Year : 2007 | Volume
: 51 | Issue : 5 | Page : 365-
Monitoring Devices for Measuring the Depth of Anaesthesia - An Overview
Prabhat Kumar Sinha1, Thomas Koshy2,
1 MD, Associate Professor, Department of Anaesthesiology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum - 695011, Kerala, India
2 MD, Additional Professor, Department of Anaesthesiology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum - 695011, Kerala, India
Prabhat Kumar Sinha
H. No. KP IX/561, Chettikunnu, Podujanam Lane, Kumarpuram, Trivandrum -695011, Kerala
Achieving adequate depth of anaesthesia during surgical procedures is desirable. Therefore, assessment and monitoring/ measurement of the depth of anaesthesia are fundamental to anaesthetic practice. The purpose of this review is to identify the risk factors that may be associated with intraoperative awareness, provide decision tools that may enable the clinician to reduce the frequency of unintended intraoperative awareness, stimulate the pursuit and evaluation of strategies that may prevent or reduce the frequency of intraoperative awareness, different types of tools developed to date to monitor the depth of anaesthesia, provide guidance for the intraoperative use of different monitoring tools as they relate to intraoperative awareness and how to approach a patient when awareness is reported by the patient along with current guidelines in the use of current available monitors.
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Sinha PK, Koshy T. Monitoring Devices for Measuring the Depth of Anaesthesia - An Overview.Indian J Anaesth 2007;51:365-365
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Sinha PK, Koshy T. Monitoring Devices for Measuring the Depth of Anaesthesia - An Overview. Indian J Anaesth [serial online] 2007 [cited 2019 Sep 16 ];51:365-365
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Achieving adequate depth of anaesthesia during surgical procedures is desirable. While deep level of anaesthesia, resulting in cardiovascular depression (easy to detect) and prolonged awakening times (a rather harmless complication) is of minor clinical interest, the opposite - light anaesthesia - is more difficult to detect and frightening from the patients point of view. Therefore, assessment of the depth of anaesthesia is fundamental to anaesthetic practice. Prior to the use of muscle relaxants, maintaining the appropriate depth of anaesthesia was a balance between abolishing movement to pain whilst maintaining adequate respiration. With the absence of movement on incision it was safe to assume that the patient was not aware, however with the use of muscle relaxants it became necessary to be certain that the administered concentration of anaesthetic agent was adequate to prevent awareness. With the emergence of new anaesthetic techniques such as intravenous anaesthesia, the use of potent opiate analgesics, newer volatile agents and more complicated regional nerve blocks, a means of measuring depth of anaesthesia is important. However, in 1937, Dr Arthur E. Guedel refined this system and developed a chart classification of ether anaesthesia based on lacrimation, pupil size and position, respiratory pattern and peripheral movement. What began as the continuous clinical monitoring of patients' physiological parameters evolved to include the measurement of real-time airway gas volatile agent concentration and more recently the analysis of neurophysiological parameters.
The purpose of this review is to identify risk factors that may be associated with intraoperative awareness, provide decision tools that may enable the clinician to reduce the frequency of unintended intraoperative awareness, stimulate the pursuit and evaluation of strategies that may prevent or reduce the frequency of intraoperative awareness, different types of tools developed to date to monitor the depth of anaesthesia and provide guidance for the intraoperative use of different monitoring tools as they relate to intraoperative awareness and how to approach a patient when awareness is reported by the patient along with current guidelines in the use of current available monitors.
Intraoperative awareness under general anaesthesia is a rare occurrence with a reported incidence of 1 to a few in 1000 general anaesthesia cases , with three major risk factors: trauma, caesarean section and cardiovascular surgery. The hereby increased incidences of intraoperative awareness are easy to re-enact. Under these circumstances light anaesthesia is intentionally put at risk in order to avoid severe cardiovascular depression or fetal impairment respectively. However, there is a risk for the anaesthesiologist too, since some of these patients take legal action. A closed claims analysis of more than 4100 anaesthesia related claims in the U.S.A. has shown that despite all advantages in modern anaesthesia, there is an increasing incidence of claims concerning intraoperative awareness, 1% in the 1980s, 2% in the 1990s and 3% in the last decade  . Surprisingly, risk factors for claims were totally different from the above cited "classical" risk factors: age at around 40 years, ASA physical status I or II, routine surgery and female gender. Significant psychological sequelae (e.g., post-traumatic stress disorder) may occur after an episode of intraoperative awareness, and affected patients may remain severely disabled for extended periods of time  . However, in some circumstances, intraoperative awareness may be unavoidable to achieve other critically important anaesthetic goals.
Following terminology would be helpful in better understanding of the article. These are
1. Depth of anaesthesia. Depth of anaesthesia or depth of hypnosis refers to a continuum of progressive central nervous system depression and decreased responsiveness to stimulation.
2. Recall. It is the patient's ability to retrieve stored memories. Recall is assessed by a patient's report of previous events, in particular, events that occurred during general anaesthesia. Recall can be either explicit or implicit. Explicit memory: It refers to intentional or conscious recollection of prior experiences as assessed by the patient's ability to recall specific events that took place during general anaesthesia by certain tests or recall or recognition, so called direct memory test. Implicit memory (perception without conscious recall): The patient denies recall, but may remember "something" under hypnosis. Psychologists are sceptical about the existence of this phenomenon.
3. Amnesia. Amnesia is the absence of recall. Many anaesthetic drugs produce amnesia at concentrations well below those necessary for suppression of consciousness. Anterograde amnesia is intended when a drug with amnestic properties is administered before induction of anaesthesia. Retrograde amnesia is intended when a drug such as a benzodiazepine is administered after an event that may have caused or been associated with intraoperative consciousness in the hope that it will suppress memory formation and "rescue" from recall.
4. Burst suppression. Burst suppression (BS) pattern is a characteristic behaviour of the EEG which can be recognized during deep anaesthesia. It consists of periods of high amplitude (bursts) followed by periods of near "silence" or very low amplitude (suppression). The duration of both periods is in the range of seconds. BS can occur as a consequence of the administration of high concentrations of anaesthetics and is also a characteristic of a state of low brain activity associated with hypothermia or ischaemia. Caution should be exercised if BS arises when the anaesthetic concentration has not been changed or the temperature lowered. In this case BS can be an indicator of cerebral ischaemia. BS ratio (%) is the ratio of the amount of flat EEG to raw EEGX100.
5. Signal Quality Index (SQI%). SQI% measures the quality of the acquired EEG signal. The calculation is based on a number of artifacts during the last minute. The electrode-to-skin impedance is included in the SQI% calculation. Higher electrode-to-skin impedances reduce the SQI%. If the impedance of the sensors exceeds 1kΩ,, the SQI will fall gradually. Poor impedance conditions may cause the SQI to fall to 50%. Impedances at 1kΩ,) will result in a SQI% of 100. This quantity is displayed numerically as a percentage (0-100%, 100% equals best signal quality).
6. EMG%. Amount of electromyographic (EMG) activity occurring over a fixed period of time.
7. Spectral edge frequency (SEF). It indicates the spectral frequency below which containsthe power in the EEG .
8. Total power (TP). It describes the overall percentage of EEG power over the entire EEG frequency spectrum.
Classification of awareness:
It is classified by Griffith and Jones  as follows:
Conscious awareness with complaint of pain percaptionConscious awareness with explicit recall but without painConscious awareness or "wakefulness" (ability to respond to simple verbal commands)Without explicit recall and pain but possible implicit memorySubconscious awareness without explicit recall but evidence of implicit memory of intraoperative eventsNo awareness
Causes of awareness:
In practice, about 95% of cases of awareness are due to human error or faulty anaesthetic technique or apparatus failure  such as failure to turn on the anaesthetic or monitor the patient. In only about 2.5% of cases can no cause be found. It is also interesting to note that only about 2.5% of claims of awareness are spurious  . The curve relating the minimum alveolar concentration of inhaled anaesthetic to produce loss of consciousness (MAC awake ) to the number of people with that MAC awake is normally distributed, so some patients do require significantly higher doses of anaesthetic  . This variability may explain awareness in those cases where no other cause is apparent. Claims for damages from awareness have thus been successfully defended when careful anaesthetic records were kept and apparatus appropriately checked. More commonly, awareness may result when difficulty is encountered with intubation. Generally, anaesthesia is induced with an intravenous agent, followed by administration of a muscle relaxant and intubation of the trachea after which the patient's lungs are ventilated with oxygen, nitrous oxide and inhalational anaesthetic. If the process of intubation takes longer than anticipated and a short-acting intravenous agent has been used, a period of time may occur between intravenous agents declining, before starting the inhalational agent, which could lead to awareness.
Anaesthesiologists now use a variety of different indicators to measure depth of anaesthesia, many of which rely upon monitoring more accurately the changes in normal physiological variables such as heart rate and blood pressure. Although variations in these parameters can be associated with variations in the level of anaesthesia, many studies have demonstrated that they are not completely reliable. Accurate monitoring of the level of consciousness and the potential awareness of an anaesthetized patient require different techniques. Volatile agent monitoring, linked to the concept of minimum alveolar concentration (MAC), is employed currently as a reliable measurement for routine use in this area, and yet the incidence of intraoperative awareness has not changed in recent years. Indeed, a major study demonstrated the frequency of intraoperative awareness was the same whether or not end tidal agent monitoring was used during the general anaesthetic. Clearly, agent monitoring is of no value when total intravenous anaesthesia is used.
Methods of monitoring depth of anaesthesia
There are various ways to measure or monitor depth of anaesthesia based on clinical/conventional monitoring and/or brain electrical activity monitoring [Table 1]
A. Clinical techniques and conventional monitoring:
Among the clinical techniques used to assess intraoperative consciousness are checking for movement, response to commands, eyelash reflex, pupillary responses or diameters, perspiration, and tearing. Conventional monitoring systems include ASA standard monitoring as well as end-tidal anaesthetic analyzer. No clinical trials or other comparative studies were found that examine the effect of clinical techniques or conventional monitoring on the incidence of intraoperative awareness.
I. Clinical signs: The most commonly used scoring system incorporates the PRST or Evan's score  . This assesses autonomic activity related to P (systolic blood P ressure), R (heart R ate), S ( S weating) and T ( T ears). This system has the advantages of being simple and not requiring any specialized equipment, but the parameters are not specific for the effects of anaesthesia and the values can vary widely among individuals. The scores range from 0 to 8 but the midpoint is seldom exceeded, reflecting the inadequacy of this scoring system. Measurement of heart rate and blood pressure while regularly assessing pupil size, and the presence of sweating and lacrimation, provide useful information regarding the adequacy of analgesia and depth of anaesthesia. Tachycardia secondary to anticholinergic drugs such as atropine make the heart rate uninterpretable, and beta-adrenergic blocking drugs, opiates and regional anaesthetic techniques will obtund the sympathetic nervous system response to pain. It has been agreed upon by ASA task force members on practice advisory for intraoperative awareness and brain function monitoring  that clinical techniques (e.g., checking for purposeful or reflex movement) are valuable and should be used to assess intraoperative consciousness. In addition, conventional monitoring systems (e.g., electrocardiogram, blood pressure, HR, end-tidal anaesthetic analyzer, capnography) are valuable and should be used to help assess intraoperative consciousness.
II. Skin conductance: Measurement of skin conductance is, in effect, a quantification of the clinical sign of sweat production. Goddard GF  found a reasonable correlation with anaesthetic depth in 67 patients. Skin conductance was initially low and increased as anaesthetic depth was increased, reducing again with surgical incision. Other factors affecting sweating (e.g. atropine, autonomic neuropathy) can reduce the accuracy of this monitoring.
III. Isolated forearm technique: The isolated forearm technique is a method of detecting awareness during clinical practice and experimentally. A tourniquet is applied to the patient's upper arm, inflated above systolic blood pressure before the administration of muscle relaxants. Movement of the arm either spontaneously or to command indicated wakefulness, although not necessarily explicit awareness. It has been used previously as a means of detecting awareness during caesarean section under general anaesthesia and during clinical trials assessing rates of awareness. Some would argue that response to command during surgery is a late sign when attempting to prevent awareness however not all patients responding have any recall. One limitation of this technique is the limited time available before patients are unable to move their arm due to tourniquet induced ischaemia.
IV. Spontaneous surface electromyogram (SEMG): In patients who are not completely paralyzed, spontaneous surface electromyogram (SEMG) can be recorded from various muscle groups, especially facial, abdominal and neck muscles. Frontalis muscle is innervated by a branch of the facial nerve and is less affected by the neuromuscular blockade. A stick on electrode positioned over the frontalis muscle can record the frontalis electromyogram (FEMG). The level of FEMG has been observed to fall during anaesthesia and to rise to pre-anaesthetic levels just before awakening  .
V. Lower oesophageal contractility (LOC): The non-striated muscles in the lower half of oesophagus retain their potential activity even after full skeletal muscle paralysis by neuromuscular blocking agents. Measurements of LOC therefore, provide two prime derivatives.
(i) Spontaneous lower oesophageal contractility (SLOC). It arises spontaneously and can be detected by a pressure transducer. It can be induced by emotion and stress in the awake individual. It is believed that SLOC are under the control of a central oesophageal motility centre, the activity of which is influenced by higher centres.
(ii) Provoked lower oesophageal contractility (PLOC). These result from sudden distension of the oesophagus, as if due to the arrival of a food bolus. PLOC are induced by the rapid inflation of a balloon catheter in the lower oesophagus. This causes smooth muscle contraction and is detected by a more distally placed pressure transducer. The dose-response curve for PLOC is shallower than that of SLOC. Evans and colleagues  were the first to propose that depth of anaesthesia might be measured by the degree of spontaneous contractions of lower oesophagus. Spontaneous and provoked lower oesophageal contractions both reduce in latency and amplitude during general anaesthesia. These are measured using a balloon in the oesophagus; however, pub-lashed evidence of its use as a depth of anaesthesia monitor is limited. One way of improving the available information is by combining the measurement of SLOC frequency with PLOC amplitude, leading to the derivation of the oesophageal contractility index (OCI):OCI = 70 x (SLOC rate + PLOC amplitude). The OCI is easy to interpret and can be used in the presence of muscle relaxants; however, consensus opinion is against this method being a reliable measure of anaesthetic depth  .
VI. Heart rate variability: Recent research using animal models have shown that the anaesthetic agents either directly or indirectly first acts on the brain stem and then probably inhibit the cerebral cortex via ascending efferent projections from the midbrain. Therefore, objective measurement of brain stem-mediated autonomic tone that is not affected by any factor other than anaesthetic depth may be a good indicator of depth of anaesthesia. The special analysis of HRV revealed 3 components: 1) Low frequency fluctuations; believed to be circadian. 2) Medium frequency fluctuations; attributed to baroreceptor reflex. 3) High frequency fluctuations HRV coincides with the frequency of ventilation, in which heart rate increases during inspiration and decreases during expiration, through a predominantly parasympathetic reflex connecting stretch receptors in the lungs and aorta to vagal motor neurons innervating the heart. This is called as respiratory sinus arrhythmia (RSA). It is typically characterized by greater than 10% variation in the ECG P-wave interval over 5 minutes. RSA is easily visible on an ECG monitor that is time locked to an ECG R-wavepeak, but is difficult to distinguish with a rolling display. Various studies , have shown that the level of RSA reflects the level of anaesthetic depth. In addition, surgical stimulation during light anaesthesia elicits a greater increase on RSA than seen during lightening anaesthesia alone. Some monitors use HRV at respiratory frequency or respiratory sinus arrhythmia (RSA) as a method of assessing anaesthetic depth. This is useful, but depends on an intact autonomic nervous system and healthy myocardial conducting system. Beta-blockers, conduction abnormalities, autonomic neuropathy and sepsis all cause problems. The 'Fathom' (Amtec Medical Limited) is based on the use of HRV, and does not use cortical activity directly but depends on the influence of respiration on the brain stem and the resulting change in heart rate. At this stage, experience with the Fathom monitor is very limited.
B. Brain electrical activity monitoring:
Most of the devices designed to monitor brain electrical activity for the purpose of assessing anaesthetic effect record EEG activity from electrodes placed on the forehead. Systems can be subdivided into those that process spontaneous EEG and EMG activity and those that acquire evoked responses to auditory stimuli i.e. auditory evoked potential (AEPs). After amplification and conversion of the analog EEG signal to the digital domain, various signal processing algorithms are applied to the frequency, amplitude, latency, and/or phase relationship data derived from the raw EEG or AEP to generate a single number, often referred to as an "index," typically scaled between 0 and 100. This index represents the progression of clinical states of consciousness ("awake," "sedated," "light anaesthesia," "deep anaesthesia"), with a value of 100 being associated with the awake state and values of 0 occurring with an isoelectric EEG (or absent middle latency AEP). Artifact recognition algorithms intended to avoid contaminated and therefore spurious "index" values are an important component of the software in most monitors. Although EMG activity from scalp muscles can be considered an artifact from the viewpoint of pure EEG analysis, it may be an important source of clinically relevant information. Sudden appearance of frontal (forehead) EMG activity suggests somatic response to noxious stimulation resulting from inadequate analgesia and may give warning of impending arousal. For this reason, some monitors separately provide information on the level of EMG activity.
1. Spontaneous EEG activity monitors:
(i) EEG: An EEG can be obtained using the standard 19-electrode method; however, this is time-consuming and impractical and requires expert interpretation. In its unprocessed form, it is not a practical tool for monitoring depth of anaesthesia. Increasingly sophisticated, automated analysis of various EEG components has generated several potential quantitative descriptors of anaesthetic depth. There are two generic problems with processed EEG technologies: 1. Dissimilar anaesthetic agents generate different EEG patterns or signatures and 2. Various pathophysiological events also affect the EEG (e.g. hypotension, hypoxia, hypercarbia). Such events may modify both the patient's level of consciousness and the expected EEG signature that any given anaesthetic agent generates, thus confounding interpretation.
(ii) Compressed spectral analysis: The compressed spectral array (CSA) is obtained by superimposing linear plots of successive epochs of time on each other, generating a three-dimensional 'hill and valley' display of the power amplitude vertically (y-axis), frequency horizontally (x-axis) and time (z-axis). However, as successive epochs are added to the display, information can become hidden behind 'hills' of increased power at particular frequencies. In order to reduce this problem, some displays arbitrarily truncate the peaks of high-amplitude activity, consequently affecting the legibility of the trace. This reflects cerebral electrical activity rather than peripheral muscular or autonomic changes. Anaesthesia causes a reduction in high-frequency and an increase in low-frequency amplitudes, which is easier to interpret than raw EEG . However, there remain the problems of great patient- and agent variability and the confounding effects of other pathophysiological processes such as hypoxia, hypotension and hypercarbia. It is not a reliable monitor of the depth of anaesthesia, but can provide a trend for use in conjunction with clinical observations.
(iii) EEG with compressed spectral analysis: Philips EEG measurement module produces real-time waveforms from two channels. Software algorithms filter typical artifacts from eye movement and pulse, among others. The EEG module is designed for continuous, realtime monitoring of adult, paediatric and neonatal patients in anaesthesia and intermediate/critical care environments. The module provides the following measurements: Two channels of raw real-time EEG waves, CSA for each channel of EEG, Total power (TP), % TP in each frequency band (δ,γ,α,β), Spectral edge frequency, Mean dominant frequency, Peak power frequency, and Continuous impedance for each electrode.
(iv) Cerebral function monitor (CFM): This device is modified from the conventional EEG for use during anaesthesia. It uses a single biparietal or bitemporal lead (three wires) to obtain an EEG signal. This signal is filtered, semi-logarithmically compressed, and rectified. The output is displayed at a very slow chart speed, 1 mm/minute, giving a trace as seen in the accompanying examples. As a result of this processing, the output is no longer a regular EEG signal but is, rather, a representation of the overall electrocortical background activity of the brain. A high reading on the chart indicates a high level of activity. A low value indicates low activity. It has been used in cardiac, neuro- and vascular surgery, where trends in activity may reflect changes in cerebral perfusion. The CFM has been used to monitor anaesthetic depth, but interest has fallen for several reasons. It can be unreliable, especially when using inhalational anaesthetic agents and the response to increasing depth of anaesthesia is biphasic, complicating dose-response interpretation. Values similar to those seen in awake patients may be seen in anaesthetized individuals, while recovery from anaesthesia does not necessarily occur near baseline values. Additionally, burst suppression at deep levels of anaesthesia is characterized on the EEG by periods of normal or high-voltage activity alternating with periods of low or no activity. As the CFM provides a smoothed running average of the EEG voltage, early burst suppression artificially elevates the reading, producing an apparent, paradoxical rise in 'cerebral function'.
(v) Cerebral function analysis monitor (CFAM): This device produces a continuous display of an analyzed EEG signal from two symmetrical pairs of scalp electrodes. The top trace displayed shows the mean amplitude of the signal plotted in time (90% confidence interval), while the bottom trace shows the power amplitude in the frequency band. Thus, at any instant the CFAM display shows the overall mean amplitude and relative power in each frequency band (α,β,γ,δ). It is said to be more useful than the CFM, but suffers from the same drawbacks.
(vi) Bispectral Index : BIS is a proprietary algorithm (Aspect Medical Systems, Natick, MA) [Figure 1] and [Figure 2] that converts a single channel of frontal EEG into an index of hypnotic level (BIS). To compute the BIS, several variables derived from the EEG time domain (burstsuppression analysis), frequency domain (power spectrum, bispectrum:interfrequency phase relationships) are combined into a single index of hypnotic level. BIS is developed by recording EEG data from healthy adults, who underwent repeated transitions between consciousness and unconsciousness, using several different anaesthetic regimens. The raw EEG data were time stamped at various clinical end-points. A multivariate logistic regression was used in offline analysis and identified those features of the EEG recordings that best correlated with clinical depth of sedation/anaesthesia, and these were then fitted to a model. The resulting algorithm generates the BIS. The weight factors for the various components in the multivariate model that generates the BIS were empirically derived from a prospectively collected database of more than 1,500 anaesthetics. The BIS model accounts for the nonlinear stages of EEG activity by allowing different parameters to dominate the resulting BIS as the EEG changes its character with increasing plasma concentrations of various anaesthetics, resulting in a linear decrease in BIS. The BIS monitor generates a dimensionless number on a continuous scale of 0-100, with 100 representing normal cortical electrical activity and 0 indicating cortical electrical silence [Figure 1]. As with any EEG signal, BIS is subject to interference and artifact, particularly from EMG activity, which can artificially elevate the recorded BIS. The display also shows a signal quality index and an indicator of EMG interference. Because there is no 'gold standard' monitor against which to compare BIS, studies have used predictive probability outcome measures - that is, the likelihood of various clinically relevant end-points occurring (loss of consciousness, recovery of consciousness, postoperative recall, suppression of learning) at different BIS values. From these various studies, broad guidelines have emerged to aid the interpretation of BIS values. The probability of postoperative recall is very low when BIS is kept  . BIS is also regarded as valuable monitor of the level of sedation and loss of consciousness for propofol, midazolam, and isoflurane  .
Several randomized controlled trials (RCTs) have compared outcomes with BIS-guided anaesthetic administration versus standard clinical practice without BIS. In one RCT that enrolled 2,500 patients at high risk of intraoperative awareness, explicit recall occurred in 0.17% of patients when BIS monitors were used and in 0.91%of patients treated by routine clinical practice (P  . A small (n = 30), single-blinded RCT (i.e., the anaesthesiologists were blinded to the recorded BIS values) compared BIS monitoring with clinical signs during cardiac surgery and reported one episode of recall in the clinical signs group compared with no episodes in the BIS monitored group (P > 0.50)  . In other RCTs, times to awakening, first response, or eye opening and consumption of anaesthetic drugs were reduced with the use of BIS  . Another prospective nonrandomized cohort study (n =19,575) designed to establish the incidence of awareness with recall during routine general anaesthesia and to determine BIS values associated with intraoperative awareness events reported no statistically significant difference when BIS was used (0.18% of patients) compared with when BIS was not used (0.10% of patients)  . Other nonrandomized comparative studies reported higher index values on arrival in the post-anaesthesia care unit, shorter recovery times, and lower anaesthetic use among patients monitored with BIS compared with patients not monitored with BIS  . Wide ranges of mean BIS values have been reported during various intraoperative times  . Several case reports indicate that intraoperative events unrelated to titration of anaesthetic agents can produce rapid changes in BIS values (e.g., cerebral ischaemia or hypoperfusion, gasembolism, unrecognized haemorrhage, inadvertent blockage of anaesthesia drug delivery)  .
In several case reports, it is suggested that routine intraoperative events (e.g., administration of depolarizing muscle relaxants, activation of electromagnetic equipment or devices, patient warming or planned hypothermia) may interfere with BIS functioning and patients might be experiencing intraoperative awareness despite monitored values indicating an adequate depth of anaesthesia  . It is interesting to note that in patients with dementia, baseline BIS value ("awake") is found to be lower than normal subjects  .
BIS demonstrates a dose-response relationship with inhalational and hypnotic intravenous agents, such as propofol and midazolam, which is independent of the agent(s) being used and correlates with clinical assessments of the level of consciousness. Bispectral analysis is the first processed EEG technique to be correlated well with behavioural assessments of level of consciousness. Ketamine and sometime N 2 O however, cause EEG activation, complicating BIS interpretation. Baseline BIS values are not reduced by nitrous oxide, at inspired concentrations of up to 50%. Furthermore, the addition of nitrous oxide to established anaesthesia has little or no effect on BIS in the absence of surgical stimulation. However, during surgery, the anti-nociceptive effects of N 2 O may be responsible for the observed decrease in BIS.
BIS can be used as a continuous monitor of sedation in adult intensive care, and investigations have concluded that it is a useful reflector of the great inter-individual variations in pharmacokinetics and pharmacodynamics of sedatives in critically ill patients. Comparison of BIS values at various clinical end-points between adults and children suggest that BIS performs similarly in adults and children with respect to dose response to anaesthetic agents, however, it is important to note that healthy adult EEG data were used to authenticate the BIS algorithm, it cannot automatically be extrapolated to young children, as the paediatric EEG only approaches the adult pattern by about 5 years of age. However, early investigations suggest that BIS may be valid in children older than 1 year of age and recently it is concluded by Sadhasivam S et al in their study that it is a quantitative, non-disruptive and easy to use depth of sedation monitor in children  . To conclude, results from the paediatric studies conducted to date demonstrate that the current BIS provides useful clinical information in children and infants, and shows promise for use in paediatric anaesthesia practice in similar ways to its use in adults. It has been shown that BIS correlated with clinically assessed sedation levels and is useful for assessing sedation in paediatric intensive care unit and for differentiating adequate from inadequate sedation  . BIS has been proved to be useful during safe removal of LMA in children during awakening from anaesthesia and it is recommended that at BIS 60, LMA can be safely removed without much complication  .
BIS has also shown to have reduced consumption of anaesthetic agents which ultimately helps reducing overall cost of anaesthesia delivery system. Future use of BIS is quite promising especially during sleep studies, monitoring cerebral ischaemia, and use during sedation of patients in the ICU. It has been further found that significant correlation exists between Glasgow Coma Scale and BIS in patients with mild and moderate head injury, thus opening a vast era of research in this sub-set of patients  .
(vii) Entropy: Entropy monitoring is based on acquisition and processing of raw EEG and FEMG signals by using the Entropy algorithm. Entropy describes the irregularity, complexity, or unpredictability characteristics of a signal. It is a property of a physical system or data string consisting of a great number of elements. By adding the measurement of the cortical electrical activity, the clinician can assess the effect of anaesthetics more comprehensively. EEG recordings change from irregular to more regular patterns when anaesthesia deepens. Entropy of the signal has been shown to drop when a patient falls asleep and increase again when the patient wakes up. Similarly, FEMG quiets down as the deeper parts of the brain are increasingly saturated with anaesthetics.
A single sine wave represents a completely predictable signal (entropy = 0), whereas noise from a random number generator represents entropy = 1. The algorithm for calculation of entropy in the EEG signal as incorporated in the Datex-Ohmeda S/5 entropy Module (Datex-Ohmeda, Inc., Madison, WI) is in the public domain, and detailed descriptions have recently been published  . Entropy is independent of absolute scales such as the amplitude or the frequency of the signal. The commercially available Datex-Ohmeda module calculates entropy over time windows of variable duration and reports two separate entropy values. State entropy (SE) is an index ranging from 0 to 91 (awake), computed over the frequency range from 0.8 to 32 Hz, reflecting the cortical state of the patient. Response entropy (RE) is an index ranging from 0 to 100 (awake), computed over a frequency range from 0.8 to 47 Hz, containing the higher EMG-dominated frequencies, and will thus also respond to the increased EMG activity resulting from inadequate analgesia. Noxious stimulation increases the difference between RE and SE, however, it is reported that an increase in the difference does not always indicate inadequate analgesia and should be interpreted carefully during anaesthesia  . No clinical trials or other comparative studies were found that examine the impact of entropy monitoring on the incidence of intraoperative awareness. In a recent study, Bonhomme V et al found that SE is globally well correlated with BIS  . Further, Vakkuri A et al have been reported that entropy monitoring assists better 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  . Entropy also provides a reproducible hypnosis index for patients undergoing supratentorial neurosurgical procedures  .
(viii) Narcotrend®: The Narcotrend® (Monitor Technik, Bad Bramstedt, Germany) is an EEG monitor designed to measure the depth of anaesthesia and has been developed at the University Medical School of Hannover, Germany. The newest Narcotrend® software version includes a dimensionless Narcotrend index from 100 (awake) to 0 (electrical silence). The raw EEG signal can be recorded by standard ECG electrodes for single-and double-channel registration. The Narcotrend® monitor provides a vast amount of information: the actual Narcotrend® stage and index, the trend ('cerebrogram'), the raw EEG signal and a power spectrum and several derived EEG parameters. In brief, two commercially available electrodes are placed on the forehead of the patient; a third electrode serves as a reference [Figure 2]. After artifact analysis a multivariate statistical algorithm transforms the raw EEG data finally resulting in a 6-letter classification of the depth of anaesthesia. After artifact exclusion and Fourier transformation, the original electronic algorithm classified the raw frontal EEG according to the following system: A (awake), B (sedated), C (light anaesthesia), D (general anaesthesia), E (general anaesthesia with deep hypnosis), F (general anaesthesia with increasing burst suppression). The system included a series of sub-classifications resulting in a total of 14 possible sub-stages: A, B0-2, C0-2, D0-2, E0-1, and F0-1  .
In the most recent version (4.0) of the Narcotrend® software, the alphabet-based scale has been "translated" into a numerical scaling index system which called as the Narcotrend® index. This is scaled quantitatively similar to BIS scale viz. 0 (deeply anaesthetized) to 100 (awake). No clinical trials or other comparative studies were found that examine the impact of Narcotrend® monitoring on the incidence of intraoperative awareness. Kreuer S et al in a recent study demonstrate that an increase of the hypnotic component of anaesthesia as indicated by BIS is accompanied by corresponding effects as displayed by the Narcotrend® during propofolremifentanil anaesthesia. The Narcotrend® stages D or E are assumed equivalent to BIS values between 64 and 40 in > 93% cases indicating general anaesthesia  .
One RCT has compared the use of Narcotrend® controlled versus clinically controlled anaesthetic administration and found a shorter recovery time in the Narcotrend® group (i.e., opened eyes) after termination of anaesthesia  . The reported mean Narcotrend® values are as follows: after induction (loss of response), 72-80; and at emergence or end of surgery (spontaneously opened eyes), 80  . In a recent study, however, Narcotrend® is found unable to differentiate reliably between conscious and unconscious patients during general anaesthesia when neuromuscular blocking agents are used  . Narcotrend® has also been used in children during propofol/remifentanil anaesthesia and sevoflurane anaesthesia. It is found to reduce propofol consumption compared to a conventional clinical practice and end-tidal sevoflurane concentrations are more closely related with narcotrend index than with MAP or HR , .
(ix) Patient state analyzer: The Patient State Index (PSI; Physiometrix, North Billerica, MA) [Figure 3] is derived from a four-channel EEG. The derivation of the PSI is based on the observation that there are reversible spatial changes in power distribution of quantitative EEG at loss and return of consciousness. The PSI has a range of 0-100, with decreasing values indicating decreasing levels of consciousness or increasing levels of sedation, similar to BIS, entropy, and Narcotrend®. The PSI algorithm, calculated via a proprietary algorithm by a high-resolution 4-channel EEG monitor after advanced artifact rejection. The algorithm relies on EEG power, frequency and phase information from anterior-posterior relationships of the brain as well as coherence between bilateral brain regions. It is constructed using stepwise, discriminant analysis based on multivariate combinations of quantitative EEG variables, derived after Fourier transformation of the raw EEG signal, and found to be sensitive to changes in the level of anaesthesia. PSI is a clinically validated measure of the effect of anaesthesia and sedation and has been designed specifically for intra-operative and intensive care use to monitor patient sedation and drug effect. The PSI monitor, initially called the PSA 4000, is also called the SED Line monitor, the newest generation of the device. The SED Line system provides the clinician the option of storing and downloading patient data for future use as well as monitoring bilateral brain function and symmetry with a density spectral array (DSA) display. No clinical trials or other comparative studies were found that examine the impact of PSI monitoring on the incidence of intraoperative awareness. One study reported a significant correlation of the PSI with unconsciousness  . Reported mean PSI values are as follows: before induction or baseline, 92; during surgery, 32;at emergence or end of surgery, 53;and during postoperative recovery, 81  . PSI has also been used to quantify the level of propofol/ sufentanil sedation in ICU patients  .
(x) SNAP index: The SNAPII (Everest Biomedical Instruments, Chesterfield, MO) [Figure 4] calculates a "SNAP index" from a single channel device intended to monitor a patient's EEG. It samples raw EEG signals and uses its own unique algorithm, analyses both high(80-420 Hz) and low- (0-20 Hz) frequency components of the signal. This is termed the SNAP index, and it ranges from 100 (arbitrarily representing the fully awake state) to 0 to provide functional data points for patient management. The SNAP is the first commercial EEG-monitoring tool to use Personal Digital Assistant computer technology. The first version of SNAP index was introduced in 2002, and so far there has been little experience with the SNAP device reported in the literature. Compared with other EEG devices, there is no evidence that SNAP is superior to others in generating more specific information about 'depth of sedation'.
There are no published data on the actual algorithm used to calculate the SNAP index, which is based on a composite of both low-frequency (0-40 Hz) and high-frequency (80-420 Hz) components. No clinical trials or other comparative studies were found that examine the impact of SNAP monitoring on the incidence of intraoperative awareness. One correlational study was found that reported a mean SNAP index of 71 to be predictive of a loss of consciousness in 95% of elective surgery patients  . Same author, in a recent study, however, compares SNAP with BIS, and concluded that SNAP index tracks loss of consciousness and emergence from sevoflurane and sevoflurane/nitrous oxide anaesthesia and there is significant bias exists between the SNAP and BIS indices and therefore, the indices are not interchangeable. They further observed that the SNAP index returns to baseline before awakening, whereas the BIS index remains below baseline at awakening, suggesting that the SNAP index may be more sensitive to unintentional awareness  .
(xi) Cerebral State Monitor/Cerebral State Index (CSI): The Cerebral State Monitor (Danmeter A/S, Odense, Denmark) [Figure 5] is a handheld device that analyzes a single channel EEG and presents a CSI scaled from 0to 100.In addition, it also provides EEG suppression percentage and a measure of EMG activity (75-85 Hz). The EEG waveform is derived from the signal recorded between the frontal and mastoid electrodes. The frequency content is 2-35 Hz. The performance of the CSI is based on the analysis of the frequency content of the EEG signal. The energy of the EEG is evaluated in specific frequency bands. These are used to define two energy ratios called alpha (α) and beta (β). Both of these show a shift in energy content from the higher to the lower frequencies during anaesthesia. The relationship between these quantities is also analyzed as a separate parameter (β-α). The monitor also on-line evaluates the amount of instantaneous burst suppression (BS) in each thirty-second period of the EEG.The four parameters (αratio ,β ratio ,β - α shift & BS) are used as input to a fuzzy logic classifier system that calculates the CSI [Figure 6]. The CSI is a unit-less scale from 0 to 100, where 0 indicates a flat EEG and 100 indicate EEG activity corresponding to the awake state. The range of adequate anaesthesia is designed to be between 40 and 60. All values in the table are approximate values based on the mean values of the patient behaviour. The relationship between the CSI, the clinical state and the OAAS score [Table 2] is shown in the [Table 3].
High levels of facial muscular or EMG activity can interfere with the CSI under certain circumstances. The monitor incorporates an EMG filter that removes most of the potential interfering EMG activity. The EMG bar (shown in monitor) shows the energy of the EMG level in the 75-85 Hz frequency band (0-100 logarithmic). EMG activity is expected to be present when the patient is awake. When the patient is asleep, EMG activity can increase due to (i) reflex reactions to painful stimuli during surgery, (ii) lack of muscular relaxation, (iii) muscular rigidity caused by some opioids (analgesics) and, (iv) presence of large external electrical fields, e.g. diathermy. The monitor also shows a BS% indicator to show periods when the EEG is iso-electric during 20% of the last 30 seconds. It analyses the frequency shifts that take place in the EEG signal as the level of consciousness changes. Based on this principle, the monitor calculates the CSI, which is used to estimate the level of consciousness of the patient. No published literature was found that examined the impact of using the Cerebral State Monitor on the incidence of intraoperative awareness. However, Anderson RE et al reported that CSI correlated well with BIS and show similar patterns and numerical values in day-surgery anaesthesia without muscle relaxation, however, which monitor is the more dependable remains to be established in such subset of patients  . In a recent study, it has been further found that the CSI detects well the graduated levels of propofol anaesthesia when compared with the propofol effect site concentration and the OAAS score  and it behaves as other depth of anaesthesia monitors with a progressive decrease during propofol induction but loss of consciousness with N 2 O results no change in CSI  .
2. Evoked brain electrical activity monitors: Evoked potential monitors measure electrical activity in certain areas of the brain in response to stimulation of specific sensory nerve pathways.
(i) Somatosensory evoked potentials (SSEP): A supramaximal stimulus is applied to peripheral nerves while a recording scalp electrode is placed over the appropriate sensory area. In general, most anaesthetic agents increase the latency and decrease the amplitude in a dose-dependent manner. Etomidate consistently in creases the amplitude.
(ii) Visual evoked potentials (VEP): Light-emitting diodes are incorporated into specialized goggles and the optic nerve is stimulated at 2 Hz. EEG electrodes take recordings from the occiput. Mostanaesthetic agents increase the latency and decrease the amplitude of P100 in a dose-dependent manner. Although VEP are considered less reliable than AEP, they have been used to monitor function during surgery for lesions involving the pituitary gland, optic nerve and chiasma.
(iii) Auditory evoked potential (AEP): The AEP is defined as the passage of electrical activity from the cochlea to the cortex, which produces a waveform consisting of 15 waves. The waveform can be divided into three parts: Brainstem Auditory Evoked Potential (BAEP), Middle Latency Auditory Evoked Potential (MLAEP) and Long Latency Auditory Evoked Potential (LLAEP). These parts indicate the sites in the brain from which the various waves are thought to originate [Figure 7]. The BAEP is represented by the Roman numerals I - VI and extends from 0 to 10 ms after the stimulus. These waves represent the process of stimulus transduction in the brainstem: acoustic nerve (I), cochleae nucleus (II), superior olivary complex (III), ventral nucleus of the lateral leminiscus and preolivary region (IV), inferior colliculus (V), and medial geniculate body (VI). The early cortical or MLAEPs, marked by the waves N0, P0, Na, Pa and Nb, are thought to originate from the medial geniculate body and the primary auditory cortex. These waves occur from 10 to 100 ms after the stimulus. The third part, more than 100 ms after the stimulus, is called a LLAEP and consists of waves P1, N1, P2 and N2. It reflects the neural activity of the frontal cortex and association areas. The AEP window of this monitor shows the BAEP and MLAEP. The BAEP is presented as a smoothed curve; therefore, typically only wave V can be detected. In the MLAEP, typically Na, Pa and Nb can be observed. The AEP technology actively measures the brain's reaction to acoustic stimuli. It's the natural choice for measuring patient consciousness under anaesthetic because hearing is the last retained sense during anaesthesia and the first to be regained prior to waking. Re-usable headphones/ear phones deliver the active stimulation, cost-effective disposable surface electrodes are used to measure the AEP. The result is fast information to enable you to accurately measure the patient's level of consciousness.
The effects of anaesthetics on AEP have been studied since the early 1980s  . The brainstem response is relatively insensitive to anaesthetics, whereas early cortical responses (MLAEPs), change predictably with increasing concentrations of both volatile and intravenous anaesthetics. The typical AEP response to increasing anaesthetic concentrations is increased latency and decreased amplitude of the various waveform components. These signals are extremely small ( . If the SNR is adequate, the main weight is on the AEP but, if the SNR decreases, the weight on the EEG is increased in a gradual manner. When burst suppression is present, this component is included in the AAI as well. The recommended AAI values for surgical anaesthesia are 15-25 [Figure 9]. In contrast to many EEG indices, the AAI corresponding with low probability of consciousness is less than 25, rather than the higher numeric thresholds associated with the other monitors. The monitor takes advantage of the additional information provided by the spontaneous EEG activity. During loss of consciousness, the energy of the EEG frequency spectrum shifts from predominantly higher (α, & β activity) to lower frequencies (δ band). This energy shift is quantified by a proprietary algorithm analyzing frequencies in the 3-47 Hz band. This information is included in the calculation of the AAI when the Signal to Noise Ratio (SNR) of the AEP is low. Very deep anaesthesia can also cause near suppression of the AEP. In this case, spontaneous EEG enhances the AAI performance by increased resolution during this phase.
RCT that compared MLAEP monitoring (e.g., to titrate anaesthetics) to standard clinical practice without MLAEPs reported reduced times to eye opening or orientation . Descriptive studies reported ranges of mean values as follows: before induction or baseline, 73.5- 85; at or after induction, 33.4-61; during surgery, 21.1- 37.8; at emergence or end of surgery, 24.6-40; and during postoperative recovery, 89.7, [Figure 9]. Alpiger S et al in their two different studies showed that AAI indicates the depth of anaesthesia necessary for acceptable 7endotracheal intubation/laryngeal mask insertion conditions; however, end-expiratory sevoflurane concentration is found to be a better predictor and may turn out to be more useful in the clinical setting, . Nishiyama T investigated sensitiveness about arousal detector of AAI monitor during propofol-fentanyl-nitrousoxide anaesthesia and found that the AAI responded to LMA insertion or surgical incision, but not the BIS, and the AAI had smaller variations . Further, the AAI recovered faster from the disturbance by electrocautery than the BIS and concluded that the AAI may be a more sensitive and useful detector of arousal than the BIS .
AEP index and children - Anaesthesia management in children is determined by their special psychological and physiological characteristics. The assessment of anaesthetic depth can be difficult. In children, this situation becomes more evident, especially when attempting to use classic scales based on the response to verbal commands, which is often unreliable. In this sense, the paediatric anaesthesiologists can benefit from the added information provided by the AEP Monitor/2. It can be safely used on children over 2 years of age with minimal adjustments to the settings. The AAI reference values are the same for adults. For children under 10 years it is advisable to place the negative (black) electrode on the left cheekbone for improved performance.
Anaesthesia to prevent awareness and approaching the aware patient:
Since there is no readily available definition of 'unconsciousness' or a practical monitor to measure it, the proper anaesthetic technique to prevent awareness rests on careful clinical monitoring of the patient. In addition to regular checking of the apparatus and detailed recordkeeping (all of which should be good anaesthetic practice), the following approach may also help to prevent awareness:
Unpremedicated patients may need larger doses of intravenous induction agent.The level of inhalational anaesthetic agent during surgery should be monitored (i.e. end-tidal gas monitoring), recorded and maintained at a level known from published data, sufficient to keep the patient asleep.The level of analgesia should be sufficient to ensure that if the patient is aware, s/he is not in pain. If it is suspected awareness might be a possibility, consideration should be given to the use of an amnesic drug (e.g. midazolam) so that if the patient is aware and in pain, s/he will not recall the event. The patient is thus spared the ill-effects of possible post-traumatic stress disorder.It may be prudent to use earplugs or headphones transmitting music or white noise: should the patient be only semiconscious, s/he may not associate any sensations with an operation.
If a patient does declare after an operation that s/ he has been aware, then the following course of action is sensible:
The anaesthesiologists who conducted the anaesthetic should be informed and personally visit the patient.The anaesthesiologists should check the anaesthetic record and, if possible, re-check any equipment which was used for faults.The anaesthesiologists should also acknowledge that's/he believes the patient's account of events, apologize, and reassure the patient explaining how the awareness might have occurred.A note should be made in the medical records so that future anaesthesiologists are aware of the problem. A full account of the interview with the patient should also be made.Junior anaesthesiologists should inform their consultant, who should be present and/or also visit the patient.Psychological counselling may need to be arranged for the patient.
The post-operative visit may be difficult if the patient is unhappy as a result of their experience, but a sympathetic approach must be taken and make it clear that, they believe the patient. In general terms, awareness despite correct procedure and meticulous recordkeeping may be excusable; awareness with pain or awareness due to faulty anaesthetic technique is extremely difficult to defend. In some cases (e.g. the seriously ill) it may be advisable to warn patients before the operation that low doses of anaesthetic are to be used for reasons of safety, but to reassure them that they will always be pain-free. Patients usually accept this explanation: one example comes from neurosurgical patients who are sometimes woken up with their consent during surgery and asked to perform motor tasks to ensure that vital parts of the brain are intact. The checklist would be useful for the purpose [Table 4]
ASA Task force recommendation about monitoring depth of anaesthesia
Intraoperative monitoring of depth of anaesthesia, for the purpose of minimizing the occurrence of awareness, should rely on multiple modalities, including clinical techniques (e.g., checking for clinical signs such as purposeful or reflex movement) and conventional monitoring systems (e.g., electrocardiogram, blood pressure, HR, end-tidal anaesthetic analyzer, capnography). The use of neuromuscular blocking drugs may mask purposeful or reflex movements and adds additional importance to the use of monitoring methods that assure the adequate delivery of anaesthesia.Brain electrical activity monitor is valuable in monitoring depth of anaesthesia but should not be used to assess intraoperative depth of anaesthesia for all patients. It should be used to assess intraoperative depth of anaesthesia for selected patients that may place the mat risk and patients requiring smaller doses of general anaesthetics.Brain function monitoring is not routinely indicated for patients undergoing general anaesthesia, either to reduce the frequency of intraoperative awareness or to monitor depth of anaesthesia. Use of a brain function monitor should be made on a case-by-case basis by the individual practitioner for selected patients that may place them at risk and patients requiring smaller doses of general anaesthetics, trauma surgery, caesarean delivery, and total intravenous anaesthesia.
Monitoring depth of anaesthesia is a newer advance in the monitoring of anaesthesia. Its increasing use may help prevent awareness of anaesthesia which is not uncommon because of development of short acting anaesthetics and increase in number of high risk patients subjected for different surgery where anaesthesia is tailored to avoid haemodynamic disturbances. However, prevention of awareness not only involves sophisticated monitoring but also involves fine clinical judgment, the checking of all equipment, ensuring the uninterrupted delivery of anaesthetic to patients via intact circuits and intravenous access and the use of familiar, appropriate techniques by competent practitioners. Also, reassuring those patients, who had awareness despite best use of anaesthetics & monitoring devices, that they can safely have further general anaesthetics, with minimal risk of a further episode of awareness and offering psychological support, apart from documenting that this has been offered remain a cornerstone in the quality management of anaesthesia.
|1||Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: A prospective case study. Lancet 2000; 355: 707-11.|
|2||Sebel PS, Bowdle TA, Ghoneim MM, et al. The incidence of awareness during anaesthesia: A multicenter United States study. Anesth Analg 2004; 99: 833-39.|
|3||Domino KB, Posner KL, Caplan RA, Cheney FW. Awareness during anesthesia - A closed claim analysis. Anesthesiology 1999; 90: 1053-61.|
|4||Lennmarken C, Bildfors K, Enlund G, SamuelssonP, Sandin R. Victims of awareness. ActaAnaesthesiol Scand 2002; 46:229-31.|
|5||Griffith D, Jones JB. Awareness and memory in anaesthetised patients. Br J Anaesth 1990; 65: 603-7.|
|6||Hargrove RL. Awareness under anaesthesia. J Medical Defence Union 1987; (Spring): 9-11.|
|7||Stoelting RK, Longnecker DE, Eger El 2nd. Minimum alveolar concentrations in man on awakening from methoxyflurane, halothane, ether and fluroxene anesthesia: MAC awake. Anesthesiology 1970; 33: 5-9.|
|8||Evans JM, Davies WL. Monitoring anaesthesia. Clin Anesth 1984; 2: 243-62.|
|9||Anonymous. Practice advisory for intraoperative awareness and brain function monitoring, AReport by theAmerican Society of Anesthesiologists Task Force on Intraoperative Awareness. Anesthesiology 2006; 104: 847-64.|
|10||Goddard GF. Apilot study of changes in skin electrical conductance in patients undergoing general anaesthesia and surgery. Anaesthesia 1982; 37: 408-15.|
|11||Herregots L, Rolly G, Mortier E, Bogaert M, Mergaert C. EEG and SEMG monitoring during induction and maintenance of anaesthesia with propofol. Int J Clin Monit Comput 1989; 6: 67-73.|
|12||Evan JM, Davies WL, Wise CC. Lower oesophageal contractility: A new monitor of anaesthesia. Lancet 1984; 1: 1157.|
|13||Isaac PA, Rosen M. Lower oesophageal contractility and detection of awareness during anaesthesia. Br J Anaesth 1990; 65: 319-24.|
|14||Healy TEJ, Bellman MH, Pomfrett CJD. Respiratory sinus arrhythmia indicates light anaesthesia during caesarean section. Anesth Analg 1994; 78: S156.|
|15||Pomfrett LJD, Barric JR, Healy TEJ. Respiratory sinus arrhythmia reflects surgical stimulation during light enflurane anaesthesia. Anesth Analg 1994; 78: S 334.|
|16||Rosow C, Manberg PJ. Bispectral index monitoring. Anesth Clin N Am 2001; 19: 947-66.|
|17||Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997; 86: 836-47.|
|18||Myles PS, Leslie K, McNeil J, Forbes A, Chan MTV. Bispectral index monitoring to prevent awareness during anaesthesia: The B-aware randomized controlled trial. Lancet 2004; 363: 1757-63.|
|19||Puri GD, Murthy SS. Bispectral index monitoring in patients undergoing cardiac surgery under cardiopulmonary bypass. Eur J Anaesth 2003; 20: 451-6.|
|20||Burrow B, McKenzie B, Case C. Do anaesthetized patients recover better after bispectral index monitoring? Anaesth Intensive Care 2001; 29: 239-45.|
|21||Renna M, Handy J, Shah A. Low baseline Bispectral Index of the electroencephalogram in patients with dementia. Anesth Analg 2003; 96: 1380-85.|
|22||Sadhasivam S, Ganesh A, Robison A, et al. Validation of the bispectral index monitor for measuring the depth of sedation in children. Anesth Analg 2006; 102: 383-88.|
|23||Berkenbosch JW, Fichter CR, Tobias JD. The correlation of the bispectral index monitor with clinical sedation scores during mechanical ventilation in the pediatric intensive care unit. Anesth Analg 2002; 94: 506-11.|
|24||Sinha A, Sood J. Safe removal of LMA in children - at what BIS? Paediatr Anaesth 2006; 16:1144-47.|
|25||Paul DB, Umamaheswara Rao GS. Correlation of Bispectral Index with Glasgow Coma Score in mild and moderate head injuries. J Clin Monit Comput 2006; 20: 399-404.|
|26||Viertio-Oja H, Maja V, Sarkela M, et al. Description of the entropy algorithm as applied in the Datex-Ohmeda S/5 Entropy Module. Acta Anaesth Scand 2004; 48: 154-61.|
|27||Takamatsu I, Ozaki M, Kazama T. Entropy indices vs the bispectral index for estimating nociception during sevoflurane anaesthesia. Br J Anaesth 2006; 96: 620-26.|
|28||Bonhomme V, Deflandre E, Hans P. Correlation and agreement between bispectral index and state entropy of the electroencephalogram during propofol anaesthesia.Br J Anaesth 2006; 97:340-46.|
|29||Vakkuri A, Yli-Hankala A, Sandin R, et al. Spectral entropy monitoring is associated with reduced propofol use and faster emergence in propofol-nitrous oxide-alfentanil anesthesia. Anesthesiology 2005; 103: 274-79.|
|30||Paolo Martorano P, Falzetti G, Pelaia PJ. Bispectral index and spectral entropy in neuroanesthesia. J Neurosurg Anesthesiol 2006; 18: 205-10.|
|31||Schultz B, Schultz A, Grouven U. Sleeping stage based systems (Narcotrend), In, New Aspects of High Technology in Medicine 2000. Eds. Bruch HP, Kockerling F, Bouchard R, Schug-Pab C. Bolognia, Monduzzi Editore, pp. 285-91.|
|32||Kreuer S, Biedler A, Larsen R, et al. The Narcotrend™ M - a new EEG monitor designed to measure the depth of anaesthesia. A comparison with bispectral index monitoring during propofol-remifentanil-anaesthesia. Anaesthesist 2001; 50: 921-25.|
|33||Kreuer S, Biedler A, Larsen R, Altmann S, Wilhelm W. Narcotrend monitoring allows faster emergence and a reduction of drug consumption in propofol-remifentanil anaesthesia. Anesthesiology 2003; 99: 34-41.|
|34||Kreuer S, BruhnJ, Larsen R, Bialas P, Wilhelm W. Comparability of Narcotrend index and bispectral index during propofol anaesthesia. Br J Anaesth 2004; 93: 235-40.|
|35||Russell IF. The Narcotrend 'depth of anaesthesia' monitor cannot reliably detect consciousness during general anaesthesia: an investigation using the isolated forearm technique. Br J Anaesth 2006; 96: 346-52.|
|36||Weber F, Pohl F, Hollnberger H, Taeger K. Impact of the Narcotrend Index on propofol consumption and emergence times during total intravenous anaesthesia with propofol and remifentanil in children: a clinical utility study. Eur JAnaesthesiol 2005; 22:741-47.|
|37||Weber F, Hollnberger H, Gruber M, et al. The correlation of the Narcotrend Index with endtidal sevoflurane concentrations and hemodynamic parameters in children. Paediatr Anaesth 2005; 15:727-32.|
|38||Chen X, Tang J, White PF, et al. A comparison of patient state index and bispectral index values during the perioperative period. Anesth Analg 2002; 95: 1669-74.|
|39||Schneider G, Heglmeier S, Schneider J, et al. Patient State Index(PSI) measures depth of sedation in intensive care patients. Intensive Care Med 2004; 30: 213-16.|
|40||Wong CA, Fragen RJ, Fitzgerald PC, McCarthy RJ. The association between propofol-induced loss of consciousness and the SNAP TM index. Anesth Analg 2005; 100: 141-48.|
|41||Wong CA, Fragen RJ, Fitzgerald P, McCarthy RJ. A comparison of the SNAP II and BIS XP indices during sevoflurane and nitrous oxide anaesthesia at 1 and 1.5 MAC and at awakening. Br J Anaesth 2006;97:181-86.|
|42||Anderson RE, Jakobsson JG. Cerebral state monitor, a new small handheld EEG monitor for determining depth of anaesthesia: a clinical comparison with the bispectral index during day-surgery. Eur J Anaesthesiol 2006; 23: 208-12.|
|43||Jensen EW, Litvan H, Revuelta M, et al. Cerebral state index during propofol anesthesia: a comparison with the bispectral index and the A-line ARX index. Anesthesiology 2006; 105: 28-33.|
|44||Anderson RE, Barr G, Jakobsson JG. Cerebral state index during anaesthetic induction: a comparative study with propofol or nitrous oxide. Acta Anaesthesiol Scand 2005; 49: 750-53.|
|45||Schwender D, Conzen P, Klasing S, et al. The effects of anaesthesia with increasing end-expiratory concentrations of sevoflurane on mid-latency auditory evoked potentials. Anesth Analg 1995; 81: 817-22.|
|46||Recart A, Gasanova I, White PF, et al. The effect of cerebral monitoring on recovery after general anaesthesia: A comparison of the auditory evoked potential and bispectral index devices with standard clinical practice. Anesth Analg 2003; 97: 1667-74.|
|47||Kreuer S, Bruhn J, Larsen R, Hoepstein M, Wilhelm W. Comparison of AlarisAEP index and bispectral index during propofol-remifentanil anaesthesia. Br J Anaesth 2003; 91: 336-40.|
|48||Anderson RE, Barr G, Assareh H, Jakobsson J. The AAI index, the BIS index and end-tidal concentration during wash in and wash out of sevoflurane. Anaesthesia 2003; 58: 531-35.|
|49||Alpiger S, Helbo-Hansen HS, Vach W, Ording H. Efficacy of A-line AEP Monitor as a tool for predicting acceptable tracheal intubation conditions during sevoflurane anaesthesia. Br J Anaesth 2005; 94: 601-606.|
|50||Alpiger S, Helbo-Hansen HS, Vach W, Ording H. Efficacy of the A-line AEP monitor as a tool for predicting successful insertion of a laryngeal mask during sevoflurane anesthesia. Acta Anaesthesiol Scand 2004; 48: 888-93.|
|51||Nishiyama T, Hanaoka K. The A-line ARX index may be a more sensitive detector of arousal than the bispectral index during propofol-fentanyl-nitrous oxide anesthesia: a preliminary investigation. Can J Anaesth 2004; 51: 539-44.|