Mathieu Jospin

Detrended Fluctuation Analysis of EEG as a Measure of Depth of Anesthesia

For several decades, a number of methods have been developed for the noninvasive assessment of the level of consciousness during general anesthesia. In this paper, detrended fluctuation analysis is used to study the scaling behavior of the electroencephalogram as a measure of the level of consciousness. Three indexes are proposed in order to characterize the patient state. Statistical analysis demonstrates that they allow significant discrimination between the awake, sedated and anesthetized states. Two of them present a good correlation with established indexes of depth of anesthesia. The scaling behavior has been found related to the depth of anesthesia and the methodology allows real-time implementation, which enables its application in monitoring devices

Modeling the Effect of Propofol and Remifentanil Combinations for Sedation-Analgesia in Endoscopic Procedures Using an Adaptive Neuro Fuzzy Inference System (ANFIS)

BACKGROUND:The increasing demand for anesthetic procedures in the gastrointestinal endoscopy area has not been followed by a similar increase in the methods to provide and control sedation and analgesia for these patients. In this study, we evaluated different combinations of propofol and remifentanil, administered through a target-controlled infusion system, to estimate the optimal concentrations as well as the best way to control the sedative effects induced by the combinations of drugs in patients undergoing ultrasonographic endoscopy. METHODS:One hundred twenty patients undergoing ultrasonographic endoscopy were randomized to receive, by means of a target-controlled infusion system, a fixed effect-site concentration of either propofol or remifentanil of 8 different possible concentrations, allowing adjustment of the concentrations of the other drug. Predicted effect-site propofol (Cepro) and remifentanil (Ceremi) concentrations, parameters derived from auditory evoked potential, autoregressive auditory evoked potential index (AAI/2) and electroencephalogram (bispectral index [BIS] and index of consciousness [IoC]) signals, as well as categorical scores of sedation (Ramsay Sedation Scale [RSS] score) in the presence or absence of nociceptive stimulation, were collected, recorded, and analyzed using an Adaptive Neuro Fuzzy Inference System. The models described for the relationship between Cepro and Ceremi versus AAI/2, BIS, and IoC were diagnosed for inaccuracy using median absolute performance error (MDAPE) and median root mean squared error (MDRMSE), and for bias using median performance error (MDPE). The models were validated in a prospective group of 68 new patients receiving different combinations of propofol and remifentanil. The predictive ability (Pk) of AAI/2, BIS, and IoC with respect to the sedation level, RSS score, was also explored. RESULTS:Data from 110 patients were analyzed in the training group. The resulting estimated models had an MDAPE of 32.87, 12.89, and 8.77; an MDRMSE of 17.01, 12.81, and 9.40; and an MDPE of −1.86, 3.97, and 2.21 for AAI/2, BIS, and IoC, respectively, in the absence of stimulation and similar values under stimulation. Pk values were 0.82, 0.81, and 0.85 for AAI/2, BIS, and IoC, respectively. The model predicted the prospective validation data with an MDAPE of 34.81, 14.78, and 10.25; an MDRMSE of 16.81, 15.91, and 11.81; an MDPE of −8.37, 5.65, and −1.43; and Pk values of 0.81, 0.8, and 0.8 for AAI/2, BIS, and IoC, respectively. CONCLUSION:A model relating Cepro and Ceremi to AAI/2, BIS, and IoC has been developed and prospectively validated. Based on these models, the (Cepro, Ceremi) concentration pairs that provide an RSS score of 4 range from (1.8 &mgr;g·mL−1, 1.5 ng·mL−1) to (2.7 &mgr;g·mL−1, 0 ng·mL−1). These concentrations are associated with AAI/2 values of 25 to 30, BIS of 71 to 75, and IoC of 72 to 76. The presence of noxious stimulation increases the requirements of Cepro and Ceremi to achieve the same degree of sedative effects.

Monitoring hypnotic effect and nociception with two EEG-derived indices, qCON and qNOX, during general anaesthesia

The objective of the present study was to validate the qCON index of hypnotic effect and the qNOX index of nociception. Both indices are derived from the frontal electroencephalogram (EEG) and implemented in the qCON 2000 monitor (Quantium Medical, Barcelona, Spain).

Validation of the Index of Consciousness (IoC) during sedation/analgesia for ultrasonographic endoscopy

The level of consciousness of patients undergoing surgery evolves continuously as the effect of the anesthetic agents is counteracted by the surgical stimuli. The monitors of depth of anesthesia, based on the analysis of the electroencephalogram (EEG), have been progressively introduced into the daily practice to provide additional information about the state of the patient. In this work, the Index of Consciousness (IoC), a recent index which uses the information from EEG spectrum and symbolic dynamics through a fuzzy inference system, is introduced. The bispectral index BIS, a well-established index, is used to validate the IoC. A good correlation is found between both indexes. Furthermore, IoC presents a significantly higher prediction probability Pk of the level of sedation than BIS, and can thus be considered as an interesting measure of the level of consciousness.

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. Methods: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 ke0 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 ke0 for propofol and remifentanil were 0.122 and 0.148min−1. Propofol and remifentanil were synergistic with respect to the BIS (&agr; = 1.85). EC50 estimate for propofol was 3.86 µg/ml and for remifentanil 19.6 ng/ml in normal patients and 326ng/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 1–5ng/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.

Prediction of nociceptive responses during sedation by time-frequency representation

The level of sedation in patients undergoing medical procedures evolves continuously, such as the effect of the anesthetic and analgesic agents is counteracted by pain stimuli. The monitors of depth of anesthesia, based on the analysis of the electroencephalogram (EEG), have been progressively introduced into the daily practice to provide additional information about the state of the patient. However, the quantification of analgesia still remains an open problem. The purpose of this work is to analyze the capability of prediction of nociceptive responses based on the time-frequency representation (TFR) of EEG signal. Functions of spectral entropy, instantaneous power and instantaneous frequency were calculated in order to predict the presence or absence of the nociceptive responses to different stimuli during sedation in endoscopy procedure. Values of prediction probability of Pk above 0.75 and percentages of sensitivity and specificity above 70% and 65% respectively were achieved combining TFR functions with bispectral index (BIS) and with concentrations of propofol (CeProp) and remifentanil (CeRemi).

Auto-mutual information function of the EEG as a measure of depth of anesthesia

Monitoring the depth of anesthesia (DOA) is necessary in order to decrease the incident of awareness in anesthesia and to prevent delays in the recovery phase. In the last decades a number of noninvasive methods have been proposed for the analysis of the electroencephalogram (EEG) for monitoring DOA. The objective of this work was to apply auto mutual information function (AMIF) to EEGs of patients under anesthesia in order to find variables able to characterize the following 4 states: awake, sedated, anesthetized and burst suppression episodes. The results show that the single and combined AMIF parameters were able to correctly classify the states in the range 72.2%–94.1% and 61.1%–100%, respectively.

Prediction of Nociceptive Responses during Sedation by Linear and Non-Linear Measures of EEG Signals in High Frequencies

The level of sedation in patients undergoing medical procedures evolves continuously, affected by the interaction between the effect of the anesthetic and analgesic agents and the pain stimuli. The monitors of depth of anesthesia, based on the analysis of the electroencephalogram (EEG), have been progressively introduced into the daily practice to provide additional information about the state of the patient. However, the quantification of analgesia still remains an open problem. The purpose of this work is to improve the prediction of nociceptive responses with linear and non-linear measures calculated from EEG signal filtered in frequency bands higher than the traditional bands. Power spectral density and auto-mutual information function was applied in order to predict the presence or absence of the nociceptive responses to different stimuli during sedation in endoscopy procedure. The proposed measures exhibit better performances than the bispectral index (BIS). Values of prediction probability of Pk above 0.75 and percentages of sensitivity and specificity above 70% were achieved combining EEG measures from the traditional frequency bands and higher frequency bands.

Sedation-analgesia with propofol and remifentanil: concentrations required to avoid gag reflex in upper gastrointestinal endoscopy.

BACKGROUND:The purpose of this study was to identify optimal target propofol and remifentanil concentrations to avoid a gag reflex in response to insertion of an upper gastrointestinal endoscope. METHODS:Patients presenting for endoscopy received target-controlled infusions (TCI) of both propofol and remifentanil for sedation-analgesia. Patients were randomized to 4 groups of fixed target effect-site concentrations: remifentanil 1 ng•mL−1 (REMI 1) or 2 ng•mL−1 (REMI 2) and propofol 2 &mgr;g•mL−1 (PROP 2) or 3 &mgr;g•mL−1 (PROP 3). For each group, the other drug (propofol for the REMI groups and vice versa) was increased or decreased using the “up-down” method based on the presence or absence of a gag response in the previous patient. A modified isotonic regression method was used to estimate the median effective Ce,50 from the up-down method in each group. A concentration-effect (sigmoid Emax) model was built to estimate the corresponding Ce,90 for each group. These data were used to estimate propofol bolus doses and remifentanil infusion rates that would achieve effect-site concentrations between Ce,50 and Ce,90 when a TCI system is not available for use. RESULTS:One hundred twenty-four patients were analyzed. To achieve between a 50% and 90% probability of no gag response, propofol TCIs were between 2.40 and 4.23 &mgr;g•mL−1 (that could be achieved with a bolus of 1 mg•kg−1) when remifentanil TCI was fixed at 1 ng•mL−1, and target propofol TCIs were between 2.15 and 2.88 &mgr;g•mL−1 (that could be achieved with a bolus of 0.75 mg•kg−1) when remifentanil TCI was fixed at 2 ng•mL−1. Remifentanil ranges were 1.00 to 4.79 ng•mL−1 and 0.72 to 3.19 ng•mL−1 when propofol was fixed at 2 and 3 &mgr;g•mL−1, respectively. CONCLUSIONS:We identified a set of propofol and remifentanil TCIs that blocked the gag response to endoscope insertion in patients undergoing endoscopy. Propofol bolus doses and remifentanil infusion rates designed to achieve similar effect-site concentrations can be used to prevent gag response when TCI is not available.

Assessment of the depth of anesthesia based on symbolic dynamics of the EEG

Methodologies based on symbolic dynamics have successfully demonstrated to reflect the nonlinear behavior of biological signals. In the present study, symbolic dynamics was applied to the electroencephalogram (EEG) in order to describe the level of depth of anesthesia. The EEG was transformed to symbol sequences. Words of three symbols were built from this symbolic series. The results obtained from the EEGs of 36 patients undergoing anesthesia showed that the probabilities of the word types were able to reflect the depth of anesthesia in a similar way to the auditory evoked potential index AAI, a commercial index.