Article

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

Authors:
  • Quantium Medical
  • Universidad de San Buenaventura, Cali, Colombia
  • Ziekenhuis Oost-Limburg Genk (Belgium) and Hospital Clinic Barcelona
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Abstract

Background: 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). Methods: The study was approved by the local ethics committee, including data from 60 patients scheduled for ambulatory surgery undergoing general anaesthesia with propofol and remifentanil, using TCI. The Bis (Covidien, Boulder, CO, USA) was recorded simultaneously with the qCON. Loss of eyelash reflex [loss of consciousness (LOC)] was recorded, and prediction probability for Bis and qCON was calculated. Movement as a response to noxious stimulation [laryngeal mask airway (LMA) insertion, laryngoscopy and tracheal intubation] was registered. The correlation coefficient between qCON and Bis was calculated. The patients were divided into movers/non-movers as a response to noxious stimulation. A paired t-test was used to assess significant difference for qCON and qNOX for movers/non-movers. Results: The prediction probability (Pk) and the standard error (SE) for qCON and Bis for detecting LOC was 0.92 (0.02) and 0.94 (0.02) respectively (t-test, no significant difference). The R between qCON and Bis was 0.85. During the general anaesthesia (Ce propofol > 2 μg/ml, Ce remifentanil > 2 ng/ml), the mean value and standard deviation (SD) for qCON was 45 (8), while for qNOX it was 40 (6). The qNOX pre-stimuli values were significantly different (P < 0.05) for movers/non-movers as a response to LMA insertion [62.5 (24.0) vs. 45.5 (24.1)], tracheal intubation [58.7 (21.8) vs. 41.4 (20.9)], laryngoscopy [54.1 (21.4) vs. 41.0 (20.8)]. There were no significant differences in remifentanil or propofol effect-site concentrations for movers vs. non-movers. Conclusion: The qCON was able to reliably detect LOC during general anaesthesia with propofol and remifentanil. The qNOX showed significant overlap between movers and non-movers, but it was able to predict whether or not the patient would move as a response to noxious stimulation, although the anaesthetic concentrations were similar.

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... 3e5 The score is based on data of 590 anaesthetised, sedated and awake patients and volunteers. 3 However, no independent data are available to validate such claims. As the depth of intraoperative analgesia is notoriously difficult to validate, we hypothesised that QNox measured at the end of surgery, but before patient arousal, may show a relationship with the level of acute postoperative pain just after awakening. ...
... The same authors also state that QNox was likely to be influenced by EMG activity or the lack thereof in completely paralysed patients. 3 However, the current study did only investigate patients who were nonparalysed at the end of surgery, directly before arousal (arousal defined as a state entropy of >60 or an end-tidal sevoflurane concentration of <0.8 MAC). It is therefore unlikely that (too) deep anaesthesia or neuromuscular paralysis may have contributed to the results. ...
... Ultimately, QNox may be confined to offer a prediction of 'arousability' by noxious stimulation as stated by Jensen and colleagues. 3 Thus, QNox may not offer an assessment of the level of nociception per se, but more likely a secondary measurement of the depth of anaesthesia. The value of such parameter over QCon, BIS, or SE alone remains unclear. ...
Article
Background: The QNox score (Quantium Medical S.L., distributed by Fresenius Kabi) has recently been introduced as a tool to quantify intraoperative analgesia. Being based on the analysis of electroencephalographic data, QNox is distinctly different to other methods of nociception monitoring that rely almost entirely on the assessment of sympathetic activity. However, there are currently no published data to validate use of QNox in a clinical setting. We investigated the value of pre-arousal QNox data at the end of surgery for prediction of acute postoperative pain in the PACU. Methods: A total of 150 patients scheduled for non-emergency surgery under sevoflurane-opioid general anaesthesia were included in the study. At the end of surgery but before patient arousal, QNox was measured minutely for 5 min. After admission to the recovery room, pain scores (numeric rating scale [NRS], 0-10) were obtained 5 minutely for 15 min. Results: Data from 144 patients were analysed. QNox before arousal showed no correlation (ρ=0.057) with acute postoperative pain in the PACU. Furthermore, the score was found to have no value for the prediction of acute postoperative pain (area under the receiver operating curve, 0.501; 95% confidence interval, 0.406-0.597). Conclusion: QNox at the end of surgery before arousal showed no association with and allowed no prediction of acute pain in the PACU. Clinical trial registration: ACTRN12618001662257.
... Recently, the CONOX ® monitor (Fresenius Kabi, Brézins, France) has been made available to assess hypnotic effect and nociception during general anesthesia [14]. This twoparameter monitor analyzes frontal encephalographic signals which permits to obtain two indices, the qCON, assessing the level of unconsciousness, and the qNOX, assessing the level of noxious stimulation during surgery [15]. ...
... This twoparameter monitor analyzes frontal encephalographic signals which permits to obtain two indices, the qCON, assessing the level of unconsciousness, and the qNOX, assessing the level of noxious stimulation during surgery [15]. However, only few data concerning qCON and qNOX variations during general anesthesia is currently available [14,15]. ...
... To our knowledge, this is the first study assessing qCON and qNOX variations during different phases of laparoscopic surgery. The validation of qCON for the monitoring of hypnotic effect and of qNOX for nociception was first reported in patients undergoing ambulatory surgery on general anesthesia with propofol and remifentanil using target-controlled infusion (TCI) [14]. The prediction probability (P k ) [standard error (SE)] of qCON to detect loss of consciousness (LOC) was 0.92 [0.02], with mean ± SD qCON values for awake and LOC of 87 ± 14 and 55 ± 16, respectively. ...
Article
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This study was designed to investigate qCON and qNOX variations during outpatient laparoscopic cholecystectomy using remifentanil and desflurane without muscle relaxants and compare these indices with ANI and MAC. Adult patients undergoing outpatient laparoscopic cholecystectomy were included in this prospective observational study. Maintenance of anesthesia was performed using remifentanil targeted to ANI 50–80 and desflurane targeted to MAC 0.8–1.2 without muscle relaxants. The ANI, qCON and qNOX and desflurane MAC values were collected at different time-points and analyzed using repeated measures ANOVA. The relationship between ANI and qNOX and between qCON and MAC were analyzed by linear regression. The ANI was comprised between 50 and 80 during maintenance of anesthesia. Higher values of qNOX and qCON were observed at induction and extubation than during all other time-points where they were comprised between 40 and 60. A poor but significant negative linear relationship (r² = 0.07, p < 0.001) was observed between ANI and qNOX. There also was a negative linear relationship between qCON and MAC (r² = 0.48, p < 0.001) and between qNOX and remifentanil infusion rate (r² = 0.13, p < 0.001). The linear mixed-effect regression correlation (r²) was 0.65 for ANI-qNOX and 0.96 for qCON-MAC. The qCON and qNOX monitoring seems informative during general anesthesia using desflurane and remifentanil without muscle relaxants in patients undergoing ambulatory laparoscopic cholecystectomy. While qCON correlated with MAC, the correlation of overall qCON and ANI was poor but significant. Additionally, the qNOX weakly correlated with the remifentanil infusion rate. This observational study suggests that the proposed ranges of 40–60 for both indexes may correspond to adequate levels of hypnosis and analgesia during general anesthesia, although this should be confirmed by further research.
... Overall, these changes describe common observations in stressed humans: a fast HR, dilated pupils, and cold and sweaty hands. In addition to these 'simple' reactions, stress may also influence the HR variability (HRV), 7 electroencephalographic and electromyographic patterns, 8 and the threshold of peripheral reflexes 9 dobviously, more subtle changes usually hidden from simple observation. ...
... 16 The assessment of the pupillary diameter may be hindered by the miotic effects of opioids, and neuromuscular blocking drugs may hinder the monitoring of electromyographic changes in scores, such as qNOX. 8 Although methods, such as the nociception flexion reflex (NFR) threshold, may be less prone to the confounding effects of perioperative medication (neuromuscular blocking agents possibly exempted), the more awkward set-up and limited access to the patient's leg may still pose a significant hindrance to its routine use. ...
... qCON has been shown to correlate relatively well with other measures of anaesthetic depth, such as the bispectral index. 8 The qNOX score (0e99) is an EEG-and EMG-based dimensionless proprietary score. The mathematical model used for the development of qNOX is an adaptive neuro fuzzy inference system, which has been described in more detail in an early validation study for the score by Jensen and colleagues. ...
Article
Nociception, in contrast to pain, is not a subjective feeling, but the physiological encoding and processing of nociceptive stimuli. However, monitoring nociception remains a challenge in attempts to lower the incidence of acute postoperative pain and the move towards a more automated approach to analgesia and anaesthesia. To date, several commercialised devices promise a more accurate reflection of nociception than the traditionally used vital signs, blood pressure and heart rate. This narrative review presents an overview of existing technologies and commercially available devices, and offers a perspective for future research. Although firm conclusions about individual methods may be premature, none currently appears to offer a sufficiently broad applicability. Furthermore, there is currently no firm evidence for any clinically relevant influence of such devices on patient outcome. However, the available monitors have significantly aided the understanding of underlying mechanisms and identification of potential pitfalls.
... These issues may hinder the indices to reliably separate conscious or responsive states from unconscious or unresponsive states on-line at the state transitions [14][15][16]. Specific information regarding the performance of a relatively new index, the qCON (Quantium Medical, Mataro, Spain) [17], that is now integrated in the CONOX monitor (Fresenius Kabi AG, Bad Homburg, Germany) [18], is not available to a great extent. Here we present the results regarding the time delay of the qCON as well as its ability to distinguish (goal-directed) responsiveness from unresponsiveness [19,20] state transitions. ...
... The qCON processes frontal EEG information and reflects the estimated anesthetic level as a dimensionless number between 99 (fully awake) and 0 (isoelectric EEG) and the detailed algorithm is described in the article by Jensen et al. [17] In short, the index is based on four spectral parameters that are calculated from the signal energy of different EEG frequency bands. Prior to the calculation of these parameters the recorded EEG is checked for artefacts using an artefact rejection routine. ...
... The SQI ranges from 0 to 100% and provides information regarding the reliability of the qCON index. In previous studies SQI < 50 were excluded from analyses because of low signal quality [17,25]. In accordance, we evaluated the performance of the qCON for the (i) entire data set, (ii) only cases with SQI > 50, and (iii) SQI > 75. ...
Article
Full-text available
We investigated the performance of the qCON index regarding its time delay for sudden changes in the anesthetic level as well as to separate responsiveness from unresponsiveness during loss and return of responsiveness (LOR and ROR). For evaluation of the time delay, we replayed relevant EEG episodes to the qCON to simulate sudden changes between the states (i) awake/sedation, (ii) adequate anesthesia, or (iii) suppression. We also replayed EEG from 40 patients during LOR and ROR to evaluate the qCON’s ability to separate responsiveness from unresponsiveness. The time delays depended on the type of transition. The delays for the important transition between awake/sedation and adequate anesthesia were 21(5) s from awake/sedation to adequate anesthesia and 26(5) s in the other direction. The performance of the qCON to separate responsiveness from unresponsiveness depended on signal quality, the investigation window, i.e. ± 30 s or ± 60 s around LOR/ROR, and the specific transition being tested. AUC was 0.63–0.90 for LOR and 0.61–0.79 for ROR. Time delay and performance during state transitions of the qCON were similar to other monitoring systems such as bispectral index. The better performance of qCON during LOR than ROR probably reflects the sudden change in EEG activity during LOR and the more heterogeneous EEG during ROR.
... It depends on the observer and the parameters employed which may be related to the cortex (response to orders) and the brainstem (palpebral reflex) [9]. In addition to the isolated forearm technique [10], other indicators have been developed, particularly those based on electroencephalogram (EEG) analysis [11][12][13][14] in order to accurately and objectively define LOC. ...
... The authors described two distinct patterns of phase-amplitude modulation: Trough-max and Peak-max. In the Trough-max pattern, alpha oscillation The graph above depicts the increase in alpha power (7)(8)(9)(10)(11)(12)(13)(14) in the frontal (blue) and parieto-occipital (red) regions, from the moment of initiating propofol (PS, pink vertical bar). This increase was more marked from the moment of loss of verbal command (LVC), in gray, and the loss of palpebral reflex (LER), in green. ...
Article
Full-text available
During anesthesia induction with propofol the level of arousal progressively decreases until reaching loss of consciousness (LOC). In addition, there is a shift of alpha activity from parieto-occipital to frontal zones, defined as anteriorization. Whilst monitoring LOC and anteriorization would be useful to improve propofol dosage and patient safety, the current devices for anesthetic depth monitoring are unable to detect these events. The aim of this study was to observe LOC and anteriorization during anesthesia induction with propofol by applying electrodes placed in the frontal and parietal areas. Bispectral index (BIS) and quantium consciousness index (qCON) monitors were simultaneously employed. BIS™ and qCON sensors were placed in the frontal and parieto-occipital regions of 10 alopecic patients who underwent anesthesia with propofol, alfentanil, and remifentanil. The initial biophase target of propofol was 2.5 mcg/mL which was gradually increased until reaching LOC. Wilcoxon signed-rank test was used to study differences in alpha power and qCON/BIS indices along the study; and Pk value to evaluate predictive capability of anteriorization of BIS, qCON, and alpha waves. Parietal BIS and qCON values became significantly higher than frontal values 15 min after loss of eye reflex. Anteriorization was observed with both monitors. Pk values for BIS and qCON were strongly predictive of frontal alpha absolute power. During anesthesia induction with propofol it is possible to identify anteriorization with BIS and qCON in the frontal and parieto-occipital regions. Both indices showed different patterns which need to be further studied.
... Reich et al., have reported a decrease in mean arterial pressure (MAP) of over 40% (MAP<70mmHg or MAP<60 mmHg) in the first 10 minutes after induction (p<0.001) [77]. Moreover, this study (n=2406 patients) reported an increase in the time spent in the recovery room (13.3%, p<0.05) and in postoperative mortality rates (8.6%, p<0.02) in patients that presented perioperative hypotension. ...
... Moreover, this study (n=2406 patients) reported an increase in the time spent in the recovery room (13.3%, p<0.05) and in postoperative mortality rates (8.6%, p<0.02) in patients that presented perioperative hypotension. Another interesting phenomenon presented by the group was that post-induction hypotension was more frequent in the 5-10 minutes interval, in comparison to the 0-5 minutes interval after induction of general anesthesia [77]. A similar study carried out by Hug et al., reported that over 15% of the patients that present a decrease in systolic blood pressure (SBP) under 90 mmHg after induction with propofol in the first 10 minutes after administration [78]. ...
Preprint
With the development of general anesthesia techniques and anesthetic substances, brought new horizons for the expansion and improvement of surgical techniques. Nevertheless, more complex surgical procedures brought a higher complexity and longer duration for general anesthesia that led to a series of adverse events such as hemodynamic instability, under- or overdosage of anesthetic drugs, as well as an increased number of post-anesthetic events. In order to adapt the anesthesia according to the particularities of each patient, the multimodal monitoring of these patients is highly recommended. Classically, general anesthesia monitoring consists of the analysis of vital functions and gas exchange. Multimodal monitoring refers to the concomitant monitoring of the degree of hypnosis and the nociceptive-antinociceptive balance. By titrating anesthetic drugs according to these parameters, clinical benefits can be obtained, such as hemodynamic stabilization, reduction of awakening times, and the reduction of post-operative complications. Another important aspect is the impact on the status of inflammation and the redox balance. By minimizing inflammatory and oxidative impact one can achieve a faster recovery that will lead to both increased patient satisfaction and an increase in patient safety. The purpose of this literature review is to present the most modern multimodal monitoring techniques, respectively to discuss the particularities of each technique.
... Hypotension frequently occurs, especially after the induction of anesthesia, that is, between the moment of induction and the start of surgery. Reich et al. reported a decrease in mean arterial pressure (MAP) of over 40% (MAP < 70mmHg or MAP < 60 mmHg) in the first 10 min after induction (p < 0.001) [77]. Moreover, this study (n = 2406 patients) reported an increase in the time spent in the recovery room (13.3%, p < 0.05) and in postoperative mortality rates (8.6%, p < 0.02) in patients that presented perioperative hypotension. ...
... Moreover, this study (n = 2406 patients) reported an increase in the time spent in the recovery room (13.3%, p < 0.05) and in postoperative mortality rates (8.6%, p < 0.02) in patients that presented perioperative hypotension. Another interesting phenomenon presented by the group was that post-induction hypotension was more frequent in the 5-10 min interval in comparison to the 0-5 min interval after induction of general anesthesia [77]. A similar study carried out by Hug et al. reported that over 15% of patients presented a decrease in systolic blood pressure (SBP) under 90 mmHg after induction with propofol in the first 10 min after administration [78]. ...
Article
Full-text available
The development of general anesthesia techniques and anesthetic substances has opened new horizons for the expansion and improvement of surgical techniques. Nevertheless, more complex surgical procedures have brought a higher complexity and longer duration for general anesthesia, which has led to a series of adverse events such as hemodynamic instability, under- or overdosage of anesthetic drugs, and an increased number of post-anesthetic events. In order to adapt the anesthesia according to the particularities of each patient, the multimodal monitoring of these patients is highly recommended. Classically, general anesthesia monitoring consists of the analysis of vital functions and gas exchange. Multimodal monitoring refers to the concomitant monitoring of the degree of hypnosis and the nociceptive-antinociceptive balance. By titrating anesthetic drugs according to these parameters, clinical benefits can be obtained, such as hemodynamic stabilization, the reduction of awakening times, and the reduction of postoperative complications. Another important aspect is the impact on the status of inflammation and the redox balance. By minimizing inflammatory and oxidative impact, a faster recovery can be achieved that increases patient safety. The purpose of this literature review is to present the most modern multimodal monitoring techniques to discuss the particularities of each technique.
... qCON qCON is also a processed frontal EEG parameter index. qCON development has been previously described in detail by Jensen et al. 15 In short, qCON is calculated by feeding in frequency power ratios of 4 different EEG frequencies bands (4)(5)(6)(7)(8)(8)(9)(10)(11)(12)(13)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44) and the burst suppression ratio into a mathematical model called "Quadratic Equation." It generates an output on a 0-99 scale where decreasing output numbers indicates increasing hypnotic drug effect. ...
... qCON qCON is also a processed frontal EEG parameter index. qCON development has been previously described in detail by Jensen et al. 15 In short, qCON is calculated by feeding in frequency power ratios of 4 different EEG frequencies bands (4)(5)(6)(7)(8)(8)(9)(10)(11)(12)(13)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44) and the burst suppression ratio into a mathematical model called "Quadratic Equation." It generates an output on a 0-99 scale where decreasing output numbers indicates increasing hypnotic drug effect. ...
Article
Background: Clinicians can optimize propofol titration by using 2 sources of pharmacodynamic (PD) information: the predicted effect-site concentration for propofol (Ceprop) and the electroencephalographically (EEG) measured drug effect. Relation between these sources should be time independent, that is, perfectly synchronized. In reality, various issues corrupt time independency, leading to asynchrony or, in other words, hysteresis. This asynchrony can lead to conflicting information, making effective drug dosing challenging. In this study, we tried to quantify and minimize the hysteresis between the Ceprop (calculated using the Schnider model for propofol) and EEG measured drug effect, using nonlinear mixed-effects modeling (NONMEM). Further, we measured the influence of EEG-based monitor choice, namely Bispectral index (BIS) versus qCON index (qCON) monitor, on propofol PD hysteresis. Methods: We analyzed the PD data from 165 patients undergoing propofol-remifentanil anesthesia for outpatient surgery. Drugs were administered using target-controlled infusion (TCI) pumps. Pumps were programmed with Schnider model for propofol and Minto model for remifentanil. We constructed 2 PD models (direct models) relating the Schnider Ceprop to the measured BIS and qCON monitor values. We quantified the models' misspecification due to hysteresis, on an individual level, using the root mean squared errors (RMSEs). Subsequently, we optimized the PD models' predictions by adding a lag term to both models (lag-time PD models) and quantified the optimization using the RMSE. Results: There is a counterclockwise hysteresis between Ceprop and BIS/qCON values. Not accounting for this hysteresis results in a direct PD model with an effect-site concentration which produces 50% of the maximal drug effect (Ce50) of 6.24 and 8.62 µg/mL and RMSE (median and interquartile range [IQR]) of 9.38 (7.92-11.23) and 8.41 (7.04-10.2) for BIS and qCON, respectively. Adding a modeled lag factor of 49 seconds to the BIS model and 53 seconds to the qCON model improved both models' prediction, resulting in similar Ce50 (3.66 and 3.62 µg/mL for BIS and qCON) and lower RMSE (median (IQR) of 7.87 (6.49-9.90) and 6.56 (5.28-8.57) for BIS and qCON. Conclusions: There is a significant "Ceprop versus EEG measured drug effect" hysteresis. Not accounting for it leads to conflicting PD information and false high Ce50 for propofol in both monitors. Adding a lag term improved the PD model performance, improved the "pump-monitor" synchrony, and made the estimates of Ce50 for propofol more realistic and less monitor dependent.
... EEG amplitude (total power) under general anesthesia decreases with age; complicating the interpretation of EEG signals (Schultz et al., 2004;Purdon et al., 2015;Kreuzer et al., 2020). Current commercial monitoring approaches mainly focus on the identification of the isoelectric episodes, i.e., they rather perform a ''suppression detection'' than a ''burst and suppression detection'' (Rampil, 1998;Särkelä et al., 2002;Jensen et al., 2014). These approaches may underestimate the real occurrence of burst suppression (Muhlhofer et al., 2017). ...
... Most BSR algorithms focus on the detection of suppressed EEG as evidence for a BSUPP episode. If the EEG amplitude is below a set threshold for a defined duration, BSUPP is detected (Rampil, 1998;Särkelä et al., 2002;Jensen et al., 2014). Artifacts (i.e., EKG or motion) for instance can contaminate the signal and can spuriously cause increased EEG activity, thus hindering algorithms that detect BSUPP by identifying suppression (Willingham and Avidan, 2017). ...
Article
Full-text available
Electroencephalographic (EEG) Burst Suppression (BSUPP) is a discontinuous pattern characterized by episodes of low voltage disrupted by bursts of cortical synaptic activity. It can occur while delivering high-dose anesthesia. Current research suggests an association between BSUPP and the occurrence of postoperative delirium in the post-anesthesia care unit (PACU) and beyond. We investigated burst micro-architecture to further understand how age influences the neurophysiology of this pharmacologically-induced state. We analyzed a subset of EEG recordings (n = 102) taken from a larger data set previously published. We selected the initial burst that followed a visually identified “silent second,” i.e., at least 1 s of iso-electricity of the EEG during propofol induction. We derived the (normalized) power spectral density [(n)PSD], the alpha band power, the maximum amplitude, the maximum slope of the EEG as well as the permutation entropy (PeEn) for the first 1.5 s of the initial burst of each patient. In the old patients >65 years, we observed significantly lower (p < 0.001) EEG power in the 1–15 Hz range. In general, their EEG contained a significantly higher amount of faster oscillations (>15 Hz). Alpha band power (p < 0.001), EEG amplitude (p = 0.001), and maximum EEG slope (p = 0.045) all significantly decreased with age, whereas PeEn increased (p = 0.008). Hence, we can describe an age-related change in features during EEG burst suppression. Sub-group analysis revealed no change in results based on pre-medication. These EEG changes add knowledge to the impact of age on cortical synaptic activity. In addition to a reduction in EEG amplitude, age-associated burst features can complicate the identification of excessive anesthetic administration in patients under general anesthesia. Knowledge of these neurophysiologic changes may not only improve anesthesia care through improved detection of burst suppression but might also provide insight into changes in neuronal network organization in patients at risk for age-related neurocognitive problems.
... [1][2][3] Nociception in anesthetized patients is typically demonstrated as a sympathetic response to surgery and other noxious stimuli. 4,5 Excessive nociception not only affects the stability of hemodynamics but may also exacerbate postoperative pain, disturb the balance of inflammation, and produce adverse outcomes. 6,7 Analgesic administration is the key component when enhancing anti-nociceptive forces. ...
... A previous study illustrates that the increasing likelihood of a response to a noxious stimulus is associated with increasing qNOX score values. 4 The qNOX represents an interesting alternative to most other monitors that rely on autonomic activity changes for the assessment of nociception. It is promising for predicting nociception under general anesthesia; however, additional solid and in-depth studies are required. ...
Article
Full-text available
Purpose: The pain threshold index (PTI) is a novel measure of nociception based on integrated electroencephalogram parameters during general anesthesia. The wavelet index (WLI) reflects the depth of sedation. This study aims to evaluate the ability of the PTI and WLI to predict hemodynamic reactivity after tracheal intubation and skin incision in pediatric patients. Patients and methods: Pediatric patients (n=134) undergoing elective general surgery or urinary surgery were analyzed. Measurements at predefined time-points during tracheal intubation and skin incision included the PTI, WLI, heart rate (HR), and mean blood pressure (MBP). Receiver-operating characteristic (ROC) curves were computed to evaluate the predictive performance of the PTI and WLI in measuring hemodynamic reactivity (an increase of more than 20% in either MBP or HR) during general anesthesia. Results: Of the 134 patients evaluated, positive reactivity of HR and MBP was observed in 95 (70.9%) and 61 (45.5%) patients induced by intubation, respectively, and 19 (14.2%) and 24 (17.9%) patients induced by skin incision, respectively. Using either HR or MBP reactivity induced by intubation as a dichotomous variable, the areas under the curves (AUCs) [95% CI] of PTI and WLI were 0.81[0.73-0.87] and 0.58[0.49-0.67] with the best cutoff values of 62 and 49. The AUCs [95% CI] of PTI and WLI were 0.82[0.75-0.88] and 0.61[0.52-0.69] after skin incision. The best cutoff values of PTI and WLI were 60 and 46, respectively. Conclusion: The PTI can predict hemodynamic reactivity with the best cutoff values of 62 and 60 after tracheal intubation and skin incision in pediatric patients during general anesthesia. The WLI failed in predicting hemodynamic changes.
... Besides, there was a significant difference in qNOX before and after stimulation, and the movers' group had higher qNOX values after stimulation than the non-movers group, which indicated that this movement was associated with mild analgesia. 13 Both the qCON and qNOX indices can detect movements in response to a noxious stimulus, even though the response in qNOX appears to be higher than qCON. This discrepancy is probably because the increase in qNOX is a direct effect of EEG on noxious stimulus, while the increase in qCON is a secondary result of the effect of awakening due to noxious stimulus. ...
... This discrepancy is probably because the increase in qNOX is a direct effect of EEG on noxious stimulus, while the increase in qCON is a secondary result of the effect of awakening due to noxious stimulus. 13 There have not been previous studies analyzing the effectiveness of ketamine administration as preemptive analgesia assessed by the qNOX score. However, research on the analgesic effect of a combination of fentanyl and ketamine by Tucker et al. in 10 healthy individuals explained an increase in pain threshold when fentanyl was combined with ketamine compared to when each drug was given individually. ...
Article
Background: Inadequate management of intraoperative pain poses a risk of postoperative chronic pain complications. The use of preemptive analgesia before the onset of surgical incision stimulation was considered to prevent central sensitization. Clinical research around the terms of preemptive analgesia needs to be proven by nociception-based intraoperative monitoring. An objective modality with EEG guidance can provide information on noxious stimuli.Objective: To determine the effectiveness of ketamine and fentanyl administration as preemptive analgesia measured by qNOX scores through the CONOX tool.Methods: This study is a single-blinded randomized experiment with the division of two groups: control and treatment. The control group received preemptive fentanyl, and the treatment group received preemptive ketamine and fentanyl. Then the qNOX score was assessed during operation.Result: The qNOX score of the treatment group in minute-15 and 30 was lower than the control group (p = 0.007; p = 0.025), while in the minute-90 it was higher than the control group (p = 0.001). The mean first 1-hour qNOX score was lower in the treatment group (p <0.001), while in the second 1-hour was higher in the treatment group (p = 0.003). The mean total dose of fentanyl supplementation in the treatment group was lower than in the control group (71.3 ± 25.1 grams vs. 92.0 ± 28.3 grams; p = 0.044).Conclusion: The administration of combined ketamine and fentanyl as preemptive analgesia is more effective in the first hour of surgery compared to single preemptive fentanyl measured by qNOX score. Preemptive ketamine and fentanyl decrease the total dose of intraoperative fentanyl supplementation compared with single-dose preemptive fentanyl administration.
... The qCON index is an indication of the patient's level of consciousness, and the qNOX index can be used to gauge the probability that a patient will respond to noxious stimuli. Similar to the qCON index, which links different EEG spectral components to distinct aspects of hypnosis (loss of consciousness event, hypnotic concentrations, level of alertness/sedation scales) using a quadratic model, the qNOX index integrates the spectral components into an equivalent model that best predicts whether a patient will respond to noxious stimuli [45]. The likelihood of movement response to external stimuli is described on a scale ranging from 0 to 100. ...
... In one study of 60 patients, significant increments in the qNOX values pre-and post-noxious stimuli (LMA insertion, tracheal intubation, and laryngoscopy) were found; however, the remifentanil or propofol effect-site concentrations were not correlated with whether the patient moved in response [45]. ...
Article
A safe anesthesia is achieved by possessing objective methods that estimate the patient's state along the different phases of the surgery. The patient's state under anesthesia is characterized by three major aspects linked to the main effects produced by each of the families of anesthetic agents administered: hypnosis, analgesia, and muscular relaxation. While muscular relaxation assessment, under neuromuscular blocking agents, has a relatively long history of quantification techniques with a high degree of standardization and understanding, such as the train-of-four, the depth of hypnosis estimation, due to the brain complexity, suffers from a lesser degree in both monitoring standardization and interpretation. The problem of analgesia and nociception monitoring standardization and interpretation increases significantly since more systems get involved, the central nervous system and the autonomic system, which illustrates why currently, there are multiple a priori valid approaches to develop the nociception monitoring from different interpretations and physiological bases of the noxious stimuli processing. This review describes the main current monitoring technologies available in the daily clinic for estimating the patient's nociception under general anesthesia.
... This monitor provides a uCON of the qEEGi using mono-spectral power analysis and an Adaptive Neural Fuzzy Inference System (ANFIS), identical to the qCON index (Quantium Medical, Barcelona, Spain). Moreover, the ADMS ® was made to be more stable while minimizing electrical interference and offering a more convenient graphical user interface, which the qCON has been reported to maintain acceptable correlation with the BIS [9]. ...
... In the Bland-Altman analysis of qEEGi data during anesthesia, although the BIS and the uCON were not identical, they did show good agreement. Jensen et al. [9] found that the bias between BIS and qCON was -2, the SD was 12, and the 95% of limits of agreement were calculated as -26 to 22, whereas our study showed positive bias of difference. However, visual inspection of the Bland-Altman plots from that study might indicate a positive bias during a moderate hypnosis range of 40 to 60 on the mean axis. ...
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Background: Hypnosis monitors analyze small-amplitude electrical signals transmitted from the brain that could be exposed to the electromagnetic field that occurs around the body during electrocautery (ECT). We investigated the influence of ECT on hypnosis monitoring during anesthesia. Methods: We simultaneously monitored BIS and uCON during 50 gynecologic oncology surgeries. During the episodes of ECT, we compared the absolute difference (a-Diff) between the baseline index and the most deviated index after ECT over either 30-60 s (ECT30-60) or more than 60 s (ECT > 60) between the monitors. We also investigated the bias and the limits of agreement between the monitors. Results: Between the two monitors, the a-Diff of ECT30-60 was 1.4 ± 1.1 for the BIS, which was significantly greater than 0.6 ± 0.9 for the uCON (P = 0.003), and the a-Diff of ECT > 60 was 16.5 ± 8.2 for the BIS, which was also significantly greater than 1.4 ± 1.3 for uCON (P < 0.001). The intra-monitor index differences showed that the BIS during ECT > 60 was significantly greater than that during ECT30-60 (P < 0.001), but the uCON showed no significant difference between ECT30-60 and ECT > 60 (P = 0.056). The estimated bias between the monitors was 6.3 ± 9.8 and 95% limits agreement was -12.3 to 25.0. Conclusions: Prolonged ECT intervention might lead to spurious estimations of quantitative EEG indexes. Therefore, hypnosis should be clinically assessed in combination with scrutinized judgment of relevant clinical symptoms and signs for hypnosis.
... The detailed algorithm is proprietary for most monitors. Currently, at least 10 monitors are available on the market, including the AEP Monitor/2 (Danmeter A/S, Odense, Denmark), which combines information from MLAEP and EEG 26,27 ; the Bispectral Index (BIS) Monitor (Medtronic, Minneapolis, MN), which is characterized by weighted influence of b activity, synchronized fastslow activity, quasi-flat activity, and burst suppression; the Cerebral State Monitor (Danmeter A/S), which uses relative a and b powers, the difference between them, and burst suppression 28 ; the Entropy Module (GE Healthcare, Chicago, IL), which is characterized by spectral entropy of the EEG 29 ; the IoC-View display of the index of consciousness (Morpheus Medical, Barcelona, Spain), which is characterized by symbolic dynamics combined with spectral ratios and EEG suppression rate 30 ; the Narcotrend Monitor (MonitorTechnik, Bad Bramstedt, Germany), which is characterized by 15 different EEG patterns identified by a set of EEG parameters, including spectrum, entropy, and auto-regression 31 ; the NeuroSENSE Monitor WAV CNS (Wavelet-based Anesthetic Value for Central Nervous System) (NeuroWave Systems Inc, Cleveland Heights, OH), which is characterized by wavelet coefficients 5 ; the SedLine Monitor (patient state index) (Masimo, Irvine, CA), which is derived from 4 EEG channels, relative activity in specific frequency bands, interhemispheric coherence information, anteroposterior frequency, and phase relationships 32 ; the SNAPII Monitor (Stryker Inc, Kalamazoo, MI), which uses high-frequency and low-frequency EEG activity 33 ; the qCON 2000 Monitor (Quantium Medical, Barcelona, Spain), which uses a combination of frequency bands (adaptive neuro fuzzy inference system) 34 ; and the Composite Cortical State (Cortical Dynamics LTD, North Perth, Western Australia), which uses a scaled mean pole location of the EEG. 35,36 The BIS was the first to be launched and has been the most studied, but to date, none of the available processed EEG monitors has proven superior to another one in terms of depth of anesthesia monitoring and patient outcome. ...
Article
In this narrative review, different aspects of electroencephalogram (EEG) monitoring during anesthesia are approached, with a special focus on cardiothoracic and vascular anesthesia, from the basic principles to more sophisticated diagnosis and monitoring utilities. The available processed EEGÀderived indexes of the depth of the hypnotic component of anesthesia have well-defined limitations and usefulness. They prevent intraoperative awareness with recall in specific patient populations and under a specific anesthetic regimen. They prevent intraoperative overdose, and they shorten recovery times. They also help to avoid lengthy intraoperative periods of suppression activity, which are known to be deleterious in terms of outcome. Other than those available indexes, the huge amount of information contained in the EEG currently is being used only partially. Several other areas of interest regarding EEG during anesthesia have emerged in terms of anesthesia mechanisms elucidation, nociception monitoring, and diagnosis or prevention of brain insults.
... The qNOX index for example results from the analysis of four EEG spectral bands between 0.5 and 44 Hz. Clinical studies have shown that the qNOX was mildly correlated with the effectsite concentration of remifentanil and with the probability of response to nociception [9]. ...
... Studies have indicated that pain can cause changes in the electrical activities of the brain. [31][32][33] A study by Jensen et al [34] determined that IoC1 (qCON) could reliably predict the disappearance of the eyelash reflex (loss of consciousness) during intravenous anesthesia with propofol and remifentanil, and that IoC2 (qNOX) could predict whether patients would exhibit body movements when they encountered noxious stimulation under a similar depth of anesthesia. In this study, the induction and maintenance of anesthesia was achieved using target-controlled infusion of propofol and remifentanil. ...
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Toxic effects of neoadjuvant chemotherapy (NC) on nervous, hepatorenal, and pulmonary systems might affect general anesthesia depth. This study aimed to evaluate the effects of NC on depth of total intravenous anesthesia.This prospective observational study enrolled 60 patients undergoing elective unilateral modified radical mastectomy during total intravenous anesthesia with propofol and remifentanil (January-June 2015; Liaocheng People's Hospital, China): the NC group (n = 30) received NC, while the control group (n = 30) did not. Propofol and remifentanil dosages were adjusted according to indexes of consciousness (IoC1: sedation; IoC2: analgesia) to control fluctuations of blood pressure and heart rate within 20% of baseline values. Parameters reflecting propofol/remifentanil dosages, intraoperative adverse events, and quality of anesthetic recovery were recorded.The duration of propofol infusion (1.3 ± 0.4 vs 1.8 ± 0.5 hours, P < .05), mean propofol dosage (8.0 ± 1.0 vs 9.3 ± 1.5 mg kg h, P < .05), and adjustment frequency of target-controlled remifentanil infusion (2.9 ± 1.8 vs 4.4 ± 2.6 times/surgery, P < .05) were significantly lower in the NC group than in the control group; adjustment frequency of target-controlled propofol infusion was also numerically lower (2.0 ± 1.1 vs 2.7 ± 1.5 times/surgery, P = .053). Duration of remifentanil infusion, mean remifentanil dosage, voluntary eye opening, extubation time, and recovery score were not significantly different between groups. The incidence of tachycardia was lower in the NC group than in the control group (7.1% vs 37.0%, P < .05), but there was no significant difference in the incidence of total adverse events between groups.NC can enhance the sensitivity of breast cancer patients to the anesthetic effect of propofol.
... The predominance of sympathetic response is usually used to assess surgical stress. Hemodynamic, pupillary, electroencephalographic, electromyographic, nociceptive flexion reflex or galvanic skin conductance changes have been used by different nociception monitors to reflect the response to surgical stress [5][6][7][8][9][10][11][12][13]. Nevertheless, the optimum option for monitoring nociception is not yet known. ...
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The Analgesia Nociception Index (ANI), derived from heart rate variability is a proposed guide to obtain an adequate control of the analgesic component during anaesthesia. This single blind observational study was designed to evaluate the relationship between intraoperative ANI values and length of stay in Day Surgery Units (DSU) in patients undergoing varicose vein intervention. 131 patients (ASA I-II) scheduled for elective varicose vein surgery were studied. A propofol closed-loop TCI was used to maintain a specific level of BIS. To control analgesia, a remifentanil TCI was used, modifying the target according to hemodynamic changes. Patients were included in the ANI > 50 sub-group or in the ANI < 50 sub-group depending on whether the ANI value was greater than 50 for at least 60% of the anaesthesia maintenance period (AMP) or not. The primary endpoint was the length of stay in DSU. Other variables studied were ANI values, duration of the AMP, remifentanil TCI target average, postoperative pain, rescue-analgesia needs and postoperative nausea and vomiting (PONV) were analysed. Statistical analysis of length of stay in DSU was performed with Mann–Whitney test. ANI > 50 sub-group showed a lower length of stay in the DSU [165 min (118–212) vs 186.5 min (119–254), p = 0.0425]. Discharge timing from DSU was statistically different among study sub-groups (p = 0.005). An adequate nociception level measured by ANI during varicose vein surgery might reduce the length of stay at DSU. Further studies are needed to assess the usefulness of ANI in other anaesthesia conditions.
... [18] The BIS index was strictly maintained within the range of 45-55 and any increase in HR and BP in this range of BIS was considered to be due to inadequate analgesia and additional fentanyl was administered. Even though the recently introduced "qCON/qNOX" monitors claims to separately analyze the hypnotic and analgesic components of anesthesia, [19] they are presently not widely available and consequently have not been studied extensively. ...
Article
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Objective: Transcutaneous electrical nerve stimulation (TENS) is a common modality used to treat acute and chronic painful conditions. The aim of this study is to find out the effect of immediate preoperative TENS on intraoperative anesthetic drug consumption in patients undergoing lumbar discectomy under general anesthesia. Methods: Sixty patients undergoing lumbar discectomy were randomly divided into two study groups. In TENS group (Group T), TENS was applied for 1 h in the immediate preoperative period with 20 mA current, at 100 Hz frequency, in pulses of 250 μs on either side of the planned incision site. In Sham TENS group (Group S), TENS was applied for 1 h preoperatively to the patients, although with the current intensity set at “zero” mA. The pain intensity during rest as well as movement was recorded before and after TENS, by using the Visual Analog Scale (VAS) scores in both the groups. Intraoperatively, titrated doses of propofol were used to maintain a bispectral index value of 50 ± 5, and IV fentanyl was administered to maintain the heart rate and blood pressure within 20% of baseline values. Postoperatively, fentanyl 0.5 μg/kg IV was administered to achieve VAS of <4. Results: Application of TENS was found to significantly reduce the preoperative VAS score (P < 0.001). Intraoperatively, no difference in propofol and fentanyl consumption was observed in either group (P < 0.6) (P < 0.27). Recovery time and postoperative VAS scores recorded at various time intervals were comparable in both the groups. No difference in fentanyl consumption or rescue analgesia was noted in the postoperative period in both groups. Conclusions: Application of preoperative TENS provided immediate relief from pain, although without any significant decrease in the intraoperative or postoperative analgesic requirement. Furthermore, no difference was noted in the intraoperative anesthetic consumption.
... The qNOX is an index using a scale from 0 to 99 where 99 indicates high probability of response to noxious stimulation. Decreasing index values mean less probability of response to surgical stimuli [1]. There are other methods for prediction of the antinociception balance based on hemodynamic parameters such as heart rate variability [5] or the surgical pleth index [6]. ...
... Therefore this EEG-derived index may reflects the integrated information processing of noxious input to brain, which is less susceptible to hemodynamic fluctuations. Several nociception indices derived from frontal EEG have been developed, for example, qNOX index, can predict whether or not the patient would move as a response to noxious stimulation during anesthesia [25]. However, its predictive ability for postoperative pain seems to have poor performance [26]. ...
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Recently a novel pain recognition indicator derived from electroencephalogram(EEG) signals, pain threshold index(PTI) has been developed. The aim of this study was to determine whether PTI can be used for prediction of postoperative acute pain while surgical pleth index(SPI) applied as control. Eighty patients undergoing laparoscopic urological surgery under general anesthesia were enrolled. Data of SPI, PTI and a sedative index-wavelet index(WLI) were recorded within last 10 min at the end of surgery. The postoperative pain scores (NRS, numerical rating scale) were obtained. The Bland–Altman analysis was used for evaluation of consistency between PTI and SPI, whereas receiver-operating characteristic (ROC) curves was used for the mean values of PTI, SPI, and WLI to distinguish between mild (NRS 0–3) and moderate-severe (NRS 4–10) pain, and calculate their “best-fit” cut-off values. Data from 76 patients were included for final analysis. There was a good agreement between SPI and PTI values at the end of surgery. The ROC analysis showed a cut-off PTI value of 53 to discriminate between mild and moderate-to-severe pain, while SPI is 44 for this discrimination. Further analysis indicated that PTI had a best predictive accuracy reflected by highest area under curve (AUC)(0.772, 95% CI: 0.661–0.860)with sensitivity(62.50%) and specificity(90.91%) and a best positive predictive value(83.3%,95% CI: 68.4–98.2%). PTI obtained at the end of surgery, which have better predictive accuracy for postoperative pain than SPI, could differentiate the patients with moderate-to-severe pain from those with mild pain after they awaken from anesthesia. Clinical trial registration Chinese Clinical Trials Registry: ChiCTR1900024789.
... Benefits range from reducing the incidence of awareness [7,21,33], to tailoring anesthesia to optimize drug consumption [25,30,32], to potentially attenuating post-operative adverse effects [5,16,17]. Studies of anesthesia under propofol and sevoflurane showed that despite these technologies relying on different signal processing frameworks, their agreement is strong [3,12,20], mainly because they share a common source of information, the EEG signal. Unfortunately, due to the lack of a gold standard on establishing the patient's real hypnotic state, DA monitoring systems work on its estimation, which needs to be continuously evaluated on distinct drugs and surgical scenarios where relative differences in index performances are shown [11,24]. ...
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Comparison of two depth of anesthesia indices, qCON (Conox) and PSI (Sedline), during desflurane sedation and their sensitivity to random ketamine boluses in patients undergoing routine surgery. The performance of desflurane and ketamine on both indices was analyzed for 11 patients, and the ketamine sensitivity was compared with another group of 11 patients under sevoflurane and propofol. The MOAA/S was used to determine sedation level and pain. Different boluses of ketamine ranging from 10 to 30 mg where randomly administered in both groups and the effect on the indexes were measured after 4 min. The indices were recorded during the whole surgery, and their correlations with the desflurane concentration and the discrimination between awake and anesthetized states were evaluated with the prediction probability statistic (Pk). The Pk values, mean (se), discriminating between awake and anesthetized states were 0.974(0.016) for the qCON and 0.962(0.0123) for the PSI, while the 1-Pk statistic for the qCON and the PSI with respect to the desflurane concentration were 0.927(0.016) and 0.918(0.018), respectively, with no statistically significant differences. The agreement between both depth of hypnosis parameters was assessed under the Bland-Altman plot and the Spearman correlation, rs = 0.57(p < 0.001). During the sevoflurane-propofol anesthesia, which served as a control group, both indices experienced a similar behavior with a no significant change of their median values after ketamine. However, during desflurane anesthesia the qCON index did not change significantly after ketamine administration, qCON (before = 33 (4), after = 30 (17); Wilcoxon, p = 0.89), while the PSI experienced a significant increase, PSI (before = 31(6), after = 39(16) Wilcoxon, p = 0.013). This study shows that qCON and PSI have similar performance under desflurane with good discrimination between the awake and anesthetized states. While both indices exhibited similar behavior under ketamine boluses under a sevoflurane-propofol anesthesia, the qCON index had a better performance under ketamine during desflurane anesthesia.
... Le qNOX a été évalué durant trois stimulations douloureuses cliniques : l'insertion de masque laryngé, la laryngoscopie et l'intubation trachéale. Le qNOX était significativement plus élevé chez les patients qui avaient un mouvement de réaction à la stimulation douloureuse [4]. Dans une étude similaire, Melia et al. ont montré que le qNOX avait une bonne capacité de prédiction des mouvements de patients à l'insertion d'un masque laryngé [5]. ...
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Résumé Introduction Au cours de la dernière décennie, de nombreuses études ont porté sur des outils permettant d’évaluer la nociception et de guider l’analgésie des patients anesthésiés. Actuellement, il n’existe pas de moniteur de référence pour l’évaluation de l’équilibre nociception/anti-nociception. Objectifs Le but de cette conférence d’actualisation est de passer en revue les différentes approches existantes pour le monitorage de la balance nociception/anti-nociception lors d’une intervention chirurgicale sous anesthésie générale. Méthodes Une recherche dans la littérature concernant le monitorage de la nociception peropératoire a été effectuée sur le moteur de recherche PubMed, Scopus et CENTRAL à l’aide du mot clé : pain monitor. Nous avons rapporté les articles les plus importants de notre recherche. La présente revue ne portant que sur la chirurgie sous anesthésie générale, le monitorage de la nociception ne sera pas abordé chez les patients conscients, en unité de soins intensifs ou aux urgences. Résultats Les mesures dérivées de l’électro-encéphalogramme ont un intérêt pour identifier une stimulation nociceptive sous anesthésie générale, et pour prédire un mouvement en réponse. La pupillométrie est sensible pour détecter des stimuli nociceptifs, et permettrait de guider l’administration d’opioïdes sous anesthésie, avec une réduction de la douleur postopératoire précoce. La pléthysmographie varie en réponse au stimulus nociceptif et au bolus analgésique, et permettrait une réduction de la consommation d’opioïdes intraopératoire lors d’une analgésie rémifentanil guidée par le SPI. La conductance cutanée a un intérêt modéré dans la détection de stimulations nociceptives sous anesthésie générale. L’analyse de variation de fréquence cardiaque par ANI permet un monitorage de l’équilibre nociception anti-nociception. Une anesthésie guidée par ANI permettrait une réduction de la consommation opioïde en SSPI. L’analyse multiparamétrique avec le NOL permettrait un monitorage continu et précis de l’intensité de stimulation douloureuse et des doses d’opioïdes intraopératoires, tout en étant plus robuste face aux artéfacts. Conclusion Les principaux outils de surveillance de l’équilibre nociception/anti-nociception sous anesthésie ont été décrits. Bien que les dispositifs présentés puissent constituer des solutions pour optimiser l’analgésie pendant l’anesthésie générale, cet examen de la littérature souligne que le choix de l’un ou l’autre des dispositifs dépend du contexte clinique et du but général de la surveillance. De nouveaux index multiparamétriques pourraient dans l’avenir permettre une analyse plus robuste de la nociception intraopératoire.
... This parameter is based on the evaluation of EEG and EMG patterns, with values between 0 and 99. Jensen et al., carried out a study on 60 patients undergoing general anesthesia with propofol and remifentanil and have shown a series of statistically significant correlations concluding that qNOX can detect fine changes in the nociception-antinociception balance [76]. The Nociception Level Index (NOL indes, Medasense, Ramat Gau, Israel) is another widely used technology for titrating analgesic drugs during general anesthesia and is based on analysisng the photoplethysmographic wave, temperature, skin galvanic conductance response, and accelerometry [63]. ...
Preprint
Worldwide, an increasing number of patients undergo complex surgeries. With the development of general anesthesia techniques and anesthetic substances, the most complex surgical techniques could be developed. In order to adapt the anesthesia according to the particularities of each patient, it is recommended the multimodal monitoring of these patients. Classically, general anesthesia monitoring consists of the analysis of vital functions and gas exchange. Multimodal monitoring refers to the concomitant monitoring of the degree of hypnosis and the nociceptive-antinociceptive balance. By titrating anesthetic drugs according to these parameters, clinical benefits can be obtained, such as hemodynamic stabilization, reduction of awakening times, reduction of post-operative complications. Also, there is an important impact on the status of inflammation and the redox balance. The purpose of this literature review is to present the most modern multimodal monitoring techniques, respectively to discuss the particularities of each technique.
... CONOX's qCON index is based on an easily readable 0-99 scale, resulting from the processing of EEG readings. A qCON index between 40 and 60 points to an adequate anesthesia level, while 0 points to an isoelectric EEG. 12 Only a few published studies show its utility during the intraoperative period, 11,13,14 but no study has investigated it for the depth of sedation or correlated with clinical sedation scales in ICU patients on mechanical ventilation. The primary objective of this study was to correlate the sedation objectively with processed EEG (qCON) using the CONOX module to the subjective scoring system, RASS, in patients on propofol-fentanyl sedation, requiring mechanical ventilation in the ICU. ...
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Background: The quantium consciousness index (qCON), an electroencephalography (EEG)-based modality, has no studies regarding intensive care unit (ICU) sedation, though very few studies describe its use for assessing depth of anesthesia in the operation theater. In this study, we evaluated qCON for assessing sedation compared with Richmond Agitation Sedation Scale (RASS) in patients on a mechanical ventilator in the ICU. Materials and methods: Eighty-seven mechanically ventilated patients aged between 18 and 60 years were investigated over a 12-hour period. They were given a standardized dosage of sedation comprised of a bolus dose of propofol 0.5 mg/kg and fentanyl 1 µg/kg, and then infusions of propofol 2-5 mg/kg/hour and fentanyl 0.5-2 µg/kg/hour. These drug infusions were adjusted to achieve a RASS score between 0 and -3. Using the qCON monitor, the investigator recorded the qCON values and then assessed the RASS score. Results: A total of 1,218 readings were obtained. After contrasting each qCON value correspondingly with time to each RASS value, we found their correlation to be statistically significant (ρ = 0.288, p <0.0001). With the help of receiver operating characteristic (ROC) curves, we were able to differentiate appropriate from inappropriate levels of sedation. A qCON value of 80 had a sensitivity of 72.67% and a specificity of 67.42% (AUC 0.738 with SE 0.021). Conclusion: qCON can be used for assessing sedation levels in mechanically ventilated critically ill patients. Clinical trial registration: CTRI/2019/07/020064. How to cite this article: Harsha MS, Bhatia PK, Sharma A, Sethi P. Comparison of Quantium Consciousness Index and Richmond Agitation Sedation Scale in Mechanically Ventilated Critically Ill Patients: An Observational Study. Indian J Crit Care Med 2022;26(4):491-495.
... 30,31 The minority of EEG-based monitoring systems that explicitly aim at evaluating the analgesic component are: the Brain Anaesthesia Response monitor (BAR; Cortical Dynamics Ltd, North Perth, Australia), 7,32 the composite variability index (CVI) from the bispectral index (Medtronic), 9,33,34 and the qNOX (Qantium Medical, Barcelona, Spain), which uses the ratios between the energies of the EEG signal in different frequency ranges to track noxious stimulation. 8 It was calibrated to nail-bed pressure as a noxious stimulus, 8 but seems to work for stimuli such as laryngeal mask airway insertion, 6 a stimulus known to also trigger beta arousal. Hence, it may be comparable with the response entropy index. ...
Article
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Electroencephalographic (EEG) activity is used to monitor the neurophysiology of the brain, which is a target organ of general anaesthesia. Besides its use in evaluating hypnotic states, neurophysiologic reactions to noxious stimulation can also be observed in the EEG. Recognising and understanding these responses could help optimise intraoperative analgesic management. This review describes three types of changes in the EEG induced by noxious stimulation when the patient is under general anaesthesia: (1) beta arousal, (2) (paradoxical) delta arousal, and (3) alpha dropout. Beta arousal is an increase in EEG power in the beta-frequency band (12–25 Hz) in response to noxious stimulation, especially at lower doses of anaesthesia drugs in the absence of opioids. It is usually indicative of a cortical depolarisation and increased cortical activity. At higher concentrations of anaesthetic drug, and with insufficient opioids, delta arousal (increased power in the delta band [0.5–4 Hz]) and alpha dropout (decreased alpha power [8–12 Hz]) are associated with noxious stimuli. The mechanisms of delta arousal are not well understood, but the midbrain reticular formation seems to play a role. Alpha dropout may indicate a return of thalamocortical communication, from an idling mode to an operational mode. Each of these EEG changes reflect an incomplete modulation of pain signals and can be mitigated by administration of opioid or the use of regional anaesthesia techniques. Future studies should evaluate whether titrating analgesic drugs in response to these EEG signals reduces postoperative pain and influences other postoperative outcomes, including the potential development of chronic pain.
... In this study it was found that qCON and qNOX indices behave differently during general anesthesia than compared to natural sleep. During anesthesia, anesthetic and analgesic agents are administrated to reduce both consciousness and nociception levels [6], whereas during night sleep, loss of consciousness is not accompanied by a similar nociception reduction. ...
... Most current anesthesia/analgesia monitoring methods are multimodal to characterize complex brain responses to noxious stimuli. For example, the qNOX index [186] takes different EEG frequency band data and electromyography (EMG) data as inputs into a fuzzy inference neural network, which is trained to return a composite index ranging from 0 to 99 to describe a noxious stimulus by referring to the body movement stimulated by laryngeal mask intubation. Because of the introduction of the EMG signal, qNOX will be affected when neuromuscular blocking agents are used. ...
Article
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Although the relationship between anesthesia and consciousness has been investigated for decades, our understanding about the underlying neural mechanisms of anesthesia and consciousness are still rudimentary that limits the development of system for anesthesia monitoring and consciousness evaluation. Moreover, the current practices for anesthesia monitoring are mainly based on methods that do not provide adequate information and may present obstacles to the precise application of anesthesia. Most recently, there is a trend in the field to utilize brain network analysis to reveal the mechanisms of anesthesia, with the aim of providing novel insights to promote practical application. This review summarizes recent works on brain network studies of anesthesia and compares the underlying neural mechanisms of consciousness and anesthesia along with the neural signs and measures of distinct aspects of neural activity. Using the theory of cortical fragmentation as a starting point, we emphatically introduce important methods and research involving connectivity and network analysis. We demonstrate that whole-brain multimodal network data could provide important supplementary clinical information. More importantly, this review posits that brain network methods, if simplified, are likely to play an important role in improving current clinical anesthesia monitoring systems.
... The ADMS applies qCON and qNOX monitor technology, and pCON was reported to have acceptable correlation with the BIS. 22 The algorithm calculating qCON is based on the adaptive neuro fuzzy inference system composed of the energy of four frequency ratios and the value of the EEG suppression rate. 23 The ADMS and BIS values were measured similarly during dental-procedural sedation and general anesthesia. ...
Article
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The neuromuscular block state may affect the electroencephalogram-derived index representing the anesthetic depth. We applied an Anesthetic Depth Monitoring for Sedation (ADMS) to patients undergoing laparoscopic cholecystectomy under total intravenous anesthesia, and evaluated the requirement of propofol according to the different neuromuscular block state. Adult patients scheduled to undergo laparoscopic cholecystectomy were enrolled and randomly assigned to either the moderate (MB) or deep neuromuscular block (DB) group. The UniCon sensor of ADMS was applied to monitor anesthetic depth and the unicon value was maintained between 40 and 50 during the operation. According to the group assignment, intraoperative rocuronium was administered to maintain proper neuromuscular block state, moderate or deep block state. The unicon value, electromyography (EMG) index, and total dose of propofol and rocuronium were analyzed. At similar anesthetic depth, less propofol was used in the DB group compared to the MB group (6.19 ± 1.36 in the MB mg/kg/h group vs 4.93 ± 3.02 mg/kg/h in the DM group, p = 0.042). As expected, more rocuronium were used in the DB group than in the MB group (0.8 ± 0.2 mg/kg in the MB group vs 1.2 ± 0.2 mg/kg in the DB group, p = 0.023) and the EMG indices were lower in the DB group than in the MB group, at several time points as follows: at starting operation ( p < 0.001); at 15 ( p = 0.019), 45 ( p = 0.011), and 60 min ( p < 0.001) after the initiation of the operation; at the end of operation ( p = 0.003); and at 5 min after the administration of sugammadex ( p < 0.001). At similar anesthetic depth, patients under the deep neuromuscular block state required less propofol with lower intraoperative EMG indices compared to those under the moderate neuromuscular block state during general anesthesia.
... Jensen et al. (12) did a study to validate the monitoring of hypnotic effect and nociception with two EEG derived indices, CON and NOX during general anaesthesia. They stated that although qCON was able to reliably detect loss of consciousness during general anaesthesia with propofol and remifentanil, the qNOX showed significant overlap between movers and non movers, but it was able to predict whether or not the patient would move as a response to noxious stimulation, although the anaesthetic concentrations were similar. ...
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Background: The qCON and qNOX scores in the conox monitor measures depth of anaesthesia and analgesia respectively. qNOX, a parameter extracted from the raw EEG could predict the likelihood of movement response to different anaesthetic and surgical stimuli. Various workers have used various doses of fentanyl to find an optimal dose that will achieve adequate analgesia and at the same time will reduce the occurrence of its side effects. Purpose: Primary objective was to study and compare the effect of three different doses of fentanyl on nociception score qNOX and secondary objective was to compare the number of doses of Inj paracetamol used and extubation time in three groups. Material and Methods: Study was done in ninety patients scheduled for elective surgery under general anaesthesia who were randomly assigned to group I, II and III to receive fentanyl in the dose of 1, 1.5 and 2 microgram/kg respectively. Parameters recorded were values of qNOX scores at various time intervals, number of patients requiring Inj paracetamol intraoperatively, extubation time and any side effect of study drug in all the three groups. Results: The mean values of qNOX score and Inj paracetamol required intraoperatively was highest in the group of patients who received fentanyl in the dose of 1 mcg/kg and lowest in patients who received fentanyl in the dose of 2 mcg/kg. The difference between all the three groups was statistically significant (p<0.05). The mean extubation time was insignificant between group 1 and II, Group II and III but was significant between I and III (p<0.05). Conclusion: Fentanyl in a dose of 2 micrograms per kg was able the achieve desired qNOX scores intraoperatively without any serious side effects.
... The stronger relative contribution of faster frequencies causes an increase in the beta ratio for the BIS [14]. The qCON is calculated by an undisclosed proprietary algorithm using an adaptive neuro fuzzy inference system that combines the EEG energy in different frequency bands [36]. The state entropy index is derived from the spectral entropy; which is the Shannon entropy applied to the normalized power spectrum of the EEG [33]. ...
Article
Study objective In the upcoming years there will be a growing number of elderly patients requiring general anaesthesia. As age is an independent risk factor for postoperative delirium (POD) the incidence of POD will increase concordantly. One approach to reduce the risk of POD would be to avoid excessively high doses of anaesthetics by using neuromonitoring to guide anaesthesia titration. Therefore, we evaluated the influence of patient's age on various electroencephalogram (EEG)-based anaesthesia indices. Design and patients We conducted an analysis of previously published data by replaying single electrode EEG episodes of maintenance of general anaesthesia from 180 patients (18–90 years; ASA I-IV) into the five different commercially available monitoring systems and evaluated their indices. We included the State/Response Entropy, Narcotrend, qCON/qNOX, bispectral index (BIS), and Treaton MGA-06. For a non-commercial comparison, we extracted the spectral edge frequency (SEF) from the BIS. To evaluate the influence of the age we generated linear regression models. We also assessed the correlation between the various indices. Main results During anaesthetic maintenance the values of the SEF, State/Response Entropy, qCON/qNOX and BIS all significantly increased (0.05 Hz/0.19–0.26 index points per year) with the patient's age (p < 0.001); whereas the Narcotrend did not change significantly with age (0.06 index points per year; p = 0.28). The index values of the Treaton device significantly decreased with age (−0.09 index points per year; p < 0.001). These findings were independent of the administered dose of anaesthetics. Conclusions Almost all current neuromonitoring devices are influenced by age, with the potential to result in inappropriately high dosage of anaesthetics. Therefore, anaesthesiologists should be aware of this phenomenon, and the next generation of monitors should correct for these changes.
... The primary outcomes were intra-operative and postoperative pain values. The former was measured with the presence of movement and changes in heart rate and mean arterial pressure and the conox monitor 4,5 (Fresinus Kabi, Germany) which displayed qnox scores. The postoperative pain values were measured with the Numeric rating scale (NRS) scores. ...
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Background: The postoperative analgesic efficacy of trans-muscular quadratus lumborum block in abdominal surgeries is well established; however, its intraoperative safety and efficacy as an anesthetic is still being explored. This retrospective case review was conducted to investigate the efficacy and safety of combined quadaratus lumburoum block and low-dose subarachnoid block for anesthesia in complex abdominal operations. Methods: Perioperative data of 29 patients, who underwent abdominal operations during the period of June/2019 to October/2019 under the combined technique, was analyzed. The primary outcome was intra and postoperative pain scores with the conox as qnox and numeric rating scale respectively at different time points. The secondary outcomes were intraoperative sedation scores with conox as qcon and perioperative dosage of fentanyl, changes in mean arterial pressure and the incidence of adverse events. Results: The mean qnox scores at incision, viscera dissection, closure and before transport to the post anesthesia care unit were between 44.66 and 55.79. The mean numeric rating scale scores before bed on the operation day, at 8 am on the first postoperative day, before bed on the first postoperative day and at 8 am on the second postoperative day were between 3.41 and 3.86. The mean qcon scores during the operations were between 61.31 and 65.82 while it was 85.66 following the stoppage of all sedations. The mean total perioperative consumption of fentanyl was 38.7mcg. The proportion of patients having MAP changes of less than 20% from baseline was 85.72%. The incidence of peri-operative adverse events was low. Conclusions: For complex abdominal operations, a combination of ultrasound-guided QLB-TM and low dose spinal anesthesia achieves adequate analgesia and is a safe technique.
... Первая группа основана на регистрации и анализе сигналов головного мозга -электроэнцефалографии (ЭЭГ) и слуховых вызванных потенциалов (СВП) [2,3]. Существенным недостатком регистрации СВП, по мнению ряда авторов, является их слабый отклик на нанесение болевого стимула, а так же их крайне малая амплитуда и «зашумленность» сигнала [4]. Вторая группа методов оценки адекватности уровня интраоперационной анальгезии основана на регистрации параметров вегетативной нервной системы -вариабельности сердечного ритма, барорефлекса, кожной проводимости или их комбинации [5][6][7][8]. ...
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The aim of the research is to evaluate the informativeness of methods for assessing analgesia qNOX and ANI level. Material and methods. The study included 24 patients who were operated on the spine under general anesthesia. The patients were divided into 2 groups; in 12 patients the level of analgesia was assessed using qNOX index, and in 12 patients using ANI index. Hemodynamic parameters were assessed in patients, among them: blood pressure and heart rate. Statistical analysis was carried out using Statistica 20.0 Software package. Results. Intravenous dose of fentanyl of 2.4 ± 0.4 μg / kg made it possible to reach ANI 50 level in 4.2 ± 0.6 minutes since the moment of its administration. At stage II, ANI reached 65. After intravenous fentanyl administration qNOX reached 39 in 4.1 ± 0.5 min. At stage II, 15.3% of qNOX decrease was noted. Conclusion. qNOX and ANI values are equally objective criteria for the adequacy of analgesia, objectively reflecting the achieved level of nociceptive protection
Article
Purpose of review: In an unconscious patient, there can be significant challenges to monitoring nociception and proper dosing of analgesic medications. The traditional measures of intraoperative nociception have poor sensitivity and specificity with little predictive value in postoperative outcomes such as postoperative pain, opioid-induced side effects, length of stay or incidence of opioid use disorder. To date, several monitoring modalities are in development to establish objective measures of the balance between nociception and analgesia with the goal of guiding anesthesiologists and improve patient outcomes. In this review, some of the most promising monitoring modalities are discussed with the most recent findings. Recent findings: Multiple modalities are beginning to demonstrate utility compared with traditional care. Most, but not all, of these studies show decreased intraoperative opioid use and some show lower pain scores and opioid requirements in the postanesthesia care unit. Summary: Recent evidence points to promising efficacy for these monitoring modalities; however, this field is in its infancy. More investigation is required to demonstrate differences in outcome compared with traditional care, and these differences need to be of sufficient import to achieve widespread adoption.
Article
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 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 accurate detect the moment of loss of consciousness during induction of general anaesthesia. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.
Article
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.
Article
The intraoperative dosing of opioids is a challenge in routine anesthesia as the potential effects of intraoperative overdosing and underdosing are not completely understood. In recent years an increasing number of monitors were approved, which were developed for the detection of intraoperative nociception and therefore should enable a better control of opioid titration. The nociception monitoring devices use either continuous hemodynamic, galvanic or thermal biosignals reflecting the balance between parasympathetic and sympathetic activity, measure the pupil dilatation reflex or the nociceptive flexor reflex as a reflexive response to application of standardized nociceptive stimulation. This review article presents the currently available nociception monitors. Most of these monitoring devices detect nociceptive stimulations with higher sensitivity and specificity than changes in heart rate, blood pressure or sedation depth monitoring devices. There are only few studies on the effect of opioid titration guided by nociception monitoring and the possible postoperative benefits of these devices. All nociception monitoring techniques are subject to specific limitations either due to perioperative confounders (e.g. hypovolemia) or special accompanying medical conditions (e.g. muscle relaxation). There is an ongoing discussion about the clinical relevance of nociceptive stimulation in general anesthesia and the effect on patient outcome. Initial results for individual monitor systems show a reduction in opioid consumption and in postoperative pain level. Nevertheless, current evidence does not enable the routine use of nociception monitoring devices to be recommended as a clear beneficial effect on long-term outcome has not yet been proven.
Article
The depth of anesthesia is commonly assessed in clinical practice by the patient’s clinical signs. However, during cardiopulmonary bypass and hypothermia, common symptoms of nociception such as tachycardia, hypertension, sweating, or movement have low sensitivity and specificity in the description of the patient nociception and hypnosis, in particular, detecting nociceptive stimuli. Better monitoring of the depth of analgesia during hypothermia under cardiopulmonary bypass will avoid underdosage or overdosage of analgesia, especially opioids. Induced hypothermia has a multifactorial effect on the level of analgesia and hypnosis. Thermoregulatory processes appear essential for the activation of analgesic mechanisms, ranging from a physiological strong negative affiliation between nerve conduction velocity and temperature, until significant repercussions on the pharmacological dynamics of the analgesic drugs, the latter decreasing the clearance rate with a subsequent increase in the effect-site concentrations. Under the hypothesis that deep hypothermia induces massive effects on the analgesia and hypnosis levels of the patient, we studied whether hypothermia effects were mirrored by several neuromonitoring indices: two hypnosis indices, consciousness index and bispectral index, and a novel nociception index designed to evaluate the analgesic depth. In this clinical trial, 39 patients were monitored during general anesthesia with coronary atherosclerosis cardiopathy who were elective for on-pump coronary artery bypass graft surgery under hypothermia. The changes and correlation between the consciousness index, bispectral index, and nociception index with respect to the temperature were compared in different timepoints at basic state, during cardiopulmonary bypass and after cardiopulmonary bypass. While the three neuromonitoring indices showed significant correlations with respect to the temperature, the nociception index and consciousness index showed the strongest sensitivities, indicating that these two indices could be an important means of intraoperative neuromonitoring during induced hypothermia under cardiopulmonary bypass.
Chapter
Starting from the first half of the nineteenth century, investigations proved that anesthetics are able to induce significant modifications in the brain's electrical activity and, in turn, in the recorded electroencephalogram (EEG). The anesthesia-related electrical activity involves different EEG correlates. Stage of anesthesia and type of anesthetics used influence EEG expression. Nevertheless, the complex waves of unprocessed EEG may not be easily interpreted. Moreover, several issues obstacle the utilization of standard EEG in anesthesia. These limitations stimulated the search for easy and solid techniques and tools. The EEG raw signal has been sectioned to extract its core element and to simplify the interpretation of the huge amount of data that it contains. Technically, the increased flexibility, speed, and economy of digital circuits, as well as progress in computer hardware and signal-processing algorithms, induced radical changes in the field of signal processing. This evolutionary process involved the application of mathematical models such as the Fourier analysis and its improvement by the bispectral (BIS) analysis. Technical advances and algorithms allowed to process the EEG raw (processing EEG, pEEG) and extrapolate values (indices) which express the depth of anesthesia (DoA) status and other features (e.g., response to noxious stimuli). Apart from the pEEG-based brain monitoring devices, other instruments work on acoustic evoked potentials. Because many mathematical models are proprietary algorithms, it is usually problematic to precisely interpret mechanisms underlying of DoA monitors.
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Cambridge Core - Anesthesia, Intensive Care, Pain Management - Taking on TIVA - edited by Michael G. Irwin
Article
Objective: To review monitors currently available for the assessment of nociception-antinociception in veterinary medicine. Databases used: PubMed, Web of Science and Google Scholar. The results were initially filtered manually based on the title and the abstract. Conclusions: The provision of adequate antinociception is difficult to achieve in veterinary anaesthesia. Currently, heart rate and arterial blood pressure are used to monitor the response to a noxious stimulus during anaesthesia, with minimum alveolar concentration-sparing effect and stress-related hormones used for this purpose in research studies. However, since none of these variables truly assess intraoperative nociception, several alternative monitoring devices have been developed for use in humans. These nociceptive-antinociceptive monitoring systems derive information from variables, such as electroencephalography, parasympathetic nervous system (PNS) response, sympathetic nervous system response and electromyography. Several of these monitoring systems have been investigated in veterinary medicine, although few have been used to assess intraoperative nociception in animals. There is controversy regarding their effectiveness and clinical use in animals. A nociceptive-antinociceptive monitoring system based on the PNS response has been developed for use in cats, dogs and horses. It uses the parasympathetic tone activity index, which is believed to detect inadequate intraoperative nociception-antinociception balance in veterinary anaesthesia. Nonetheless, there are limited published studies to date, and cardiovascular variables remain the gold standard. Consequently, further studies in this area are warranted.
Article
Nociception refers to the process of encoding and processing noxious stimuli. Its monitoring can have potential benefits. Under anesthesia, nociceptive signals are continuously generated to cause involuntary effects on the autonomic nervous system, reflex movement, and stress response. Most available systems depend on the identification and measurement of these indirect effects to indicate nociception-antinociception balance. Despite advances in monitoring technology and availability, their limitations presently override their benefits. Hence, their utility and applicability in present-day anesthesia care is uncertain. Future technologies might allow automated closed-loop multimodal anesthesia systems, which includes the components of hypnosis and analgesic balance for a patient.
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Electroencephalographic (EEG) monitoring to indicate brain state during anesthesia has become widely available. It remains unclear whether EEG-guided anesthesia influences perioperative outcomes. The sixth Perioperative Quality Initiative (POQI-6) brought together an international team of multidisciplinary experts from anesthesiology, biomedical engineering, neurology, and surgery to review the current literature and to develop consensus recommendations on the utility of EEG monitoring during anesthesia. We retrieved a total of 1023 articles addressing the use of EEG monitoring during anesthesia and conducted meta-analyses from 15 trials to determine the effect of EEG-guided anesthesia on the rate of unintentional awareness, postoperative delirium, neurocognitive disorder, and long-term mortality after surgery. After considering current evidence, the working group recommends that EEG monitoring should be considered as part of the vital organ monitors to guide anesthetic management. In addition, we encourage anesthesiologists to be knowledgeable in basic EEG interpretation, such as raw waveform, spectrogram, and processed indices, when using these devices. Current evidence suggests that EEG-guided anesthesia reduces the rate of awareness during total intravenous anesthesia and has similar efficacy in preventing awareness as compared with end-tidal anesthetic gas monitoring. There is, however, insufficient evidence to recommend the use of EEG monitoring for preventing postoperative delirium, neurocognitive disorder, or postoperative mortality.
Book
This book, based on a selection of invited presentations from a topical workshop, focusses on time-variable oscillations and their interactions. The problem is challenging, because the origin of the time variability is usually unknown. In mathematical terms, the oscillations are nonautonomous, reflecting the physics of open systems where the function of each oscillator is affected by its environment. Time-frequency analysis being essential, recent advances in this area, including wavelet phase coherence analysis and nonlinear mode decomposition, are discussed. Some applications to biology and physiology are described. Although the most important manifestation of time-variable oscillations is arguably in biology, they also crop up in, e.g. astrophysics, or for electrons on superfluid helium. The book brings together the research of the best international experts in seemingly very different disciplinary areas.
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Background The use of processed electroencephalography (pEEG) for depth of sedation (DOS) monitoring is increasing in anesthesia; however, how to use of this type of monitoring for critical care adult patients within the intensive care unit (ICU) remains unclear. Methods A multidisciplinary panel of international experts consisting of 21 clinicians involved in monitoring DOS in ICU patients was carefully selected on the basis of their expertise in neurocritical care and neuroanesthesiology. Panelists were assigned four domains (techniques for electroencephalography [EEG] monitoring, patient selection, use of the EEG monitors, competency, and training the principles of pEEG monitoring) from which a list of questions and statements was created to be addressed. A Delphi method based on iterative approach was used to produce the final statements. Statements were classified as highly appropriate or highly inappropriate (median rating ≥ 8), appropriate (median rating ≥ 7 but < 8), or uncertain (median rating < 7) and with a strong disagreement index (DI) (DI < 0.5) or weak DI (DI ≥ 0.5 but < 1) consensus. Results According to the statements evaluated by the panel, frontal pEEG (which includes a continuous colored density spectrogram) has been considered adequate to monitor the level of sedation (strong consensus), and it is recommended by the panel that all sedated patients (paralyzed or nonparalyzed) unfit for clinical evaluation would benefit from DOS monitoring (strong consensus) after a specific training program has been performed by the ICU staff. To cover the gap between knowledge/rational and routine application, some barriers must be broken, including lack of knowledge, validation for prolonged sedation, standardization between monitors based on different EEG analysis algorithms, and economic issues. Conclusions Evidence on using DOS monitors in ICU is still scarce, and further research is required to better define the benefits of using pEEG. This consensus highlights that some critically ill patients may benefit from this type of neuromonitoring.
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The aim of the present study was to develop and validate an objective index for nociception level (NoL) of patients under general anesthesia, based on a combination of multiple physiological parameters. Twenty-five patients scheduled for elective surgery were enrolled. For clinical reference of NoL, the combined index of stimulus and analgesia was defined as a composite of the surgical stimulus level and a scaled effect-site concentration of opioid. The physiological parameters heart rate, heart rate variability (0.15-0.4 Hz band power), plethysmograph wave amplitude, skin conductance level, number of skin conductance fluctuations, and their time derivatives, were extracted. Two techniques to incorporate these parameters into a single index representing the NoL have been proposed: NoLlinear, based on an ordinary linear regression, and NoLnon-linear, based on a non-linear Random Forest regression. NoLlinear and NoLnon-linear significantly increased after moderate to severe noxious stimuli (Wilcoxon rank test, p < 0.01), while the individual parameters only partially responded. Receiver operating curve analysis showed that NoL index based on both techniques better discriminated noxious and non-noxious surgical events [area under curve (AUC) = 0.97] compared with individual parameters (AUC = 0.56-0.74). NoLnon-linear better ranked the level of nociception compared with NoLlinear (R = 0.88 vs. 0.77, p < 0.01). These results demonstrate the superiority of multi-parametric approach over any individual parameter in the evaluation of nociceptive response. In addition, advanced non-linear technique may have an advantage over ordinary linear regression for computing NoL index. Further research will define the usability of the NoL index as a clinical tool to assess the level of nociception during general anesthesia.
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Background: The analgesia/nociception index (ANI), a 0-100 non-invasive index calculated from heart rate variability, reflects the analgesia/nociception balance during general anaesthesia. The aim of this study was to evaluate the ANI in the assessment of immediate postoperative pain in adult patients undergoing general anaesthesia. Methods: Two-hundred patients undergoing scheduled surgery or endoscopy with general anaesthesia were included in this prospective observational study. Pain intensity was assessed using a 0-10 numerical rating scale (NRS) after arousal from general anaesthesia. Receiver-operating characteristic (ROC) curves were built to assess the performance of ANI to detect patients with NRS>3 and NRS ≥ 7 on arrival in the postoperative care unit. Results: A negative linear relationship was observed between ANI and NRS (ANI=-5.2 × NRS+77.9, r(2)=0.41, P<0.05). At the threshold of 57, the sensitivity and specificity of ANI to detect patients with NRS>3 were 78 and 80%, respectively, with a negative predictive value of 88%, corresponding to an area under the ROC curve (AUC) of 0.86. At the threshold of 48, the sensitivity and specificity of ANI to detect NRS ≥ 7 were 92 and 82%, respectively, with a negative predictive value of 99%, corresponding to a ROC curve AUC of 0.91. Conclusions: A measurement of ANI during the immediate postoperative period is significantly correlated with pain intensity. The measurement of ANI appears to be a simple and non-invasive method to assess immediate postoperative analgesia.
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Unresolved issues with propofol include whether the pharmacokinetics are linear with dose, are influenced by method of administration (bolus vs. infusion), or are influenced by age. Recently, a new formulation of propofol emulsion, containing disodium edetate (EDTA), was introduced in the United States. Addition of EDTA was found by the manufacturer to significantly reduce bacterial growth. This study investigated the influences of method of administration, infusion rate, patient covariates, and EDTA on the pharmacokinetics of propofol. Twenty-four healthy volunteers aged 26-81 yr were given a bolus dose of propofol, followed 1 h later by a 60-min infusion. Each volunteer was randomly assigned to an infusion rate of 25, 50, 100, or 200 microg x kg(-1) x min(-1). Each volunteer was studied twice under otherwise identical circumstances: once receiving propofol without EDTA and once receiving propofol with EDTA. The influence of the method of administration and of the volunteer covariates was explored by fitting a three-compartment mamillary model to the data. The influence of EDTA was investigated by direct comparison of the measured concentrations in both sessions. The concentrations of propofol with and without EDTA were not significantly different. The concentration measurements after the bolus dose were significantly underpredicted by the parameters obtained just from the infusion data. The kinetics of propofol were linear within the infusion range of 25-200 microg x kg(-1) x min(-1). Age was a significant covariate for Volume2 and Clearance2, as were weight, height, and lean body mass for the metabolic clearance. These results demonstrate that method of administration (bolus vs. infusion), but not EDTA, influences the pharmacokinetics of propofol. Within the clinically relevant range, the kinetics of propofol during infusions are linear regarding infusion rate.
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To the Editor: Avidan and colleagues (Aug. 18 issue)(1) reported that monitoring with the use of the bispectral index (BIS), as compared with the use of the end-tidal anesthetic-agent concentration (ETAC), does not reduce awareness during anesthesia (the BIS or Anesthetic Gas to Reduce Explicit Recall [BAG-RECALL] trial; ClinicalTrials.gov number, NCT00682825). However, they did not discuss the B-Aware trial, a large trial involving almost 2500 patients, in which BIS monitoring reduced the risk of awareness in at-risk adults undergoing general anesthesia.(2) In the study by Avidan et al., general anesthesia was based on inhaled agents, whereas in the B-Aware trial, . . .
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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. 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 (C(e)pro) and remifentanil (C(e)remi) 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 C(e)pro and C(e)remi 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 (P(k)) of AAI/2, BIS, and IoC with respect to the sedation level, RSS score, was also explored. 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. P(k) 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 P(k) values of 0.81, 0.8, and 0.8 for AAI/2, BIS, and IoC, respectively. A model relating C(e)pro and C(e)remi to AAI/2, BIS, and IoC has been developed and prospectively validated. Based on these models, the (C(e)pro, C(e)remi) concentration pairs that provide an RSS score of 4 range from (1.8 μg·mL(-1), 1.5 ng·mL(-1)) to (2.7 μg·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 C(e)pro and C(e)remi to achieve the same degree of sedative effects.
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The Surgical Pleth Index (SPI) is proposed as a means to assess the balance between noxious stimulation and the anti-nociceptive effects of anaesthesia. In this study, we compared SPI, mean arterial pressure (MAP), and heart rate (HR) as a means of assessing this balance. We studied a standard stimulus [head-holder insertion (HHI)] and varying remifentanil concentrations (CeREMI) in a group of patients undergoing neurosurgery. Patients receiving target-controlled infusions were randomly assigned to one of the three CeREMI (2, 4, or 6 ng m⁻¹), whereas propofol target was fixed at 3 µg ml⁻¹. Steady state for both targets was achieved before HHI. Intravascular volume status (IVS) was evaluated using respiratory variations in arterial pressure. Prediction probability (Pk) and ordinal regression were used to assess SPI, MAP, and HR performance at indicating CeREMI, and the influence of IVS and chronic treatment for high arterial pressure, as possible confounding factors. The maximum SPI, MAP, or HR observed after HHI correctly indicated CeREMI in one of the two patients [accurate prediction rate (APR)=0.5]. When IVS and chronic treatment for high arterial pressure were taken into account, the APR was 0.6 for each individual variable and 0.8 when all of them predicted the same CeREMI. That increase in APR paralleled an increase in Pk from 0.63 to 0.89. SPI, HR, and MAP are of comparable value at gauging noxious stimulation-CeREMI balance. Their interpretation is improved by taking account of IVS, treatment for chronic high arterial pressure, and concordance between their predictions.
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Obtaining an adequate depth of anesthesia is a continuous challenge to the anesthetist. With the introduction of muscle-relaxing agents the traditional signs of awareness are often obscured, or difficult to interpret. These signs include blood pressure, heart rate, pupil size, etc. However, these factors do not describe the depth of anesthesia (DA) in a cerebral activity sense. Hence, a better measure of the DA is required. It has been suggested that Auditory-Evoked Potentials (AEP) can provide additional information about the DA. The general method of extracting AEP is by use of a Moving Time Average (MTA). However, the MTA is time consuming because a large number of repetitions is needed to produce an estimate of the AEP. Hence, changes occurring over a small number of sweeps will not be detected by the MTA average. We describe a system-identification method, an autoregressive model with exogeneous input (ARX) model, to produce a sweep-by-sweep estimate of the AEP. The method was clinically evaluated in 10 patients anesthetized with alfentanil and propofol. The time interval between propofol induction and the time when the Na-Pa amplitude was decreased to 25% of the initial amplitude was measured. These measurements showed that ARX-estimated compared to MTA-estimated AEP was significantly faster in tracing transition from consciousness to unconsciousness during propofol induction (p < 0.05).
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This paper presents the architecture and learning procedure underlying ANFIS (Adaptive-Network-based Fuzzy Inference System), a fuzzy inference system implemented in the framework of adaptive networks. By using a hybrid learning procedure, the proposed ANFIS can construct an input-output mapping based on both human knowledge (in the form of fuzzy if-then rules) and stipulated input-output data pairs. In our simulation, we employ the ANFIS architecture to model nonlinear functions, identify nonlinear components on-linely in a control system, and predict a chaotic time series, all yielding remarkable results. Comparisons with artificail neural networks and earlier work on fuzzy modeling are listed and discussed. Other extensions of the proposed ANFIS and promising applications to automatic control and signal processing are also suggested. I. Introduction System modeling based on conventional mathematical tools (e.g., differential equations) is not well suited for dealing with ill-defin...
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A mathematical tool to build a fuzzy model of a system where fuzzy implications and reasoning are used is presented. The premise of an implication is the description of fuzzy subspace of inputs and its consequence is a linear input-output relation. The method of identification of a system using its input-output data is then shown. Two applications of the method to industrial processes are also discussed: a water cleaning process and a converter in a steel-making process.
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Background: Intraoperative awareness with explicit recall occurs in approximately 0.15% of all surgical cases. Efficacy trials based on the Bispectral Index® (BIS) monitor (Covidien, Boulder, CO) and anesthetic concentrations have focused on high-risk patients, but there are no effectiveness data applicable to an unselected surgical population. Methods: We conducted a randomized controlled trial of unselected surgical patients at three hospitals of a tertiary academic medical center. Surgical cases were randomized to alerting algorithms based on either BIS values or anesthetic concentrations. The primary outcome was the incidence of definite intraoperative awareness; prespecified secondary outcomes included postanesthetic recovery variables. Results: The study was terminated because of futility. At interim analysis the incidence of definite awareness was 0.12% (11/9,376) (95% CI: 0.07-0.21%) in the anesthetic concentration group and 0.08% (8/9,460) (95% CI: 0.04-0.16%) in the BIS group (P = 0.48). There was no significant difference between the two groups in terms of meeting criteria for recovery room discharge or incidence of nausea and vomiting. By post hoc secondary analysis, the BIS protocol was associated with a 4.7-fold reduction in definite or possible awareness events compared with a cohort receiving no intervention (P = 0.001; 95% CI: 1.7-13.1). Conclusion: This negative trial could not detect a difference in the incidence of definite awareness or recovery variables between monitoring protocols based on either BIS values or anesthetic concentration. By post hoc analysis, a protocol based on BIS monitoring reduced the incidence of definite or possible intraoperative awareness compared with routine care.
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The goal of much effort in recent years has been to provide a simplified interpretation of the electroencephalogram (EEG) for a variety of applications, including the diagnosis of neurological disorders and the intraoperative monitoring of anesthetic efficacy and cerebral ischemia. Although processed EEG variables have enjoyed limited success for specific applications, few acceptable standards have emerged. In part, this may be attributed to the fact that commonly usedsignal processing tools do not quantify all of the information available in the EEG. Power spectral analysis, for example, quantifies only power distribution as a function offrequency, ignoring phase information. It also makes the assumption that thesignal arises from alinear process, thereby ignoring potential interaction betweencomponents of the signal that are manifested asphase coupling, a common phenomenon in signals generated fromnonlinear sources such as the central nervous system (CNS). This tutorial describes bispectral analysis, a method of signal processing that quantifies the degree of phase coupling between the components of a signal such as the EEG. The basic theory underlying bispectral analysis is explained in detail, and information obtained from bispectral analysis is compared with that available from thepower spectrum. The concept of abispectral index is introduced. Finally, several model signals, as well as a representative clinical case, are analyzed using bispectral analysis, and the results are interpreted.
A mathematical tool to build a fuzzy model of a system where fuzzy implications and reasoning are used is presented. The premise of an implication is the description of fuzzy subspace of inputs and its consequence is a linear input-output relation. The method of identification of a system using its input-output data is then shown. Two applications of the method to industrial processes are also discussed: a water cleaning process and a converter in a steel-making process.
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The problems of structure identification of a fuzzy model are formulated. A criterion for the verification of a structure is discussed. Using the criterion, an algorithm for identifying a structure is suggested. Further, a successive identification algorithm of the parameters is suggested. The proposed methods are applied to an example.
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Monitors of hypnotic depth help anesthesiologists to guide the anesthetic. The performance of different monitors depends on several factors, index variability at a steady state of hypnotic depth being one. We compared the recently introduced AAI1.6 with the established bispectral index (BIS), regarding index variability during stable values of propofol effect-site concentration. After ethics committee approval and written informed consent, anesthesia was performed in 40 patients with propofol as the target controlled infusion and fentanyl. Variability of BIS and AAI1.6 was calculated during periods of constant predicted propofol effect compartment concentration and constant levels of surgical stimulation as the median absolute deviation (MAD) from the median value. A variability index was calculated as 1.48*MAD/(threshold - median value), with threshold being the division line between awake and asleep. Threshold crossing time was used to evaluate the performance in predicting return of consciousness. Variability index, however, was significantly larger for the AAI1.6, despite similar absolute variability measured as MAD. Lightening of anesthesia before recovery could be noticed earlier using the BIS than the AAI1.6, although consciousness was detected with a significantly higher Pk-value by the AAI1.6. Variability in relation to the difference between the median index value during anesthesia and the threshold necessary to detect consciousness with high sensitivity is higher for the AAI1.6 than for the BIS. This, as well as the steeper concentration-response function found for AAI1.6, impairs the performance of the AAI1.6 in predicting imminent return of consciousness during decreasing propofol concentrations. However, it makes AAI1.6 well suited to detect consciousness when it has occurred.
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Incluye bibliografía e índice Reimprisión en 1992.
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The skin conductance algesimeter (SCA) reflects the sympathetic nervous system influenced by changes in emotions, which releases the acetylcholine that acts on muscarine receptors, causing a subsequent burst of sweat and increased skin conductance. The SCA reacts immediately and is not influenced by hemodynamic variability or neuromuscular blockade. The use of SCA for pain and nociceptive assessment is outlined in this review. When pain was monitored by verbal reporting in postoperative patients, the SCA had a sensitivity of about 90% and specificity up to 74% to identify the pain, better than heart rate and blood pressure. In general anesthetized patients, both the sensitivity and specificity were about 90% to detect responses to noxious stimulation when compared with clinical stress variables. The SCA reflects changes in norepeinephrine levels induced by nociception better than heart rate, blood pressure, and electroencephalograph (EEG) monitors. Unlike EEG monitors, the SCA response is sensitive to experimental noxious stimuli during general anesthesia, and the measured response was attenuated by analgesic medication. This SCA response is significantly associated with genetically modulated pain sensitivity. Moreover, noxious stimuli in artificially ventilated patients and in preterm infants increase the SCA index, and the increase correlates to the clinical discomfort. The SCA detects nociceptive pain fast and continuously, specific to the individual, with higher sensitivity and specificity than other available objective methods.
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The goal of much effort in recent years has been to provide a simplified interpretation of the electroencephalogram (EEG) for a variety of applications, including the diagnosis of neurological disorders and the intraoperative monitoring of anesthetic efficacy and cerebral ischemia. Although processed EEG variables have enjoyed limited success for specific applications, few acceptable standards have emerged. In part, this may be attributed to the fact that commonly used signal processing tools do not quantify all of the information available in the EEG. Power spectral analysis, for example, quantifies only power distribution as a function of frequency, ignoring phase information. It also makes the assumption that the signal arises from a linear process, thereby ignoring potential interaction between components of the signal that are manifested as phase coupling, a common phenomenon in signals generated from nonlinear sources such as the central nervous system (CNS). This tutorial describes bispectral analysis, a method of signal processing that quantifies the degree of phase coupling between the components of a signal such as the EEG. The basic theory underlying bispectral analysis is explained in detail, and information obtained from bispectral analysis is compared with that available from the power spectrum. The concept of a bispectral index is introduced. Finally, several model signals, as well as a representative clinical case, are analyzed using bispectral analysis, and the results are interpreted.
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An appropriate measure of performance is needed to identify anesthetic depth indicators that are promising for use in clinical monitoring. To avoid misleading results, the measure must take into account both desired indicator performance and the nature of available performance data. Ideally, anesthetic depth indicator value should correlate perfectly with anesthetic depth along a lighter-deeper anesthesia continuum. Experimentally, however, a candidate anesthetic depth indicator is judged against a "gold standard" indicator that provides only quantal observations of anesthetic depth. The standard anesthetic depth indicator is the patient's response to a specified stimulus. The resulting observed anesthetic depth scale may consist only of patient "response" versus "no response," or it may have multiple levels. The measurement scales for both the candidate anesthetic depth indicator and observed anesthetic depth are no more than ordinal; that is, only the relative rankings of values on these scales are meaningful. Criteria were established for a measure of anesthetic depth indicator performance and the performance measure that best met these criteria was found. The performance measure recommended by the authors is prediction probability PK, a rescaled variant of Kim's dy.x measure of association. This performance measure shows the correlation between anesthetic depth indicator value and observed anesthetic depth, taking into account both desired performance and the limitations of the data. Prediction probability has a value of 1 when the indicator predicts observed anesthetic depth perfectly, and a value of 0.5 when the indicator predicts no better than a 50:50 chance. Prediction probability avoids the shortcomings of other measures. For example, as a nonparametric measure, PK is independent of scale units and does not require knowledge of underlying distributions or efforts to linearize or to otherwise transform scales. Furthermore, PK can be computed for any degree of coarseness or fineness of the scales for anesthetic depth indicator value and observed anesthetic depth; thus, PK fully uses the available data without imposing additional arbitrary constraints, such as the dichotomization of either scale. And finally, PK can be used to perform both grouped- and paired-data statistical comparisons of anesthetic depth indicator performance. Data for comparing depth indicators, however, must be gathered via the same response-to-stimulus test procedure and over the same distribution of anesthetic depths. Prediction probability PK is an appropriate measure for evaluating and comparing the performance of anesthetic depth indicators.
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The pharmacokinetics and pharmacodynamics of remifentanil were studied in 65 healthy volunteers using the electroencephalogram (EEG) to measure the opioid effect. In a companion article, the authors developed complex population pharmacokinetic and pharmacodynamic models that incorporated age and lean body mass (LBM) as significant covariates and characterized intersubject pharmacokinetic and pharmacodynamic variability. In the present article, the authors determined whether remifentanil dosing should be adjusted according to age and LBM, or whether these covariate effects were overshadowed by the interindividual variability present in the pharmacokinetics and pharmacodynamics. Based on the typical pharmacokinetic and pharmacodynamic parameters, nomograms for bolus dose and infusion rates at each age and LBM were derived. Three populations of 500 individuals each, ages 20, 50, and 80 yr, were simulated base on the interindividual variances in model parameters as estimated by the NONMEM software package. The peak EEG effect in response to a bolus, the steady-state EEG effect in response to an infusion, and the time course of drug effect were examined in each of the three populations. Simulations were performed to examine the time necessary to achieve a 20%, 50%, and 80% decrease in remifentanil effect site concentration after a variable-length infusion. The variability in the time for a 50% decrease in effect site concentrations was examined in each of the three simulated populations. Titratability using a constant-rate infusion was also examined. After a bolus dose, the age-related changes in V1 and Ke0 nearly offset each other. The peak effect site concentration reached after a bolus dose does not depend on age. However, the peak effect site concentration occurs later in elderly individuals. Because the EEG shows increased brain sensitivity to opioids with increasing age, an 80-yr old person required approximately one half the bolus dose of a 20-yr old of similar LBM to reach the same peak EEG effect. Failure to adjust the bolus dose for age resulted in a more rapid onset of EEG effect and prolonged duration of EEG effect in the simulated elderly population. The infusion rate required to maintain 50% EEG effect in a typical 80-yr old is approximately one third that required in a typical 20-yr old. Failure to adjust the infusion rate for age resulted in a more rapid onset of EEG effect and more profound steady-state EEG effect in the simulated elderly population. The typical times required for remifentanil effect site concentrations to decrease by 20%, 50%, and 80% after prolonged administration are rapid and little affected by age or duration of infusion. These simulations suggest that the time required for a decrease in effect site concentrations will be more variable in the elderly. As a result, elderly patients may occasionally have a slower emergence from anesthesia than expected. A step change in the remifentanil infusion rate resulted in a rapid and predictable change of EEG effect in both the young and the elderly. Based on the EEG model, age and LBM are significant demographic factors that must be considered when determining a dosage regimen for remifentanil. This remains true even when interindividual pharmacokinetic and pharmacodynamic variability are incorporated in the analysis.
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Previous studies have reported conflicting results concerning the influence of age and gender on the pharmacokinetics and pharmacodynamics of fentanyl, alfentanil, and sufentanil. The aim of this study was to determine the influence of age and gender on the pharmacokinetics and pharmacodynamics of the new short-acting opioid remifentanil. Sixty-five healthy adults (38 men and 27 women) ages 20 to 85 y received remifentanil by constant-rate infusion of 1 to 8 micrograms.kg-1.min-1 for 4 to 20 min. Frequent arterial blood samples were drawn and assayed for remifentanil concentration. The electroencephalogram was used as a measure of drug effect. Population pharmacokinetic and pharmacodynamic modeling was performed using the software package NONMEM. The influence of volunteer covariates were analyzed using a generalized additive model. The performances of the simple (without covariates) and complex (with covariates) models were evaluated prospectively in an additional 15 healthy participants ages 41 to 84 y. The parameters for the simple three-compartment pharmacokinetic model were V1 = 4.98 l, V2 = 9.01 l, V3 = 6.54 l, Cl1 = 2.46 l/min, Cl2 = 1.69 l/min, and Cl3 = 0.065 l/min. Age and lean body mass were significant covariates. From the ages of 20 to 85 y, V1 and Cl1 decreased by approximately 25% and 33%, respectively. The parameters for the simple sigmoid Emax pharmacodynamic model were Ke0 = 0.516 min-1, E0 = 20 Hz, Emax = 5.62 Hz, EC50 = 11.2 ng/ml, and gamma = 2.51. Age was a significant covariate of EC50 and Ke0, with both decreasing by approximately 50% for the age range studied. The complex pharmacokinetic-pharmacodynamic model performed better than did the simple model when applied prospectively. This study identified (1) an effect of age on the pharmacokinetics and pharmacodynamics of remifentanil; (2) an effect of lean body mass on the pharmacokinetic parameters; and (3) no influence of gender on any pharmacokinetic or pharmacodynamic parameter.
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The authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect. The authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in persons older than 65 yr) and an infusion (25, 50, 100, or 200 microg x kg(-1) x min(-1)) of the older or the new (containing EDTA) formulation of propofol were given on each of two different study days. The propofol concentration was determined in frequent arterial samples. The electroencephalogram (EEG) was used to measure drug effect. A statistical technique called semilinear canonical correlation was used to select components of the EEG power spectrum that correlated optimally with the effect-site concentration. The effect-site concentration was related to drug effect with a biphasic pharmacodynamic model. The plasma effect-site equilibration rate constant was estimated parametrically. Estimates of this rate constant were validated by comparing the predicted time of peak effect with the time of peak EEG effect. The probability of being asleep, as a function of age, was determined from steady state concentrations after 60 min of propofol infusion. Twenty-four volunteers completed the study. Three parameters of the biphasic pharmacodynamic model were correlated linearly with age. The plasma effect-site equilibration rate constant was 0.456 min(-1). The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6 min (range, 1-2.4 min). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C50 values for loss of consciousness of 2.35, 1.8, and 1.25 microg/ml in volunteers who were 25, 50, and 75 yr old, respectively. Semilinear canonical correlation defined a new measure of propofol effect on the EEG, the canonical univariate parameter for propofol. Using this parameter, propofol plasma effect-site equilibration is faster than previously reported. This fast onset was confirmed by inspection of the EEG data. Elderly patients are more sensitive to the hypnotic and EEG effects of propofol than are younger persons.
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Unlabelled: Bispectral index (BIS) is an electroencephalographic variable promoted for measuring depth of anesthesia. Electromyographic activity influences surface electroencephalography and the calculation of BIS. In this study, we sought to determine the effect of spontaneous electromyographic activity on BIS. BIS was monitored in three volunteers by using an Aspect A-1000 monitor. The experiment was repeated in one volunteer. Electromyographic activity was recorded. Alcuronium and succinylcholine were administered. No other drugs were used. In parallel with spontaneous electromyographic activity of the facial muscles, BIS decreased in response to muscle relaxation to a minimum value of 33 and, in the repeated measurement, to a minimum value of 9 when total neuromuscular block was achieved. In two volunteers, no total block was achieved. BIS decreased to a minimal value of 64 and 57, respectively. In turn, recovery of BIS coincided with the reappearance of spontaneous electromyographic activity. During the entire experiment, the volunteers had full consciousness. BIS, assessed by software Version 3.31, correlates with spontaneous electromyographic activity of the facial muscles. BIS failed to detect awareness in completely paralyzed subjects. Thus, in paralyzed patients, BIS monitoring may not reliably indicate a decline in sedation and imminent awareness. Implications: The bispectral index (BIS) is an electroencephalographic variable intended for measuring depth of anesthesia. Electromyographic activity influences the calculation of BIS. We found that the administration of a muscle relaxant to unanesthetized volunteers decreases the bispectral index value. Thus, awareness in totally paralyzed patients cannot be excluded.
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The auditory evoked potential (AEP) monitor provides an electroencephalogram-derived index (AAI) that has been reported to correlate with the central nervous system depressant effects of anesthetic drugs. This clinical utility study was designed to test the hypothesis that AAI-guided administration of the maintenance anesthetics and analgesics would improve their titration and thereby provide a faster recovery from general anesthesia. Seventy consenting patients undergoing elective general surgery procedures were randomly assigned to either a control (standard clinical practice) or AEP-monitored group. Although the AEP monitor was connected to all patients, the information from the monitor was only made available to the anesthesiologists assigned to patients in the AEP-monitored group. In the AEP-monitored group, the inspired desflurane concentration was titrated to maintain an AAI value of 15-20. In the control group, the inspired desflurane concentration was varied based on standard clinical signs. The AAI values and hemodynamic variables, as well as end-tidal desflurane concentrations, were recorded at 3- to 5-min intervals. The recovery times to achieve a White fast-track score greater than 12 and an Aldrete score of 10, as well as the actual duration of the PACU stay, were evaluated at 5- to 10-min intervals. Patient satisfaction with recovery from anesthesia was assessed using a 100-point verbal rating scale at 24 h after surgery. The average intraoperative AAI value in the AEP-monitored group was significantly higher than in the control group (16 +/- 5 vs. 11 +/- 8, P < 0.05). Use of the AEP monitor reduced the desflurane requirement by 26% compared to the control group (P < 0.01). In addition, the AEP-monitored group received less intraoperative fentanyl (270 +/- 120 vs. 390 +/- 203 microg, P < 0.05) and more rapidly achieved fast-track eligibility (29 +/- 19 vs. 56 +/- 41 min, P < 0.05). The time required to achieve an Aldrete score of 10 (60 +/- 31 vs. 98 +/- 55 min) and the duration of stay in the recovery room (78 +/- 32 vs. 106 +/- 54 min) were also significantly reduced in the AEP-monitored (vs. control) group (P < 0.05). Use of AEP monitoring as an adjunct to standard clinical monitors improved titration of anesthetic drugs, thereby facilitating the early recovery process after laparoscopic surgery.
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Little is known about the effect of anesthetic management on long-term outcomes. We designed a prospective observational study of adult patients undergoing major noncardiac surgery with general anesthesia to determine if mortality in the first year after surgery is associated with demographic, preoperative clinical, surgical, or intraoperative variables. One-year mortality was 5.5% in all patients (n = 1064) and 10.3% in patients > or =65 yr old (n=243). Multivariate Cox Proportional Hazards modeling identified three variables as significant independent predictors of mortality: patient comorbidity (relative risk, 16.116; P <0.0001), cumulative deep hypnotic time (Bispectral Index <45) (relative risk=1.244/h; P=0.0121) and intraoperative systolic hypotension (relative risk=1.036/min; P=0.0125). Death during the first year after surgery is primarily associated with the natural history of preexisting conditions. However, cumulative deep hypnotic time and intraoperative hypotension were also significant, independent predictors of increased mortality. These associations suggest that intraoperative anesthetic management may affect outcomes over longer time periods than previously appreciated.
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Studies on monitoring the depth of anaesthesia have shown that with the use of these monitors the peroperative consumption of anaesthetics can be reduced. Studies have also indicated that the peroperative depth of anaesthesia may affect the postoperative course. The purpose of this study was to evaluate a possible relation between the depths of anaesthesia and the postoperative pain score and consumption of morphine. We used middle latency auditory evoked potentials (MLAEPs) for monitoring the depth of anaesthesia. The study was prospective, observer blinded and included 50 women sche