Semimechanistic models to relate noxious stimulation, movement, and pupillary dilation responses in the presence of opioids.

Intraoperative targeting of the analgesic effect still lacks an optimal solution. Opioids are currently the main drug used to achieve antinociception, and although underdosing can lead to an increased stress response, overdose can also lead to undesirable adverse effects. To better understand how to achieve the optimal analgesic effect of opioids, we studied the influence of remifentanil on the pupillary reflex dilation (PRD) and its relationship with the reflex movement response to a standardized noxious stimulus. The main objective was to generate population pharmacodynamic models relating remifentanil predicted concentrations to movement and to pupillary dilation during general anesthesia. A total of 78 patients undergoing gynecological surgery under general anesthesia were recruited for the study. PRD and movement response to a tetanic stimulus were measured multiple times before and after surgery. We used nonlinear mixed effects modeling to generate a population pharmacodynamic model to describe both the time profiles of PRD and movement responses to noxious stimulation. Our model demonstrated that movement and PRD are equally depressed by remifentanil. Using the developed model, we changed the intensity of stimulation and simulated remifentanil predicted concentrations maximizing the probability of absence of movement response. An estimated effect site concentration of 2 ng/ml of remifentanil was found to inhibit movement to a tetanic stimulation with a probability of 81%.

Bilateral Bispectral Index Monitoring Performance in the Detection of Seizures in Nonanesthetized Epileptic Patients: An Observational Study.

BACKGROUND: The aim of this observational study was to determine whether bilateral bispectral index (BIS) monitoring can detect seizures in epileptic patients. METHODS: Four-channel frontal BIS monitoring and standard 40-channel electroencephalography monitoring were conducted in epileptic patients undergoing evaluation for epilepsy surgery. The BIS numerical value, signal quality index, electromyography, suppression ratio, and color density spectral array were continuously recorded. In patients with electroencephalography-confirmed seizures, the mean value and trend (slope of linear regression) of bilateral BIS monitor parameters were analyzed from 1 minute before to 1 minute after seizure onset. RESULTS: Of 48 patients included in the study, 21 (43.8%) had at least 1 seizure. BIS numerical value was not able to detect focal or focal to bilateral tonic-clonic seizures. Considering all seizures, the only significant differences between recordings 1 minute before and 1 minute after seizure onset were a decrease in the signal quality index slope from 1 hemisphere (0.039±0.297 vs. -0.085±0.321, respectively; P =0.029) and in the mean signal quality index recorded from both hemispheres (left hemisphere: 65.775±30.599 vs. 61.032±26.285; P =0.016 and right hemisphere: 63.244±31.985 vs. 59.837±27.360; 0.029); these differences were not maintained after Hochberg adjustment for multiple comparisons. In seizures occurring during sleep, there was a change in the electromyography slope of 1 hemisphere before and after seizure onset (-0.141±0.176 vs. 0.162±0.140, respectively; P =0.038). There were variable responses in BIS parameters in the 3 patients who developed focal nonconvulsive seizure clusters. CONCLUSION: Bilateral BIS monitoring was not able to detect the occurrence of seizures in epileptic patients.

Refined Multiscale Entropy Using Fuzzy Metrics: Validation and Application to Nociception Assessment.

The refined multiscale entropy (RMSE) approach is commonly applied to assess complexity as a function of the time scale. RMSE is normally based on the computation of sample entropy (SampEn) estimating complexity as conditional entropy. However, SampEn is dependent on the length and standard deviation of the data. Recently, fuzzy entropy (FuzEn) has been proposed, including several refinements, as an alternative to counteract these limitations. In this work, FuzEn, translated FuzEn (TFuzEn), translated-reflected FuzEn (TRFuzEn), inherent FuzEn (IFuzEn), and inherent translated FuzEn (ITFuzEn) were exploited as entropy-based measures in the computation of RMSE and their performance was compared to that of SampEn. FuzEn metrics were applied to synthetic time series of different lengths to evaluate the consistency of the different approaches. In addition, electroencephalograms of patients under sedation-analgesia procedure were analyzed based on the patient's response after the application of painful stimulation, such as nail bed compression or endoscopy tube insertion. Significant differences in FuzEn metrics were observed over simulations and real data as a function of the data length and the pain responses. Findings indicated that FuzEn, when exploited in RMSE applications, showed similar behavior to SampEn in long series, but its consistency was better than that of SampEn in short series both over simulations and real data. Conversely, its variants should be utilized with more caution, especially whether processes exhibit an important deterministic component and/or in nociception prediction at long scales.

Assessment of sedation-analgesia by means of Poincaré analysis of the electroencephalogram.

Monitoring the levels of sedation-analgesia may be helpful for managing patient stress on minimally invasive medical procedures. Monitors based on EEG analysis and designed to assess general anesthesia cannot distinguish reliably between a light and deep sedation. In this work, the Poincaré plot is used as a nonlinear technique applied to EEG signals in order to characterize the levels of sedation-analgesia, according to observed categorical responses that were evaluated by means of Ramsay Sedation Scale (RSS). To study the effect of high frequencies due to EMG activity, three different frequency ranges (FR1=0.5-110 Hz, FR2=0.5-30 Hz and FR3=30-110 Hz) were considered. Indexes from power spectral analysis and plasma concentration of propofol and remifentanil were also compared with the bispectral index BIS. An adaptive Neurofuzzy Inference System was applied to model the interaction of the best indexes with respect to RSS score for each analysis, and leave-one-out cross validation method was used. The ability of the indexes to describe the level of sedation-analgesia, according with the RSS score, was evaluated using the prediction probability (Pk). The results showed that the ratio SD1/SD2FR3 contains useful information about the sedation level, and SD1FR2 and SD2FR2 had the best performance classifying response to noxious stimuli. Models including parameters from Poincaré plot emerge as a good estimator of sedation-analgesia levels.

Modeling Respiratory Depression Induced by Remifentanil and Propofol during Sedation and Analgesia Using a Continuous Noninvasive Measurement of pCO2.

Respiratory depression is a common adverse effect of propofol and remifentanil. We aimed to develop a model for respiratory depressant effects of propofol with remifentanil in patients undergoing endoscopy with sedation. Data were available for 136 patients undergoing endoscopy with sedation. Participants randomly received infusions of propofol and remifentanil. Predicted plasma concentrations, outputted by infusion pumps, were available. Transcutaneous arterial pressure of carbon dioxide (pCO2) was measured. Data were analyzed using nonlinear mixed-effects modeling methods. Covariate relationships were investigated for age, noxious stimuli (endoscopy tube insertion), and A118G genotype for the µ-opioid receptor (OPRM1). Participants had a median (range) age of 64.0 (25.0-88.0) years, weight of 70.0 (35.0-98.0) kg, and height of 164.0 (147.0-190.0) cm. Seven percent were recessive homozygous for OPRM1 polymorphism. An indirect-effect model with a "modulator" compartment best described pCO2 data (P < 0.001) over a direct-effect model. Remifentanil inhibited pCO2 removal with an IC50 of 1.13 ng/ml and first-order rate constant (ke 0) of 0.28 minute(-1). Propofol affected the modulator compartment with an IC50 of 4.97 µg/ml (no effect-site compartment). Propofol IC50 and remifentanil ke 0 were reduced with increasing age. Noxious stimuli and genotype were not significant covariates. An indirect-effect model with a rebound mechanism can describe remifentanil- and propofol-induced changes in pCO2 in patients undergoing noxious procedures. The model may be useful for identifying optimal dosing schedules for these drugs in a combination that provides adequate sedation but avoids respiratory depression.

Evaluation of acceleration and deceleration cardiac processes using phase-rectified signal averaging in healthy and idiopathic dilated cardiomyopathy subjects.

The aim of the present study was to investigate the suitability of the Phase-Rectified Signal Averaging (PRSA) method for improved risk prediction in cardiac patients. Moreover, this technique, which separately evaluates acceleration and deceleration processes of cardiac rhythm, allows the effect of sympathetic and vagal modulations of beat-to-beat intervals to be characterized. Holter recordings of idiopathic dilated cardiomyopathy (IDC) patients were analyzed: high-risk (HR), who suffered sudden cardiac death (SCD) during the follow-up; and low-risk (LR), without any kind of cardiac-related death. Moreover, a control group of healthy subjects was analyzed. PRSA indexes were analyzed, for different time scales T and wavelet scales s, from RR series of 24 h-ECG recordings, awake periods and sleep periods. Also, the behavior of these indexes from simulated data was analyzed and compared with real data results. Outcomes demonstrated the PRSA capacity to significantly discriminate healthy subjects from IDC patients and HR from LR patients on a higher level than traditional temporal and spectral measures. The behavior of PRSA indexes agrees with experimental evidences related to cardiac autonomic modulations. Also, these parameters reflect more regularity of the autonomic nervous system (ANS) in HR patients.

Monitorización de la actividad cerebral: ¿Dónde estamos y hacia dónde debemos dirigirnos? / Monitoring brain activity: Where are we now and in which direction should we move in the future?

Anesthesiology is a medical specialty in which quantification-the capacity to measure-is of major importance. The basic principle of our interventions as anesthesiologists is based on the administration of drugs, the observation of the effect that these drugs have on the patient, and the adjustment of drug delivery depending on the response that is observed. The magnitude ofthis response depends on: 1. Factors directly related to the patient such as their age, physical state, and the medication he/she is taking and, 2. Contextual factors such as the type of surgical procedure, its urgency, the point of time within the procedure, and the complications that can appear (bleeding, hypothermia, state of shock) to cite just a few of the most relevant aspects. Observing, adjusting, and magnitude-they are concepts that imply the possibility of measuring to precisely evaluate how the patient reacts in each and every moment of anesthetic drug delivery process.

Multiscale complexity analysis of the cardiac control identifies asymptomatic and symptomatic patients in long QT syndrome type 1.

The study assesses complexity of the cardiac control directed to the sinus node and to ventricles in long QT syndrome type 1 (LQT1) patients with KCNQ1-A341V mutation. Complexity was assessed via refined multiscale entropy (RMSE) computed over the beat-to-beat variability series of heart period (HP) and QT interval. HP and QT interval were approximated respectively as the temporal distance between two consecutive R-wave peaks and between the R-wave apex and T-wave end. Both measures were automatically taken from 24-hour electrocardiographic Holter traces recorded during daily activities in non mutation carriers (NMCs, n = 14) and mutation carriers (MCs, n = 34) belonging to a South African LQT1 founder population. The MC group was divided into asymptomatic (ASYMP, n = 11) and symptomatic (SYMP, n = 23) patients according to the symptom severity. Analyses were carried out during daytime (DAY, from 2PM to 6PM) and nighttime (NIGHT, from 12PM to 4AM) off and on beta-adrenergic blockade (BBoff and BBon). We found that the complexity of the HP variability at short time scale was under vagal control, being significantly increased during NIGHT and BBon both in ASYMP and SYMP groups, while the complexity of both HP and QT variability at long time scales was under sympathetic control, being smaller during NIGHT and BBon in SYMP subjects. Complexity indexes at long time scales in ASYMP individuals were smaller than those in SYMP ones regardless of therapy (i.e. BBoff or BBon), thus suggesting that a reduced complexity of the sympathetic regulation is protective in ASYMP individuals. RMSE analysis of HP and QT interval variability derived from routine 24-hour electrocardiographic Holter recordings might provide additional insights into the physiology of the cardiac control and might be fruitfully exploited to improve risk stratification in LQT1 population.

Refined multiscale entropy analysis of heart period and QT interval variabilities in long QT syndrome type-1 patients.

This study assesses complexity of cardiovascular control in patients affected by type-1 variant of long QT (LQT1) syndrome. Complexity was assessed by refined multiscale entropy of heart period (HP) and QT interval variabilities. HP was taken as the time distance between two consecutive R peaks (RR) and QT interval was approximated as the time distance between the R-peak and T-wave apex (RTa) and between R-peak and T-wave end (RTe). RR, RTa and RTe intervals were automatically extracted from 24h Holter recordings and the daytime period was analyzed (from 02:00 to 06:00 PM). Non mutation carrier (NMC) individuals (n=11), utilized as a control group, were taken from the same family line of the mutation carrier (MC) subjects (n=26). We found that, while NMC and MC groups were indistinguishable based on time domain and complexity analyses of RR dynamics, complexity analysis of RTa and RTe variabilities clearly separates the two populations and suggests an impairment in the cardiac control mechanisms acting on the ventricles.

Modeling the influence of the A118G polymorphism in the OPRM1 gene and of noxious stimulation on the synergistic relation between propofol and remifentanil: sedation and analgesia in endoscopic procedures.

BACKGROUND: The presence of the A118G single nucleotide polymorphism in the OPRM1 gene as well as noxious stimulation might affect the requirements of remifentanil for patients undergoing ultrasonographic endoscopy under sedation-analgesia with propofol and remifentanil. Bispectral index (BIS) was used as a surrogate measure of effect. METHOD: A total of 207 patients were screened for A118G and randomly received different combinations of propofol and remifentanil, changed depending on the nausea response to endoscopy tube introduction. Nonlinear mixed effects modelling was used to establish the relation between propofol and remifentanil with respect to BIS and to investigate the influence of A118G or noxious stimulation. The value of k e0 for propofol and remifentanil was estimated to avoid the hysteresis between predicted effect site concentration (Ce) and BIS. RESULTS: Data from 176 patients were analysed. Eleven were recessive homozygous for A118G (OPRM = 1). A total of 165 patients were either dominant homozygous or heterozygous and considered normal (OPRM = 0). The estimated values of k e0 for propofol and remifentanil were 0.122 and 0.148 min(-1). Propofol and remifentanil were synergistic with respect to the BIS (α = 1.85). EC50 estimate for propofol was 3.86 µg/ml and for remifentanil 19.6 ng/ml in normal patients and 326 ng/ml in OPRM = 1 patients. BIS increases around 4% for the same effect site concentrations with noxious stimulation. CONCLUSIONS: Predicted effect site concentration of remifentanil ranging 1-5 ng/ml synergistically potentiates the effects of propofol on the BIS but has no effect in A118G patients. Noxious stimulation increases BIS values by 4% at the same concentrations of propofol and remifentanil.

Ischemic risk stratification by means of multivariate analysis of the heart rate variability.

In this work, a univariate and multivariate statistical analysis of indexes derived from heart rate variability (HRV) was conducted to stratify patients with ischemic dilated cardiomyopathy (IDC) in cardiac risk groups. Indexes conditional entropy, refined multiscale entropy (RMSE), detrended fluctuation analysis, time and frequency analysis, were applied to the RR interval series (beat-to-beat series), for single and multiscale complexity analysis of the HRV in IDC patients. Also, clinical parameters were considered. Two different end-points after a follow-up of three years were considered: (i) analysis A, with 151 survivor patients as a low risk group and 13 patients that suffered sudden cardiac death as a high risk group; (ii) analysis B, with 192 survivor patients as a low risk group and 30 patients that suffered cardiac mortality as a high risk group. A univariate and multivariate linear discriminant analysis was used as a statistical technique for classifying patients in risk groups. Sensitivity (Sen) and specificity (Spe) were calculated as diagnostic criteria in order to evaluate the performance of the indexes and their linear combinations. Sen and Spe values of 80.0% and 72.9%, respectively, were obtained during daytime by combining one clinical parameter and one index from RMSE, and during nighttime Sen = 80% and Spe = 73.4% were attained by combining one clinical factor and two indexes from RMSE. In particular, relatively long time scales were more relevant for classifying patients into risk groups during nighttime, while during daytime shorter scales performed better. The results suggest that the left atrial size, indexed to body surface and RMSE indexes are those that allow enhanced classification of ischemic patients in their respective risk groups, confirming that a single measurement is not enough to fully characterize ischemic risk patients and the clinical relevance of HRV complexity measures.

Language use and stereotyping: the role of approach and avoidance motivation goals.

The use of more abstract language to describe expected behaviors as opposed to unexpected behaviors has traditionally been considered a way of stereotype maintenance. This tendency is known as linguistic expectancy bias. Two experiments examined the influence of approach and avoidance motivational orientations on the production of this linguistic expectancy bias. It was predicted that approach strategic orientation is likely to describe expectancy consistent behaviors at a higher level of linguistic abstraction than expectancy inconsistent behaviors. In contrast, avoidance strategic orientation is likely to describe both expectancy consistent behaviors and expectancy inconsistent behaviors at a lower level of linguistic abstraction, thus facilitating the disappearance of linguistic expectancy bias. Two experiments confirmed these expectations, using strategic orientation manipulations based either on communication goals or on motor action, and measuring linguistic abstraction either on forced-choice answer format or on free descriptions. Implications for the generalisation of linguistic expectancy bias are discussed.

Language use and stereotyping: the role of approach and avoidance motivation goals

The use of more abstract language to describe expected behaviors as opposed to unexpected behaviors has traditionally been considered a way of stereotype maintenance. This tendency is known as linguistic expectancy bias. Two experiments examined the influence of approach and avoidance motivational orientations on the production of this linguistic expectancy bias. It was predicted that approach strategic orientation is likely to describe expectancy consistent behaviors at a higher level of linguistic abstraction than expectancy inconsistent behaviors. In contrast, avoidance strategic orientation is likely to describe both expectancy consistent behaviors and expectancy inconsistent behaviors at a lower level of linguistic abstraction, thus facilitating the disappearance of linguistic expectancy bias. Two experiments confirmed these expectations, using strategic orientation manipulations based either on communication goals or on motor action, and measuring linguistic abstraction either on forced-choice answer format or on free descriptions. Implications for the generalisation of linguistic expectancy bias are discussed (AU)

El uso de un lenguaje más abstracto para describir los comportamientos congruentes con las expectativas que los comportamientos incongruentes con las expectativas es una forma de mantener los estereotipos. Esta tendencia se conoce como el sesgo lingüístico de expectativa. Dos experimentos analizan la influencia de las orientaciones motivacionales de aproximación y evitación en la producción del sesgo lingüístico de expectativa. Se predijo que la orientación estratégica de aproximación promovería que comportamientos consistentes con la expectativa se describiesen con un mayor nivel de abstracción lingüística que los comportamientos inconsistentes con la expectativa. En cambio, la orientación estratégica de evitación induciría a que tanto los comportamientos consistentes como los inconsistentes con las expectativas se describiesen a un menor nivel de abstracción, facilitando con ello la desaparición del sesgo lingüístico de expectativa. Los dos experimentos que se presentan confirmaron dichas predicciones utilizando manipulaciones de orientación estratégica de aproximación y evitación formuladas en forma de metas comunicativas y en forma de acción motora. Además, se midió la abstracción lingüística tanto en formato de respuesta de elección múltiple como en descripción libre. El artículo debate las implicaciones de los estudios para la generalización del sesgo lingüístico de expectativa (AU)

Complexity of the short-term heart-rate variability.

This work has proposed a methodology based on the concept of entropy rates to study the complexity of the short-term heart-rate variability (HRV) for improving risk stratification to predict sudden cardiac death (SCD) of patients with established ischemic-dilated cardiomyopathy (IDC). The short-term HRV was analyzed during daytime and nighttime by means of RR series. An entropy rate was calculated on the RR series, previously transformed to symbol sequences by means of an alphabet. A statistical analysis permitted to stratify high- and low-risk patients of suffering SCD, with a specificity (SP) of 95% and sensitivity (SE) of 83.3%.

Multiscale sample entropy in heart rate variability of aortic stenosis patients.

In the present document the multiscale entropy (MSE) methodology has been applied to analyze the complex behavior of the heart rate variability (HRV), in patients with aortic stenosis (AS). A set of healthy voluntaries have been used as a control group. MSE analysis calculates an entropy rate over different time scales to assess the complexity of time series, evaluating short-term and long-term correlations. Daytime and nighttime have been considered to study variations of the complexity inside the same group of population. A statistical analysis showed that entropy was significantly higher in healthy subjects than in AS subjects in all the scales during daytime, with exception at scale 1. During nighttime, entropy in healthy subjects was significantly higher than in AS subjects only in scales from 1 to 7. Multiscale entropy is helpful to characterize AS patients and distinguish them from healthy subjects.

Representaciones Sociales e Identidad Social: origen y Desarrollo de la Inteligencia y Rol Docente / Social Representations and Social IdentityIntelligence conceptions –origins and development- and teachers role

Desde el marco de la Teoría de las Representaciones Sociales se realizaron una serie de estudios orientados a analizar las concepciones de sentido común acerca de la Inteligencia. Dada la importancia que en nuestras sociedades tiene el ser calificado de inteligente es relevante conocer qué es bueno pensar acerca de la inteligencia en estos días. En tanto problemática siempre controversial y de multiplicidad creciente, se hace necesario contar con más estudios dedicados al análisis de la forma en que los adultos y los estudiantes explican y caracterizan a la inteligencia y su desarrollo, haciendo así saliente la dinámica socio-cognitiva subyacente. Mugny y Doise (1985) enfatizan el poco conocimiento que hay respecto de las representaciones de aquellos individuos para quienes el problema de la solución de las diferencias de inteligencia es un desafío cotidiano. En este trabajo se enfatiza la relación entre representaciones sociales e identidad focalizando en la comparación de las concepciones acerca del origen y desarrollo de la inteligencia entre maestros y no maestros. Sobre la base de una muestra intencional de 787 sujetos adultos de la ciudad de Buenos Aires los resultados muestran cómo una concepción innatista, relacionada al don y a un desarrollo naturalmente programa, aparentemente rechazada o con escaso consenso, aparece como relevante cuando la identidad es tenida en cuenta.

Linguistic signatures of regulatory focus: how abstraction fits promotion more than prevention.

In 3 experiments, the authors investigated how strategic inclinations associated with promotion versus prevention orientations--that is, eager approach versus vigilant avoidance, respectively--affect the use of language. It is hypothesized that eager promotion strategies used to attain desired end states entail using more abstract language than used with vigilant prevention strategies. This is shown to hold for experimentally induced relationship goals (Experiment 1) and communication goals (Experiment 2). In the 3rd experiment, the authors examined the impact of abstractly and concretely worded messages upon the behavioral intentions of chronically prevention- and promotion-oriented individuals and found support for the hypothesis that behavioral intentions to engage in specific activities are stronger when there is a fit between message wording and chronic orientation than when there is no fit. The broader implications of these findings are discussed.