). At LOC, the presence of brain stem reflexes, EEG index (PSI) and infusion time/mass of drug were registered. Fisher's exact test was used to describe differences between brain stem reflexes and respiration components of the FOUR score and CeCALC for 4 propofo models at LOC time. Results16 patients divided in two groups were included. All patient in SI had brainstem reflexes free at LOC. In the RI, all patients had brain stem reflexes abolished and 1 patient had B and R of 4 points in the FOUR score (brain stem reflexes unaffected; P < .001). CeCALC at LOC time were contradictory at LOC in both groups and using 4 different Pk/Pd models. ConclusionsDepending of the infusion rate, propofol CeCALC at LOC calculated by different Pk/Pd models could be the source of confuse data to be used to guide the state of general anesthesia." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methodology" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "AntecedentesSe han debatido los modelos de curso temporal del sitio de efecto del propofol.Nosotros supusimos que la tasa de administración es un gran factor contributivo que afecta a la construcción de un modelo de sitio de efecto útil: elaborando distintas concentraciones plasmáticas, la pérdida de consciencia puede producirse debido a diferentes mecanismos más complejos que el sitio del efecto farmacológico. MetodologíaSe aleatorizaron pacientes ASA I-II en dos grupos: el grupo de inducción rápida (IR) recibió TCI de sitio de efecto de propofol (CeCALC) 5,4 μg/mL (modelo Marsh modificado) y el grupo de inducción lenta (IL) recibió una infusión de propofol de 10 mg/kg/h. Un neurólogo, a quien se ocultó el método de inducción, realizó las evaluaciones neurológicas utilizando la escala FOUR hasta lograr la pérdida de consciencia (LOC). Una vez lograda, se registraron la presencia de reflejos troncoencefálicos, el índice EEG (PSI) y el tiempo de infusión/masa del fármaco. Se realizó la prueba exacta de Fisher para describir las diferencias entre los reflejos troncoencefálicos y los componentes respiratorios de la escala FOUR, así como CeCALC para los 4 modelos de propofol en el momento de la LOC. ResultadosSe incluyeron 16 pacientes, divididos en dos grupos. Todos los pacientes del grupo IL tuvieron reflejos troncoencefálicos libres en LOC. En el grupo IR, en todos los pacientes se suprimieron los reflejos troncoencefálicos, y un paciente obtuvo 4 puntos B y R en la escala FOUR (reflejos troncoencefálicos no afectados; p < 0,001). CeCALC en el momento de LOC fue contradictorio en ambos grupos, utilizando 4 modelos Pk/Pd diferentes. ConclusionesDependiendo de la tasa de infusión, CeCALC de propofol en el momento de la LOC, calculado mediante modelos Pk/Pd diferentes, podría ser la fuente de datos de confusión a utilizar para guiar el estado de la anestesia general." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Metodología" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Sepúlveda P, Acosta I, Hoppe A, Lobo FA, Carrasco E. Influencia de la tasa de administración en el mecanismo subyacente a la pérdida de consciencia inducida por propofol. Rev Esp Anestesiol Reanim. 2021;68:245–251." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "This study is a supplement to Anesthesia 2019, doi: https://doi.org/10.1111/anae.14885." ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1176 "Ancho" => 2083 "Tamanyo" => 158363 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Loss of consciousness curve (probability of remaining conscious over time)." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Eye response (E)</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">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">Eyelids open or opened, tracking, or blinking to command \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">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">Eyelids open but not tracking \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">2 \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">Eyelids closed but open to loud voice \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">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">Eyelids closed but open to pain \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">0 \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">Eyelids remain closed with pain \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Motor response (M)</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">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">Thumbs-up, fist, or peace sign \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">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">Localizing to pain \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">2 \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">Flexion response to pain \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">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">Extension response to pain \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">0 \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">No response to pain or generalized myoclonus status \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Brainstem reflexes (B)</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">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">Pupil and corneal reflexes present \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">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">One pupil wide and fixed \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">2 \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">Pupil or corneal reflexes absent \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">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">Pupil and corneal reflexes absent \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">0 \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">Absent pupil, corneal, and cough reflex \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Respiration (D)</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">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">Not intubated, regular breathing pattern \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">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">Not intubated, Cheyne–Stokes breathing pattern \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">2 \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">Not intubated, irregular breathing \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">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">Breathes above ventilator rate \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">0 \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">Breathes at ventilator rate or apnoea \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2623053.png" ] ] ] ] "descripcion" => array:1 [ "en" => "FOUR score (Full Outline of UnResponsiveness).<a class="elsevierStyleCrossRef" href="#bib0060">12</a>." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SBP: systolic blood pressure.Values expressed as mean (range)." "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">Variables \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">Slow induction (n = 8) \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">Rapid induction (n = 8) \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">Age (years) \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">37 (23−55) \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">40 (29−60) \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">Weight (kg) \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 (58−95) \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">80 (53−92) \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">Height (cm) \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">173 (160−189) \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">175.5 (160−180) \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">SBP (mmHg) \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">127 (110−144) \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 (109−141) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2623050.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline patient characteristics." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "*f < 0.001." "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">B and R response to LOC \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">Slow induction (n = 8) \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">Rapid induction (n = 8) \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">B = 0 + R = 0 \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 (0%) \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">7 (87.5%) \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">Other than B = 0 + R = 0 \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">8 (100%) \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 (12.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2623051.png" ] ] ] ] "descripcion" => array:1 [ "en" => "FOUR score brainstem components in loss of consciousness." ] ] 4 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "TLOC: time to loss of consciousness.Values are expressed as median (± SD) or mean (range)." "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">Variables \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">Slow induction (n = 8) \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">Rapid induction (n = 8) \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">TLOC; s \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">630 (378−1128) \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">84 (84−96)<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">Drug volume at LOC; mg/kg \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">1.67 (1.05−3.25) \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">1.91 \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">PSI Sedline at TLOC \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">67 (87−57) \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">87 (93−75)<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">SEF95 in LOC Hz \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">18 (19−14) \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">15 (23−10) \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">CeLOC, Marsh; μg ml−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">2.15(±0.66) \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">1.8 (±0.56) \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">CeLOC, Marsh (ke0 1.6); μg ml−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">2.7 (±0.44) \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">4.6 (±0.76)<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">CeLOC, Schnider; μg ml−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">3.2 (±0.38) \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">6.6 (±0.93)<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">CeLOC, Eleved; μg ml−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">3.2 (±0.9) \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">3.1 (±1.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2623052.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "p < 0.01." ] ] ] "descripcion" => array:1 [ "en" => "Effect-site concentration loss of consciousness (CeLOC) parameters with different pharmacokinetic models." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anesthetic effects of propofol in the healthy human brain: functional imaging evidence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "X.X. Song" 1 => "B.W. Yu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00540-014-1889-4" "Revista" => array:6 [ "tituloSerie" => "J Anesth." "fecha" => "2015" "volumen" => "29" "paginaInicial" => "279" "paginaFinal" => "288" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25056258" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Disruption of frontal-parietal communication by ketamine, propofol, and sevoflurane" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "U. Lee" 1 => "S. Ku" 2 => "G. Noh" 3 => "S. Baek" 4 => "B. Choi" 5 => "G.A. Mashour" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/ALN.0b013e31829103f5" "Revista" => array:6 [ "tituloSerie" => "Anesthesiology." "fecha" => "2013" "volumen" => "118" "paginaInicial" => "1264" "paginaFinal" => "1275" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23695090" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Understanding the hysteresis loop conundrum in pharmacokinetic/pharmacodynamic relationships" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. Louizos" 1 => "J.A. Yanez" 2 => "M.L. Forrest" 3 => "N.M. Davies" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Pharm Pharm Sci." "fecha" => "2014" "volumen" => "17" "paginaInicial" => "34" "paginaFinal" => "91" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24735761" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Top-down mechanisms of anesthetic-induced unconsciousness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.A. Mashour" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fnsys.2014.00115" "Revista" => array:5 [ "tituloSerie" => "Front Syst Neurosci." "fecha" => "2014" "volumen" => "8" "paginaInicial" => "115" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25002838" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The influence of target concentration, equilibration rate constant (ke0) and pharmacokinetic model on the initial propofol dose delivered in effect-site target-controlled infusion" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.B. Glen" 1 => "F.H. Engbers" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/anae.13345" "Revista" => array:6 [ "tituloSerie" => "Anaesthesia." "fecha" => "2016" "volumen" => "71" "paginaInicial" => "306" "paginaFinal" => "314" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26682512" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Individual effect-site concentrations of propofol are similar at loss of consciousness and at awakening" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H.N.N. Iwakiri" 1 => "O. Nagata" 2 => "T. Matsukawa" 3 => "M. Ozaki" 4 => "D.I. Sessler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1213/01.ANE.0000139358.15909.EA" "Revista" => array:6 [ "tituloSerie" => "Anesth Analg." "fecha" => "2005" "volumen" => "100" "paginaInicial" => "107" "paginaFinal" => "110" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15616062" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Induction speed is not a determinant of propofol pharmacodynamics" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.G. Doufas" 1 => "M. Bakhshandeh" 2 => "A.R. Bjorksten" 3 => "S.L. Shafer" 4 => "D.I. Sessler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00000542-200411000-00010" "Revista" => array:6 [ "tituloSerie" => "Anesthesiology." "fecha" => "2004" "volumen" => "101" "paginaInicial" => "1112" "paginaFinal" => "1121" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15505446" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacokinetic models for propofol—defining and illuminating the devil in the detail" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.R. Absalom" 1 => "V. Mani" 2 => "T. de Smet" 3 => "M.M. Struys" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/bja/aep143" "Revista" => array:6 [ "tituloSerie" => "Br J Anaesth." "fecha" => "2009" "volumen" => "103" "paginaInicial" => "26" "paginaFinal" => "37" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19520702" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is unconsciousness simply the reverse of consciousness?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F. Engbers" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/anae.14121" "Revista" => array:6 [ "tituloSerie" => "Anaesthesia." "fecha" => "2018" "volumen" => "73" "paginaInicial" => "6" "paginaFinal" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29057452" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of plasma compartment versus two methods for effect compartment—controlled target-controlled infusion for propofol" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.M. Struys" 1 => "T. De Smet" 2 => "B. Depoorter" 3 => "L.F. Versichelen" 4 => "E.P. Mortier" 5 => "F.J. Dumortier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00000542-200002000-00021" "Revista" => array:6 [ "tituloSerie" => "Anesthesiology." "fecha" => "2000" "volumen" => "92" "paginaInicial" => "399" "paginaFinal" => "406" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10691226" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Targeting effect compartment or central compartment concentration of propofol: what predicts loss of consciousness?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H.G. Wakeling" 1 => "J.B. Zimmerman" 2 => "S. Howell" 3 => "P.S. Glass" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00000542-199901000-00014" "Revista" => array:6 [ "tituloSerie" => "Anesthesiology." "fecha" => "1999" "volumen" => "90" "paginaInicial" => "92" "paginaFinal" => "97" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9915317" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Validation of a new coma scale: the FOUR score" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E.F. Wijdicks" 1 => "W.R. Bamlet" 2 => "B.V. Maramattom" 3 => "E.M. Manno" 4 => "R.L. McClelland" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ana.20611" "Revista" => array:6 [ "tituloSerie" => "Ann Neurol." "fecha" => "2005" "volumen" => "58" "paginaInicial" => "585" "paginaFinal" => "593" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16178024" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The development of ‘Diprifusor’: a TCI system for propofol" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.B. Glen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2044.1998.53s115.x" "Revista" => array:6 [ "tituloSerie" => "Anaesthesia." "fecha" => "1998" "volumen" => "53 Suppl 1" "paginaInicial" => "13" "paginaFinal" => "21" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9640110" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The influence of age on propofol pharmacodynamics" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "T.W.M.C. Schnider" 1 => "S.L. Shafer" 2 => "P.L. Gambus" 3 => "C. Andresen" 4 => "D.B. Goodale" 5 => "E.J. Youngs" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00000542-199906000-00003" "Revista" => array:6 [ "tituloSerie" => "Anesthesiology." "fecha" => "1999" "volumen" => "90" "paginaInicial" => "1502" "paginaFinal" => "1516" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10360845" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A general purpose pharmacokinetic model for propofol" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.J. Eleveld" 1 => "J.H. Proost" 2 => "L.I. Cortinez" 3 => "A.R. Absalom" 4 => "M.M. Struys" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1213/ANE.0000000000000165" "Revista" => array:6 [ "tituloSerie" => "Anesth Analg." "fecha" => "2014" "volumen" => "118" "paginaInicial" => "1221" "paginaFinal" => "1237" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24722258" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictive ability of propofol effect-site concentrations during fast and slow infusion rates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P.O. Sepulveda" 1 => "L.I. Cortinez" 2 => "A. Recart" 3 => "H.R. Munoz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1399-6576.2009.02183.x" "Revista" => array:6 [ "tituloSerie" => "Acta Anaesthesiol Scand." "fecha" => "2010" "volumen" => "54" "paginaInicial" => "447" "paginaFinal" => "452" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20003124" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cerebral state index during propofol anesthesia: a comparison with the bispectral index and the A-line ARX index" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.W. Jensen" 1 => "H. Litvan" 2 => "M. Revuelta" 3 => "B.E. Rodríguez" 4 => "P. Caminal" 5 => "P. Martinez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00000542-200607000-00009" "Revista" => array:6 [ "tituloSerie" => "Anesthesiology." "fecha" => "2006" "volumen" => "105" "paginaInicial" => "28" "paginaFinal" => "36" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16809991" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The determinants of propofol induction of anesthesia dose" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Y.U. Adachi" 1 => "K. Watanabe" 2 => "H. Higuchi" 3 => "T. Satoh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00000539-200103000-00020" "Revista" => array:6 [ "tituloSerie" => "Anesth Analg." "fecha" => "2001" "volumen" => "92" "paginaInicial" => "656" "paginaFinal" => "661" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11226096" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of administration rate on propofol plasma-effect site equilibration" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.M.C.M. Struys" 1 => "N. de Neve" 2 => "E.P. Mortier" 3 => "A.G. Doufas" 4 => "J.F. van Bocxlaer" 5 => "S.L. Shafer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.anes.0000278902.15505.f8" "Revista" => array:6 [ "tituloSerie" => "Anesthesiology." "fecha" => "2007" "volumen" => "107" "paginaInicial" => "386" "paginaFinal" => "396" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17721240" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early phase pharmacokinetics but not pharmacodynamics are influenced by propofol infusion rate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Masui" 1 => "M. Kira" 2 => "T. Kazama" 3 => "S. Hagihira" 4 => "E.P. Mortier" 5 => "M.M. Struys" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/ALN.0b013e3181b799c1" "Revista" => array:6 [ "tituloSerie" => "Anesthesiology." "fecha" => "2009" "volumen" => "111" "paginaInicial" => "805" "paginaFinal" => "817" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19741485" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neural correlates of consciousness: progress and problems" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. Koch" 1 => "M. Massimini" 2 => "M. Boly" 3 => "G. Tononi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Nat Rev Neurosci." "fecha" => "2016" "volumen" => "17" "paginaInicial" => "395" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Are the neural correlates of consciousness in the front or in the back of the cerebral cortex? Clinical and neuroimaging evidence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Boly" 1 => "M. Massimini" 2 => "N. Tsuchiya" 3 => "B.R. Postle" 4 => "C. Koch" 5 => "G. Tononi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1523/JNEUROSCI.3218-16.2017" "Revista" => array:6 [ "tituloSerie" => "J Neurosci." "fecha" => "2017" "volumen" => "37" "paginaInicial" => "9603" "paginaFinal" => "9613" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28978697" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bottom-up and top-down mechanisms of general anesthetics modulate different dimensions of consciousness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G.A. Mashour" 1 => "A.G. Hudetz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fncir.2017.00044" "Revista" => array:5 [ "tituloSerie" => "Front Neural Circuits." "fecha" => "2017" "volumen" => "11" "paginaInicial" => "44" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28676745" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modulation of pursuit eye movements by stimulation of cortical areas MT and MST" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H. Komatsu" 1 => "R.H. Wurtz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/jn.1989.62.1.31" "Revista" => array:6 [ "tituloSerie" => "J Neurophysiol." "fecha" => "1989" "volumen" => "62" "paginaInicial" => "31" "paginaFinal" => "47" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2754480" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Monitoring the brain: processed electroencephalogram and peri-operative outcomes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.E. Escallier" 1 => "M.R. Nadelson" 2 => "D. Zhou" 3 => "M.S. Avidan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/anae.12711" "Revista" => array:6 [ "tituloSerie" => "Anaesthesia." "fecha" => "2014" "volumen" => "69" "paginaInicial" => "899" "paginaFinal" => "910" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24905798" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Limitations of anaesthesia depth monitoring" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F.A. Lobo" 1 => "S. Schraag" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/ACO.0b013e32834c7aba" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Anaesthesiol." "fecha" => "2011" "volumen" => "24" "paginaInicial" => "657" "paginaFinal" => "664" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21971394" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Validity of the FOUR score coma scale in the medical intensive care unit" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "V.N. Iyer" 1 => "J.N. Mandrekar" 2 => "R.D. Danielson" 3 => "A.Y. Zubkov" 4 => "J.L. Elmer" 5 => "E.F. Wijdicks" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0025-6196(11)60519-3" "Revista" => array:6 [ "tituloSerie" => "Mayo Clin Proc." "fecha" => "2009" "volumen" => "84" "paginaInicial" => "694" "paginaFinal" => "701" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19648386" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Critical view of the effect site modelling of propofol" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P. Sepúlveda" 1 => "C. Demaría" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Esp Anestesiol Reanim." "fecha" => "2019" "volumen" => "66" "paginaInicial" => "425" "paginaFinal" => "433" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23411929/0000006800000005/v1_202106150624/S2341192921000810/v1_202106150624/en/main.assets" "Apartado" => array:4 [ "identificador" => "34051" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23411929/0000006800000005/v1_202106150624/S2341192921000810/v1_202106150624/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341192921000810?idApp=UINPBA00004N"]

Statistics

Original article

Influence of rate of administration on the mechanism behind propofol induced loss of consciousness

Influencia de la tasa de administración en el mecanismo subyacente a la pérdida de consciencia inducida por propofol

P. Sepúlvedaa,

Corresponding author

pasevou@gmail.com

Corresponding author.

, I. Acostab, A. Hoppeb, F.A. Loboc, E. Carrascod

a Servicio de Anestesiología y Dolor, Hospital Base San José Osorno, Osorno, Chile

b Departamento de Neurología, Clínica Alemana Santiago, Vitacura, Santiago, Chile

c Centro Hospitalar do Porto, Hospital Geral de Santo António, Porto, Portugal

d Universidad del Desarrollo, Facultad de Medicina Clínica Alemana

Read

Times
was read the article

Total PDF

Total HTML

Share statistics

 array:23 [
  "pii" => "S2341192921000810"
  "issn" => "23411929"
  "doi" => "10.1016/j.redare.2020.05.025"
  "estado" => "S300"
  "fechaPublicacion" => "2021-05-01"
  "aid" => "1236"
  "copyright" => "Sociedad Espa&#241;ola de Anestesiolog&#237;a&#44; Reanimaci&#243;n y Terap&#233;utica del Dolor"
  "copyrightAnyo" => "2020"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "cita" => "Revista Espa&#241;ola de Anestesiolog&#237;a y Reanimaci&#243;n &#40;English Version&#41;. 2021;68:245-51"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0034935620302590"
      "issn" => "00349356"
      "doi" => "10.1016/j.redar.2020.05.024"
      "estado" => "S300"
      "fechaPublicacion" => "2021-05-01"
      "aid" => "1236"
      "copyright" => "Sociedad Espa&#241;ola de Anestesiolog&#237;a&#44; Reanimaci&#243;n y Terap&#233;utica del Dolor"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "fla"
      "cita" => "Rev Esp Anestesiol Reanim. 2021;68:245-51"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:1 [
        "total" => 0
      ]
      "es" => array:14 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Original</span>"
        "titulo" => "Influencia de la tasa de administraci&#243;n en el mecanismo subyacente a la p&#233;rdida de consciencia inducida por propofol"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:3 [
          0 => "es"
          1 => "es"
          2 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "245"
            "paginaFinal" => "251"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Influence of rate of administration on the mechanism behind propofol induced loss of consciousness"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Figura 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 1176
                "Ancho" => 2083
                "Tamanyo" => 156151
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Curva de supervivencia de la p&#233;rdida de consciencia &#40;probabilidad de permanecer consciente en el tiempo&#41;&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "P&#46; Sep&#250;lveda, I&#46; Acosta, A&#46; Hoppe, F&#46;A&#46; Lobo, E&#46; Carrasco"
            "autores" => array:5 [
              0 => array:2 [
                "nombre" => "P&#46;"
                "apellidos" => "Sep&#250;lveda"
              ]
              1 => array:2 [
                "nombre" => "I&#46;"
                "apellidos" => "Acosta"
              ]
              2 => array:2 [
                "nombre" => "A&#46;"
                "apellidos" => "Hoppe"
              ]
              3 => array:2 [
                "nombre" => "F&#46;A&#46;"
                "apellidos" => "Lobo"
              ]
              4 => array:2 [
                "nombre" => "E&#46;"
                "apellidos" => "Carrasco"
              ]
            ]
          ]
        ]
        "resumen" => array:1 [
          0 => array:2 [
            "clase" => "author-highlights"
            "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Puntos clave</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0005" class="elsevierStylePara elsevierViewall">Dependiendo de la tasa de infusi&#243;n&#44; los modelos del sitio de efecto del propofol calcularon concentraciones diferentes en el momento de p&#233;rdida de consciencia&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0010" class="elsevierStylePara elsevierViewall">La inducci&#243;n r&#225;pida produce inconsciencia que realza el efecto en las estructuras del tronco encef&#225;lico&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0015" class="elsevierStylePara elsevierViewall">La inducci&#243;n lenta produce inconsciencia con efecto predominante en las estructuras corticales&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Los modelos farmacol&#243;gicos de propofol podr&#237;an ser la fuente de datos de confusi&#243;n a utilizar para guiar el estado de anestesia general en las inducciones r&#225;pidas&#46;</p></li></ul></p></span>"
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2341192921000810"
          "doi" => "10.1016/j.redare.2020.05.025"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341192921000810?idApp=UINPBA00004N"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0034935620302590?idApp=UINPBA00004N"
      "url" => "/00349356/0000006800000005/v3_202110060547/S0034935620302590/v3_202110060547/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2341192921000822"
    "issn" => "23411929"
    "doi" => "10.1016/j.redare.2020.11.003"
    "estado" => "S300"
    "fechaPublicacion" => "2021-05-01"
    "aid" => "1259"
    "copyright" => "Sociedad Espa&#241;ola de Anestesiolog&#237;a&#44; Reanimaci&#243;n y Terap&#233;utica del Dolor"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Revista Espa&#241;ola de Anestesiolog&#237;a y Reanimaci&#243;n &#40;English Version&#41;. 2021;68:252-7"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn"><span class="elsevierStyleSup">Original article</span></span>"
      "titulo" => "Incidence of electrocardiographic alterations in the preoperative period of non-cardiac surgery"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "252"
          "paginaFinal" => "257"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Incidencia de alteraciones electrocardiogr&#225;ficas en el preoperatorio de cirug&#237;a no cardiaca"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "D&#46; Guti&#233;rrez Mart&#237;nez, C&#46; Jim&#233;nez-M&#233;ndez, R&#46; M&#233;ndez Hern&#225;ndez, A&#46; Hern&#225;ndez-Aceituno, A&#46; Planas Roca, R&#46;J&#46; Aguilar Torres"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "D&#46;"
              "apellidos" => "Guti&#233;rrez Mart&#237;nez"
            ]
            1 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "Jim&#233;nez-M&#233;ndez"
            ]
            2 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "M&#233;ndez Hern&#225;ndez"
            ]
            3 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Hern&#225;ndez-Aceituno"
            ]
            4 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Planas Roca"
            ]
            5 => array:2 [
              "nombre" => "R&#46;J&#46;"
              "apellidos" => "Aguilar Torres"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0034935620303157"
        "doi" => "10.1016/j.redar.2020.11.004"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0034935620303157?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341192921000822?idApp=UINPBA00004N"
    "url" => "/23411929/0000006800000005/v1_202106150624/S2341192921000822/v1_202106150624/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Influence of rate of administration on the mechanism behind propofol induced loss of consciousness"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "245"
        "paginaFinal" => "251"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "P&#46; Sep&#250;lveda, I&#46; Acosta, A&#46; Hoppe, F&#46;A&#46; Lobo, E&#46; Carrasco"
        "autores" => array:5 [
          0 => array:4 [
            "nombre" => "P&#46;"
            "apellidos" => "Sep&#250;lveda"
            "email" => array:1 [
              0 => "pasevou@gmail.com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "&#42;"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "I&#46;"
            "apellidos" => "Acosta"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "A&#46;"
            "apellidos" => "Hoppe"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "F&#46;A&#46;"
            "apellidos" => "Lobo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "E&#46;"
            "apellidos" => "Carrasco"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Servicio de Anestesiolog&#237;a y Dolor&#44; Hospital Base San Jos&#233; Osorno&#44; Osorno&#44; Chile"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Departamento de Neurolog&#237;a&#44; Cl&#237;nica Alemana Santiago&#44; Vitacura&#44; Santiago&#44; Chile"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Centro Hospitalar do Porto&#44; Hospital Geral de Santo Ant&#243;nio&#44; Porto&#44; Portugal"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Universidad del Desarrollo&#44; Facultad de Medicina Cl&#237;nica Alemana"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Influencia de la tasa de administraci&#243;n en el mecanismo subyacente a la p&#233;rdida de consciencia inducida por propofol"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1176
            "Ancho" => 2083
            "Tamanyo" => 158363
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Loss of consciousness curve &#40;probability of remaining conscious over time&#41;&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The mechanisms involved in propofol-induced loss of unconsciousness &#40;LOC&#41; are not yet fully understood&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The concept of depth of anaesthesia has been used when processing electroencephalogram &#40;EEG&#41; signals&#44; and is based on the assumption that there is an inverse linear relationship between propofol concentration and cerebral depression on EEG&#46; From a pharmacological and neurobiological perspective&#44; there are several inconsistencies&#44; inaccuracies and limitations in the current notion of depth of anaesthesia as a simplifying mechanism&#44; even when it is accompanied by the &#8220;effect-site&#8221; concept&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> For example&#44; the recently observed concentration-effect hysteresis loop has been attributed solely to the equilibration delay between plasma and effect-site concentration&#44; and other possible explanations such as slow activation&#47;disassociation of receptors and neural pathways&#44; changes in pharmacodynamics over time&#44; or an indirect drug action mechanism<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> have been ignored&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">At the same time&#44; the mechanisms of anaesthesia-induced LOC are more likely related to specific episodes of localized disconnection and lack of information processing&#44; rather than global central nervous system depression&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In current pharmacological models of propofol&#44; the time course of the effect of the drug is described on the basis of the interaction between pharmacokinetic and pharmacodynamic parameters with an effect-site rate constant &#40;ke0&#41;&#46; The rate constant ke0&#44; a component of target controlled infusion &#40;TCI&#41; devices&#44; allows clinicians to calculate the effect site concentration &#40;CeCALC&#41; for any particular administration&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Glen and Engbers<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> recently highlighted the advantages of effect-site TCI systems over plasma concentration-based TCI systems&#46; CeCALC models are still widely debated&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Design differences &#40;for example&#44; the different electroencephalographic processing methods used to quantify the hypnotic effect&#44; the parameters used to determine the moment of LOC&#44; the rate and route &#91;arterial or venous&#93; of drug administration&#41; have led the development of very different models that can cause confusion in clinical practice &#8211; an issue that is widely discussed in the literature&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Although the effect-site approach assumes that LOC is induced by a simple mechanism&#44; and is followed by a stable state of unconsciousness&#44; there is evidence to suggest the existence of predominately cortical or brainstem mechanisms due to the rate of drug administration and the effect-site concentration&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We hypothesised that LOC can be achieved through different mechanisms&#44; depending on the rate of induction&#58; slow administration of propofol during induction would be associated with preservation of brainstem function at the time of LOC&#44; while rapid administration would supress these functions during LOC&#46; The existence of different mechanisms&#44; and hence different effect-sites&#44; could produce different states of neurological depression in LOC&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In this study&#44; therefore&#44; we investigate whether the CeCALC of propofol resulting from different rates of administration may represent a unique neurological condition called &#8220;effect site&#8221;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design</span><p id="par0045" class="elsevierStylePara elsevierViewall">This was a single-centre&#44; blinded&#44; randomized trial approved by the Ethics Committee of the Cl&#237;nica Alemana de Santiago&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Inclusion and exclusion</span><p id="par0050" class="elsevierStylePara elsevierViewall">All patients signed an informed consent form prior to randomization and other study procedures&#46; Inclusion criteria were&#58; age 18&#8211;65 years of age&#44; scheduled for hip arthroscopy&#44; ASA I-II&#44; no previous medication&#44; no history of neurological disease&#44; and normal neurological evaluation&#46; Patients with a history of substance or alcohol abuse&#44; documented adverse reactions to propofol&#44; and those who had received neurotropic drugs within the 48&#160;h preceding the procedure were excluded&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Intervention</span><p id="par0055" class="elsevierStylePara elsevierViewall">The study coordinator used the random number generator SPLUS &#40;TIBCO Software Inc&#46;&#44; Palo Alto&#44; CA&#44; USA&#41; to assign subjects evenly to either the rapid induction &#40;RI&#41; or slow induction &#40;SI&#41; group&#46; Subjects assigned to the RI group received propofol using the TCI Marsh model &#40;ke0 1&#46;21&#160;min<span class="elsevierStyleSup">&#8722;1</span>&#41; for a calculated target infusion of 5&#46;4&#160;&#181;g&#47;mL &#40;loading dose of 1&#46;9&#160;mg&#47;kg EC95 of propofol for LOC&#41;&#44; and those assigned to the SI group received propofol at a rate of 10&#160;mg&#47;kg&#47;h&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> The Primea Orchestra &#40;Fresenius-Kabi&#44; Brezins&#44; France&#41; infusion pump was used in both groups&#44; and we obtained effect site concentration &#40;Ce&#41; data at the time of LOC from the infusion pump&#46; Once the SI group had achieved LOC&#44; the infusion mode was changed to TCI&#44; using the effect site concentration at loss of consciousness &#40;Ce<span class="elsevierStyleInf">LOC</span>&#41; value as a target&#46; Infusion was maintained for 10&#160;min in both groups to allow us to conduct spectrogram analysis&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Systematic neurological evaluation&#58; Full Outline of UnResponsiveness &#40;FOUR&#41; score</span><p id="par0060" class="elsevierStylePara elsevierViewall">The FOUR score was used to assess neurological changes during induction of LOC&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The clinical outcome assessments were performed by a single neurologist &#40;IA&#41; blinded to group assignment&#46; The FOUR score is a coma scale that evaluates four components&#58; ocular response &#40;E&#41;&#44; motor response &#40;M&#41;&#44; stem-brain reflexes &#40;B&#41;&#44; and respiration pattern &#40;D&#41;&#46; Each component has a maximum score of 4&#46; The motor component combines the withdrawal reflex and decorticate rigidity responses&#59; the position of the hands &#40;thumb up&#44; fist and peace sign&#41; is a valid and reliable method to assess alertness&#46; The three reflexes tested &#40;photomotor&#44; corneal and cough&#41; in the B component assess the integrity of the mesencephalon&#44; the pontine tegmentum and the medulla in different combinations&#46; The respiration pattern component shows bi-hemispheric or lower brainstem dysfunction&#44; where a score of 0 could indicate brain death&#46; The FOUR score&#44; together with other coma scales&#44; gives a rapid&#44; reproducible clinical assessment of brainstem reflexes&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">We did not perform serial cough reflex evaluations&#44; as this involves the use of an endotracheal tube in all evaluations&#46; The FOUR score uses this reflex to detect lack of medullary response as evidence of brain death&#46; Our aim was to evaluate the activity of the brainstem nuclei involved in generating unconsciousness&#44; mainly the midbrain-pontine structures&#44; so we did not measure &#8220;absent pupil&#44; corneal and cough reflexes&#8221; &#40;B0&#41;&#44; and instead measured only &#8220;absent pupil and corneal reflexes&#8221; &#40;B1&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; and took this as B0&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Endpoints and results</span><p id="par0070" class="elsevierStylePara elsevierViewall">The primary endpoint is the suppression of brainstem function in LOC&#44; which was defined as the absolute absence of eye opening &#40;E&#160;&#61;&#160;0&#41; and the absence of response to verbal and painful stimuli &#40;M&#160;&#61;&#160;0&#41;&#46; Suppression of brainstem function was defined as the absence of brainstem reflexes &#40;pupil&#44; cornea&#44; and cough&#58; B&#160;&#61;&#160;0&#41; and respiration pattern score &#40;breaths at ventilator rate or apnoea&#58; D&#160;&#61;&#160;0&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">A neurologist &#40;IA&#41; blinded to the induction technique performed the neurological evaluation using the FOUR score every 30&#160;s from the start of propofol infusion to LOC&#46; The Patient State Index &#40;PSI&#41; calculated using the Sedline monitor&#174; &#40;Masimo&#44; Irvine&#44; CA&#44; USA&#41; and the propofol CeCALC were recorded from the start of induction&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Following this&#44; based on drug volume and infusion time&#44; we used the Anestfusor Series II Pro &#40;Faculty of Medicine&#44; University of Chile&#44; available at <a href="http://www.smb.cl">www&#46;smb&#46;cl</a>&#41; and Tivatrainer &#40;GuttaBV&#44; Aerdenhout&#44; The Netherlands&#44; available at <a href="https://www.eurosiva.eu/tivatrainer/TTweb/TTinfo.html">https&#58;&#47;&#47;www&#46;eurosiva&#46;eu&#47;tivatrainer&#47;TTweb&#47;TTinfo&#46;html</a>&#41; software to simulate the respective behaviour and CeCALC of propofol at the time of LOC of 3 other Pk&#47;Pd models&#58; the original Marsh model &#40;ke0 0&#46;2&#160;min<span class="elsevierStyleSup">&#8722;1</span>&#41;&#44; the modified Marsh model &#40;ke0 1&#46;21&#160;min<span class="elsevierStyleSup">&#8722;1</span>&#41;&#44; the Schnider model &#40;ke0 0&#46;45&#160;min<span class="elsevierStyleSup">&#8722;1</span>&#41; and the Eleved model &#40;ke0 0&#46;26&#160;min<span class="elsevierStyleSup">&#8722;1</span>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;13&#8211;15</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0085" class="elsevierStylePara elsevierViewall">With an estimated 10&#37; loss of brainstem function in slow induction and 90&#37; in rapid induction&#44; we needed to recruit at least 8 patients in each group to detect a difference with a significance of 5&#37; and a statistical power of 80&#37;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">We used Fisher&#39;s exact test to analyse the primary endpoint &#40;presence of brainstem reflex&#41;&#44; and time to LOC was described using the Kaplan&#8211;Meyer estimator compared with the Log-rank test&#46; We used a 2-sample t-test to analyse the differences in CeCALC and PSI between study groups&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Internal analysis</span><p id="par0095" class="elsevierStylePara elsevierViewall">There were no significant differences in demographic data between groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The probabilities of remaining conscious &#40;awake&#41; over time in both arms are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">We observed statistically significant differences in the presence or absence of brainstem reflexes at the time of LOC &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">All subjects undergoing slow induction scored 4 points on FOUR B and R &#40;pupil and corneal reflexes present and regular breathing pattern&#41;&#44; 7 subjects in the RI group scored 0 on both FOUR B and R &#40;pupil and corneal reflexes absent&#44; apnoea&#41;&#44; and 1 subject scored 4 on both B and R &#40;pupil and corneal reflexes present and regular breathing pattern&#41;&#46; Fisher&#39;s exact test &#40;p&#160;&#61;&#160;0&#46;001&#41; showed significant differences in terms of brainstem reflexes at the time of LOC&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Drug volume&#44; mean time to LOC&#44; SEF95&#44; and SEDline PSI&#8482; at the time of LOC are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; This table also shows the mean CeCALC values at the time of LOC using the 4 different propofol effect-site models&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">The results of this study show that propofol-induced LOC is accompanied by different responses during suppression of brainstem function that are determined by the rate of administration and shown by different effect-site concentrations&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Rapid infusion mainly affected the subcortical mechanism&#44; whereas slow propofol infusion until LOC was not associated with the loss of brainstem reflexes&#44; suggesting a predominantly cortical of loss of consciousness mechanism&#46; These findings support the hypothesis that anaesthesia-induced LOC occurs through mechanisms&#44; and these are not consistent with the theoretical CeCALC predicted by conventional Pk&#47;Pd models created to show the varying time course of the effect&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In a previous study evaluating rapid and intermediate rates of propofol administration using the Cerebral State Index monitor&#44; Sep&#250;lveda et al&#46; found different CeCALCs at the time of LOC&#46; Inconsistencies and differences in CeCALC at LOC between groups are related to the design of the effect-site model&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a> The time course described by the rate constant ke0 is proportional to the concentration gradient between the central volume and the empirical and theoretical effect-site concept&#44; and the correlation between ke0 and the rate of administration differs among authors&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;16&#44;18</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Effect site modelling is greatly affected by inaccuracies during the first 5&#160;min of the mixing phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> Recently&#44; Glen and Engbers<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> conducted a simulation study to clarify these discrepancies&#44; and found that they could be due to various pharmacokinetic misinterpretations&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The results of our study help explain the discrepancies in another way&#46; The mechanisms underlying the generation of anaesthesia-induced LOC &#40;predominantly cortical vs&#46; brainstem&#41; are different pharmacodynamic and neurological phenomena&#44; although both lead to clinical LOC&#46; Therefore&#44; the effect should be shown using different effect-site models for each mode of induction&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The effect-site model is based on different methods of processing EEG activity during drug administration&#44; and shows a linear reduction in cortical neuroelectric activity described as anaesthesia depth&#46; These parameters&#44; however&#44; are derived from pharmacokinetic models of neural correlates of consciousness based on incorrect descriptions of the mixing phase and an EEG processing index with low specificity and no sensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Therefore&#44; the concept of a unique&#44; extended effect-site correlated with clinical anaesthesia-induced LOC is incorrect&#44; and warrant a different approach that includes the different neural correlates of consciousness&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The effects after rapid administration of a bolus of propofol are difficult to model&#44; showing problems with frontal kinetics&#46; This highly concentrated but unstable bolus ascends through the cerebral arterial circulation and rapidly reaches the GABAergic neurons of the pontine-medullary respiratory circuits and the pontine and mesencephalic structures of the reticular formation&#44; together with their thalamic and hypothalamic projections&#44; and ultimately blocks input from stimuli&#46; All of this has been described as part of the bottom-up mechanism of LOC&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">In the SI group&#44; we observed various clinical signs suggestive of a top-down phenomenon in which LOC occurs with preserved brainstem function and is probably associated with the breakdown of frontoparietal connectivity&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Subjects consistently showed a loss of pursuit eye movement&#44; suggesting impairment of the medial temporal cortical and lateral parietal networks involved in the potentials that determine the speed and direction of tracking eye movement&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> These data suggest that the phenomenon of cortical detachment associated with slow induction of LOC would be sufficient to generate a state of unconsciousness similar to NREM sleep and avoid the creation and activation of episodes of wakefulness&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The correlation between speed of induction and the mechanisms of unconsciousness has potential relevance for anaesthesia in clinical practice&#44; especially when calculating the Ce required for LOC in an individual patient&#44; and avoid unnecessary overdose of anaesthesia agents&#46; We believe slow&#44; progressive&#44; gradual induction is more accurate&#44; since the Pk&#47;Pd prediction models for slow infusions have shown better performance&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">The use of anaesthesia induction targets based on mean population values&#44; or &#8220;statistics&#8221;&#44; leads not only to the familiar haemodynamic effects of overdose&#44; but also prevents clinicians from calculating anaesthesia requirements individually&#44; bearing in mind that modern EEG-based monitors for measuring depth of anaesthesia do not reflect the complexity of the LOC processes that occur during anaesthesia&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;26</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Although slow infusion through cortical circuits prolongs time to LOC&#44; it is more predictable in terms of plasma mixture concentration and establishment of LOC&#44; which is less influenced by brainstem structures&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Differences found in CeCALC using the Marsh and Schnider models can be explained in various ways&#46; The time to maximum effect in the Schnider model was obtained on the basis of rapid manual boluses &#40;1&#46;6&#160;min&#41;&#44; which contradicts his own Emax pharmacodynamic model obtained by slow infusions&#44; showing an EC50 of 2&#46;35&#160;&#956;g ml<span class="elsevierStyleSup">&#8722;1</span> for LOC in subjects aged 25 years&#46; The Ce<span class="elsevierStyleInf">LOC</span> values in our study were quite high in the rapid infusion group&#46; As such&#44; they were not appropriate as anaesthesia maintenance targets and would have led to an overdose&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The original Marsh model&#44; meanwhile&#44; shows less CeCALC mismatch between groups&#59; however&#44; this model &#40;which cannot be used in effect-site TCI systems&#41; shows a similar CeCALC for different neurological conditions revealed by the FOUR score and different PSI values &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The modified Marsh model &#40;available on modern infusion pumps&#41; has a time to peak effect &#40;TTPE&#41; of 1&#46;6&#160;min&#44; and has the same problem as Schnider&#39;s model&#46; The ke0 in this model was derived from a TTPE following rapid bolus administration and is similar &#40;2&#160;mg&#47;kg&#41; to that of Schnider&#44; though slightly slower &#40;1200&#160;ml&#47;h&#41;&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">We used the FOUR score to evaluate our study subjects because it has been validated for clinical use&#44; and estimates alertness &#40;awakening&#41; as well as mesencephalic &#40;pontine&#41; and medullary &#40;respiratory&#41; reflexes&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The FOUR was also quick to administer and reproducible in the clinical setting&#46; This allowed us to perform serial evaluations at short intervals &#40;less than 30&#160;s&#41; during anaesthesia induction and to compare reactive &#40;E and M&#41; against reflective &#40;B and D&#41; components of the FOUR score as a function of time&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">In our study&#44; LOC was also defined as the absence of motor response&#44; and was evaluated using both physical and auditory stimuli&#46; We believe this criterion is more specific and consistent with the LOC level required under anaesthetic conditions&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The limitations of this study concern the characteristics of the clinical evaluation used &#8211; the FOUR score &#8211; which does not provide any information on superior functions&#46; However&#44; this instrument is highly effective in assessing the brainstem and cortical components of anaesthesia induction&#44; even though it was designed and validated in very different clinical contexts from that used in this study&#46; Another limitation is that we were only able to use surrogate parameters to build the effect-site PD models&#46; Future research will make it possible to progress from effect modelling to managing general anaesthesia based on actual pharmacodynamics&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Despite the small size of our cohort&#44; it was large enough to shown the vast difference in clinical status between the two types of induction strategies&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Although our results are probably not new to many clinicians&#44; the inconsistency of current effect site models has not hitherto been discussed in depth&#46; Our findings allow us to suggest that rapid anaesthesia induction produces a type of &#34;bottom-up&#34; LOC that predominantly affects brainstem structures&#44; while slow induction produces a &#34;top-down&#34; LOC that predominantly affects cortical structures and their connections&#46; Pharmacological descriptions based on models that do not distinguish between these two LOC mechanisms and assume the existence of a single effect site&#44; together with the difficulties in modelling the kinetics of the first minutes of rapid administration&#44; would explain the frequent discrepancies found between effect-time prediction models&#46; More importantly&#44; this impacts the way we use these models to assess &#40;individualize needs&#41; and adjust drug delivery&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Authorship</span><p id="par0210" class="elsevierStylePara elsevierViewall">P&#46; Sep&#250;lveda&#58; designed the protocol&#44; performed the study techniques&#44; and drafted the manuscript&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">I&#46; Acosta&#58; designed the protocol&#44; performed the study techniques&#44; analysed the data&#44; wrote the manuscript and organised the logistics&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">E&#46; Carrasco&#58; designed the protocol&#44; performed the study techniques&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">A&#46; Hoppe&#58; designed the protocol and drafted the manuscript&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">F&#46;A&#46; Lobo&#58; performed a critical review and drafted the manuscript&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interests</span><p id="par0235" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:11 [
        0 => array:3 [
          "identificador" => "xres1526130"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Background"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Methodology"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Conclusions"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1383581"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1526131"
          "titulo" => "Resumen"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Antecedentes"
            ]
            1 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Metodolog&#237;a"
            ]
            2 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Resultados"
            ]
            3 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Conclusiones"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1383580"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Methods"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Design"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Inclusion and exclusion"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Intervention"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Systematic neurological evaluation&#58; Full Outline of UnResponsiveness &#40;FOUR&#41; score"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Endpoints and results"
            ]
            5 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0045"
          "titulo" => "Results"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Internal analysis"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Authorship"
        ]
        9 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Conflict of interests"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-01-31"
    "fechaAceptado" => "2020-05-26"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1383581"
          "palabras" => array:4 [
            0 => "Propofol"
            1 => "Effect-site"
            2 => "Pharmacodynamics"
            3 => "Infusion rate"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1383580"
          "palabras" => array:4 [
            0 => "Propofol"
            1 => "Sitio de efecto"
            2 => "Farmacodin&#225;mica"
            3 => "Tasa de infusi&#243;n"
          ]
        ]
      ]
    ]
    "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="spar0055" class="elsevierStyleSimplePara elsevierViewall">Propofol effect-site time course models included in TCI systems have been under discussion&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">We hypothesized that the rate of administration is a major contributor affecting the construction of a useful effect-site model&#58; yielding different plasmatic concentrations&#44; loss of consciousness may occur by different mechanisms more complex than the pharmacological effect-site&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methodology</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">ASA I<span class="elsevierStyleGlyphsbnd"></span>II patients were randomized in two groups&#58; rapid induction &#40;RI&#41; received TCI of propofol effect-site &#40;CeCALC&#41; 5&#46;4&#160;&#956;g&#47;mL &#40;modified Marsh model&#41;&#44; and slow induction &#40;SI&#41; propofol infusion of 10&#160;mg&#47;kg&#47;hour&#46; A neurologist&#44; blinded to induction method&#44; performed neurological assessments using the FOUR score until the loss of consciousness &#40;LOC&#41;&#46; At LOC&#44; the presence of brain stem reflexes&#44; EEG index &#40;PSI&#41; and infusion time&#47;mass of drug were registered&#46; Fisher&#39;s exact test was used to describe differences between brain stem reflexes and respiration components of the FOUR score and CeCALC for 4 propofo models at LOC time&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">16 patients divided in two groups were included&#46; All patient in SI had brainstem reflexes free at LOC&#46; In the RI&#44; all patients had brain stem reflexes abolished and 1 patient had B and R of 4 points in the FOUR score &#40;brain stem reflexes unaffected&#59; <span class="elsevierStyleItalic">P</span>&#160;&#60;&#160;&#46;001&#41;&#46; CeCALC at LOC time were contradictory at LOC in both groups and using 4 different Pk&#47;Pd models&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Depending of the infusion rate&#44; propofol CeCALC at LOC calculated by different Pk&#47;Pd models could be the source of confuse data to be used to guide the state of general anesthesia&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methodology"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Se han debatido los modelos de curso temporal del sitio de efecto del propofol&#46;</p><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Nosotros supusimos que la tasa de administraci&#243;n es un gran factor contributivo que afecta a la construcci&#243;n de un modelo de sitio de efecto &#250;til&#58; elaborando distintas concentraciones plasm&#225;ticas&#44; la p&#233;rdida de consciencia puede producirse debido a diferentes mecanismos m&#225;s complejos que el sitio del efecto farmacol&#243;gico&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Metodolog&#237;a</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Se aleatorizaron pacientes ASA&#160;I-II en dos grupos&#58; el grupo de inducci&#243;n r&#225;pida &#40;IR&#41; recibi&#243; TCI de sitio de efecto de propofol &#40;CeCALC&#41; 5&#44;4&#160;&#956;g&#47;mL &#40;modelo Marsh modificado&#41; y el grupo de inducci&#243;n lenta &#40;IL&#41; recibi&#243; una infusi&#243;n de propofol de 10&#160;mg&#47;kg&#47;h&#46; Un neur&#243;logo&#44; a quien se ocult&#243; el m&#233;todo de inducci&#243;n&#44; realiz&#243; las evaluaciones neurol&#243;gicas utilizando la escala FOUR hasta lograr la p&#233;rdida de consciencia &#40;LOC&#41;&#46; Una vez lograda&#44; se registraron la presencia de reflejos troncoencef&#225;licos&#44; el &#237;ndice EEG &#40;PSI&#41; y el tiempo de infusi&#243;n&#47;masa del f&#225;rmaco&#46; Se realiz&#243; la prueba exacta de Fisher para describir las diferencias entre los reflejos troncoencef&#225;licos y los componentes respiratorios de la escala FOUR&#44; as&#237; como CeCALC para los 4 modelos de propofol en el momento de la LOC&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 16 pacientes&#44; divididos en dos grupos&#46; Todos los pacientes del grupo IL tuvieron reflejos troncoencef&#225;licos libres en LOC&#46; En el grupo IR&#44; en todos los pacientes se suprimieron los reflejos troncoencef&#225;licos&#44; y un paciente obtuvo 4 puntos B y R en la escala FOUR &#40;reflejos troncoencef&#225;licos no afectados&#59; p&#160;&#60;&#160;0&#44;001&#41;&#46; CeCALC en el momento de LOC fue contradictorio en ambos grupos&#44; utilizando 4 modelos Pk&#47;Pd diferentes&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Dependiendo de la tasa de infusi&#243;n&#44; CeCALC de propofol en el momento de la LOC&#44; calculado mediante modelos Pk&#47;Pd diferentes&#44; podr&#237;a ser la fuente de datos de confusi&#243;n a utilizar para guiar el estado de la anestesia general&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Antecedentes"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Metodolog&#237;a"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Sep&#250;lveda P&#44; Acosta I&#44; Hoppe A&#44; Lobo FA&#44; Carrasco E&#46; Influencia de la tasa de administraci&#243;n en el mecanismo subyacente a la p&#233;rdida de consciencia inducida por propofol&#46; Rev Esp Anestesiol Reanim&#46; 2021&#59;68&#58;245&#8211;251&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">This study is a supplement to <span class="elsevierStyleItalic">Anesthesia</span> 2019&#44; doi&#58; <span class="elsevierStyleInterRef" id="intr0010" href="https://doi.org/10.1111/anae.14885">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1111&#47;anae&#46;14885</span>&#46;</p>"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1176
            "Ancho" => 2083
            "Tamanyo" => 158363
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Loss of consciousness curve &#40;probability of remaining conscious over time&#41;&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Eye response &#40;E&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>4&nbsp;\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">Eyelids open or opened&#44; tracking&#44; or blinking to command&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>3&nbsp;\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">Eyelids open but not tracking&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\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">Eyelids closed but open to loud voice&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\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">Eyelids closed but open to pain&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>0&nbsp;\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">Eyelids remain closed with pain&nbsp;\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 " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Motor response &#40;M&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>4&nbsp;\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">Thumbs-up&#44; fist&#44; or peace sign&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>3&nbsp;\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">Localizing to pain&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\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">Flexion response to pain&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\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">Extension response to pain&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>0&nbsp;\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">No response to pain or generalized myoclonus status&nbsp;\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 " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Brainstem reflexes &#40;B&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>4&nbsp;\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">Pupil and corneal reflexes present&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>3&nbsp;\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">One pupil wide and fixed&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\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">Pupil or corneal reflexes absent&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\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">Pupil and corneal reflexes absent&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>0&nbsp;\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">Absent pupil&#44; corneal&#44; and cough reflex&nbsp;\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 " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Respiration &#40;D&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>4&nbsp;\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">Not intubated&#44; regular breathing pattern&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>3&nbsp;\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">Not intubated&#44; Cheyne&#8211;Stokes breathing pattern&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\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">Not intubated&#44; irregular breathing&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\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">Breathes above ventilator rate&nbsp;\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"><span class="elsevierStyleHsp" style=""></span>0&nbsp;\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">Breathes at ventilator rate or apnoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2623053.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">FOUR score &#40;Full Outline of UnResponsiveness&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">SBP&#58; systolic blood pressure&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Values expressed as mean &#40;range&#41;&#46;</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">Variables&nbsp;\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">Slow induction &#40;n&#160;&#61;&#160;8&#41;&nbsp;\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">Rapid induction &#40;n&#160;&#61;&#160;8&#41;&nbsp;\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">Age &#40;years&#41;&nbsp;\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">37 &#40;23&#8722;55&#41;&nbsp;\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">40 &#40;29&#8722;60&#41;&nbsp;\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">Weight &#40;kg&#41;&nbsp;\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 &#40;58&#8722;95&#41;&nbsp;\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">80 &#40;53&#8722;92&#41;&nbsp;\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">Height &#40;cm&#41;&nbsp;\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">173 &#40;160&#8722;189&#41;&nbsp;\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">175&#46;5 &#40;160&#8722;180&#41;&nbsp;\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">SBP &#40;mmHg&#41;&nbsp;\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">127 &#40;110&#8722;144&#41;&nbsp;\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 &#40;109&#8722;141&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2623050.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Baseline patient characteristics&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">&#42;f&#160;&#60;&#160;0&#46;001&#46;</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">B and R response to LOC&nbsp;\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">Slow induction &#40;n&#160;&#61;&#160;8&#41;&nbsp;\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">Rapid induction &#40;n&#160;&#61;&#160;8&#41;&nbsp;\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">B&#160;&#61;&#160;0&#160;&#43;&#160;R&#160;&#61;&#160;0&nbsp;\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 &#40;0&#37;&#41;&nbsp;\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">7 &#40;87&#46;5&#37;&#41;&nbsp;\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">Other than B&#160;&#61;&#160;0&#160;&#43;&#160;R&#160;&#61;&#160;0&nbsp;\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">8 &#40;100&#37;&#41;&nbsp;\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 &#40;12&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2623051.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">FOUR score brainstem components in loss of consciousness&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">T<span class="elsevierStyleInf">LOC</span>&#58; time to loss of consciousness&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Values are expressed as median &#40;&#177; SD&#41; or mean &#40;range&#41;&#46;</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">Variables&nbsp;\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">Slow induction &#40;n&#160;&#61;&#160;8&#41;&nbsp;\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">Rapid induction &#40;n&#160;&#61;&#160;8&#41;&nbsp;\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">T<span class="elsevierStyleInf">LOC</span>&#59; s&nbsp;\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">630 &#40;378&#8722;1128&#41;&nbsp;\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">84 &#40;84&#8722;96&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\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">Drug volume at LOC&#59; mg&#47;kg&nbsp;\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&#46;67 &#40;1&#46;05&#8722;3&#46;25&#41;&nbsp;\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&#46;91&nbsp;\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">PSI Sedline at T<span class="elsevierStyleInf">LOC</span>&nbsp;\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">67 &#40;87&#8722;57&#41;&nbsp;\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">87 &#40;93&#8722;75&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\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">SEF95 in LOC Hz&nbsp;\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">18 &#40;19&#8722;14&#41;&nbsp;\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">15 &#40;23&#8722;10&#41;&nbsp;\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">Ce<span class="elsevierStyleInf">LOC</span>&#44; Marsh&#59; &#956;g&#160;ml<span class="elsevierStyleSup">&#8722;1</span>&nbsp;\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&#46;15&#40;&#177;0&#46;66&#41;&nbsp;\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&#46;8 &#40;&#177;0&#46;56&#41;&nbsp;\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">Ce<span class="elsevierStyleInf">LOC</span>&#44; Marsh &#40;ke0 1&#46;6&#41;&#59; &#956;g&#160;ml<span class="elsevierStyleSup">&#8722;1</span>&nbsp;\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&#46;7 &#40;&#177;0&#46;44&#41;&nbsp;\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&#46;6 &#40;&#177;0&#46;76&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\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">Ce<span class="elsevierStyleInf">LOC</span>&#44; Schnider&#59; &#956;g&#160;ml<span class="elsevierStyleSup">&#8722;1</span>&nbsp;\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&#46;2 &#40;&#177;0&#46;38&#41;&nbsp;\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">6&#46;6 &#40;&#177;0&#46;93&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\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">Ce<span class="elsevierStyleInf">LOC</span>&#44; Eleved&#59; &#956;g&#160;ml<span class="elsevierStyleSup">&#8722;1</span>&nbsp;\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&#46;2 &#40;&#177;0&#46;9&#41;&nbsp;\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&#46;1 &#40;&#177;1&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2623052.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">p&#160;&#60;&#160;0&#46;01&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Effect-site concentration loss of consciousness &#40;Ce<span class="elsevierStyleInf">LOC</span>&#41; parameters with different pharmacokinetic models&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:28 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anesthetic effects of propofol in the healthy human brain&#58; functional imaging evidence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "X&#46;X&#46; Song"
                            1 => "B&#46;W&#46; Yu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00540-014-1889-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Anesth&#46;"
                        "fecha" => "2015"
                        "volumen" => "29"
                        "paginaInicial" => "279"
                        "paginaFinal" => "288"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25056258"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Disruption of frontal-parietal communication by ketamine&#44; propofol&#44; and sevoflurane"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "U&#46; Lee"
                            1 => "S&#46; Ku"
                            2 => "G&#46; Noh"
                            3 => "S&#46; Baek"
                            4 => "B&#46; Choi"
                            5 => "G&#46;A&#46; Mashour"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/ALN.0b013e31829103f5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesthesiology&#46;"
                        "fecha" => "2013"
                        "volumen" => "118"
                        "paginaInicial" => "1264"
                        "paginaFinal" => "1275"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23695090"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Understanding the hysteresis loop conundrum in pharmacokinetic&#47;pharmacodynamic relationships"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Louizos"
                            1 => "J&#46;A&#46; Yanez"
                            2 => "M&#46;L&#46; Forrest"
                            3 => "N&#46;M&#46; Davies"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pharm Pharm Sci&#46;"
                        "fecha" => "2014"
                        "volumen" => "17"
                        "paginaInicial" => "34"
                        "paginaFinal" => "91"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24735761"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Top-down mechanisms of anesthetic-induced unconsciousness"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "G&#46;A&#46; Mashour"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fnsys.2014.00115"
                      "Revista" => array:5 [
                        "tituloSerie" => "Front Syst Neurosci&#46;"
                        "fecha" => "2014"
                        "volumen" => "8"
                        "paginaInicial" => "115"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25002838"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The influence of target concentration&#44; equilibration rate constant &#40;ke0&#41; and pharmacokinetic model on the initial propofol dose delivered in effect-site target-controlled infusion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;B&#46; Glen"
                            1 => "F&#46;H&#46; Engbers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/anae.13345"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anaesthesia&#46;"
                        "fecha" => "2016"
                        "volumen" => "71"
                        "paginaInicial" => "306"
                        "paginaFinal" => "314"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26682512"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Individual effect-site concentrations of propofol are similar at loss of consciousness and at awakening"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "H&#46;N&#46;N&#46; Iwakiri"
                            1 => "O&#46; Nagata"
                            2 => "T&#46; Matsukawa"
                            3 => "M&#46; Ozaki"
                            4 => "D&#46;I&#46; Sessler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1213/01.ANE.0000139358.15909.EA"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesth Analg&#46;"
                        "fecha" => "2005"
                        "volumen" => "100"
                        "paginaInicial" => "107"
                        "paginaFinal" => "110"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15616062"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Induction speed is not a determinant of propofol pharmacodynamics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;G&#46; Doufas"
                            1 => "M&#46; Bakhshandeh"
                            2 => "A&#46;R&#46; Bjorksten"
                            3 => "S&#46;L&#46; Shafer"
                            4 => "D&#46;I&#46; Sessler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00000542-200411000-00010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesthesiology&#46;"
                        "fecha" => "2004"
                        "volumen" => "101"
                        "paginaInicial" => "1112"
                        "paginaFinal" => "1121"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15505446"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacokinetic models for propofol&#8212;defining and illuminating the devil in the detail"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;R&#46; Absalom"
                            1 => "V&#46; Mani"
                            2 => "T&#46; de Smet"
                            3 => "M&#46;M&#46; Struys"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/bja/aep143"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Anaesth&#46;"
                        "fecha" => "2009"
                        "volumen" => "103"
                        "paginaInicial" => "26"
                        "paginaFinal" => "37"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19520702"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Is unconsciousness simply the reverse of consciousness&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "F&#46; Engbers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/anae.14121"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anaesthesia&#46;"
                        "fecha" => "2018"
                        "volumen" => "73"
                        "paginaInicial" => "6"
                        "paginaFinal" => "9"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29057452"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of plasma compartment versus two methods for effect compartment&#8212;controlled target-controlled infusion for propofol"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;M&#46; Struys"
                            1 => "T&#46; De Smet"
                            2 => "B&#46; Depoorter"
                            3 => "L&#46;F&#46; Versichelen"
                            4 => "E&#46;P&#46; Mortier"
                            5 => "F&#46;J&#46; Dumortier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00000542-200002000-00021"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesthesiology&#46;"
                        "fecha" => "2000"
                        "volumen" => "92"
                        "paginaInicial" => "399"
                        "paginaFinal" => "406"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10691226"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Targeting effect compartment or central compartment concentration of propofol&#58; what predicts loss of consciousness&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "H&#46;G&#46; Wakeling"
                            1 => "J&#46;B&#46; Zimmerman"
                            2 => "S&#46; Howell"
                            3 => "P&#46;S&#46; Glass"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00000542-199901000-00014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesthesiology&#46;"
                        "fecha" => "1999"
                        "volumen" => "90"
                        "paginaInicial" => "92"
                        "paginaFinal" => "97"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9915317"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Validation of a new coma scale&#58; the FOUR score"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46;F&#46; Wijdicks"
                            1 => "W&#46;R&#46; Bamlet"
                            2 => "B&#46;V&#46; Maramattom"
                            3 => "E&#46;M&#46; Manno"
                            4 => "R&#46;L&#46; McClelland"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ana.20611"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Neurol&#46;"
                        "fecha" => "2005"
                        "volumen" => "58"
                        "paginaInicial" => "585"
                        "paginaFinal" => "593"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16178024"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The development of &#8216;Diprifusor&#8217;&#58; a TCI system for propofol"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;B&#46; Glen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2044.1998.53s115.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anaesthesia&#46;"
                        "fecha" => "1998"
                        "volumen" => "53 Suppl 1"
                        "paginaInicial" => "13"
                        "paginaFinal" => "21"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9640110"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The influence of age on propofol pharmacodynamics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "T&#46;W&#46;M&#46;C&#46; Schnider"
                            1 => "S&#46;L&#46; Shafer"
                            2 => "P&#46;L&#46; Gambus"
                            3 => "C&#46; Andresen"
                            4 => "D&#46;B&#46; Goodale"
                            5 => "E&#46;J&#46; Youngs"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00000542-199906000-00003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesthesiology&#46;"
                        "fecha" => "1999"
                        "volumen" => "90"
                        "paginaInicial" => "1502"
                        "paginaFinal" => "1516"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10360845"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A general purpose pharmacokinetic model for propofol"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46;J&#46; Eleveld"
                            1 => "J&#46;H&#46; Proost"
                            2 => "L&#46;I&#46; Cortinez"
                            3 => "A&#46;R&#46; Absalom"
                            4 => "M&#46;M&#46; Struys"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1213/ANE.0000000000000165"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesth Analg&#46;"
                        "fecha" => "2014"
                        "volumen" => "118"
                        "paginaInicial" => "1221"
                        "paginaFinal" => "1237"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24722258"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Predictive ability of propofol effect-site concentrations during fast and slow infusion rates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "P&#46;O&#46; Sepulveda"
                            1 => "L&#46;I&#46; Cortinez"
                            2 => "A&#46; Recart"
                            3 => "H&#46;R&#46; Munoz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1399-6576.2009.02183.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Anaesthesiol Scand&#46;"
                        "fecha" => "2010"
                        "volumen" => "54"
                        "paginaInicial" => "447"
                        "paginaFinal" => "452"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20003124"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cerebral state index during propofol anesthesia&#58; a comparison with the bispectral index and the A-line ARX index"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;W&#46; Jensen"
                            1 => "H&#46; Litvan"
                            2 => "M&#46; Revuelta"
                            3 => "B&#46;E&#46; Rodr&#237;guez"
                            4 => "P&#46; Caminal"
                            5 => "P&#46; Martinez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00000542-200607000-00009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesthesiology&#46;"
                        "fecha" => "2006"
                        "volumen" => "105"
                        "paginaInicial" => "28"
                        "paginaFinal" => "36"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16809991"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The determinants of propofol induction of anesthesia dose"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Y&#46;U&#46; Adachi"
                            1 => "K&#46; Watanabe"
                            2 => "H&#46; Higuchi"
                            3 => "T&#46; Satoh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/00000539-200103000-00020"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesth Analg&#46;"
                        "fecha" => "2001"
                        "volumen" => "92"
                        "paginaInicial" => "656"
                        "paginaFinal" => "661"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11226096"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Influence of administration rate on propofol plasma-effect site equilibration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;M&#46;C&#46;M&#46; Struys"
                            1 => "N&#46; de Neve"
                            2 => "E&#46;P&#46; Mortier"
                            3 => "A&#46;G&#46; Doufas"
                            4 => "J&#46;F&#46; van Bocxlaer"
                            5 => "S&#46;L&#46; Shafer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.anes.0000278902.15505.f8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesthesiology&#46;"
                        "fecha" => "2007"
                        "volumen" => "107"
                        "paginaInicial" => "386"
                        "paginaFinal" => "396"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17721240"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early phase pharmacokinetics but not pharmacodynamics are influenced by propofol infusion rate"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "K&#46; Masui"
                            1 => "M&#46; Kira"
                            2 => "T&#46; Kazama"
                            3 => "S&#46; Hagihira"
                            4 => "E&#46;P&#46; Mortier"
                            5 => "M&#46;M&#46; Struys"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/ALN.0b013e3181b799c1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesthesiology&#46;"
                        "fecha" => "2009"
                        "volumen" => "111"
                        "paginaInicial" => "805"
                        "paginaFinal" => "817"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19741485"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neural correlates of consciousness&#58; progress and problems"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Koch"
                            1 => "M&#46; Massimini"
                            2 => "M&#46; Boly"
                            3 => "G&#46; Tononi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Nat Rev Neurosci&#46;"
                        "fecha" => "2016"
                        "volumen" => "17"
                        "paginaInicial" => "395"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Are the neural correlates of consciousness in the front or in the back of the cerebral cortex&#63; Clinical and neuroimaging evidence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Boly"
                            1 => "M&#46; Massimini"
                            2 => "N&#46; Tsuchiya"
                            3 => "B&#46;R&#46; Postle"
                            4 => "C&#46; Koch"
                            5 => "G&#46; Tononi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1523/JNEUROSCI.3218-16.2017"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Neurosci&#46;"
                        "fecha" => "2017"
                        "volumen" => "37"
                        "paginaInicial" => "9603"
                        "paginaFinal" => "9613"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28978697"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bottom-up and top-down mechanisms of general anesthetics modulate different dimensions of consciousness"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46;A&#46; Mashour"
                            1 => "A&#46;G&#46; Hudetz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fncir.2017.00044"
                      "Revista" => array:5 [
                        "tituloSerie" => "Front Neural Circuits&#46;"
                        "fecha" => "2017"
                        "volumen" => "11"
                        "paginaInicial" => "44"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28676745"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Modulation of pursuit eye movements by stimulation of cortical areas MT and MST"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46; Komatsu"
                            1 => "R&#46;H&#46; Wurtz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/jn.1989.62.1.31"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Neurophysiol&#46;"
                        "fecha" => "1989"
                        "volumen" => "62"
                        "paginaInicial" => "31"
                        "paginaFinal" => "47"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2754480"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Monitoring the brain&#58; processed electroencephalogram and peri-operative outcomes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "K&#46;E&#46; Escallier"
                            1 => "M&#46;R&#46; Nadelson"
                            2 => "D&#46; Zhou"
                            3 => "M&#46;S&#46; Avidan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/anae.12711"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anaesthesia&#46;"
                        "fecha" => "2014"
                        "volumen" => "69"
                        "paginaInicial" => "899"
                        "paginaFinal" => "910"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24905798"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Limitations of anaesthesia depth monitoring"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46;A&#46; Lobo"
                            1 => "S&#46; Schraag"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/ACO.0b013e32834c7aba"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Anaesthesiol&#46;"
                        "fecha" => "2011"
                        "volumen" => "24"
                        "paginaInicial" => "657"
                        "paginaFinal" => "664"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21971394"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Validity of the FOUR score coma scale in the medical intensive care unit"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "V&#46;N&#46; Iyer"
                            1 => "J&#46;N&#46; Mandrekar"
                            2 => "R&#46;D&#46; Danielson"
                            3 => "A&#46;Y&#46; Zubkov"
                            4 => "J&#46;L&#46; Elmer"
                            5 => "E&#46;F&#46; Wijdicks"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0025-6196(11)60519-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mayo Clin Proc&#46;"
                        "fecha" => "2009"
                        "volumen" => "84"
                        "paginaInicial" => "694"
                        "paginaFinal" => "701"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19648386"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Critical view of the effect site modelling of propofol"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46; Sep&#250;lveda"
                            1 => "C&#46; Demar&#237;a"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Esp Anestesiol Reanim&#46;"
                        "fecha" => "2019"
                        "volumen" => "66"
                        "paginaInicial" => "425"
                        "paginaFinal" => "433"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/23411929/0000006800000005/v1_202106150624/S2341192921000810/v1_202106150624/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "34051"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/23411929/0000006800000005/v1_202106150624/S2341192921000810/v1_202106150624/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341192921000810?idApp=UINPBA00004N"
]