Do we have today a reliable method to detect the moment of loss of consciousness during induction of general anaesthesia? | Revista Española de Anestesiología y Reanimación (English Edition)

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"apellidos" => "Amorim" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "LAETA/INEGI, Faculdade de Engenharia da Universidade do Porto, Porto, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Investigação Clínica em Anestesiologia, Serviço de Anestesiologia, Centro Hospitalar do Porto, Porto, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Ciências e Tecnologia, Universidade Aberta, Porto, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Contamos actualmente con un método fiable para detectar el momento de pérdida de consciencia durante la inducción de la anestesia?" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1980 "Ancho" => 3167 "Tamanyo" => 281998 ] ] "descripcion" => array:1 [ "en" => "Overshoot and hysteresis between plasma and effect-site concentration of propofol (mg/mL) versus time for different infusion rates of propofol: (A) 1200mL/h until LOC (14s); (B) 200mL/h until LOC (2min)." ] ] ] "textoCompleto" => "IntroductionGeneral anaesthesia is a drug-induced, reversible condition that produces unconsciousness, analgesia, amnesia and akinesia while maintaining physiological stability.<a class="elsevierStyleCrossRef" href="#bib0280">1</a> Of all behavioural states, unconsciousness is perhaps the most fascinating. Unconsciousness can be achieved by altering the patient's level of arousal and/or cognition by the administration of anaesthetic drugs.Induction of anaesthesia may be performed intravenously, using a constant rate or intermittent infusion (bolus), or by using a target-controlled infusion (TCI) system. TCI systems administer drugs based on the simulated concentration for a specific patient, usually taking into account age, weight, height and gender. These systems continuously simulate the drug concentration in the human body, and thus control drug administration either by effect-site or by plasma concentration targeting. This means that the anaesthesiologist may choose the drug target concentration for that specific patient based on the simulated expected response, and administer the necessary dose to achieve the desired target automatically. TCI systems have been implemented in some commercially available electronic syringe pumps, and may be used in clinical practice.There are various pharmacokinetic (PK) models for the use of drugs in TCI, while manual infusion can be performed with or without an initial bolus. However, if an initial bolus is not administered, more time will be needed to achieve the desired hypnotic effect. For the use of propofol in TCI, the most widely used PK models are Marsh's<a class="elsevierStyleCrossRef" href="#bib0285">2</a> and Schnider's.<a class="elsevierStyleCrossRef" href="#bib0290">3</a> For remifentanil, fentanyl/alfentanil and sufentanil, the most widely used PK models are Minto's,<a class="elsevierStyleCrossRef" href="#bib0295">4</a> Shafer's<a class="elsevierStyleCrossRef" href="#bib0300">5</a> and Hudson's,<a class="elsevierStyleCrossRef" href="#bib0305">6</a> respectively. Although TCI systems are sold in several countries, they have not been approved by the US Food and Drug Administration (FDA).Loss of consciousness (LOC) occurs during the induction of general anaesthesia. Detecting the moment the patient loses consciousness is important in general anaesthesia induction. Identifying the exact moment of LOC will determine the individual response of each patient to the hypnotic, and will provide important information to guide the infusion rate required to maintain an adequate level of anaesthesia, ensuring safe and an effective care. This will help to prevent intraoperative awareness and overdose, two serious and frequently preventable problems that have caught the attention of clinicians and patients alike.Intraoperative awareness occurs when a patient under general anaesthesia regains consciousness with recall during intraoperative events. It is usually the result of insufficient hypnotics, and is considered a very traumatic experience that causes long term morbidity in some patients.<a class="elsevierStyleCrossRefs" href="#bib0285">2,3</a> The incidence of awareness established by large multicentre studies was approximately 1–2 per 1000 cases.<a class="elsevierStyleCrossRef" href="#bib0310">7</a> Moreover, awareness during anaesthesia is grounds for compensation claims,<a class="elsevierStyleCrossRef" href="#bib0315">8</a> even when they may depend on social or cultural factors. There are no recent studies analysing this phenomenon, and the medical and legal consequences of intraoperative awareness have yet to be clarified.Overdose occurs when the patient receives too much hypnotic drug, and may be caused by overshooting the control system, which is a phenomenon that occurs due to another important factor known as hysteresis.<a class="elsevierStyleCrossRef" href="#bib0320">9</a> For better understanding of this phenomena, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a and b presents an example of a simulation made for an infusion rate of propofol of 1200mL/h and 200mL/h until LOC, respectively. Hysteresis is the time delay between peak plasmatic concentration (Cp) and peak effect-site concentration (Ce). This leads to an increase in Ce, even after infusion has stopped. The difference between the maximum value of Ce and the effective Ce at LOC is then described as overshoot. The magnitude of the overshoot and hysteresis depend on the pharmacokinetic model. Overdose may lead to severe brain stem or medullary depression; this can result in respiratory and cardiovascular collapse, which can be fatal. From a pharmacological point of view, excessive hypnotic drug dosages will increase the probability of delayed recovery due to accumulation of anaesthetic drugs in the fatty tissues.<a class="elsevierStyleCrossRef" href="#bib0325">10</a> The importance of administering hypnotics slowly to avoid overdose is widely accepted.<a class="elsevierStyleCrossRef" href="#bib0330">11</a> Studies have shown that the required doses for anaesthesia onset were affected by changes in the rate of injection.<a class="elsevierStyleCrossRefs" href="#bib0330">11,12</a> The use of a slow infusion rate results in longer induction time, but requires a lower total dose, and reduces the incidence of apnoea and loss of blood pressure.<a class="elsevierStyleCrossRef" href="#bib0340">13</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>This is why it is so important to control the level of anaesthesia during routine anaesthesia. However, because depth of anaesthesia has yet to be clearly defined, adequate anaesthesia control remains elusive. In the absence of an incontrovertible definition of depth of anaesthesia, a variety of methods for the assessment of the hypnotic component of anaesthesia have been developed. It is presented in the work of Rodríguez et al.,<a class="elsevierStyleCrossRef" href="#bib0345">14</a> in an excellent, detailed, non-systematic review, analyze the usefulness of hypnotic depth monitoring. Anaesthesia monitoring includes both subjective and/or objective methods. Subjective methods are based on movement and autonomic response to stimuli, and rely on the opinion and experience of the anaesthesiologist. Objective methods rely on the sensitivity and accuracy of a monitor. A detailed description of subjective and objectives methods to assess the hypnotic component of anaesthesia is presented in the state of the knowledge section of this paper. Despite the existence of a variety of methods to assess the hypnotic component of anaesthesia, there is no fail-safe way of ascertaining when the patient has passed from the conscious to the unconscious state. Identifying the precise moment of LOC during the induction phase of general anaesthesia is extremely important, because it will determine the dose of hypnotic drugs required for each patient, and will provide important information to guide the infusion rate needed to maintain an adequate level of anaesthesia, ensuring safe and effective care.This review gives an overview of the current state of the knowledge on anaesthesia monitoring systems and detection of drug-induced loss of consciousness, from the first clinical signs in anaesthesia to the latest monitoring technologies.Methods to assess the hypnotic component of anaesthesiaSubjective methodsDuring induction of anaesthesia, a dichotomous “all-or-nothing” assessment of responsiveness can be performed in clinical practice to determine if a patient is conscious or unconscious. This dichotomous assessment involves the isolated forearm technique (IFT): a tourniquet is placed on the patient's forearm with the cannula placed proximal to this tourniquet or on the other arm. During anaesthesia, the patient is asked to squeezes their hand, indicating that they may be awake and able to interact, until they no longer respond. Despite being a simple technique and an interesting research tool, the IFT has limitations as a monitor of depth of anaesthesia, namely, very low sensitivity and specificity. Since the introduction of muscle relaxants, the levels of anaesthesia needed to prevent movement in patients are far higher than those usually used; patients have reported hearing commands to move the isolated arm, but were unable to do so, even though nerve stimulation would suggest that the arm was not paralyzed, interpreting the non-specific startle response as a level of consciousness.Loss of response to name calling, to verbal commands, or to a painful stimulus and loss of eyelash reflex are also used: the anaesthetist repeats the stimulus at regular intervals until the patient no longer responds.The Modified Observer's Assessment of Alertness and Sedation Scale (OAA/S),<a class="elsevierStyleCrossRef" href="#bib0350">15</a> derived from the original Observer's Assessment of Alertness/Sedation scale,<a class="elsevierStyleCrossRef" href="#bib0350">15</a> originally validated for use with midazolam, was introduced to standardize the clinical signs of hypnotic drug onset. The OAAS describes the level of sedation on a 0–5 numerical scale, where the observer rates the patient's responsiveness, speech and facial expression/eye movements. The modified form uses only the responsiveness component of the original scale [Unresponsive (1)–Awake (5)].These clinical observations are used in daily practice due to their simplicity. However, they are very imprecise and depend on the patient's collaboration. Clinical signs are based on a voluntary act by the patient and often fail because patients loose critical judgement before losing consciousness. Besides that, as the dose of hypnotic is increased during induction, the patient may enter a state of paradoxical excitation because the drug is intended to induce unconsciousness, but the stimulus induces excitation instead.Objective methodsThe limitations of clinical observations of anaesthetic drug effect prompted the development of continuous monitors of the hypnotic component of anaesthesia. The transition from consciousness to unconsciousness occurs in the brain; therefore, the level of anaesthesia is measured on the main target organ of anaesthesia, the brain. Electroencephalography (EEG) is used to monitor the electrical activity of the brain during anaesthesia by placing electrodes on the forehead of the patient. There are two types of electrical signal: those that process spontaneous EEG activity, and electromyography (EMG), which is based on evoked potentials (EP).EEG records spontaneous electrical activity in the brain, which may be measured using non-invasive electrodes attached to several positions on the patient's head (an international electrode placement system is available<a class="elsevierStyleCrossRef" href="#bib0355">16</a>). In general, anaesthetics produce a frequency shift in the EEG signal, from high to low frequencies, and an increase in the EEG signal amplitude, creating an EEG signal with synchronous properties. Typically, the EEG spectrum is divided into five frequency bands called delta (0.5–4Hz), theta (4–8Hz), alpha (8–13Hz), beta (13–30Hz) and gamma (>30Hz). Each band behaves differently under the effect of hypnotics, depending on the type of anaesthetic drug administered. Propofol, the most widely used hypnotic drug for general anaesthesia, changes the EEG from a low-voltage, high-frequency awake signal to a progressive high-amplitude, low-frequency signal.EPs are detected by electrodes that are positioned over the primary receiving area for a visual, auditory or somatosensory stimulus. The patient is subjected to a large number of repeated stimuli and the EEG is recorded during a fixed period after each one. The signal is then amplified before the EPs are obtained by taking the average of all responses. All EP responses are described in terms of latency (the time from the stimulus until the response) and amplitude (the size of the response). Auditory evoked potentials (AEP) are the most widely used EPs to evaluate general anaesthesia. A functional auditory system is the basic requirement for AEP analysis. According to latencies, the AEP is divided into three components: early component (latencies <10ms), middle component (latencies 10–50ms) and late component (latencies >50ms). The early component is relatively resistant to the effects of anaesthesia while the late component disappears with low concentrations of anaesthetic. During anaesthesia, the middle component increases in latency and decreases in amplitude.Studies have provided moderate-quality evidence that optimized anaesthesia guided by EEG or EPs indices probably reduces the risk of postoperative delirium in patients aged 60 years or over undergoing non-cardiac surgical and non-neurosurgical procedures,<a class="elsevierStyleCrossRef" href="#bib0360">17</a> and reduces the risk of patient awareness during surgical procedures.<a class="elsevierStyleCrossRef" href="#bib0365">18</a>There are many different EEG-based depth-of-anaesthesia monitors that provide anaesthesia indexes, including the Bispectral Index System Monitor (BIS Monitor; Covidien, USA); Entropy Module (GE Healthcare, USA); Narcotrend (MonitorTechnik, Germany); Patient State Index Monitor, SEDLine (Masimo, USA); Cerebral State Monitor (Danmeter, Denmark); loC-View Monitor (Aircraft Medical, Barcelona, Spain); qCon (Quantium Medical, Spain) and AEP Monitor (Danmeter, Denmark). In general, commercial depth-of-anaesthesia monitors use a dimensionless monotonic index as a measure of depth of anaesthesia, typically scaled from 100 (awake state) to 0 (deep coma).Bispectral index (BIS)The bispectral index (BIS) combines Fast Fourier Transformation (FFT) with an EEG quadratic analysis model, the bispectral analysis. The BIS consists of the following four subcomponents: the bispectral component SyncFastSlow log (bispectrum [0.5–47Hz]/bispectrum[40–47Hz]), the BetaRatio spectral component log (power [30–47Hz]/power [11–20Hz]), the burst suppression ratio (BSR) and the QUAZI suppression component. The resulting bispectral index, BIS, is a nonlinear combination of these four sub-parameters.Entropy moduleEntropy is by definition a measure of disorder, irregularity, complexity and signal prediction. During general anaesthesia, the entropy module relies on a method of assessing the degree of irregularity in EEG signals, which changes from irregular to more regular patterns as anaesthesia deepens. The entropy module calculates two parameters: response entropy (RE), shannon entropy of the power spectrum (0.8–47Hz), and state entropy (SE), shannon entropy of the power spectrum (0.8–32Hz).NarcotrendThe Narcotrend monitor automatically analyses raw EEG data using spectral analysis to produce six states of hypnosis, which are then translated into 15 different patterns displayed during anaesthesia. Each of these stages is used to calculate the narcotrend index from a set of EEG parameters, including spectrum, entropy and autoregression.Patient state index (PSI), SEDLineThe SedLine monitor measures the effects of anaesthesia and sedation by monitoring both sides of the brain's electrical activity to enable more individualized titration and improve the care of patients under anaesthesia or sedation. The result is a patient state index (PSI) value, which is calculated using an algorithm that combines several parameters of frequency analysis: absolute power gradient between frontopolar and vertex regions in the gamma band; absolute power changes between midline and central regions in beta and between midline frontal and parietal regions in the alpha frequency; total spectral power (0.5–50Hz) in the frontopolar region; mean frequency of the total spectrum in midline frontal region; absolute power in delta frequency at the vertex and posterior relative power in the slow delta range. All parameters are included in a plausibility analysis to calculate the PSI. Additionally, surrogate analysis is performed by calculating burst suppression and arousal detection, which means that these parameters modulate PSI index if signal quality is poor. Finally, before the index is displayed, it is post-processed with an averaging algorithm to provide a more stable output.Cerebral state monitorThe cerebral state monitor combines four sub-parameters extracted from the EEG to calculate a cerebral state index (CSI). These parameters are: the spectral parameters beta ratio logE(30–42.5Hz)/E(11–21Hz), alpha ratio logE(30–42.5Hz)/E(6–12Hz), the beta-alpha ratio logE(6–12Hz)/E(11–21Hz), and the burst suppression ratio. All parameters are then fed to a fuzzy inference logic system to calculate the CSI index.IoC-view monitor (IoC)The IoC-view monitor displays the index of consciousness (IoC) using three sub-parameters: symbolic dynamics, which detects the complex non-linear properties of the EEG; beta ratio (during superficial anaesthesia), and the amount of burst suppression of the EEG (during deep anaesthesia). All these parameters are then combined through a set of fuzzy logic rules into a single index.qConThe anaesthetic depth monitor qCon was developed to determine the probability that a patient will respond to pain and nociception during different levels of arousal. It defines an index of consciousness (qCon) from EEG raw data, calculated using adaptive fuzzy inference systems (ANFIS).AEP monitorThe auditory evoked potentials (AEP) monitor uses autoregressive models with exogenous input (ARX) to detect the AEP and then calculate the AEP – ARX – Index (or AAI autoregressive index). AEPs are detected in the frequency range 25–65Hz, using ARX. After ARX analysis, the reconstructed amplitudes and latencies are evaluated. Meanwhile, an undisclosed algorithm is used to analyze the EEG in the frequency band between 3 and 47Hz. The decision how the AAI is constructed from AEP and EEG analyses is made by the weighting function, based on the signal-to-noise ratio. The AEP index (AEPex) is exclusively based on an AEP parameter that is the morphology of the AEP signal.<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the recommended ranges for the aforementioned indices of the hypnotic component of anaesthesia. As can be seen, these ranges differ from index to index. BIS, entropy, CSI and IoC indicate that anaesthesia will be adequate at values between 40 and 60, the other indices consider different ranges. Although multiple indices have been developed, some incorporated in commercialized devices and others only developed for academic purposes, only BIS and entropy have had a significant commercial impact. On the one hand, spontaneous EEG monitoring has several confounding factors that may impede interpretation of EEG-derived indices and lead to erroneous conclusions. These include artefacts from the surrounding environment, interindividual variability in terms of baseline EEG characteristics, erroneous site of EEG recording, delay between EEG acquisition and value display, specific clinical conditions, and the effect of the interactions between different anaesthetics. On the other hand, the use of AEPs is not very reproducible, as there are large interindividual differences of response to different anaesthetic regimens. Additionally, despite the fact that anaesthesiologists care for thousands of patients daily, only about half use depth of anaesthesia monitors.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>MethodsStudies containing trials with subjects receiving intravenous drugs for anaesthesia in which the authors reported out the values of the monitoring indexes at the time of LOC were considered. Studies were identified by searching electronic databases for reference articles. No limits were applied for language, and foreign papers were translated. The PubMed (2004–present) and IEEE Xplore Digital Library (2004–present) databases were searched. The last search was run on 30 April 2018.The search was performed using the following terms (in all clinical trials and databases): death due to anaesthesia, monitoring, loss of consciousness, clinical trials, humans, BIS, and each of the existing indexes. The following information was extracted from each trial: (1) the inclusion and exclusion criteria; (2) anaesthetic protocol used for induction, inclusion of pre-medication, type of drugs, dose, and pharmacokinetic models; (4) method used to assess the moment of LOC, including the index used; and finally, (5) values of the different indexes at LOC.In all studies the primary outcome assessed was the value of the hypnotic index at the moment of LOC. Secondary outcomes were the anaesthetic protocol and the clinical evaluation of LOC.Quantitative analyses were performed in order to compare the values of the different indexes at LOC within the several anaesthetic protocols and clinical assessment of LOC.ResultsA total of 35 studies were identified for inclusion in this review. The database search provided a total of 304 studies. After removing duplicates, 145 articles remained. Of these, 82 were excluded because after reviewing the abstracts it appeared that these papers clearly did not meet the criteria. Five additional studies were excluded because the full text of the study was not available or the paper could not be accurately translated into English. The full text of the remaining 77 studies was examined in more detail. A total of 42 studies were excluded because they did not meet the inclusion criteria. The main exclusion criterion was the absence of drugs affecting the different depth of anaesthesia monitoring techniques: prior to induction of anaesthesia, patients had not been given pre-medication or other sedatives.Thirty-five studies met the anaesthetic protocol criteria and were included in the systematic review. No unpublished relevant studies were obtained.A summary of included studies reporting the values of each index at the moment of LOC is presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>From the 35 articles analyzed, 12, 8, 2, 4, 2, 1, 4 and 2 studies identified, respectively, BIS, Entropy, PSI, CSI, Narcotrend, IoC, qCon and AAI values at LOC. The average LOC values on BIS vary between 42 and 75.4; for entropy they vary between 34 and 79, for PSI between 30 and 45; for CSI between 56 and 72.6, for Narcotrend between 44.3 and 58.3, for qCon between 21.33 and 67.72; and for AAI between 30 and 57. In most cases, the deviation from the average value is very significate, which means that there is greater interindividual variability. It is also important to note the strong correlation between these values and the anaesthetic protocol used: at LOC, only hypnotics, both hypnotics and analgesics, or only analgesics may be present.Different index values are also obtained according to the clinical criteria used to determine the moment of LOC. These criteria, therefore, not coincident in time, so a systematic error may occur by associating all the index values to the same moment of LOC. Considerable variations in the values associated with LOC are also observed even when the same clinical criteria and the same anaesthetic protocol are used. None of the studies that analyzed the entropy index used the OAAS scale to determine the moment of LOC. Only one study was found to use the IoC at LOC. Some indices have extremely high sensitivity and specificity for identifying consciousness and unconsciousness, but none can detect the transition between both states or detect the moment of LOC precisely.DiscussionClosed-loop systems have been developed to control administration of drugs during anaesthesia using BIS as a target for control. Studies have investigated the performance of the seven different closed-loop systems: CLADS,<a class="elsevierStyleCrossRef" href="#bib0505">46</a> Rugloop,<a class="elsevierStyleCrossRef" href="#bib0510">47</a> HSS,<a class="elsevierStyleCrossRef" href="#bib0515">48</a> Infusion Toolbox 95,<a class="elsevierStyleCrossRef" href="#bib0520">49</a> Self-Designed Interface,<a class="elsevierStyleCrossRef" href="#bib0525">50</a> McSleepy,<a class="elsevierStyleCrossRef" href="#bib0530">51</a> CONCERT-CL<a class="elsevierStyleCrossRef" href="#bib0535">52</a> and Monitor.<a class="elsevierStyleCrossRef" href="#bib0540">53</a> Compared with manual control, these BIS-guided systems reduce propofol requirements during induction, are more efficient at maintaining a target depth of anaesthesia, and reduce recovery time.<a class="elsevierStyleCrossRef" href="#bib0545">54</a> Given the interindividual variability observed from the studies presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> for the index values at LOC, the adequacy of these closed-loop systems is questionable, since all assume that the same amount of drug is administrated to all patients, irrespective of the anaesthesia protocol.It is also important to point out that the indices used in the studies presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> have three major drawbacks: the recordings from the monitors include artefacts from movement, electrical inference, noise from electrodes, and quantification errors in analogue to digital conversion; they require some time to process the algorithms to compute the indices, and this may take several seconds or even minutes, which during induction can result in excessive anaesthesia with clinical consequences; and, although the raw EEG and its frequency components can give direct, detailed information about brain states under anaesthesia, most current brain monitoring systems reduce the complex EEG signal to a single number that could not accurately reflect the underlying physiological processes that create the patterns.Propofol is one of the most commonly used anaesthetic drugs. An important study, Purdon et al.<a class="elsevierStyleCrossRef" href="#bib0550">55</a> took highly detailed EEG readings from 10 healthy volunteers during propofol-induced general anaesthesia, in which dosage was slowly increased to a target level then slowly decreased while study participants listened to pre-recorded sounds at four-second intervals, and were asked to identify the type of sound they heard by pressing a button. A loss of response to clicks indicated the onset of sedation, and a persistent loss of response to words was considered loss of consciousness. The readings identified characteristic changes in EEG patterns that indicated sedation, loss and return of consciousness, and a state of profound unconsciousness. One particular pattern, which the researchers called “trough-max” occurred during transitions in consciousness. The implications of this study are huge, because it would mean that the authors have found a brain state where they know patients will be unconscious, and could monitor the brain state in the operating room using EEG. With these fundamental neurophysiological markers of the sedative and unconscious states under propofol and with some existing EEG equipment, it may be possible to start monitoring EEG signatures when administering propofol. This may be seen as an introduction to new control systems endpoints.ConclusionIn conclusion, clinical signs allow anaesthesiologists to decide whether a patient is (or is not) unconscious during induction of hypnotics under general anaesthesia, but they do not provide information on the precise time when the transition from consciousness to unconsciousness occurs. This is because either patients do not lose all reflexes simultaneously, or the verification of such signs is in most cases evaluated discontinuously.With anaesthesia monitors based on EEG and AEP, continuously monitoring response signals allow anaesthesiologists to directly evaluate the patient's brain activity over time. However, studies show that these monitors fail in identifying the instant at which consciousness is lost. The computation delays, the difficulty in separating the different electrical signals produced by the body, and the large interindividual variability of the monitor indices mean that these devices are good indicators of the evolution of the patient during the procedure, but cannot indicate the moment of loss of consciousness.Other studies show that combining depth-of-anaesthesia monitors with the information provided by the clinical signs reduced the incidence of intraoperative awakening and overdosing. However, there is still a need for a system that detects the exact moment in which the patient loses consciousness. Identifying this moment during the induction phase of general anaesthesia will determine the dose of hypnotics required by each patient, and will provide important information to guide the infusion rate required to maintain an adequate level of anaesthesia, ensuring safe and effective care. This could open the door to automated systems based solely on the patient's state of consciousness, and could contribute significant advances in the field of anaesthesia itself. Furthermore, detecting the moment the patient loses consciousness is the first step in the development of a fully automated personalized anaesthesia delivery systems based on the conscious state of the patients.FundingSupported by the Fundação para a Ciência e Tecnologia with the reference projects SFRH/BD/98915/2013 and UID/SEM/50022/2013.Conflicts of interestThe authors declare no conflict of interests." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1145567" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1075748" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1145566" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1075749" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods to assess the hypnotic component of anaesthesia" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Subjective methods" ] 1 => array:3 [ "identificador" => "sec0020" "titulo" => "Objective methods" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Bispectral index (BIS)" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Entropy module" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Narcotrend" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Patient state index (PSI), SEDLine" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Cerebral state monitor" ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "IoC-view monitor (IoC)" ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "qCon" ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "AEP monitor" ] ] ] ] ] 6 => array:2 [ "identificador" => "sec0065" "titulo" => "Methods" ] 7 => array:2 [ "identificador" => "sec0070" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusion" ] 10 => array:2 [ "identificador" => "sec0085" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflicts of interest" ] 12 => array:2 [ "identificador" => "xack390387" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-02-08" "fechaAceptado" => "2018-06-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1075748" "palabras" => array:4 [ 0 => "General anaesthesia" 1 => "Loss of consciousness" 2 => "Depth of anaesthesia" 3 => "Patient monitoring" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1075749" "palabras" => array:4 [ 0 => "Anestesia general" 1 => "Pérdida de consciencia" 2 => "Profundidad de la anestesia" 3 => "Monitorización del paciente" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "This review aims to give an overview of the current state of monitoring depth of anaesthesia and detecting the moment of loss of consciousness, from the first clinical signs involved in anaesthesia to the latest technologies used in this area. Such techniques are extremely important for the development of automatic systems for anaesthesia control, including preventing intraoperative awareness episodes and overdoses. A search in the databases Pubmed and IEEE Xplore was performed using terms such as anaesthetic monitoring, depth of anaesthesia, loss of consciousness, as well as anaesthesia indexes, namely BIS. Despite the several methods capable of monitoring the hypnotic state of anaesthesia, there is still no methodology to accurately detect the moment of loss of consciousness during induction of general anaesthesia." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Esta revisión pretende ofrecer una visión general del estado de conocimiento actual sobre la monitorización de la profundidad anestésica y la detección del momento de pérdida de consciencia, desde los primeros signos clínicos implicados en la anestesia hasta las últimas tecnologías utilizadas en esta área. Tales técnicas son extremadamente importantes para el desarrollo de sistemas automáticos de control de la anestesia y para prevenir episodios de percepción intraoperatoria y sobredosis. Realizamos investigaciones en bases de datos (Pubmed, IEEE Xplore) utilizando términos como control anestésico, profundidad de la anestesia, pérdida de consciencia, BIS y cada uno de los índices existentes. A pesar de los diversos métodos capaces de controlar el estado hipnótico de la anestesia, aún no existe una metodología que detecte con precisión el momento de la pérdida de consciencia durante la inducción de la anestesia general." ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Ferreira AL, Nunes C, Mendes JG, Amorim P. ¿Contamos actualmente con un método fiable para detectar el momento de pérdida de consciencia durante la inducción de la anestesia? Rev Esp Anestesiol Reanim. 2019;66:93–103." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "This article is part of the Anaesthesiology and Resuscitation Continuing Medical Education Program. An evaluation of the questions on this article can be made through the Internet by accessing the Education Section of the following web page:" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1980 "Ancho" => 3167 "Tamanyo" => 281998 ] ] "descripcion" => array:1 [ "en" => "Overshoot and hysteresis between plasma and effect-site concentration of propofol (mg/mL) versus time for different infusion rates of propofol: (A) 1200mL/h until LOC (14s); (B) 200mL/h until LOC (2min)." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "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=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="9" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Depth of anaesthesia indexes</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hypnotic component of anaesthesia \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BIS \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Entropy \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Narcotrend \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PSI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CSI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IoC \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">qCon \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AAI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AEPex \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EEG suppression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Burst suppression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deep anaesthesia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20–40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15–35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5–35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deep anaesthesia with burst suppression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10–40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anaesthesia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40–60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40–60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35–65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30–65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40–60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40–60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40–60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15–25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25–45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sedation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60–80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65–95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65–85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60–90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60–80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25–40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45–60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Awake \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80 –100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60–90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95–100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85–100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90–100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80–100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80–100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40–100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60–100 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1955097.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Recommended ranges for the different EEG-based indices of the hypnotic component of anaesthesia. Values are dimensionless and range from 0 to 100." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "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=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Source \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Depth of anaesthesia index \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Values at loss of consciousness \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Anaesthetic technique \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical judgement of loss of consciousness \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Xu et al.<a class="elsevierStyleCrossRef" href="#bib0370">19</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BIS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58 (58–59) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Marsh's model)+Remifentanil (TCI: Minto's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OAAS less than 1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chen et al.<a class="elsevierStyleCrossRef" href="#bib0375">20</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">63.2 (60.3–66.9) 71.1 (67.6–74.5) 71.4 (68.9–73.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Marsh's model) Dexmedetomidine (0.5μg/kg)+Propofol (TCI: Marsh's model) Dexmedetomidine (1.0μg/kg)+Propofol (TCI: Marsh's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OAAS less than 2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gao et al.<a class="elsevierStyleCrossRef" href="#bib0380">21</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Schnider's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal command or eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lysakowski et al.<a class="elsevierStyleCrossRef" href="#bib0385">22</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58 (40–70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Schnider's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OAAS less than 2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kaneda et al.<a class="elsevierStyleCrossRef" href="#bib0390">23</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Etomidate 0.2% (300mg/kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Koppens et al.<a class="elsevierStyleCrossRef" href="#bib0395">24</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65 (18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Remifentanil (TCI: Minto's model)+Propofol (600mL/h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OAAS less than 2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kanata et al.<a class="elsevierStyleCrossRef" href="#bib0400">25</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61.5 (18.7) 73.8 (15.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ropivacaine 0.2% + Propofol (TCI: Marsh's model) Ropivacaine 1%+Propofol (TCI: Marsh's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands, dropping a syringe or eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Karalapillai et al.<a class="elsevierStyleCrossRef" href="#bib0405">26</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60 (15) 75 (18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Marsh's model) Propofol (TCI: Marsh's model)+NO2 67% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">González et al.<a class="elsevierStyleCrossRef" href="#bib0410">27</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">69.5 (15.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Remifentanil (TCI: Minto's model)+Propofol (Schnider's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands and tap on the hand \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mi et al.<a class="elsevierStyleCrossRef" href="#bib0415">28</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">74.1 60.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (30mg/kg/h)+Fentanyl (2μg/kg) Propofol (30mg/kg/h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lysakowski et al.<a class="elsevierStyleCrossRef" href="#bib0420">29</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60.5 (58–63) 69.5 (67.8–71.1) 74.6 (72.9–76.2) 66.2 (62.6–69.1) 74.6 (72.9–76.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Placebo+Propofol (Marsh's model) Fentanyl (TCI: Shafer's model)+Propofol (Marsh's model) Alfentanil (TCI: Shafer's model)+Propofol (Marsh's model) Sufentanil (TCI: Hudson's model)+Propofol (Marsh's model) Remifentanil (TCI: Minto's model)+Propofol (Marsh's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OAAS less than 3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cortínez et al.<a class="elsevierStyleCrossRef" href="#bib0425">30</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46.6 (42.9–50.4) 61.3 (57.3–65.3) 75.4 (70.4–80.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (300mL/h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eyelash reflex Verbal contact Drop a syringe \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gao et al.<a class="elsevierStyleCrossRef" href="#bib0380">21</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="4" align="left" valign="top">SE</td><td class="td" title="table-entry " align="left" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Schnider's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal command or eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liu et al.<a class="elsevierStyleCrossRef" href="#bib0430">31</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75 (11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Remifentanil (TCI: Minto's model)+Propofol (TCI: Schnider's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands and gentle shaking \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hokki et al.<a class="elsevierStyleCrossRef" href="#bib0435">32</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67 (5–89) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (1mg/kg/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dropping a bottle \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anderson and Jakobsson<a class="elsevierStyleCrossRef" href="#bib0440">33</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">34 (17–70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (15mg/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gao et al.<a class="elsevierStyleCrossRef" href="#bib0380">21</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="4" align="left" valign="top">RE</td><td class="td" title="table-entry " align="left" valign="top">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Schnider's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands, eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liu et al.<a class="elsevierStyleCrossRef" href="#bib0430">31</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">79 (14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Remifentanil (TCI: Minto's model)+Propofol (TCI: Schnider's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands and gentle shaking \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hokki et al.<a class="elsevierStyleCrossRef" href="#bib0435">32</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">79 (20–99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (1mg/kg/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dropping a bottle \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anderson and Jakobsson<a class="elsevierStyleCrossRef" href="#bib0440">33</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 (23–76) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (15mg/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Schneider et al.<a class="elsevierStyleCrossRef" href="#bib0445">34</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">PSI</td><td class="td" title="table-entry " align="left" valign="top">32 (7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (2.3±1.9mg/min)+Sufentanil (5.6±4.5μg/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ramsay sedation score=6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kuizenga et al.<a class="elsevierStyleCrossRef" href="#bib0450">35</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 39 30 42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Schnider's model) Sevoflurane (0.5–4.5vol%) Propofol (TCI: Schnider's model)+Remifentanil (TCI: Minto's model) Sevoflurane (0.5–4.5vol%)+Remifentanil (TCI: Minto's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MOAAS=2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pilge et al.<a class="elsevierStyleCrossRef" href="#bib0455">36</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="4" align="left" valign="top">CSI</td><td class="td" title="table-entry " align="left" valign="top">71.2 (18.1) 58.5 (11.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sevoflurane (5vol%)+Remifentanil (0.2μg/kg) Propofol (0.7mg/kg)+Remifentanil (0.2μg/kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sepúlveda et al.<a class="elsevierStyleCrossRef" href="#bib0460">37</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70 (4) 71 (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (1.8mg/kg) Propofol (TCI: Schnider's or Marsh's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anderson et al.<a class="elsevierStyleCrossRef" href="#bib0465">38</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">56 (40–76) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (15mg/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cortínez et al.<a class="elsevierStyleCrossRef" href="#bib0425">30</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58.7 (55.1–62.2) 64.2 (60.6–67.8) 72.6 (68.7–76.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (300mL/h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eyelash reflex Verbal commands Drop a syringe \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weber et al.<a class="elsevierStyleCrossRef" href="#bib0470">39</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Narcotrend</td><td class="td" title="table-entry " align="left" valign="top">58.3 (17.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Remifentanil (1μg/kg)+Propofol (2mg/kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tan et al.<a class="elsevierStyleCrossRef" href="#bib0475">40</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47 (7.2) 44.3 (8.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Marsh's model) Sevoflurane 8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Litvan et al.<a class="elsevierStyleCrossRef" href="#bib0480">41</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IoC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47.3 (3.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sevoflurane 8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OAAS less than 1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Melia et al.<a class="elsevierStyleCrossRef" href="#bib0485">42</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="4" align="left" valign="top">qCon</td><td class="td" title="table-entry " align="left" valign="top">67.72 (17.88) 58.27 (16.80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Schnider's model)+Remifentanil (TCI: Minto's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands Eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Jesen et al.<a class="elsevierStyleCrossRef" href="#bib0490">43</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Schnider's model)+Remifentanil (TCI: Minto's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Litvan et al.<a class="elsevierStyleCrossRef" href="#bib0480">41</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.33 (6.11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sevoflurane 8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OAAS less than 1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mi et al.<a class="elsevierStyleCrossRef" href="#bib0415">28</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32.9 31.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (30mg/kg/h)+Fentanyl (2μg/kg) Propofol (30mg/kg/h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tang et al.<a class="elsevierStyleCrossRef" href="#bib0495">44</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">AAI</td><td class="td" title="table-entry " align="left" valign="top">57 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No pre-medication Propofol (2mg/kg)+Fentanyl (1μg/kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Verbal commands, eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Struys et al.<a class="elsevierStyleCrossRef" href="#bib0500">45</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 (20–39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Propofol (TCI: Schnider's model) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eyelash reflex \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1955098.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Indicative values of the loss of consciousness moment. 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Do we have today a reliable method to detect the moment of loss of consciousness during induction of general anaesthesia?

¿Contamos actualmente con un método fiable para detectar el momento de pérdida de consciencia durante la inducción de la anestesia?

A.L. Ferreiraa,b,

Corresponding author

ana.leitao.ferreira@gmail.com

Corresponding author.

, C. Nunesb,c, J.G. Mendesa, P. Amorimb

a LAETA/INEGI, Faculdade de Engenharia da Universidade do Porto, Porto, Portugal

b Centro de Investigação Clínica em Anestesiologia, Serviço de Anestesiologia, Centro Hospitalar do Porto, Porto, Portugal

c Departamento de Ciências e Tecnologia, Universidade Aberta, Porto, Portugal

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">General anaesthesia is a drug-induced&#44; reversible condition that produces unconsciousness&#44; analgesia&#44; amnesia and akinesia while maintaining physiological stability&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">1</span></a> Of all behavioural states&#44; unconsciousness is perhaps the most fascinating&#46; Unconsciousness can be achieved by altering the patient&#39;s level of arousal and&#47;or cognition by the administration of anaesthetic drugs&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Induction of anaesthesia may be performed intravenously&#44; using a constant rate or intermittent infusion &#40;bolus&#41;&#44; or by using a target-controlled infusion &#40;TCI&#41; system&#46; TCI systems administer drugs based on the simulated concentration for a specific patient&#44; usually taking into account age&#44; weight&#44; height and gender&#46; These systems continuously simulate the drug concentration in the human body&#44; and thus control drug administration either by effect-site or by plasma concentration targeting&#46; This means that the anaesthesiologist may choose the drug target concentration for that specific patient based on the simulated expected response&#44; and administer the necessary dose to achieve the desired target automatically&#46; TCI systems have been implemented in some commercially available electronic syringe pumps&#44; and may be used in clinical practice&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">There are various pharmacokinetic &#40;PK&#41; models for the use of drugs in TCI&#44; while manual infusion can be performed with or without an initial bolus&#46; However&#44; if an initial bolus is not administered&#44; more time will be needed to achieve the desired hypnotic effect&#46; For the use of propofol in TCI&#44; the most widely used PK models are Marsh&#39;s<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">2</span></a> and Schnider&#39;s&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">3</span></a> For remifentanil&#44; fentanyl&#47;alfentanil and sufentanil&#44; the most widely used PK models are Minto&#39;s&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">4</span></a> Shafer&#39;s<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">5</span></a> and Hudson&#39;s&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">6</span></a> respectively&#46; Although TCI systems are sold in several countries&#44; they have not been approved by the US Food and Drug Administration &#40;FDA&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Loss of consciousness &#40;LOC&#41; occurs during the induction of general anaesthesia&#46; Detecting the moment the patient loses consciousness is important in general anaesthesia induction&#46; Identifying the exact moment of LOC will determine the individual response of each patient to the hypnotic&#44; and will provide important information to guide the infusion rate required to maintain an adequate level of anaesthesia&#44; ensuring safe and an effective care&#46; This will help to prevent intraoperative awareness and overdose&#44; two serious and frequently preventable problems that have caught the attention of clinicians and patients alike&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Intraoperative awareness occurs when a patient under general anaesthesia regains consciousness with recall during intraoperative events&#46; It is usually the result of insufficient hypnotics&#44; and is considered a very traumatic experience that causes long term morbidity in some patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">2&#44;3</span></a> The incidence of awareness established by large multicentre studies was approximately 1&#8211;2 per 1000 cases&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">7</span></a> Moreover&#44; awareness during anaesthesia is grounds for compensation claims&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">8</span></a> even when they may depend on social or cultural factors&#46; There are no recent studies analysing this phenomenon&#44; and the medical and legal consequences of intraoperative awareness have yet to be clarified&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Overdose occurs when the patient receives too much hypnotic drug&#44; and may be caused by overshooting the control system&#44; which is a phenomenon that occurs due to another important factor known as hysteresis&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">9</span></a> For better understanding of this phenomena&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a and b presents an example of a simulation made for an infusion rate of propofol of 1200<span class="elsevierStyleHsp" style=""></span>mL&#47;h and 200<span class="elsevierStyleHsp" style=""></span>mL&#47;h until LOC&#44; respectively&#46; Hysteresis is the time delay between peak plasmatic concentration &#40;Cp&#41; and peak effect-site concentration &#40;Ce&#41;&#46; This leads to an increase in Ce&#44; even after infusion has stopped&#46; The difference between the maximum value of Ce and the effective Ce at LOC is then described as overshoot&#46; The magnitude of the overshoot and hysteresis depend on the pharmacokinetic model&#46; Overdose may lead to severe brain stem or medullary depression&#59; this can result in respiratory and cardiovascular collapse&#44; which can be fatal&#46; From a pharmacological point of view&#44; excessive hypnotic drug dosages will increase the probability of delayed recovery due to accumulation of anaesthetic drugs in the fatty tissues&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">10</span></a> The importance of administering hypnotics slowly to avoid overdose is widely accepted&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">11</span></a> Studies have shown that the required doses for anaesthesia onset were affected by changes in the rate of injection&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">11&#44;12</span></a> The use of a slow infusion rate results in longer induction time&#44; but requires a lower total dose&#44; and reduces the incidence of apnoea and loss of blood pressure&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">13</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">This is why it is so important to control the level of anaesthesia during routine anaesthesia&#46; However&#44; because depth of anaesthesia has yet to be clearly defined&#44; adequate anaesthesia control remains elusive&#46; In the absence of an incontrovertible definition of depth of anaesthesia&#44; a variety of methods for the assessment of the hypnotic component of anaesthesia have been developed&#46; It is presented in the work of Rodr&#237;guez et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">14</span></a> in an excellent&#44; detailed&#44; non-systematic review&#44; analyze the usefulness of hypnotic depth monitoring&#46; Anaesthesia monitoring includes both subjective and&#47;or objective methods&#46; Subjective methods are based on movement and autonomic response to stimuli&#44; and rely on the opinion and experience of the anaesthesiologist&#46; Objective methods rely on the sensitivity and accuracy of a monitor&#46; A detailed description of subjective and objectives methods to assess the hypnotic component of anaesthesia is presented in the state of the knowledge section of this paper&#46; Despite the existence of a variety of methods to assess the hypnotic component of anaesthesia&#44; there is no fail-safe way of ascertaining when the patient has passed from the conscious to the unconscious state&#46; Identifying the precise moment of LOC during the induction phase of general anaesthesia is extremely important&#44; because it will determine the dose of hypnotic drugs required for each patient&#44; and will provide important information to guide the infusion rate needed to maintain an adequate level of anaesthesia&#44; ensuring safe and effective care&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">This review gives an overview of the current state of the knowledge on anaesthesia monitoring systems and detection of drug-induced loss of consciousness&#44; from the first clinical signs in anaesthesia to the latest monitoring technologies&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Methods to assess the hypnotic component of anaesthesia</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Subjective methods</span><p id="par0045" class="elsevierStylePara elsevierViewall">During induction of anaesthesia&#44; a dichotomous &#8220;all-or-nothing&#8221; assessment of responsiveness can be performed in clinical practice to determine if a patient is conscious or unconscious&#46; This dichotomous assessment involves the isolated forearm technique &#40;IFT&#41;&#58; a tourniquet is placed on the patient&#39;s forearm with the cannula placed proximal to this tourniquet or on the other arm&#46; During anaesthesia&#44; the patient is asked to squeezes their hand&#44; indicating that they may be awake and able to interact&#44; until they no longer respond&#46; Despite being a simple technique and an interesting research tool&#44; the IFT has limitations as a monitor of depth of anaesthesia&#44; namely&#44; very low sensitivity and specificity&#46; Since the introduction of muscle relaxants&#44; the levels of anaesthesia needed to prevent movement in patients are far higher than those usually used&#59; patients have reported hearing commands to move the isolated arm&#44; but were unable to do so&#44; even though nerve stimulation would suggest that the arm was not paralyzed&#44; interpreting the non-specific startle response as a level of consciousness&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Loss of response to name calling&#44; to verbal commands&#44; or to a painful stimulus and loss of eyelash reflex are also used&#58; the anaesthetist repeats the stimulus at regular intervals until the patient no longer responds&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The Modified Observer&#39;s Assessment of Alertness and Sedation Scale &#40;OAA&#47;S&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">15</span></a> derived from the original Observer&#39;s Assessment of Alertness&#47;Sedation scale&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">15</span></a> originally validated for use with midazolam&#44; was introduced to standardize the clinical signs of hypnotic drug onset&#46; The OAAS describes the level of sedation on a 0&#8211;5 numerical scale&#44; where the observer rates the patient&#39;s responsiveness&#44; speech and facial expression&#47;eye movements&#46; The modified form uses only the responsiveness component of the original scale &#91;Unresponsive &#40;1&#41;&#8211;Awake &#40;5&#41;&#93;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">These clinical observations are used in daily practice due to their simplicity&#46; However&#44; they are very imprecise and depend on the patient&#39;s collaboration&#46; Clinical signs are based on a voluntary act by the patient and often fail because patients loose critical judgement before losing consciousness&#46; Besides that&#44; as the dose of hypnotic is increased during induction&#44; the patient may enter a state of paradoxical excitation because the drug is intended to induce unconsciousness&#44; but the stimulus induces excitation instead&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objective methods</span><p id="par0065" class="elsevierStylePara elsevierViewall">The limitations of clinical observations of anaesthetic drug effect prompted the development of continuous monitors of the hypnotic component of anaesthesia&#46; The transition from consciousness to unconsciousness occurs in the brain&#59; therefore&#44; the level of anaesthesia is measured on the main target organ of anaesthesia&#44; the brain&#46; Electroencephalography &#40;EEG&#41; is used to monitor the electrical activity of the brain during anaesthesia by placing electrodes on the forehead of the patient&#46; There are two types of electrical signal&#58; those that process spontaneous EEG activity&#44; and electromyography &#40;EMG&#41;&#44; which is based on evoked potentials &#40;EP&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">EEG records spontaneous electrical activity in the brain&#44; which may be measured using non-invasive electrodes attached to several positions on the patient&#39;s head &#40;an international electrode placement system is available<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">16</span></a>&#41;&#46; In general&#44; anaesthetics produce a frequency shift in the EEG signal&#44; from high to low frequencies&#44; and an increase in the EEG signal amplitude&#44; creating an EEG signal with synchronous properties&#46; Typically&#44; the EEG spectrum is divided into five frequency bands called delta &#40;0&#46;5&#8211;4<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#44; theta &#40;4&#8211;8<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#44; alpha &#40;8&#8211;13<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#44; beta &#40;13&#8211;30<span class="elsevierStyleHsp" style=""></span>Hz&#41; and gamma &#40;&#62;30<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#46; Each band behaves differently under the effect of hypnotics&#44; depending on the type of anaesthetic drug administered&#46; Propofol&#44; the most widely used hypnotic drug for general anaesthesia&#44; changes the EEG from a low-voltage&#44; high-frequency awake signal to a progressive high-amplitude&#44; low-frequency signal&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">EPs are detected by electrodes that are positioned over the primary receiving area for a visual&#44; auditory or somatosensory stimulus&#46; The patient is subjected to a large number of repeated stimuli and the EEG is recorded during a fixed period after each one&#46; The signal is then amplified before the EPs are obtained by taking the average of all responses&#46; All EP responses are described in terms of latency &#40;the time from the stimulus until the response&#41; and amplitude &#40;the size of the response&#41;&#46; Auditory evoked potentials &#40;AEP&#41; are the most widely used EPs to evaluate general anaesthesia&#46; A functional auditory system is the basic requirement for AEP analysis&#46; According to latencies&#44; the AEP is divided into three components&#58; early component &#40;latencies &#60;10<span class="elsevierStyleHsp" style=""></span>ms&#41;&#44; middle component &#40;latencies 10&#8211;50<span class="elsevierStyleHsp" style=""></span>ms&#41; and late component &#40;latencies &#62;50<span class="elsevierStyleHsp" style=""></span>ms&#41;&#46; The early component is relatively resistant to the effects of anaesthesia while the late component disappears with low concentrations of anaesthetic&#46; During anaesthesia&#44; the middle component increases in latency and decreases in amplitude&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Studies have provided moderate-quality evidence that optimized anaesthesia guided by EEG or EPs indices probably reduces the risk of postoperative delirium in patients aged 60 years or over undergoing non-cardiac surgical and non-neurosurgical procedures&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">17</span></a> and reduces the risk of patient awareness during surgical procedures&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">18</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">There are many different EEG-based depth-of-anaesthesia monitors that provide anaesthesia indexes&#44; including the Bispectral Index System Monitor &#40;BIS Monitor&#59; Covidien&#44; USA&#41;&#59; Entropy Module &#40;GE Healthcare&#44; USA&#41;&#59; Narcotrend &#40;MonitorTechnik&#44; Germany&#41;&#59; Patient State Index Monitor&#44; SEDLine &#40;Masimo&#44; USA&#41;&#59; Cerebral State Monitor &#40;Danmeter&#44; Denmark&#41;&#59; loC-View Monitor &#40;Aircraft Medical&#44; Barcelona&#44; Spain&#41;&#59; qCon &#40;Quantium Medical&#44; Spain&#41; and AEP Monitor &#40;Danmeter&#44; Denmark&#41;&#46; In general&#44; commercial depth-of-anaesthesia monitors use a dimensionless monotonic index as a measure of depth of anaesthesia&#44; typically scaled from 100 &#40;awake state&#41; to 0 &#40;deep coma&#41;&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Bispectral index &#40;BIS&#41;</span><p id="par0090" class="elsevierStylePara elsevierViewall">The bispectral index &#40;BIS&#41; combines Fast Fourier Transformation &#40;FFT&#41; with an EEG quadratic analysis model&#44; the bispectral analysis&#46; The BIS consists of the following four subcomponents&#58; the bispectral component SyncFastSlow log &#40;bispectrum &#91;0&#46;5&#8211;47<span class="elsevierStyleHsp" style=""></span>Hz&#93;&#47;bispectrum&#91;40&#8211;47<span class="elsevierStyleHsp" style=""></span>Hz&#93;&#41;&#44; the BetaRatio spectral component log &#40;power &#91;30&#8211;47<span class="elsevierStyleHsp" style=""></span>Hz&#93;&#47;power &#91;11&#8211;20<span class="elsevierStyleHsp" style=""></span>Hz&#93;&#41;&#44; the burst suppression ratio &#40;BSR&#41; and the QUAZI suppression component&#46; The resulting bispectral index&#44; BIS&#44; is a nonlinear combination of these four sub-parameters&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Entropy module</span><p id="par0095" class="elsevierStylePara elsevierViewall">Entropy is by definition a measure of disorder&#44; irregularity&#44; complexity and signal prediction&#46; During general anaesthesia&#44; the entropy module relies on a method of assessing the degree of irregularity in EEG signals&#44; which changes from irregular to more regular patterns as anaesthesia deepens&#46; The entropy module calculates two parameters&#58; response entropy &#40;RE&#41;&#44; shannon entropy of the power spectrum &#40;0&#46;8&#8211;47<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#44; and state entropy &#40;SE&#41;&#44; shannon entropy of the power spectrum &#40;0&#46;8&#8211;32<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Narcotrend</span><p id="par0100" class="elsevierStylePara elsevierViewall">The Narcotrend monitor automatically analyses raw EEG data using spectral analysis to produce six states of hypnosis&#44; which are then translated into 15 different patterns displayed during anaesthesia&#46; Each of these stages is used to calculate the narcotrend index from a set of EEG parameters&#44; including spectrum&#44; entropy and autoregression&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Patient state index &#40;PSI&#41;&#44; SEDLine</span><p id="par0105" class="elsevierStylePara elsevierViewall">The SedLine monitor measures the effects of anaesthesia and sedation by monitoring both sides of the brain&#39;s electrical activity to enable more individualized titration and improve the care of patients under anaesthesia or sedation&#46; The result is a patient state index &#40;PSI&#41; value&#44; which is calculated using an algorithm that combines several parameters of frequency analysis&#58; absolute power gradient between frontopolar and vertex regions in the gamma band&#59; absolute power changes between midline and central regions in beta and between midline frontal and parietal regions in the alpha frequency&#59; total spectral power &#40;0&#46;5&#8211;50<span class="elsevierStyleHsp" style=""></span>Hz&#41; in the frontopolar region&#59; mean frequency of the total spectrum in midline frontal region&#59; absolute power in delta frequency at the vertex and posterior relative power in the slow delta range&#46; All parameters are included in a plausibility analysis to calculate the PSI&#46; Additionally&#44; surrogate analysis is performed by calculating burst suppression and arousal detection&#44; which means that these parameters modulate PSI index if signal quality is poor&#46; Finally&#44; before the index is displayed&#44; it is post-processed with an averaging algorithm to provide a more stable output&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Cerebral state monitor</span><p id="par0110" class="elsevierStylePara elsevierViewall">The cerebral state monitor combines four sub-parameters extracted from the EEG to calculate a cerebral state index &#40;CSI&#41;&#46; These parameters are&#58; the spectral parameters beta ratio log<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">E</span>&#40;30&#8211;42&#46;5<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#47;<span class="elsevierStyleItalic">E</span>&#40;11&#8211;21<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#44; alpha ratio log<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">E</span>&#40;30&#8211;42&#46;5<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#47;<span class="elsevierStyleItalic">E</span>&#40;6&#8211;12<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#44; the beta-alpha ratio log<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">E</span>&#40;6&#8211;12<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#47;<span class="elsevierStyleItalic">E</span>&#40;11&#8211;21<span class="elsevierStyleHsp" style=""></span>Hz&#41;&#44; and the burst suppression ratio&#46; All parameters are then fed to a fuzzy inference logic system to calculate the CSI index&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">IoC-view monitor &#40;IoC&#41;</span><p id="par0115" class="elsevierStylePara elsevierViewall">The IoC-view monitor displays the index of consciousness &#40;IoC&#41; using three sub-parameters&#58; symbolic dynamics&#44; which detects the complex non-linear properties of the EEG&#59; beta ratio &#40;during superficial anaesthesia&#41;&#44; and the amount of burst suppression of the EEG &#40;during deep anaesthesia&#41;&#46; All these parameters are then combined through a set of fuzzy logic rules into a single index&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">qCon</span><p id="par0120" class="elsevierStylePara elsevierViewall">The anaesthetic depth monitor qCon was developed to determine the probability that a patient will respond to pain and nociception during different levels of arousal&#46; It defines an index of consciousness &#40;qCon&#41; from EEG raw data&#44; calculated using adaptive fuzzy inference systems &#40;ANFIS&#41;&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">AEP monitor</span><p id="par0125" class="elsevierStylePara elsevierViewall">The auditory evoked potentials &#40;AEP&#41; monitor uses autoregressive models with exogenous input &#40;ARX&#41; to detect the AEP and then calculate the AEP &#8211; ARX &#8211; Index &#40;or AAI autoregressive index&#41;&#46; AEPs are detected in the frequency range 25&#8211;65<span class="elsevierStyleHsp" style=""></span>Hz&#44; using ARX&#46; After ARX analysis&#44; the reconstructed amplitudes and latencies are evaluated&#46; Meanwhile&#44; an undisclosed algorithm is used to analyze the EEG in the frequency band between 3 and 47<span class="elsevierStyleHsp" style=""></span>Hz&#46; The decision how the AAI is constructed from AEP and EEG analyses is made by the weighting function&#44; based on the signal-to-noise ratio&#46; The AEP index &#40;AEPex&#41; is exclusively based on an AEP parameter that is the morphology of the AEP signal&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the recommended ranges for the aforementioned indices of the hypnotic component of anaesthesia&#46; As can be seen&#44; these ranges differ from index to index&#46; BIS&#44; entropy&#44; CSI and IoC indicate that anaesthesia will be adequate at values between 40 and 60&#44; the other indices consider different ranges&#46; Although multiple indices have been developed&#44; some incorporated in commercialized devices and others only developed for academic purposes&#44; only BIS and entropy have had a significant commercial impact&#46; On the one hand&#44; spontaneous EEG monitoring has several confounding factors that may impede interpretation of EEG-derived indices and lead to erroneous conclusions&#46; These include artefacts from the surrounding environment&#44; interindividual variability in terms of baseline EEG characteristics&#44; erroneous site of EEG recording&#44; delay between EEG acquisition and value display&#44; specific clinical conditions&#44; and the effect of the interactions between different anaesthetics&#46; On the other hand&#44; the use of AEPs is not very reproducible&#44; as there are large interindividual differences of response to different anaesthetic regimens&#46; Additionally&#44; despite the fact that anaesthesiologists care for thousands of patients daily&#44; only about half use depth of anaesthesia monitors&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Methods</span><p id="par0135" class="elsevierStylePara elsevierViewall">Studies containing trials with subjects receiving intravenous drugs for anaesthesia in which the authors reported out the values of the monitoring indexes at the time of LOC were considered&#46; Studies were identified by searching electronic databases for reference articles&#46; No limits were applied for language&#44; and foreign papers were translated&#46; The PubMed &#40;2004&#8211;present&#41; and IEEE Xplore Digital Library &#40;2004&#8211;present&#41; databases were searched&#46; The last search was run on 30 April 2018&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The search was performed using the following terms &#40;in all clinical trials and databases&#41;&#58; death due to anaesthesia&#44; monitoring&#44; loss of consciousness&#44; clinical trials&#44; humans&#44; BIS&#44; and each of the existing indexes&#46; The following information was extracted from each trial&#58; &#40;1&#41; the inclusion and exclusion criteria&#59; &#40;2&#41; anaesthetic protocol used for induction&#44; inclusion of pre-medication&#44; type of drugs&#44; dose&#44; and pharmacokinetic models&#59; &#40;4&#41; method used to assess the moment of LOC&#44; including the index used&#59; and finally&#44; &#40;5&#41; values of the different indexes at LOC&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In all studies the primary outcome assessed was the value of the hypnotic index at the moment of LOC&#46; Secondary outcomes were the anaesthetic protocol and the clinical evaluation of LOC&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Quantitative analyses were performed in order to compare the values of the different indexes at LOC within the several anaesthetic protocols and clinical assessment of LOC&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0155" class="elsevierStylePara elsevierViewall">A total of 35 studies were identified for inclusion in this review&#46; The database search provided a total of 304 studies&#46; After removing duplicates&#44; 145 articles remained&#46; Of these&#44; 82 were excluded because after reviewing the abstracts it appeared that these papers clearly did not meet the criteria&#46; Five additional studies were excluded because the full text of the study was not available or the paper could not be accurately translated into English&#46; The full text of the remaining 77 studies was examined in more detail&#46; A total of 42 studies were excluded because they did not meet the inclusion criteria&#46; The main exclusion criterion was the absence of drugs affecting the different depth of anaesthesia monitoring techniques&#58; prior to induction of anaesthesia&#44; patients had not been given pre-medication or other sedatives&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Thirty-five studies met the anaesthetic protocol criteria and were included in the systematic review&#46; No unpublished relevant studies were obtained&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">A summary of included studies reporting the values of each index at the moment of LOC is presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">From the 35 articles analyzed&#44; 12&#44; 8&#44; 2&#44; 4&#44; 2&#44; 1&#44; 4 and 2 studies identified&#44; respectively&#44; BIS&#44; Entropy&#44; PSI&#44; CSI&#44; Narcotrend&#44; IoC&#44; qCon and AAI values at LOC&#46; The average LOC values on BIS vary between 42 and 75&#46;4&#59; for entropy they vary between 34 and 79&#44; for PSI between 30 and 45&#59; for CSI between 56 and 72&#46;6&#44; for Narcotrend between 44&#46;3 and 58&#46;3&#44; for qCon between 21&#46;33 and 67&#46;72&#59; and for AAI between 30 and 57&#46; In most cases&#44; the deviation from the average value is very significate&#44; which means that there is greater interindividual variability&#46; It is also important to note the strong correlation between these values and the anaesthetic protocol used&#58; at LOC&#44; only hypnotics&#44; both hypnotics and analgesics&#44; or only analgesics may be present&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Different index values are also obtained according to the clinical criteria used to determine the moment of LOC&#46; These criteria&#44; therefore&#44; not coincident in time&#44; so a systematic error may occur by associating all the index values to the same moment of LOC&#46; Considerable variations in the values associated with LOC are also observed even when the same clinical criteria and the same anaesthetic protocol are used&#46; None of the studies that analyzed the entropy index used the OAAS scale to determine the moment of LOC&#46; Only one study was found to use the IoC at LOC&#46; Some indices have extremely high sensitivity and specificity for identifying consciousness and unconsciousness&#44; but none can detect the transition between both states or detect the moment of LOC precisely&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0180" class="elsevierStylePara elsevierViewall">Closed-loop systems have been developed to control administration of drugs during anaesthesia using BIS as a target for control&#46; Studies have investigated the performance of the seven different closed-loop systems&#58; CLADS&#44;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">46</span></a> Rugloop&#44;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">47</span></a> HSS&#44;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">48</span></a> Infusion Toolbox 95&#44;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">49</span></a> Self-Designed Interface&#44;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">50</span></a> McSleepy&#44;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">51</span></a> CONCERT-CL<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">52</span></a> and Monitor&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">53</span></a> Compared with manual control&#44; these BIS-guided systems reduce propofol requirements during induction&#44; are more efficient at maintaining a target depth of anaesthesia&#44; and reduce recovery time&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">54</span></a> Given the interindividual variability observed from the studies presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> for the index values at LOC&#44; the adequacy of these closed-loop systems is questionable&#44; since all assume that the same amount of drug is administrated to all patients&#44; irrespective of the anaesthesia protocol&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">It is also important to point out that the indices used in the studies presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> have three major drawbacks&#58; the recordings from the monitors include artefacts from movement&#44; electrical inference&#44; noise from electrodes&#44; and quantification errors in analogue to digital conversion&#59; they require some time to process the algorithms to compute the indices&#44; and this may take several seconds or even minutes&#44; which during induction can result in excessive anaesthesia with clinical consequences&#59; and&#44; although the raw EEG and its frequency components can give direct&#44; detailed information about brain states under anaesthesia&#44; most current brain monitoring systems reduce the complex EEG signal to a single number that could not accurately reflect the underlying physiological processes that create the patterns&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Propofol is one of the most commonly used anaesthetic drugs&#46; An important study&#44; Purdon et al&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">55</span></a> took highly detailed EEG readings from 10 healthy volunteers during propofol-induced general anaesthesia&#44; in which dosage was slowly increased to a target level then slowly decreased while study participants listened to pre-recorded sounds at four-second intervals&#44; and were asked to identify the type of sound they heard by pressing a button&#46; A loss of response to clicks indicated the onset of sedation&#44; and a persistent loss of response to words was considered loss of consciousness&#46; The readings identified characteristic changes in EEG patterns that indicated sedation&#44; loss and return of consciousness&#44; and a state of profound unconsciousness&#46; One particular pattern&#44; which the researchers called &#8220;trough-max&#8221; occurred during transitions in consciousness&#46; The implications of this study are huge&#44; because it would mean that the authors have found a brain state where they know patients will be unconscious&#44; and could monitor the brain state in the operating room using EEG&#46; With these fundamental neurophysiological markers of the sedative and unconscious states under propofol and with some existing EEG equipment&#44; it may be possible to start monitoring EEG signatures when administering propofol&#46; This may be seen as an introduction to new control systems endpoints&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusion</span><p id="par0195" class="elsevierStylePara elsevierViewall">In conclusion&#44; clinical signs allow anaesthesiologists to decide whether a patient is &#40;or is not&#41; unconscious during induction of hypnotics under general anaesthesia&#44; but they do not provide information on the precise time when the transition from consciousness to unconsciousness occurs&#46; This is because either patients do not lose all reflexes simultaneously&#44; or the verification of such signs is in most cases evaluated discontinuously&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">With anaesthesia monitors based on EEG and AEP&#44; continuously monitoring response signals allow anaesthesiologists to directly evaluate the patient&#39;s brain activity over time&#46; However&#44; studies show that these monitors fail in identifying the instant at which consciousness is lost&#46; The computation delays&#44; the difficulty in separating the different electrical signals produced by the body&#44; and the large interindividual variability of the monitor indices mean that these devices are good indicators of the evolution of the patient during the procedure&#44; but cannot indicate the moment of loss of consciousness&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Other studies show that combining depth-of-anaesthesia monitors with the information provided by the clinical signs reduced the incidence of intraoperative awakening and overdosing&#46; However&#44; there is still a need for a system that detects the exact moment in which the patient loses consciousness&#46; Identifying this moment during the induction phase of general anaesthesia will determine the dose of hypnotics required by each patient&#44; and will provide important information to guide the infusion rate required to maintain an adequate level of anaesthesia&#44; ensuring safe and effective care&#46; This could open the door to automated systems based solely on the patient&#39;s state of consciousness&#44; and could contribute significant advances in the field of anaesthesia itself&#46; Furthermore&#44; detecting the moment the patient loses consciousness is the first step in the development of a fully automated personalized anaesthesia delivery systems based on the conscious state of the patients&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding</span><p id="par0210" class="elsevierStylePara elsevierViewall">Supported by the Funda&#231;&#227;o para a Ci&#234;ncia e Tecnologia with the reference projects SFRH&#47;BD&#47;98915&#47;2013 and UID&#47;SEM&#47;50022&#47;2013&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0215" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests&#46;</p></span></span>"
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          "identificador" => "sec0005"
          "titulo" => "Introduction"
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          "identificador" => "sec0010"
          "titulo" => "Methods to assess the hypnotic component of anaesthesia"
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            0 => array:2 [
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              "titulo" => "Subjective methods"
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                  "identificador" => "sec0025"
                  "titulo" => "Bispectral index &#40;BIS&#41;"
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                1 => array:2 [
                  "identificador" => "sec0030"
                  "titulo" => "Entropy module"
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                2 => array:2 [
                  "identificador" => "sec0035"
                  "titulo" => "Narcotrend"
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                3 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Patient state index &#40;PSI&#41;&#44; SEDLine"
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                4 => array:2 [
                  "identificador" => "sec0045"
                  "titulo" => "Cerebral state monitor"
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                5 => array:2 [
                  "identificador" => "sec0050"
                  "titulo" => "IoC-view monitor &#40;IoC&#41;"
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                6 => array:2 [
                  "identificador" => "sec0055"
                  "titulo" => "qCon"
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                7 => array:2 [
                  "identificador" => "sec0060"
                  "titulo" => "AEP monitor"
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          "titulo" => "Acknowledgments"
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          "titulo" => "References"
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    "fechaRecibido" => "2018-02-08"
    "fechaAceptado" => "2018-06-13"
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          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "General anaesthesia"
            1 => "Loss of consciousness"
            2 => "Depth of anaesthesia"
            3 => "Patient monitoring"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1075749"
          "palabras" => array:4 [
            0 => "Anestesia general"
            1 => "P&#233;rdida de consciencia"
            2 => "Profundidad de la anestesia"
            3 => "Monitorizaci&#243;n del paciente"
          ]
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">This review aims to give an overview of the current state of monitoring depth of anaesthesia and detecting the moment of loss of consciousness&#44; from the first clinical signs involved in anaesthesia to the latest technologies used in this area&#46; Such techniques are extremely important for the development of automatic systems for anaesthesia control&#44; including preventing intraoperative awareness episodes and overdoses&#46; A search in the databases Pubmed and IEEE Xplore was performed using terms such as anaesthetic monitoring&#44; depth of anaesthesia&#44; loss of consciousness&#44; as well as anaesthesia indexes&#44; namely BIS&#46; Despite the several methods capable of monitoring the hypnotic state of anaesthesia&#44; there is still no methodology to accurately detect the moment of loss of consciousness during induction of general anaesthesia&#46;</p></span>"
      ]
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Esta revisi&#243;n pretende ofrecer una visi&#243;n general del estado de conocimiento actual sobre la monitorizaci&#243;n de la profundidad anest&#233;sica y la detecci&#243;n del momento de p&#233;rdida de consciencia&#44; desde los primeros signos cl&#237;nicos implicados en la anestesia hasta las &#250;ltimas tecnolog&#237;as utilizadas en esta &#225;rea&#46; Tales t&#233;cnicas son extremadamente importantes para el desarrollo de sistemas autom&#225;ticos de control de la anestesia y para prevenir episodios de percepci&#243;n intraoperatoria y sobredosis&#46; Realizamos investigaciones en bases de datos &#40;Pubmed&#44; IEEE Xplore&#41; utilizando t&#233;rminos como control anest&#233;sico&#44; profundidad de la anestesia&#44; p&#233;rdida de consciencia&#44; BIS y cada uno de los &#237;ndices existentes&#46; A pesar de los diversos m&#233;todos capaces de controlar el estado hipn&#243;tico de la anestesia&#44; a&#250;n no existe una metodolog&#237;a que detecte con precisi&#243;n el momento de la p&#233;rdida de consciencia durante la inducci&#243;n de la anestesia general&#46;</p></span>"
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    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ferreira AL&#44; Nunes C&#44; Mendes JG&#44; Amorim P&#46; &#191;Contamos actualmente con un m&#233;todo fiable para detectar el momento de p&#233;rdida de consciencia durante la inducci&#243;n de la anestesia&#63; Rev Esp Anestesiol Reanim&#46; 2019&#59;66&#58;93&#8211;103&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar1005">This article is part of the Anaesthesiology and Resuscitation Continuing Medical Education Program&#46; An evaluation of the questions on this article can be made through the Internet by accessing the Education Section of the following web page&#58;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Overshoot and hysteresis between plasma and effect-site concentration of propofol &#40;mg&#47;mL&#41; versus time for different infusion rates of propofol&#58; &#40;A&#41; 1200<span class="elsevierStyleHsp" style=""></span>mL&#47;h until LOC &#40;14<span class="elsevierStyleHsp" style=""></span>s&#41;&#59; &#40;B&#41; 200<span class="elsevierStyleHsp" style=""></span>mL&#47;h until LOC &#40;2<span class="elsevierStyleHsp" style=""></span>min&#41;&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="9" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Depth of anaesthesia indexes</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Hypnotic component of anaesthesia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BIS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Entropy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Narcotrend&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PSI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CSI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IoC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">qCon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AAI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AEPex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EEG suppression&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Burst suppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deep anaesthesia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#8211;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#8211;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#8211;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deep anaesthesia with burst suppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#8211;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anaesthesia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#8211;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#8211;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#8211;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&#8211;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#8211;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#8211;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#8211;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#8211;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#8211;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sedation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#8211;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&#8211;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&#8211;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#8211;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#8211;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#8211;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&#8211;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Awake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80 &#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#8211;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">90&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Recommended ranges for the different EEG-based indices of the hypnotic component of anaesthesia&#46; Values are dimensionless and range from 0 to 100&#46;</p>"
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                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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Source&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Depth of anaesthesia index&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Values at loss of consciousness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Anaesthetic technique&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical judgement of loss of consciousness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Xu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BIS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58 &#40;58&#8211;59&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Marsh&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Remifentanil &#40;TCI&#58; Minto&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OAAS less than 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&#46;2 &#40;60&#46;3&#8211;66&#46;9&#41;<br>71&#46;1 &#40;67&#46;6&#8211;74&#46;5&#41;<br>71&#46;4 &#40;68&#46;9&#8211;73&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Marsh&#39;s model&#41;<br>Dexmedetomidine &#40;0&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;TCI&#58; Marsh&#39;s model&#41;<br>Dexmedetomidine &#40;1&#46;0<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;TCI&#58; Marsh&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OAAS less than 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gao et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Schnider&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal command or eyelash 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lysakowski et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58 &#40;40&#8211;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Schnider&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OAAS less than 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kaneda et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Etomidate 0&#46;2&#37; &#40;300<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eyelash 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Koppens et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Remifentanil &#40;TCI&#58; Minto&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;600<span class="elsevierStyleHsp" style=""></span>mL&#47;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OAAS less than 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kanata et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#46;5 &#40;18&#46;7&#41;<br>73&#46;8 &#40;15&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ropivacaine 0&#46;2&#37; &#43; Propofol &#40;TCI&#58; Marsh&#39;s model&#41;<br>Ropivacaine 1&#37;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;TCI&#58; Marsh&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&#44; dropping a syringe or eyelash 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Karalapillai et al&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60 &#40;15&#41;<br>75 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Marsh&#39;s model&#41;<br>Propofol &#40;TCI&#58; Marsh&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NO<span class="elsevierStyleInf">2</span> 67&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eyelash 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gonz&#225;lez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">69&#46;5 &#40;15&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Remifentanil &#40;TCI&#58; Minto&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;Schnider&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands and tap on the hand&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&#46;1<br>60&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Fentanyl &#40;2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;<br>Propofol &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lysakowski et al&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">29</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&#46;5 &#40;58&#8211;63&#41;<br>69&#46;5 &#40;67&#46;8&#8211;71&#46;1&#41;<br>74&#46;6 &#40;72&#46;9&#8211;76&#46;2&#41;<br>66&#46;2 &#40;62&#46;6&#8211;69&#46;1&#41;<br>74&#46;6 &#40;72&#46;9&#8211;76&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Placebo<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;Marsh&#39;s model&#41;<br>Fentanyl &#40;TCI&#58; Shafer&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;Marsh&#39;s model&#41;<br>Alfentanil &#40;TCI&#58; Shafer&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;Marsh&#39;s model&#41;<br>Sufentanil &#40;TCI&#58; Hudson&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;Marsh&#39;s model&#41;<br>Remifentanil &#40;TCI&#58; Minto&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;Marsh&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OAAS less than 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cort&#237;nez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">30</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46&#46;6 &#40;42&#46;9&#8211;50&#46;4&#41;<br>61&#46;3 &#40;57&#46;3&#8211;65&#46;3&#41;<br>75&#46;4 &#40;70&#46;4&#8211;80&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;300<span class="elsevierStyleHsp" style=""></span>mL&#47;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eyelash reflex<br>Verbal contact<br>Drop a syringe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gao et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">SE</td><td class="td" title="table-entry  " align="left" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Schnider&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal command or eyelash 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">75 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Remifentanil &#40;TCI&#58; Minto&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;TCI&#58; Schnider&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands and gentle shaking&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hokki et al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">67 &#40;5&#8211;89&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dropping a bottle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anderson and Jakobsson<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">34 &#40;17&#8211;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;15<span class="elsevierStyleHsp" style=""></span>mg&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gao et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">RE</td><td class="td" title="table-entry  " align="left" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Schnider&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&#44; eyelash 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">79 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Remifentanil &#40;TCI&#58; Minto&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;TCI&#58; Schnider&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands and gentle shaking&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hokki et al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">79 &#40;20&#8211;99&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dropping a bottle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anderson and Jakobsson<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40 &#40;23&#8211;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;15<span class="elsevierStyleHsp" style=""></span>mg&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Schneider et al&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">PSI</td><td class="td" title="table-entry  " align="left" valign="top">32 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;2&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;9<span class="elsevierStyleHsp" style=""></span>mg&#47;min&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Sufentanil &#40;5&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ramsay sedation score<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kuizenga et al&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45<br>39<br>30<br><br>42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Schnider&#39;s model&#41;<br>Sevoflurane &#40;0&#46;5&#8211;4&#46;5<span class="elsevierStyleHsp" style=""></span>vol&#37;&#41;<br>Propofol &#40;TCI&#58; Schnider&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Remifentanil &#40;TCI&#58; Minto&#39;s model&#41;<br>Sevoflurane &#40;0&#46;5&#8211;4&#46;5<span class="elsevierStyleHsp" style=""></span>vol&#37;&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Remifentanil &#40;TCI&#58; Minto&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MOAAS<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pilge et al&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">CSI</td><td class="td" title="table-entry  " align="left" valign="top">71&#46;2 &#40;18&#46;1&#41;<br>58&#46;5 &#40;11&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sevoflurane &#40;5<span class="elsevierStyleHsp" style=""></span>vol&#37;&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Remifentanil &#40;0&#46;2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;<br>Propofol &#40;0&#46;7<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Remifentanil &#40;0&#46;2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sep&#250;lveda et al&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70 &#40;4&#41;<br>71 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;1&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;<br>Propofol &#40;TCI&#58; Schnider&#39;s or Marsh&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anderson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56 &#40;40&#8211;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;15<span class="elsevierStyleHsp" style=""></span>mg&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cort&#237;nez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">30</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58&#46;7 &#40;55&#46;1&#8211;62&#46;2&#41;<br>64&#46;2 &#40;60&#46;6&#8211;67&#46;8&#41;<br>72&#46;6 &#40;68&#46;7&#8211;76&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;300<span class="elsevierStyleHsp" style=""></span>mL&#47;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eyelash reflex<br>Verbal commands<br>Drop a syringe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weber et al&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Narcotrend</td><td class="td" title="table-entry  " align="left" valign="top">58&#46;3 &#40;17&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Remifentanil &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Propofol &#40;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47 &#40;7&#46;2&#41;<br>44&#46;3 &#40;8&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Marsh&#39;s model&#41;<br>Sevoflurane 8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eyelash 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Litvan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IoC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#46;3 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sevoflurane 8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OAAS less than 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Melia et al&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">42</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">qCon</td><td class="td" title="table-entry  " align="left" valign="top">67&#46;72 &#40;17&#46;88&#41;<br>58&#46;27 &#40;16&#46;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Schnider&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Remifentanil &#40;TCI&#58; Minto&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands<br>Eyelash 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Jesen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Schnider&#39;s model&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Remifentanil &#40;TCI&#58; Minto&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eyelash 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Litvan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#46;33 &#40;6&#46;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sevoflurane 8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OAAS less than 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">32&#46;9<br>31&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Fentanyl &#40;2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;<br>Propofol &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">AAI</td><td class="td" title="table-entry  " align="left" valign="top">57 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No pre-medication<br>Propofol &#40;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Fentanyl &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Verbal commands&#44; eyelash 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="table-entry ; entry_with_role_rowhead " align="left" valign="top">Struys et al&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30 &#40;20&#8211;39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Propofol &#40;TCI&#58; Schnider&#39;s model&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eyelash reflex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Indicative values of the loss of consciousness moment&#46; The values for the loss of consciousness are expressed as &#8220;mean &#40;standard deviation&#41;&#8221;&#44; &#8220;mean &#40;maximum&#8211;minimum&#41;&#8221;&#44; and &#8220;mean&#8221; according to the corresponding authors&#46; BIS<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>bispectral index&#59; SE<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>state entropy&#59; RE<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>response entropy&#59; PSI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>patient state index&#59; CSI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>cerebral state index&#59; IoC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>index of consciousness&#59; AAI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>AEP index&#46;</p>"
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