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 (REMI 1) or 2 ng•mL (REMI 2) and propofol 2 µg•mL (PROP 2) or 3 µg•mL (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 µg•mL (that could be achieved with a bolus of 1 mg•kg) when remifentanil TCI was fixed at 1 ng•mL, and target propofol TCIs were between 2.15 and 2.88 µg•mL (that could be achieved with a bolus of 0.75 mg•kg) when remifentanil TCI was fixed at 2 ng•mL. Remifentanil ranges were 1.00 to 4.79 ng•mL and 0.72 to 3.19 ng•mL when propofol was fixed at 2 and 3 µg•mL, 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.

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.

Interaction between EEG and drug concentration to predict response to noxious stimulation during sedation-analgesia: effect of the A118G genetic polymorphism.

The level of sedation in patients undergoing medical procedures is affected by the interaction between the effect of the anesthetic and analgesic agents and the pain stimuli. The presence of the A118G single nucleotide polymorphism (SNP) in the OPRM1 gene affects the requirements of opioids for patients undergoing sedation-analgesia. The purpose of this work is to evaluate the influence of the SNP A118G in OPRM1 on EEG measures for the prediction of the response to pain stimulation during endoscopy procedure. The proposed measures were based on power spectral density and auto-mutual information function. It was found that the statistical performances of the EEG measures improved when the presence of the SNP was taken into account (prediction probability Pk>0.9).

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).

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.

Validation of the qCO cardiac output monitor during Valsalva maneuver.

Monitoring cardiac output for a variety of patient conditions is essential to ensure tissue perfusion and oxygenation. Cardiac output can be measured either invasively using a pulmonary artery catheter or non-invasively using impedance cardiography (ICG). The objective of the present study was to validate a cardiac output monitor, the qCO (Quantium Medical, Barcelona, Spain). The qCO is based on the ICG principle. Twenty-five volunteers (18-75 years) were enrolled in the study. The duration of the study was 10 min. The subjects were asked to rest quietly in an armchair for a duration of 5 min. At 5 min they were asked to do a Valsalva maneuver which is known to decrease the cardiac output. The baseline value of the normalized cardiac output (qCO index) was compared with the minimum value during the Valsalva maneuver. The results showed (t-test, p<0.0005) significant difference between the cardiac output estimated at baseline and during the Valsalva maneuver. In conclusion, the qCO was able to indicate trend changes of the cardiac output in volunteers.

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.

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.

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.

Depth of anesthesia index using cumulative power spectrum.

Over the last ten years, monitors of depth of anesthesia have progressively been integrated in the clinical practice. Based on the analysis of the electroencephalogram (EEG), these monitors deliver an index that helps the anesthesiologist to determine the state of the patient during the surgery. Although they employ different kind of algorithms, spectral parameters are always taken into account to achieve the final indexes. In this work, a new spectral parameter based on the cumulative power spectrum is proposed. When compared to the Spectral Edge Frequency (SEF), a classic spectral parameter, the Cumulative Power Spectrum Index (CPSI) presents a higher correlation with reference indexes (AAI, BIS and CePROP) and a higher prediction probability of the state of the patient. Furthermore, when compared to the reference indexes, the CPSI shows similar performances in terms of correlation and presents a higher prediction probability than two of them (BIS and CePROP).

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.