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

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.

Modeling the effect of propofol and remifentanil combinations for sedation-analgesia in endoscopic procedures using an Adaptive Neuro Fuzzy Inference System (ANFIS).

BACKGROUND: The increasing demand for anesthetic procedures in the gastrointestinal endoscopy area has not been followed by a similar increase in the methods to provide and control sedation and analgesia for these patients. In this study, we evaluated different combinations of propofol and remifentanil, administered through a target-controlled infusion system, to estimate the optimal concentrations as well as the best way to control the sedative effects induced by the combinations of drugs in patients undergoing ultrasonographic endoscopy. METHODS: One hundred twenty patients undergoing ultrasonographic endoscopy were randomized to receive, by means of a target-controlled infusion system, a fixed effect-site concentration of either propofol or remifentanil of 8 different possible concentrations, allowing adjustment of the concentrations of the other drug. Predicted effect-site propofol (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. RESULTS: Data from 110 patients were analyzed in the training group. The resulting estimated models had an MDAPE of 32.87, 12.89, and 8.77; an MDRMSE of 17.01, 12.81, and 9.40; and an MDPE of -1.86, 3.97, and 2.21 for AAI/2, BIS, and IoC, respectively, in the absence of stimulation and similar values under stimulation. 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. CONCLUSION: 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.

Novel characterization method of impedance cardiography signals using time-frequency distributions.

The purpose of this document is to describe a methodology to select the most adequate time-frequency distribution (TFD) kernel for the characterization of impedance cardiography signals (ICG). The predominant ICG beat was extracted from a patient and was synthetized using time-frequency variant Fourier approximations. These synthetized signals were used to optimize several TFD kernels according to a performance maximization. The optimized kernels were tested for noise resistance on a clinical database. The resulting optimized TFD kernels are presented with their performance calculated using newly proposed methods. The procedure explained in this work showcases a new method to select an appropriate kernel for ICG signals and compares the performance of different time-frequency kernels found in the literature for the case of ICG signals. We conclude that, for ICG signals, the performance (P) of the spectrogram with either Hanning or Hamming windows (P = 0.780) and the extended modified beta distribution (P = 0.765) provided similar results, higher than the rest of analyzed kernels. Graphical abstract Flowchart for the optimization of time-frequency distribution kernels for impedance cardiography signals.

Sympathoadrenal activity and psychosocial stress. The significance of aging, long-term smoking, and stress models.

Recent studies have indicated that the increase in plasma norepinephrine and sympathetic activity with aging in healthy subjects is largely due to long-term cigarette smoking. In patients who have or have had duodenal ulcer the increase in plasma norepinephrine with age was markedly increased. These patients as a group perceive their lives somewhat more stressful than the general population and they tend to die prematurely due to smoking-associated diseases. These patients may select dysfunctional coping strategies like smoking, which may result in organ pathologies and a compensatory increase in plasma norepinephrine. No close correlation has been established between plasma epinephrine and "ill health." High plasma epinephrine levels may have a deleterious effect on the cardiovascular system in elderly subjects during certain conditions. In a population study, we found, however, that low resting plasma epinephrine levels were associated with an unfavorable survival rate. We speculate that an inadequate response to psychosocial stress and the choice of dysfunctional coping strategies may be more harmful and cause more "ill health" than hypersecretion of stress hormones like epinephrine and cortisol, which has been the traditional view. We suggest that there are different stress states. Stress hormones like epinephrine and cortisol may play a major role during situations like combat, illness, and strenuous exercise. In response to psychosocial stress, dysfunctional coping strategies are, however, largely responsible for harmful effects of stress.

Exercise-induced changes in plasma catecholamines and neuropeptide Y: relation to age and sampling times.

Plasma norepinephrine (NE), epinephrine (E), and neuropeptide Y (NPY) were evaluated in seven young (median age 29 yr, range 21-31) and seven elderly (median age 61 yr, range 51-72) healthy subjects. They were all nonsmokers and had never smoked. Basal values and the initial increase in plasma NE and E during exercise at 75% of maximal work load were identical in the two groups. After 5 min of exercise at this load, plasma NE and E remained constant in the elderly but were still increasing in the young subjects. Plasma NE and E increased to significantly higher values after 15 min in the young subjects: 1.68 +/- 0.18 vs. 0.92 +/- 0.11 ng/ml (NE) and 0.136 +/- 0.012 vs. 0.061 +/- 0.013 ng/ml (E). Basal plasma NPY was highest at rest and increased only during exercise in the young subjects. Our results demonstrate that in nonsmokers aging is not associated with increased plasma NE levels. The blood pressure response to exercise was the same in both groups, suggesting that the increase in the sympathetic activity was adequate in the elderly. Alternatively, the higher increase in sympathetic activity in the young subjects may be attributed to their higher work capacity.

The family routines inventory: theoretical origins.

This paper describes the conceptual foundation underlying the development of the Family Routines Inventory, a new instrument designed to measure the extent of predictability or routinization in the daily life of a family. The primary impetus for the development of this instrument is a theoretical perspective in which family routines are regarded as behaviors which may protect the health and well-being of family members by providing stability and continuity during periods of stressful change.

The family routines inventory: development and validation.

This report builds upon pertinent theoretical considerations regarding the nature and importance of routinization within families and describes the development and validation of a standardized inventory to measure family routines. The Family Routines Inventory (FRI) measures 28 positive, strength-promoting family routines, those observable, repetitive behaviours which involve two or more family members and which occur with predictable regularity in the daily life of a family. The 28 routines were selected from an extensive list of 104 routines obtained through family interviews. Scoring options for the inventory were identified based on their face validity and consistency with the underlying theoretical construct. The inventory was subsequently administered to a diverse group of families for reliability and validity testing. This testing identified an optimal scoring method (frequency score) for the inventory and revealed that the Family Routines Inventory, which measures the extent and importance of routinization within a given family, appears to be a reliable and valid measure of family cohesion, solidarity, order and overall satisfaction with family life.

EEG complexity as a measure of depth of anesthesia for patients.

A new approach for quantifying the relationship between brain activity patterns and depth of anesthesia (DOA) is presented by analyzing the spatio-temporal patterns in the electroencephalogram (EEG) using Lempel-Ziv complexity analysis. Twenty-seven patients undergoing vascular surgery were studied under general anesthesia with sevoflurane, isoflurane, propofol, or desflurane. The EEG was recorded continuously during the procedure and patients' anesthesia states were assessed according to the responsiveness component of the observer's assessment of alertness/sedation (OAA/S) score. An OAA/S score of zero or one was considered asleep and two or greater was considered awake. Complexity of the EEG was quantitatively estimated by the measure C(n), whose performance in discriminating awake and asleep states was analyzed by statistics for different anesthetic techniques and different patient populations. Compared with other measures, such as approximate entropy, spectral entropy, and median frequency, C(n) not only demonstrates better performance (93% accuracy) across all of the patients, but also is an easier algorithm to implement for real-time use. The study shows that C(n) is a very useful and promising EEG-derived parameter for characterizing the (DOA) under clinical situations.

A model for estimation of the pulmonary capillary pressure.

To estimate the pulmonary capillary pressure, a theory was introduced by Holloway and coworkers. Based upon this, a mathematical model describing the measured data was developed. Because the physiologic data are embedded in noise and the pulmonary capillary pressure cannot be measured directly, we simulated an extensive series of data. The noise properties of the data were as analyzed to design a signal-processing tool, that cancels the noise from the measured data. The signal processing tool developed for the current application consists of pre-processing with a moving time average filter and post-processing with a neural network. After a verification procedure the tool can be applied to measured data, hence a more reliable measurement of the pulmonary capillary pressure is achieved.

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

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).

On-line analysis of AEP and EEG for monitoring depth of anaesthesia.

Achieving and monitoring adequate depth of anaesthesia is a challenge to the anaesthetist. 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 anaesthesia, (DA), in a cerebral activity sense, hence there is a desire to achieve a better measure of the DA. Auditory Evoked Potentials (AEP) provide two aspects relevant to anaesthesia: (1) they have identifiable anatomical significance and, (2) their characteristics reflect the way in which the brain reacts to a stimulus. However, AEP is embedded in noise from the ongoing EEG background activity. Hence, processing is needed to improve the signal to noise ratio. The methods applied were moving time averaging (MTA) and ARX-modeling. The EEG was collected from the left hemisphere and analysed by FFT to 1 sec epochs and the spectral edge frequency was calculated. Both the changes in ARX extracted AEP and the spectral edge frequency of the EEG correlated well with the time interval between propofol induction and onset of anaesthesia measured by clinical signs (i.e., cessation of eye-lash reflex). The MTA extracted AEP was significantly slower in tracing the transition from consciousness to unconsciousness.

On-line analysis of middle latency auditory evoked potentials (MLAEP) for monitoring depth of anaesthesia in laboratory rats.

In laboratory animals as well as in human beings a depth of anaesthesia, where the subject has no pain or recall of events from the surgery, should be provided. Haemodynamic parameters such as heart rate and blood pressure are not a guarantee for an optimal depth of anaesthesia, especially when using neuromuscular blocking agents (NMBA). A number of studies suggest that the Middle Latency Auditory Evoked Potentials (MLAEP) contain information about the state of consciousness in humans. The purpose of this study was to examine whether the AEP could serve as an indicator of depth of anaesthesia in rats. The AEP was elicited with a click stimulus and monitored in an 80 ms window synchronised to the stimulus. The AEP was extracted applying an Auto Regressive Model with Exogenous Input (ARX-model) from which a Depth of Anaesthesia Index (DAI) was calculated. DAI was normalised to 100 while awake and decreasing gradually to a level between 50 and 20 as the rat was anaesthetised. Nine rats were anaesthetised and included in the study. Four doses of Hypnorm vet. and Dormicum were given as a total, each with 5 minutes interval. Clinical signs of the level of anaesthesia were observed simultaneously with the AEP. The results showed that in four rats DAI decreased to a level below 30 while anaesthetised. In the remaining five rats the AEP was only decreased to a level below 45. The results indicated that a simple dosing regimen based on weight was unable to give the same depth of anaesthesia in individual rats. The decrease in the DAI correlated well with the loss of stimulus response. In conclusion, MLAEP could be used as an indicator of depth of anaesthesia in rats during Hypnorm vet. and Dormicum administration. However studies applying other anaesthetic drugs should be carried out, before a conclusion of the general utility of the method can be made.

Middle-latency auditory evoked potentials during induction of thiopentone anaesthesia in pigs.

A method is described for measuring middle-latency auditory evoked potentials (MLAEP) in consciously awake, non-sedated pigs during the induction of thiopentone anaesthesia (0.6 ml/kg, 2.5% thiopentone solution). It was done by using autoregressive modelling with an exogenous input (ARX). The ability to perceive pain during the induction was compared with (1) the changes in latencies and amplitudes of the MLAEP, (2) the change in a depth of anaesthesia index based on the ARX-model and (3) the change in the 95% spectral edge frequency. The pre-induction MLAEP was easily recordable and looked much like the one in man, dogs and rats. The temporal resolution in the ARX method was sufficiently high to describe the fast changes occurring during induction of thiopentone anaesthesia. As previously reported from studies in man, dogs and rats, induction of thiopentone anaesthesia resulted in significantly increased latencies and decreased amplitudes of the MLAEP trace as well as in a significantly reduced depth of anaesthesia index and spectral edge frequency. None of the changes, however, related well to the ability to react to a painful stimulus. Whether an ARX-based depth of anaesthesia index designed especially for pigs might be better than the present index (designed for man) for assessing depth of anaesthesia must await the results of further studies.

Effects of CO2 anaesthesia on central nervous system activity in swine.

The objective of the study was to examine the changes in central nervous system (CNS) activity and physical behaviour during induction and awakening from CO2 anaesthesia. Two studies, each using pigs immersed into 90% CO2 gas for a period of 60 s were performed. In study 1, we monitored middle latency auditory evoked potentials (changes in latencies, amplitudes and a depth of anaesthesia index), electroencephalographic parameters (delta, theta, alpha and beta electroencephalographic power and 95% spectral edge frequency) and heart rate; and in study 2, we monitored body movements and arterial and venous partial pressure of CO2 and O2. No behavioural signs of distress were observed during the early part of the induction. The swine exhibited muscular activity from 13-30 s after induction-start as well as during awakening from anaesthesia, possibly because of a transitory weaker suppression of the brain stem than of the cortex. The CNS and blood gas parameters started to change from the very start of induction. The CNS suppression lasted only approximately one minute after the end of the induction period. The two studies indicated a good temporal relationship between changes in amplitude, depth of anaesthesia index, spectral edge frequency, and arterial PCO2 during the induction period.

[Inhalation therapy with nitric oxide--an evaluation of a dosage system and clinical examples]. / Inhalationsbehandling med nitrogenoxyd--evaluering af et doseringssystem og kliniske eksempler på anvendelsen.

In 1987 it was discovered that nitric oxide is a very potent vasodilator and in fact a natural mediator for vasodilatation. The effects of inhalation of nitric oxide on pulmonary vascular resistance were described in 1988 and a new therapeutic possibility for artificially ventilated patients with pulmonary hypertension has arisen. However, the administration of nitric oxide has to be performed with high accuracy and without reaching toxic levels of nitrogendioxide. We have evaluated a system using conventional air and oxygen rotameters for administration of nitric oxide via a ventilator. A comparison of the chemiluminescence technique with a technique based on fuel cells was also performed. With the system it was possible to administer nitric oxide with high accuracy within the range of 10-60 ppm without exceeding values for nitrogendioxide above 0.4 ppm. The analysis of nitric oxide and nitrogendioxide based on electrochemical cells proved to be comparable with the chemiluminescence technique within the same range. Nitric oxide inhalation was used in six patients with severe hypoxia and seemed to have a favorable effect on most of the patients.

[Comparison of an auditory evoked potentials index and a bispectral index versus clinical signs for determining the depth of anesthesia produced by propofol or sevoflurane]. / Comparación de la efectividad de un índice de potenciales evocados auditivos y un índice biespectral con los signos clínicos en la determinación de la profundidad hipnótica durante anestesia con propofol o sevoflurano.

OBJECTIVES: To evaluate an anesthetic depth index (ADI) obtained from auditory evoked potentials and a bispectral EEG index (BIS) in comparison with clinical assessment of anesthetic depth using the modified observer's assessment of awareness/sedation scale (MOAA/SS), for induction of anesthesia with propofol or sevoflurane as the only agent. PATIENTS AND METHODS: The ADI and BIS were recorded simultaneously in this prospective study and compared to the MOAA/SS during the anesthetic induction of 26 adults undergoing elective heart surgery. Assignment of patients to two groups was random. Group A (n = 13) patients were induced with propofol (target dose 5 micrograms.ml-1 in 5 min). Induction in group B (n = 13) was with sevoflurane (8% tidal volume). A scheme of awake-sleeping-awake-sleeping was followed. The means of the two indexes were compared (Mann-Whitney test) one minute before the patient slept (awake) and one minute later (sleeping), and the evolution of the indexes was compared during awake/sleep and sleep/awake phase changes and while the patients were in a stable sleep phase. The sensitivity and specificity of each index was analyzed in function of the MOAA/SS. We also analyzed the time elapsing from the moment the patient fell asleep (MOAA/SS 2) until the two indexes reached published reference values (ADI = 38, BIS = 60). RESULTS: After induction with propofol (group A) the ADI fell to 29.2 +/- 11.7 and the BIS fell to 63.5 +/- 13.4. After induction with sevoflurane (group B) the ADI fell to 33.8 +/- 14.9 and the BIS to 66.8 +/- 15. The ADI value that best discriminated between arousal and sleeping (sensitivity 100%) was 38; the BIS value that best discriminated was 60. The responses to sound in decibels (dB) during "awake/sleeping" and "sleeping/awake" phases were, respectively, -3.8 dB and -4.5 dB for the ADI and -1.5 dB and -0.8 dB for the BIS. With the patient in stable sleep, response to the two indexes was at -0.79 dB. In group A, the ADI detected MOAA/SS 2 significantly earlier (ADI 13.1 +/- 30 s; BIS 56 +/- 36 s; p < 0.05). No patient reported remembering the study period. CONCLUSIONS: Monitoring anesthetic depth with the ADI or BIS was technically easy and effective for detecting whether patients were awake or sleeping. The ADI response was faster and identified awake/sleeping and sleeping/awake phase changes better than did the BIS.