Article

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

July 2014
Acta Anaesthesiologica Scandinavica 58(8)

DOI:10.1111/aas.12359

Source
PubMed

Authors:

Erik Weber Jensen

Quantium Medical

Jose Fernando Valencia

Universidad de San Buenaventura, Cali, Colombia

Ana M López

Ziekenhuis Oost-Limburg Genk (Belgium) and Hospital Clinic Barcelona

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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.

Real-time evaluation of the independent analgesic efficacy of dexmedetomidine

Article

Full-text available

Mar 2023
BMC Anesthesiol

Background Dexmedetomidine has analgesic properties, but the intraoperative analgesic effect of dexmedetomidine is often masked by the effects of other general anaesthetics. Therefore, the degree to which it reduces intraoperative pain intensity remains unclear. The objective of this double-blind, randomised controlled trial was to evaluate the independent intraoperative analgesic efficacy of dexmedetomidine in real-time. Methods This single-centre study enrolled 181 patients who were hospitalised for below-knee orthopaedic surgeries between 19 January 2021 to 3 August 2021 were eligible for this is single-centre study. Peripheral neural block was performed on patients scheduled for below-knee orthopaedic surgeries. Patients were randomly assigned to the dexmedetomidine or midazolam group and were intravenously administered with 1.5 µg kg ⁻¹ h ⁻¹ dexmedetomidine or 50 µg kg ⁻¹ h ⁻¹ midazolam, respectively. The analgesic efficacy was evaluated using the real-time non-invasive nociception monitoring. The primary endpoint was the attainment rate of the nociception index target. The secondary endpoints included the occurrence of intraoperative hypoxemia, haemodynamic parameters, the consciousness index, electromyography and patient outcomes. Results On Kaplan–Meier survival analysis, the defined nociception index target was attained in 95.45% and 40.91% of patients receiving dexmedetomidine and midazolam, respectively. Log-rank analysis revealed that the dexmedetomidine group attained the nociception index target significantly faster and the median attainment time of the nociception index target in the dexmedetomidine group was 15 min. Dexmedetomidine group was associated with a significantly lower incidence of hypoxemia. There was no significant difference in blood pressure between the dexmedetomidine and midazolam groups. Further, the dexmedetomidine group had a lower maximum visual analogue scale score and lower analgesic consumption postoperatively. Conclusions Dexmedetomidine has independent analgesia and systemically administered as an adjuvant agent has better analgesic efficacy than midazolam without severe side effects. Trial registration clinicaltrial.gov Registry Identifier: NCT-04675372.Registered on 19/12 /2020.

Evaluation of Nociception during Pediatric Surgery: A Topical Review

Article

Full-text available

Jan 2023

The association between intraoperative nociception and increased patient’s morbidity is well established. However, hemodynamic parameters, such as heart rate and blood pressure, may result in an inadequate monitor of nociception during surgery. Over the last two decades, different devices have been marketed to “reliably” detect intraoperative nociception. Since the direct measure of nociception is impractical during surgery, these monitors measures nociception surrogates such as sympathetic and parasympathetic nervous systems responses (heart rate variability, pupillometry, skin conductance), electroencephalographic changes, and muscular reflex arc. Each monitor carries its own advantages and disadvantages. The manuscript aims to give an overview of the most up-to-date information available in the literature on current nociceptor monitors available in clinical practice, with particular focus on their applications in pediatrics.

Relationship between ANI and qNOX and between MAC and qCON during outpatient laparoscopic cholecystectomy using remifentanil and desflurane without muscle relaxants: a prospective observational preliminary study

Article

Full-text available

Apr 2022
J Clin Monit Comput

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.

Processed EEG as a Measure of Brain Activity During Anaesthesia

Chapter

May 2021

IntroductionMartínez-Vázquez, Pablo toGambús, Pedro L. depthWeber Jensen, Erik of anaesthesiaAnaesthesia monitoring, a crucial tool to guide anaesthesiologist for safer surgical procedures. Description of the main EEG activity changes induced by hypnotic anaesthetic agents and the distinct analysis perspectives in their characterizations. Design principles, minimal validation requirements, limitations and current challenges.

The Effects of Intraoperative Remifentanil Infusion on Postoperative Opioid Consumption in Patients Who Underwent Total Knee Arthroplasty with Femoral Nerve Block

Article

Full-text available

Jul 2023

(1) Background: Remifentanil is used for intraoperative pain control; however, it has several side effects, such as hypotension and opioid-induced hyperalgesia. We aimed to determine whether an intraoperative remifentanil infusion may increase postoperative opioid consumption in patients undergoing total knee arthroscopy (TKA) under femoral nerve block (FNB) in addition to general anesthesia. (2) Methods: We randomly assigned 66 patients who underwent total knee arthroplasty to the remifentanil (R) and control (C) groups. All patients underwent FNB and popliteal artery and posterior capsule of the knee (iPACK) block in addition to sevoflurane-based general anesthesia. Postoperative pain control was achieved using intravenous patient-controlled analgesia (IV-PCA) fentanyl. We recorded IV-PCA fentanyl consumption at various postoperative timepoints, numerical rating scale (NRS) scores, intraoperative changes in vital signs and index of nociception (qNOX), ephedrine consumption, postoperative side effects, satisfaction, and sleep quality. (3) Results: The primary outcome (the cumulative IV-PCA fentanyl usage within 48 h postoperatively) was significantly lower in the C group (541.1 ± 294.5 µg) than in the R group (717.5 ± 224.0 µg) (p < 0.001). The secondary outcome (the cumulative IV-PCA fentanyl usage within 12, 24, and 72 h) was lower in the C group than in the R group and the mean arterial pressure was lower in the R group than in the C group from immediately after tourniquet on to immediately after tourniquet off. The heart rate was lower in the R group from immediately after incision to immediately after irrigation. There was no significant between-group difference in the perioperative qNOX and NRS scores at rest and activity except for NRS scores at 72 h postoperatively. Ephedrine use was higher in the R group than in the C group (p = 0.003). There was no significant between-group difference in the incidence of postoperative nausea and vomiting, nor in the postoperative satisfaction and sleep quality. (4) Conclusions: Avoiding intraoperative remifentanil infusion may reduce total opioid consumption in patients undergoing FNB before TKA.

Nociception Monitoring

Article

Jan 2023

Tissue damage and inflammation-induced nociception during surgery are the primary reasons for administering general anesthesia to the patient. During general anesthesia, analgesics inhibit autonomic and somatic responses, hypnotic agents prevent awareness, and neuromuscular blocking agents inhibit reflex movements. Careful monitoring of the effects of general anesthesia is necessary to avoid over- or under-dosing of anesthetics and thus to prevent associated complications and adverse effects. In general, hemodynamic parameters have been used to guide the intraoperative administration of analgesics such as opioids, but hemodynamic parameters are not standardized and cannot always provide a clear assessment. There is growing interest in techniques that can objectively monitor the analgesic component of anesthesia to achieve an appropriate balance of nociception and anti-nociception and to guide analgesic administration. The purpose of this review is to provide information about nociception monitoring techniques, which are increasingly used in clinical practice. Keywords: General anesthesia, nociception, anti-nociception, monitoring

Analysis of the effectiveness of sphenopalatine ganglion block on fentanyl needs in endoscopic endonasal surgery as measured by qNOX score

Article

Full-text available

Nov 2022

Introduction: Endoscopic endonasal is one of the technological advances used as a supporting examination for diagnosis and therapy. This procedure is often used to evaluate medical problems of the nose and sinuses, such as functional endoscopic sinus surgery or FESS (functional endoscopic sinus surgery), turbinoplasty, and septoplasty. Surgery can be difficult to manage because there is often bleeding due to the large supply of blood vessels in the sinus area. This study aimed to investigate differences in qNOX scores and fentanyl requirement in patients undergoing endoscopic endonasal surgery with sphenopalatine ganglion block. Methods: The total sample was 18 patients, with each treatment 9 patients. Patients were divided into two groups: group 1 patients who received sphenopalatine ganglion block with 0.75% ropivacaine and group 2 patients who did not receive a block. The selection of patients in groups 1 or 2 was done randomly (simple random) using lottery numbers and with a single blind. Result: Statistical analysis showed significant differences in intraoperatively in qNOX scores at the 5th, 10th, 15th and 20th minute and the mean qNOX score in the first 1 hour between the control group and the sphenopalatine ganglion block group. Significant differences were also found in fentanyl requirement between the control group and intraoperative sphenopalatine ganglion block, where fentanyl requirement was lower in the treatment group. Conclusion: The sphenopalatine ganglion block is a useful adjunct in patients undergoing endoscopic surgery and may reduce the need for fentanyl. In addition, it can provide a more stable qNOX score

Different perspectives for monitoring nociception during general anesthesia

Article

Full-text available

Feb 2022

Safe anesthesia is achieved using objective methods that estimate the patient’s state during different phases of surgery. A patient’s state under anesthesia is characterized by three major aspects, which are linked to the main effects produced by each of the families of anesthetic agents administered: hypnosis, analgesia, and muscular relaxation. While quantification techniques designed to assess muscular relaxation under neuromuscular blocking agents have a relatively long history with a high degree of standardization and understanding (e.g., the train-of-four), the knowledge and techniques used to the depth of hypnosis assessment suffer from a lesser degree in both standardization and interpretation due to brain complexity. The problem of standardization and interpretation in the analgesia and nociception assessment increases since it involves more systems, the central nervous system, and the autonomic nervous system. This helps to explain why there are multiple a priori valid approaches to develop nociception monitoring from different interpretations and physiological bases of noxious stimuli processing. Thus, in this review, the current monitoring technologies clinically available for estimating a patient’s nociception under general anesthesia are described.

The use of CONOX as a guide to the general anesthesia on laparotomy patients compared with standard clinical care – A pilot study

Article

Full-text available

Jul 2021

Background: Avoiding excessive doses of anesthesia was fundamental, mainly to reduce the adverse effect of anesthesia. Electroencephalography (EEG)-based monitors can be used to measure the depth level of anesthesia and guide intraoperative hypnosis drug and opioid administration. This study aims to evaluate the benefit of using CONOX monitor when administering anesthesia drugs in laparotomy procedures. Method: Twenty patients aged 18-65 years with physical status ASA I-III who underwent major laparotomy surgery with general anesthesia total intravenous anesthesia (TIVA) were divided into two groups. Group A received general anesthesia guided with the CONOX monitor, while group B using standard clinical care. We later evaluate the total use of propofol and fentanyl, intraoperative hemodynamic profile, postoperative cognitive disorder (POCD), intraoperative awareness, postoperative nausea and vomiting (PONV), and moderate to severe pain in the post-anesthesia care unit (PACU). Results: The mean total propofol used is lower in CONOX group (63.6 ± 11.7 mcg/kg/min vs. 74 ± 17.87 mcg/kg/min). A similar result was obtained with fentanyl. The CONOX group use a lower total of fentanyl (212.5 ± 32.3 mcg vs. 249 ± 54.6 mcg) than the control group. POCD was found to be more prevalent in the control group (5 vs 2 patients). While there is no report of intraoperative awareness. Conclusion: The incidence of PONV and moderate to severe pain in PACU was similar between the two groups. This pilot study is a preliminary study to evaluate the benefit of using EEG-based monitors to adjust anesthesia drugs.

The Effectiveness of Intraoperative Ketamine and Fentanyl as Preemptive Analgesia Assessed with qNOX Score

Article

Jul 2021

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.

Multiparametric Monitoring of Hypnosis and Nociception-Antinociception Balance during General Anesthesia—A New Era in Patient Safety Standards and Healthcare Management

Article

Full-text available

Feb 2021
MED LITH

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.

Multiparametric Monitoring of Hypnosis and Nociception-Antinociception Balance During General Anesthesia - A New Era in Patient Safety Standards and Healthcare Management

Preprint

Jan 2021

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.

Article

Full-text available

Dec 2020

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.

Predicting unconsciousness after propofol administration: qCON, BIS, and ALPHA band frequency power

Article

Full-text available

Aug 2021
J Clin Monit Comput

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.

Feasibility of the pupillary pain index as a guide for depth of analgesia during opioid-sparing anesthesia with continuous infusion of dexmedetomidine

Article

Full-text available

Aug 2023

Background The pupillary dilation reflex (PDR) is an objective indicator of analgesic levels in anesthetized patients. Through measurement of the PDR during increasing tetanic stimulation (10–60 mA), it is possible to obtain the pupillary pain index (PPI), a score that assesses the level of analgesia. Objectives The depth of analgesia during opioid-sparing anesthesia (OSA) with continuous infusion of dexmedetomidine in addition to general anesthesia was assessed. Design Observational prospective feasibility pilot study Setting This study was performed in the operating rooms of the Spedali Civili University-affiliated hospital of Brescia, Italy. Patients Forty-five adults who underwent elective open (5-cm incision) surgery under general anesthesia (78% inhalation anesthesia), from Feb. 18th to Aug. 1st, 2019, were enrolled. Exclusion criteria were as follows: implanted pacemaker or ICD, ophthalmological comorbidities, chronic opioid use, peripheral neuropathy, other adjuvant drugs, epidural analgesia, or locoregional block. Main outcome measures The first aim was to verify the feasibility of applying a study protocol to evaluate the depth of analgesia during intraoperative dexmedetomidine administration using an instrumental pupillary evaluation. The secondary outcome was to evaluate appropriate analgesia, drug dosage, anesthesia depth, heart rate, blood pressure, transient side effects, postoperative nausea and vomiting (PONV), and pain numerical rating scale (NRS) score. Results Thirty out of 50 patients (60%) treated with dexmedetomidine during the study period were included in the DEX group (8 males, age 42 ± 13 years, BMI 45 ± 8), and 15 other patients were included in the N-DEX group (8 males, age 62 ± 13 years, BMI 26 ± 6). Patients who underwent bariatric, abdominal, or plastic surgery were enrolled. At least 3 pupillary evaluations were taken for each patient. PPI ≤ 3 was observed in 97% of patients in the DEX group and 53% in the N-DEX group. Additionally, the DEX group received less than half the remifentanil dose than the N-DEX group (0.13 ± 0.07 vs 0.3 ± 0.11 mcg kg ⁻¹ min ⁻¹ ). The average dose of dexmedetomidine administered was 0.17 ± 0.08 mcg kg ⁻¹ h ⁻¹ . Conclusion The feasibility of applying the protocol was verified. An OSA strategy involving dexmedetomidine may be associated with improved analgesic stability: a randomized controlled trial is necessary to verify this hypothesis. Trial registration Trial.gov registration number: NCT05785273

An in-depth analysis of parameter settings and probability distributions of specific ordinal patterns in the Shannon permutation entropy during different states of consciousness in humans

Article

Full-text available

Jul 2023
J Clin Monit Comput

As electrical activity in the brain has complex and dynamic properties, the complexity measure permutation entropy (PeEn) has proven itself to reliably distinguish consciousness states recorded by the EEG. However, it has been shown that the focus on specific ordinal patterns instead of all of them produced similar results. Moreover, parameter settings influence the resulting PeEn value. We evaluated the impact of the embedding dimension m and the length of the EEG segment on the resulting PeEn. Moreover, we analysed the probability distributions of monotonous and non-occurring ordinal patterns in different parameter settings. We based our analyses on simulated data as well as on EEG recordings from volunteers, obtained during stable anaesthesia levels at defined, individualised concentrations. The results of the analysis on the simulated data show a dependence of PeEn on different influencing factors such as window length and embedding dimension. With the EEG data, we demonstrated that the probability P of monotonous patterns performs like PeEn in lower embedding dimension (m = 3, AUC = 0.88, [0.7, 1] in both), whereas the probability P of non-occurring patterns outperforms both methods in higher embedding dimensions (m = 5, PeEn: AUC = 0.91, [0.77, 1]; P(non-occurring patterns): AUC = 1, [1, 1]). We showed that the accuracy of PeEn in distinguishing consciousness states changes with different parameter settings. Furthermore, we demonstrated that for the purpose of separating wake from anaesthesia EEG solely pieces of information used for PeEn calculation, i.e., the probability of monotonous patterns or the number of non-occurring patterns may be equally functional.

Electroencephalographic monitoring of anesthesia during surgical procedures in mice using a modified clinical monitoring system

Article

Full-text available

Jul 2023
J Clin Monit Comput

Monitoring brain activity and associated physiology during the administration of general anesthesia (GA) in mice is pivotal to guarantee postanesthetic health. Clinically, electroencephalogram (EEG) monitoring is a well-established method to guide GA. There are no established methods available for monitoring EEG in mice (Mus musculus) during surgery. In this study, a minimally invasive rodent intraoperative EEG monitoring system was implemented using subdermal needle electrodes and a modified EEG-based commercial patient monitor. EEG recordings were acquired at three different isoflurane concentrations revealing that surgical concentrations of isoflurane anesthesia predominantly contained burst suppression patterns in mice. EEG suppression ratios and suppression durations showed strong positive correlations with the isoflurane concentrations. The electroencephalographic indices provided by the monitor did not support online monitoring of the anesthetic status. The online available suppression duration in the raw EEG signals during isoflurane anesthesia is a straight forward and reliable marker to assure safe, adequate and reproducible anesthesia protocols.

The effect-site concentration of remifentanil blunting endotracheal intubation responses during anesthesia induction with etomidate: a dose-finding study

Article

Full-text available

Jun 2023
BMC Anesthesiol

Background Remifentanil can inhibit the hemodynamic responses caused by endotracheal intubation, but the effect-site concentration of it required to control intubation responses when combined with etomidate has not been demonstrated. The purpose of this study was to determine the effect-site concentration of remifentanil blunting tracheal intubation responses in 50% and 95% of patients (EC50 and EC95) during etomidate anesthesia. Methods American Society of Anesthesiologists physical status (ASA) I-II elective surgical patients receiving target-controlled infusion (TCI) of remifentanil, followed by etomidate and rocuronium for anesthesia were enrolled. The Belive Drive A2 monitor was used to calculate the MGRSSI (Maygreen Sedative state index) of hypnotic effect and the MGRNOX (Maygreen Nociception index) of nociception. The MGRSSI and the MGRNOX value were generated every 1 s. Mean arterial pressure (MAP) and heart rate (HR) were measured every minute, noninvasively. Using the modified Dixon’s up-and-down method, the concentration of remifentanil was determined based on the intubation response of the previous patient. The cardiovascular response during endotracheal intubation was defined as positive when MAP or HR is 20% higher than the pre-intubation value. A probit analysis was used for calculating EC50, EC95 and 95% confidence interval (CI). Results The EC50 and EC95 of remifentanil blunting tracheal intubation responses were found to be 7.731 ng/ml (95%CI: 7.212–8.278 ng/ml) and 8.701 ng/ml (95%CI: 8.199–11.834 ng/ml). There were statistically significant increases in HR, MGRSSI and MGRNOX value to tracheal intubation in the positive responses group compared to the negative group. The most common adverse event was postoperative nausea and vomiting, which occurred in 3 patients. Conclusion Remifentanil effect-site concentration of 7.731 ng/ml is effective in blunting sympathetic responses to tracheal intubation in 50% of patients when combined with etomidate anesthesia. Trial registration The trial was registered at the Chinese Clinical Trials Registry (www.chictr.org.cn, registration number: ChiCTR2100054565, date of registration: 20/12/2021).

Electroencephalographic monitoring of anesthesia during surgical procedures in mice using a standard clinical system

Preprint

Full-text available

Apr 2023

Monitoring brain activity and associated physiology during the administration of general anesthesia (GA) is pivotal to guarantee postanesthetic health. Clinically, electroencephalogram (EEG) monitoring is a well-established method to guide GA. There are no methods available for monitoring EEG in mice ( Mus musculus ) during surgery. Non-invasive methods of anesthetic level monitoring are limited to oximetry, capnometry, respiratory rate and the color of the mucous membrane. These methods lack direct access to the brain which is the primary target of GA. In this study, a minimally invasive rodent intraoperative EEG monitoring system was implemented using subdermal needle electrodes and a modified EEG-based commercial patient monitor. EEG recordings with the monitoring system revealed that surgical concentrations of isoflurane anesthesia predominantly contained burst suppression patterns in mice. EEG suppression ratios and durations showed strong correlations with the isoflurane concentrations. The suppression duration in the raw EEG signals during isoflurane anesthesia is an easy-to-detect and reliable marker to assure safe, adequate and reproducible anesthesia protocols.

Effects of qCON and qNOX-guided general anaesthesia management on patient opioid use and prognosis: a study protocol

Article

Full-text available

May 2023

Introduction The adverse effects of general anaesthetic drugs (especially opioids) cannot be ignored. However, current nociceptive-monitoring techniques still lack consistency in guiding the use of opioids. This trial will study the demand for opioid use and patient prognosis in qCON and qNOX-guided general anaesthesia management. Methods and analysis This prospective, randomised, controlled trial will randomly recruit 124 patients undergoing general anaesthesia for non-cardiac surgery in equal numbers to either the qCON or BIS group. The qCON group will adjust intraoperative propofol and remifentanil dosage according to qCON and qNOX values, while the BIS group will adjust according to BIS values and haemodynamic fluctuations. The differences between the two groups will be observed in remifentanil dosing and prognosis. The primary outcome will be intraoperative remifentanil use. Secondary outcomes will include propofol consumption; the predictive ability of BIS, qCON and qNOX on conscious responses, noxious stimulus and body movements; and changes in cognitive function at 90 days postoperatively. Ethics and dissemination This study involves human participants and was approved by the Ethics Committee of the Tianjin Medical University General Hospital (IRB2022-YX-075-01). Participants gave informed consent to participate in the study before taking part. The study results will be published in peer-reviewed journals and presented at relevant academic conferences. Trial registration number ChiCTR2200059877

Index of consciousness monitoring during general anesthesia may effectively enhance rehabilitation in elderly patients undergoing laparoscopic urological surgery: a randomized controlled clinical trial

Preprint

Full-text available

Mar 2023

Background Elderly patients are at a significantly higher risk of perioperative complications. Based on electroencephalogram (EEG) analysis, index of consciousness (IoC) monitoring is a new technique for monitoring anesthesia depth. IoC is divided into two parts: IoC1 (depth of sedation) and IoC2 (depth of analgesia). There have only been a few studies in which IoC1 and IoC2 are simultaneously monitored to speed up postoperative recovery. We investigated whether combined monitoring of IoC1 and IoC2 can effectively improve postoperative recovery in elderly patients undergoing laparoscopic urological surgery under general anesthesia. Methods A prospective, randomized, controlled, double-blind trial was carried out on elderly patients scheduled for laparoscopic urological surgery under total intravenous anesthesia. Patients were assigned to either the IoC group (n = 60) or control group (n = 60) at random. The prevalence of postoperative cognitive dysfunction (POCD) was the primary endpoint. Inflammatory markers, arterial blood gas analysis, postoperative complications, and length of hospital stay were among the secondary endpoints. Results The study included 120 patients with an average age of 71.20 ± 5.06 years. Compared to the control group, the incidence of POCD was significantly lower (19(31.7%) vs. 6(10%); P = 0.003), and serum C-reactive protein(CRP) and glial fibrillary acidic protein(GFAP) concentrations were lower at the end of surgery (CRP: 5.36 ± 3.36 vs. 3.11 ± 2.62; P = 0.000, GFAP: 3.29 ± 1.22 vs. 2.42 ± 1.38; P = 0.000) and 24h after surgery (CRP:11.75 ± 7.52 vs. 8.15 ± 5.24;P = 0.003, GFAP: 4.84 ± 1.20 vs. 3.96 ± 2.23; P = 0.008) in the IoC group. Blood glucose levels at the end of surgery (9.17 ± 2.04 vs. 7.11 ± 1.35; P = 0.000) and the total rate of complications at 7 days after surgery (16(26.7%) vs. 7(11.7%), P = 0.037) were significantly lower in the IoC group. Conclusion IoC monitoring for managing elderly surgical patients can hasten postoperative recovery by reducing intraoperative stress and the resulting systemic and neuroinflammation. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1900025241（17/08/2019）.

Variations of qCON and qNOX during tracheal suction in ICU patients on sedation and curarization for SARS-CoV2 pneumonia: a retrospective study

Article

Apr 2023

EEG responses to standardised noxious stimulation during clinical anaesthesia: a pilot study

Article

Full-text available

Mar 2023

Background During clinical anaesthesia, the administration of analgesics mostly relies on empirical knowledge and observation of the patient's reactions to noxious stimuli. Previous studies in healthy volunteers under controlled conditions revealed EEG activity in response to standardised nociceptive stimuli even at high doses of remifentanil and propofol. This pilot study aims to investigate the feasibility of using these standardised nociceptive stimuli in routine clinical practice. Methods We studied 17 patients undergoing orthopaedic trauma surgery under general anaesthesia. We evaluated if the EEG could track standardised noxious phase-locked electrical stimulation and tetanic stimulation, a time-locked surrogate for incisional pain, before, during, and after the induction of general anaesthesia. Subsequently, we analysed the effect of tetanic stimulation on the surgical pleth index as a peripheral, vegetative, nociceptive marker. Results We found that the phase-locked evoked potentials after noxious electrical stimulation vanished after the administration of propofol, but not at low concentrations of remifentanil. After noxious tetanic stimulation under general anaesthesia, there were no consistent spectral changes in the EEG, but the vegetative response in the surgical pleth index was statistically significant (Hedges' g effect size 0.32 [95% confidence interval 0.12–0.77], P=0.035). Conclusion Our standardised nociceptive stimuli are not optimised for obtaining consistent EEG responses in patients during clinical anaesthesia. To validate and sufficiently reproduce EEG-based standardised stimulation as a marker for nociception in clinical anaesthesia, other pain models or stimulation settings might be required to transfer preclinical studies into clinical practice. Clinical trial registration DRKS00017829.

Nociception monitors vs. standard practice for titration of opioid administration in general anesthesia: A meta-analysis of randomized controlled trials

Article

Full-text available

Aug 2022

Background Nociception monitors are being increasingly used during surgery, but their effectiveness in guiding intraoperative opioid administration is still uncertain. This meta-analysis of randomized controlled trials (RCTs) aimed to compare the effectiveness of nociception monitors vs. standard practice for opioid administration titration during general anesthesia. Methods We searched the electronic databases of PubMed, EMBASE, Cochrane Library, Clinical Trial, and Web of Science from inception up to August 1, 2021, to identify relevant articles, and extracted the relevant data. Intraoperative opioid administration, extubation time, postoperative pain score, postoperative opioid consumption and postoperative nausea and vomiting (PONV) were compared between patients receiving nociception monitoring guidance and patients receiving standard management. The standardized mean difference (SMD), with 95% confidence interval (CI), was used to assess the significance of differences. The risk ratio (RR), with 95% CI, was used to assess the difference in incidence of PONV. Heterogeneity among the included trials was evaluated by the I ² test. RevMan 5.3 software was used for statistical analysis. Results A total of 21 RCTs (with 1957 patients) were included in the meta-analysis. Intraoperative opioid administration was significantly lower in patients receiving nociception monitor-guided analgesia than in patients receiving standard management (SMD, −0.71; 95% CI, −1.07 to −0.36; P < 0.001). However, pain scores and postoperative opioid consumption were not significantly higher in the former group. Considerable heterogeneity was found among the studies (92%). Extubation time was significantly shorter (SMD, −0.22; 95% CI, −0.41 to −0.03; P = 0.02) and the incidence of PONV significantly lower (RR, 0.78; 95% CI, 0.61 to 1.00; P = 0.05) in patients receiving nociception monitoring guidance. Conclusions Intraoperative nociception monitoring guidance may reduce intraoperative opioid administration and appears to be a viable strategy for intraoperative titration of opioids. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=273619 , identifier: CRD42019129776.

Processed Electroencephalogram-Based Monitoring to Guide Sedation in Critically Ill Adult Patients: Recommendations from an International Expert Panel-Based Consensus

Article

Full-text available

Jul 2022

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.

Comparison of Quantium Consciousness Index and Richmond Agitation Sedation Scale in Mechanically Ventilated Critically Ill Patients: An Observational Study

Article

Full-text available

Mar 2022

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.

Progress of Brain Network Studies on Anesthesia and Consciousness: Framework and Clinical Applications

Article

Full-text available

Nov 2021

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.

Intraoperative Nociception Monitoring by qNOX Score Using Three Different Doses of Fentanyl

Article

Full-text available

Oct 2021

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.

USG Guided Quadaratus Lumburoum Block and Low Dose Spinal Anesthesia in Abdominal Surgeries

Article

Full-text available

Sep 2021

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.

The influence of age on EEG-based anaesthesia indices

Article

Oct 2021
J CLIN ANESTH

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 influence of moderate or deep neuromuscular block status on anesthetic depth monitoring system during total intravenous anesthesia using propofol and remifentanil: A randomized trial

Article

Full-text available

Apr 2021
Sci Progr

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.

Analysis of qCON and qNOX Anesthesia Indices and EEG Spectral Energy during Natural Sleep Stages

Article

Feb 2021

Effects of noxious stimulation on the electroencephalogram during general anaesthesia: a narrative review and approach to analgesic titration

Article

Full-text available

Feb 2021

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.

Intraoperative assessment of analgesia adequacy

Article

Full-text available

Jan 2020

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

Multiparametric Monitoring of Hypnosis and Nociception-Antinociception Balance During General Anesthesia - A New Era in Patient Safety Standards and Healthcare Management

Preprint

Nov 2020

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.

Comparison of the Conox (qCON) and Sedline (PSI) depth of anaesthesia indices to predict the hypnotic effect during desflurane general anaesthesia with ketamine

Article

Full-text available

Dec 2021
J Clin Monit Comput

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.

EEG-derived pain threshold index for prediction of postoperative pain in patients undergoing laparoscopic urological surgery: a comparison with surgical pleth index

Article

Full-text available

Dec 2021
J Clin Monit Comput

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.

The effect of opioid-free anaesthesia on the quality of recovery after endoscopic sinus surgery: A multicentre randomised controlled trial

Article

Jun 2023
EUR J ANAESTH

Background: It remains to be determined whether opioid-free anaesthesia (OFA) is consistently effective for different types of surgery. Objectives: The current study hypothesised that OFA could effectively inhibit intraoperative nociceptive responses, reduce side effects associated with opioid use, and improve the quality of recovery (QoR) in endoscopic sinus surgery (ESS). Design: A multicentre randomised controlled study. Setting: Seven hospitals participated in this multicentre trial from May 2021 to December 2021. Patients: Of the 978 screened patients who were scheduled for elective ESS, 800 patients underwent randomisation, and 773 patients were included in the analysis; 388 patients in the OFA group and 385 patients in the opioid anaesthesia group. Interventions: The OFA group received balanced anaesthesia with dexmedetomidine, lidocaine, propofol and sevoflurane; the opioid anaesthesia group received opioid-based balanced anaesthesia using sufentanil, remifentanil, propofol and sevoflurane. Outcome measures: The primary outcome was 24-h postoperative QoR as evaluated by the Quality of Recovery-40 questionnaire. The key secondary outcomes were episodes of postoperative pain and postoperative nausea and vomiting (PONV). Results: A significant difference (P = 0.0014) in the total score of 24-h postoperative Quality of Recovery-40 was found between the OFA group, median [interquartile range], 191 [185 to 196] and the opioid anaesthesia group (194 [187 to 197]). There were significant differences between the opioid anaesthesia group and the OFA group in the numerical rating scale score for pain after surgery at 30 min (P = 0.0017), 1 h (P = 0.0052), 2 h (P = 0.0079) and 24 h (P = 0.0303). The difference in the area under the curve of pain scale scores between the OFA group (24.2 [3.0 to 47.5]) and the opioid anaesthesia group (11.5 [1.0 to 39.0]) was significant (P = 0.0042). PONV occurred in 58 of 385 patients (15.1%) in the opioid anaesthesia group compared with 27 of 388 patients (7.0%) in the OFA group, suggesting the incidence of PONV in the OFA group was significantly lower than in the opioid anaesthesia group (P = 0.0021). Conclusion: OFA can provide good intraoperative analgesia and postoperative recovery quality as effectively as conventional opioid anaesthesia in patients undergoing ESS. OFA can be an alternative option in the pain management of ESS. Trial registration: The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100046158; registry URL: http://www.chictr.org.cn/enIndex.aspx.).

Monitoring of processed EEG under anesthesia II

Article

Oct 2022

Michal Horáček

Vigilancia de la profundidad de la anestesia general

Article

Feb 2023

Monitoraggio della profondità dell’anestesia generale

Article

Feb 2023

Electroencephalogram-based prediction and detection of responsiveness to noxious stimulation in critical care patients: a retrospective single-centre analysis

Article

Nov 2022

Background Monitoring of pain and nociception in critical care patients unable to self-report pain remains a challenge, as clinical signs are neither sensitive nor specific. Available technical approaches are limited by various constraints. We investigated the electroencephalogram (EEG) for correlates that precede or coincide with behavioural nociceptive responses to noxious stimulation. Methods In this retrospective study, we analysed frontal EEG recordings of 64 critical care patients who were tracheally intubated and ventilated before, during, and after tracheal suctioning. We investigated EEG power bands for correlates preceding or coinciding with behavioural responses (Behavioural Pain Scale ≥7). We applied the Mann–Whitney U-test to calculate corresponding P-values. Results Strong behavioural responses were preceded by higher normalised power in the 2.5–5 Hz band (+17.1%; P<0.001) and lower normalised power in the 0.1–1.5 Hz band (–10.5%; P=0.029). After the intervention, strong behavioural responses were associated with higher normalised EEG power in the 2.5–5 Hz band (+16.6%; P=0.021) and lower normalised power in the 8–12 Hz band (–51.2%; P=0.037) Conclusions We observed correlates in EEG band power that precede and coincide with behavioural responses to noxious stimulation. Based on previous findings, some of the power bands could be linked to processing of nociception, arousal, or sedation effects. The power bands more closely related to nociception and arousal could be used to improve monitoring of nociception and to optimise analgesic management in critical care patients. Clinical trial registration DRKS00011206.

The nociceptive response during adult cardiac surgery measured by the qNOX index: A feasibility study

Article

Full-text available

Nov 2022
Biomed Paper

Background: Monitoring nociception during general anaesthesia remains a substantial challenge. The Conox monitor uses two EEG indices, the qCon and the qNox. The qNox refers to the probability that a nociceptive stimulation triggers a movement of the patient and the response probability of reaction to nociceptive stimulation. We decided to test the feasibility of monitoring the qNOX index during adult cardiac surgery and to investigate whether this index correlates with hemodynamic and hormonal signs of nociceptive stimulation. Method: We enrolled 19 patients undergoing elective cardiac surgery. These were randomised to 2 groups receiving different doses of sufentanil via target controlled infusion: group A (n=9) 0.25 ng/mL and group B (n=10) 0.75 ng/mL. All patients were maintained at the same depth of anaesthesia. We recorded the Conox monitor indices (qNOX, qCON, electromyographic), hemodynamic variables and plasmatic levels of cortisol and noradrenaline. Results: There was significantly higher blood pressure (P=0.013) and plasmatic cortisol (P=0.003) in group A and a significant increase in plasmatic noradrenaline with increasing intensity of surgical stimulation in both groups: A (P=0.001), B (P=0.008). We found no significant corresponding changes in the qNOX index. There was a positive correlation between qNOX and hemodynamic signs of stimulation (P=0.012) and between the qNOX and EMG indices (P=0.013) after endotracheal intubation, but not later after EMG index dropped. Conclusion: Our results do not support the assumption that signs of nociceptive stimulation during adult cardiac surgery will be reflected by the qNOX index. This may be related to compounding of qNOX processing and use of muscle relaxants. Further investigation on this field is needed.

Monitoring of processed EEG under anesthesia I

Article

May 2022

Michal Horáček

The target organ of most substances applied during general anesthesia is the brain. The manifestations of its function include, above all, consciousness. It is associated with the electrical activity of neurons, which can be easily recorded from the surface of the skull – electroencephalography (EEG). The electrical activity of the brain in anesthesia changes in a predictable way depend-ing on the anesthetic used and its dose. EEG assessment is difficult but has been greatly simplified by computer development. Therefore, computer-processed EEG (pEEG) may soon become an integral part of monitoring patients under anesthesia. Anes-thesiologists’ attention with EEG monitoring initially focused on anesthesia depth indices (eg. BIS, entropy, PSI, qCON, etc.), but brain function cannot be reduced to a single number. It is also necessary to monitor simultaneously the raw EEG curves and to assess the changes in their shape. When conducting anesthesia, it is important to avoid burst suppression because it is a risk factor for postoperative delirium. Evaluation of the phase-amplitude coupling makes it possible to quantify the depth of anesthesia in more detail. Processed EEG is used to prevent unattended awareness during anesthesia and to prevent too deep anesthesia, although the benefit has not yet been safely confirmed. However, pEEG has been shown to reduce recovery times and anesthetic doses. It allows also personalized management of anesthesia, relevant studies are underway. The most widespread monitors in the Czech Republic are probably BIS, GE Entropy, and Conox. The development of pEEG continues, but its understanding and application require increasing knowledge in many fields. © 2022, Czech Medical Association J.E. Purkyne. All rights reserved.

NozizeptionsmonitoringNociception monitoring: Methode zur intraoperativen Opioidsteuerung?Method for intraoperative opioid control?

Article

Aug 2021

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.

Intraoperative Nociception Monitoring

Article

Jul 2021

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.

SpringerBook 2021

Book

Jun 2021

Vesna Vuksanovic

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.

Complexity-Based Analysis of Microvascular Blood Flow in Human Skin

Chapter

Full-text available

May 2021

The maintenance of an adequate microvascular perfusion sufficient to meet the metabolic demands of the tissue is dependent on neuralNetwork, neural, humoral and local vaso-mechanisms that determine vascular tone and blood flowBlood flow patterns within a microvascularNetworknetworkMicrovascular network. It has been argued that attenuation of these flow patterns may be a major contributor to disease risk. Thus, quantitative information on the in vivo spatio-temporal behaviour of microvascular perfusion is important if we are to understand networkNetwork functionality and flexibility in cardiovascular diseaseCardiovascular disease. Time and frequency-domainTime and frequency analysis analysis has been extensively used to describe the dynamic characteristics of Laser Doppler flowmetryLaser Doppler flowmetry (or fluximetry) (LDF) signals obtained from superficial microvascularNetworknetworksMicrovascular network such as that of the skin. However, neither approach has provided definitive and consistent information on the relative contribution of the oscillatory components of flowmotionFlowmotion (or flowmotion) (endothelial, neurogenic, myogenic, respiratory and cardiac) to a sustained and adequate microvascular perfusion; nor advance our understanding of how such processes are collectively modified in disease. More recently, non-linear complexity-based approaches have begun to yield evidence of a declining adaptability of microvascular flow patterns as disease severity increases. In this chapter we review the utility and application of these approaches for the quantitative, mechanistic exploration of microvascular (dys)function.

The importance and options of peroperative evaluation of nociception

Article

Dec 2020

Study of the evolution of the anaesthesia indices qCON and qNOX during natural sleep

Conference Paper

Jul 2020

Monitoring the nociception level: A multi-parameter approach

Article

Full-text available

Jul 2013
J Clin Monit Comput

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.

Prospective observational study of the non-invasive assessment of immediate postoperative pain using the analgesia/nociception index (ANI)

Article

Full-text available

Apr 2013
BRIT J ANAESTH

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.

The Influence of Method of Administration and Covariates on the Pharmacokinetics of Propofol in Adult Volunteers

Article

Full-text available

May 1998

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.

Prevention of Intraoperative Awareness

Article

Full-text available

Nov 2011
NEW ENGL J MED

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, . . .

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

Article

Full-text available

Feb 2011

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.

Comparison of the Surgical Pleth Index (TM) with haemodynamic variables to assess nociception-anti-nociception balance during general anaesthesia

Article

Full-text available

Nov 2010
BRIT J ANAESTH

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.

Autoregressive modeling with exogenous input of middle-latency auditory-evoked potentials to measure rapid changes in depth of anesthesia

Article

Full-text available

Sep 1996

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).

Spectral Entropy Monitoring Is Associated with Reduced Propofol Use and Faster Emergence in Propofol???Nitrous Oxide???Alfentanil Anesthesia

Article

Full-text available

Sep 2005

This multicenter study evaluated the effect of a new depth of anesthesia-monitoring device based on time-frequency-balanced spectral entropy of electroencephalogram monitoring (GE Healthcare Finland, Helsinki, Finland) on consumption of anesthetic drugs and recovery times after anesthesia. The study was a prospective, randomized, single-blind study performed in six hospitals in Finland, Sweden, and Norway. After institutional review board approval and written informed consent from each patient, the patients were randomly allocated to anesthesia with entropy values either shown (entropy group) or not shown (control group). Anesthesia was maintained with propofol, nitrous oxide, and alfentanil. In the entropy group, propofol was given to keep the state entropy value between 45 and 65, and alfentanil was given to keep the state entropy-response entropy difference below 10 units and heart rate and blood pressure within +/-20% of the baseline values. The control group patients were anesthetized to keep heart rate and blood pressure within +/-20% of the baseline values. Statistical methods included Mann-Whitney U test and unpaired t tests. A total of 368 patients were studied. In the entropy group, entropy values were higher during the whole operation and especially during the last 15 min (P < 0.001). Consequently, propofol consumption was smaller in the entropy group during the whole anesthesia period (P < 0.001) and especially during the last 15 min (P < 0.001). This shortened the time delay in the early recovery parameters in the entropy group. Entropy monitoring assisted titration of propofol, especially during the last part of the procedures, as indicated by higher entropy values, decreased consumption of propofol, and shorter recovery times in the entropy group.

Depth of anaesthesia monitoring: What's available, what's validated and what's next?

Article

Full-text available

Aug 2006

Depth of anaesthesia monitors might help to individualize anaesthesia by permitting accurate drug administration against the measured state of arousal of the patient. In addition, the avoidance of awareness or excessive anaesthetic depth might result in improved patient outcomes. Various depth of anaesthesia monitors based on processed analysis of the EEG or mid-latency auditory-evoked potentials are commercially available as surrogate measures of anaesthetic drug effect. However, not all of them are validated to the same extent.

ANFIS Adaptive-Network-based Fuzzy Inference System

Article

Full-text available

Jun 1993

Jyh-Shing R Jang

The architecture and learning procedure underlying ANFIS (adaptive-network-based fuzzy inference system) is presented, which is 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 the simulation, the ANFIS architecture is employed to model nonlinear functions, identify nonlinear components on-line in a control system, and predict a chaotic time series, all yielding remarkable results. Comparisons with artificial 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

Fuzzy identification of systems and its application to modeling and control

Article

Jan 1985

Practical Statistics For Medical Research

Article

Jun 1992

Pupillary reflex dilatation and analgesia nociception index monitoring to assess the effectiveness of regional anesthesia in children anesthetised with sevoflurane

Article

Aug 2013
PEDIATR ANESTH

Pupillary diameter (PD) monitoring and Analgesia Nociception Index (ANI) (Metrodoloris, Lille, France), an online wavelet transform-based heart rate variability index, have been used in the assessment of pain. The aim of this study was to evaluate the capacity of pupillary reflex dilatation and ANI to provide early assessment of regional anesthesia (RA) success following skin incision in children anesthetised with sevoflurane. A total of 58 children, eligible for RA, were included after sevoflurane induction. The sevoflurane concentration was adjusted to maintain a MAC of 1.3 in oxygen and nitrous oxide, and a RA was performed. Pupillary diameter and ANI were recorded just prior to skin incision and then every 30 s for a period of 2 min. Regional anesthesia failure was defined by an increase in heart rate ≥ 10% occurring during the first 2 mins following incision. Thirty-nine and 19 subjects presented RA success and failure, respectively. In the RA failure group, skin incision induced both changes in PD (P < 0.01) and ANI (P < 0.05) within 1 min of incision. Areas under the receiver-operating curves (95% confidence interval) to identify regional anesthesia failure were 0.747 (0.613-0.881) and 0.671 (0.514-0.827) for the minimal value of ANI and the maximal value of PD recorded during the 2-min period from skin incision, respectively. Both PD and ANI rapidly change after skin incision in case of RA failure. These indices may provide a useful tool alone, or in combination with heart rate changes in the assessment of RA efficacy in children anesthetised with sevoflurane.

Practical Statistic for Medical Research

Article

Nov 1990

DG Altman

Modeling the Influence of the A118G Polymorphism in the OPRM1 Gene and of Noxious Stimulation on the Synergistic Relation between Propofol and Remifentanil

Article

Mar 2013
ANESTHESIOLOGY

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

Anfis: Adaptive-Network-Based Fuzzy Inference System

Article

Jan 1993

Jyh-Shing R Jang

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...

Fuzzy Identification of Systems and Its Applications to Modeling and Control

Article

Jan 1985

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.

Prevention of Intraoperative Awareness with Explicit Recall in an Unselected Surgical Population A Randomized Comparative Effectiveness Trial

Article

Oct 2012
ANESTHESIOLOGY

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.

An introduction to bispectral analysis for electroencephalogram

Article

Jan 1994

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.

Sugeno, M.: Fuzzy Identification of Systems and its Applications to Modeling and Control. IEEE Transactions on Systems, Man, and Cybernetics SMC-15(1), 116-132

Article

Jan 1985

Kang, G.T.: Structure identification of fuzzy model. Fuzzy Sets Syst. 28, 15-33

Article

Oct 1988
FUZZY SET SYST

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.

Variability Comparison of the Composite Auditory Evoked Potential Index and the Bispectral Index During Propofol-Fentanyl Anesthesia

Article

Jul 2008

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.

Practical statistics for medical research / Douglas G. Altman

Article

Douglas G. Altman

Incluye bibliografía e índice Reimprisión en 1992.

Changes in Skin Conductance as a tool to monitor nociceptive stimulation and pain

Article

Jan 2009
Curr Opin Anaesthesiol

Hanne Storm

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.

An introduction to bispectral analysis for the electroencephalogram J

Article

Dec 1994

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.

Smith WD, Dutton RC, Smith NT: Measuring the performance of anesthetic depth indicators

Article

Feb 1996

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.

Pharmacokinetics and Pharmacodynamics of Remifentanil

Article

Feb 1997

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.

Influence of Age and Gender on the Pharmacokinetics and Pharmacodynamics of Remifentanil

Article

Feb 1997

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.

The Influence of Age on Propofol Pharmacodynamics

Article

Jul 1999

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.

The Bispectral Index Declines During Neuromuscular Block in Fully Awake Persons

Article

Sep 2003
ANESTH ANALG

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.

Effect of Auditory Evoked Potential Index Monitoring on Anesthetic Drug Requirements and Recovery Profile after Laparoscopic Surgery

Article

Nov 2003

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.

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

Abstract

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