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REVIEW ARTICLE
Year : 2009  |  Volume : 53  |  Issue : 2  |  Page : 148-157 Table of Contents     

Awareness During Anaesthesia


1 Senior Consultant, Max Institute of Neurosciences, Saket, New Delhi, India
2 Chief of Neurosciences Center & Prof. and Haad, Neuro anaesthesiology, AIIMS, New Delhi, India

Date of Web Publication3-Mar-2010

Correspondence Address:
K Sandhu
E-90, Greater Kailash -II, New Delhi -110048
India
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Source of Support: None, Conflict of Interest: None


PMID: 20640115

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Awareness is the postoperative recall of sensory perception during general anaesthesia. The incidence is quoted at 1-2 per every 1000 patients. This rare but serious adverse event can be extremely distressing for both the patient as well as the anaesthesiologist. Awareness during anaesthesia may occur despite apparently sound anaesthetic management and is usually not associated with pain. However, a few cases may experience excruciating pain and have long term neuropsychiatric sequelae like post-traumatic stress disorder. This adverse event can also have serious medicolegal implications. This article addresses the various contributory factors that may predispose to intra­operative awareness. Preventive measures in the preinduction period as well as intraoperatively are discussed, in­cluding the use of depth of anaesthesia monitors. Remedial steps to be taken when such an event occurs are also discussed.

Keywords: Intraoperative, Awareness, Anaesthesia


How to cite this article:
Sandhu K, Dash H. Awareness During Anaesthesia. Indian J Anaesth 2009;53:148-57

How to cite this URL:
Sandhu K, Dash H. Awareness During Anaesthesia. Indian J Anaesth [serial online] 2009 [cited 2020 Jan 26];53:148-57. Available from: http://www.ijaweb.org/text.asp?2009/53/2/148/60270


   Introduction Top


Intraoperative awareness is the unexpected and explicit recall of sensory perception during general ana­esthesia. One of the most common concerns of pa­tients about to undergo anaesthesia is that they will re­member the intraoperative events. Although the risks associated with anaesthesia have progressively de­creased, yet awareness during anaesthesia remains a serious complication with potential long term psycho­logical sequelae.


   Incidence Top


Awareness during anaesthesia may be experi­enced by 1 or 2 cases out of every 1000 patients who receive general anaesthesia (0.1-0.2%). [1],[2] The overall incidence is higher among obstetric and cardiac cases where it has been quoted at 0.4% and 1.1-1.5% re­spectively. [3] In children, the incidence is once again higher at 0.8-1.2%. [4],[5]

Many patients may not voluntarily report their experiences without being asked directly. Some cases may not recall events shortly after surgery but may re­call them 1-2 weeks later. [6] Intraoperative awareness is therefore best assessed by formally interviewing pa­tients postoperatively. Most of the patients have a vague auditory recall or a sense of dreaming and may not be unduly disturbed by this experience. [7] In fact dreams may be recalled more often than actual events and occasion­ally these are very distressing to the patient. In a series of 500 patients anaesthetized with nitrous oxide, Utting reported that 7% patients considered this incidence of dreams to be the worst feature of their experience as against 2% patients who rated the recall of other intra­operative events as the most distressing. [8] Some patients may even experience severe pain. In a study involving 11,785 patients who underwent general anaesthesia, awareness was reported in 0.18% cases where neuro­muscular blockade was instituted and in 0.1% cases where no muscle paralysis was imposed. [2] Out of these, 36% patients reported perception of pain ranging from soreness in the throat to pain at the site of incision. Most cases of awareness are inconsequential but some pa­tients experience prolonged and unwanted outcomes like post-traumatic stress disorder and depression. [9] These late symptoms include nightmares, flashbacks and anxi­ety and have been reported to occur in upto 33% of the cases who experienced awareness.

This vexing problem of intraoperative awareness was addressed by the Task Force on Intraoperative

Awareness which released a 'Practice Advisory for Intraoperative Awareness and Brain Function Moni­toring' in 2006. [10] This advisory identified certain pa­tient characteristics and factors that increase the risk of intraoperative awareness and put forth certain recommendations.[Table 1]


   Causes Top


Descriptive studies and case reports suggest that certain patient characteristics may be associated with intraoperative awareness including age, sex, ASA physi­cal status and drug resistance or tolerance. Patients at increased risk for intraoperative awareness include those with a history of substance use or abuse (eg opioids, benzodiazepines, cocaine) and chronic pain patients using high doses of opioids. [1] A past history of aware­ness, difficult intubation, ASA physical status of IV/V and a limited haemodynamic reserve are also risk fac­tors. [11] Procedures which are associated with a higher risk include cardiac surgery, caesarean delivery, trauma and emergency surgery. [12],[13],[14],[15] The use of reduced an­aesthetic doses in the presence of paralysis, rapid se­quence induction and total intravenous anaesthesia have also been implicated. [2], [16],[17],[18],[19]

A careful preoperative evaluation is therefore rec­ommended by the Practice Advisory for identifying patients at risk and a thorough review of the patient's medical records, a detailed physical examination and a patient or patient family interview may help identify a vulnerable patient. The Task Force is of the consensus that patients at substantially increased risk of intraop­erative awareness should be informed of its possibility by the clinician whenever possible.

The causes of intraoperative awareness are as yet not fully established and may be multifactorial. Four categories of causes have been postulated which are as follows:

• Unexpected patient specific variability in the dose requirements of anaesthetic drugs-A cer­tain group of patients have been documented to be more 'resistant' to effects of anaesthetics as compared to the others. A younger age group, smoking, long term use of drugs like opiates and alcohol consumption may in­crease the individual requirement for an anaesthetic drug. [3] The reason why some patients require a higher dose of anaesthetic is still not very clear. It has been postulated that this variability in dose requirements may be a result of altered gene expression or function of target receptors. In preclinical studies in mice, Cheng and colleagues found that a genetic deficiency in one type of receptor for the inhibitory neurotransmitter, GABA (receptors that contain the (c 5 subunit), conferred resistance to the memory blocking properties of the anaesthetic etomidate. [20] These receptors are predomi­nantly in the hippocampus region that is critically in­volved in memory. Other preclinical studies have shown that the expression of this memory blocking receptor changes after long term exposure to alcohol or persis­tent seizures. [21],[22] Concurrent medications can also af­fect the metabolism and distribution of anaesthetic agents adversely. Polymorphisms for this GABA cc receptor 5 gene (GABRA 5 ) exist in the human genome and there are at least 3 distinct messenger RNA isoforms in hu­man adult and foetal brain tissue. [23] Pharmacogenetics may therefore be an important factor contributing to intraoperative awareness.

Requirement for light anaesthesia: Certain operations like caesarean section may require the anaesthesiologist to aim for lighter anaesthesia. In other cases, patients may often be unable to tolerate a suffi­cient dose of anaesthetic because of low physiologic reserves related to factors such as poor cardiac func­tion or severe hypovolemia. Judgement about the ad­equate depth of anaesthesia can thus be imprecise in such patients.

• Pharmacological masking of signs of inad­equate depth of anaesthesia:

Anaesthetic concen­trations that block awareness are less than those that prevent motor responses to pain. [24], [25] Anonparalyzed but inadequately anaesthetized patient usually commu­nicates by movement. The use of muscle relaxants ren­der such a patient motionless and can lull the anaesthesiologist into a false sense of security. Also the use of drugs like beta blockers or vasodilator agents which have to be given preoperatively for disorders like hypertension may affect intraoperative haemodynamics. Sometimes the anaesthesiologist may use these drugs to tackle intraoperative tachycardia and hypertension without addressing the underlying cause like inadequate depth of anaesthesia. Consequently, physiologic characteristics that would indicate the need for a further deepening of anaesthesia are masked.

• Machine malfunction or misuse resulting in an inadequate delivery of anaesthesia:

This can be caused by an empty vaporizer, a malfunctioning intrave­nous pump or a disconnection of its delivery tubing


   Consequences Of Intraoperative Awareness Top


While pain during surgery is the most distressing feature of awareness, other complaints include the ability to hear conversations during the operation, feelings of anxiety, helplessness, paralysis, panic and impending death. [26] In some patients awareness causes temporary after effects including sleep disturbances, nightmares and daytime anxiety, which eventually subside. In a small group however, posttraumatic stress disorder devel­ops consisting of repetitive nightmares, irritability and anxiety. Why this disorder develops only in some pa­tients and not in others is not very clear. Factors that are cited include a patient personality, predisposition to mental illness, or the type of emotional response to the disease and surgery.

Intraoperative awareness can thus have long reach­ing consequences including medicolegal implications. Domino et al, analysed claims from the ASA Closed Claims Project and found that intraoperative aware­ness accounted for upto 2% of all claims. [11] What is significant is that this incidence was similar to rates of claims for life threatening complications like myocar­dial infarction and aspiration pneumonia. Claims were more common in females and where the nitrous oxide­opioid relaxant technique was used.


   Prevention Of Intraoperative Awareness Top


Various measures have been recommended to reduce the incidence of intraoperative awareness.

1. Preinduction measures:

i) Premedication with amnesic drugs (e.g. benzo­diazepines):

Prophylactic administration of benzodiazepines as a premedicant especially when light anaesthesia is anticipated, has been advocated. One double blind ran­domized clinical trial evaluated the efficacy of prophy­lactic administration of midazolam as an adjuvant dur­ing total intravenous anaesthesia and reported a lower frequency of intraoperative awareness in this group as compared to the placebo group. [27] The Practice Advi­sory Task Force has however yet not recommended the use of benzodiazepines as a component of anaes­thesia to reduce the risk of intraoperative awareness for all patients. Their consensus is that the decision to administer benzodiazepines prophylactically should be made on a case to case basis for selected patients es­pecially those requiring smaller doses of anaesthetics and those undergoing cardiac surgery, emergency sur­gery, trauma surgery or total intravenous anaesthesia. They have cautioned that delayed emergence may ac­company the use of benzodiazepines. [10]

ii) Meticulous checking of the anaesthesia delivery system before induction:

Cases of intraoperative awareness have been re­ported to have resulted from anaesthetic concentration delivery errors. Bergman et al, reviewed 8372 incidents reported to the Anaesthetic Incident Monitoring Study and found 81 cases where perioperative recall was consistent with awareness. Awareness was consequent to failure of delivery of volatile anaesthetic in 16 of these patients while in 32 cases a drug error resulting in inad­vertent paralysis of an awake patient had occurred. [28] The Practice Advisory Task Force has strongly rec­ommended that the functioning of anaesthesia delivery systems (eg vaporizers, infusion pumps, fresh gas flows and intravenous lines) should be checked meticulously prior to induction and regular maintenance be carried out. [10] Regular checking of the anaesthetic in the vapor­izer, monitoring of the concentrations of inspired and expired gases and inhalational agents and administra­tion of an anaesthetic infusion via a dedicated intrave­nous line are simple measures that go a long way in prevention of awareness.

2. Intraoperative monitoring:

Intraoperative awareness cannot be measured during the intraoperative period as the recall compo­nent of awareness can only be determined postopera­tively by obtaining information directly from the patient. The basic question then is whether the use of clinical techniques, conventional monitoring or brain function monitors decreases the occurrence of intraoperative awareness.

a) Clinical techniques and conventional moni­toring:

Clinical techniques used to assess intraoperative consciousness include checking for movement, response to commands, eyelash reflex, pupillary responses, respi­ratory pattern, perspiration and tearing. Conventional monitoring systems include ECG, blood pressure, heart rate, end tidal anaesthetic analyzer and capnography. No clinical trials or studies have been conducted which spe­cifically examine the sensitivity of these monitoring mo­dalities in detecting intraoperative awareness. Leslie et al.,tested the ability of estimated propofol effect- site concentration to predict movement to a stimulus in vol­unteers during propofol /nitrous oxide anaesthesia. [29] This was then compared with the predictive abilities of pupil­lary reflex, systolic blood pressure, BIS and 95% spec­tral edge frequency of EEG, in the same group. For this comparison, they used the prediction probability (P K ) which directly compares the performance of indicators having different units of measurement. Numerically, P K is the probability that an indicator predicts correctly which of a pair of randomly selected stimuli, one causing move­ment and the other not, will result in a movement. An indicator that predicts perfectly whether a movement response will occur has a P K value of 1.0 whereas an indicator that performs no better than chance has a P K value of 0.5. Based on this, their correlational study re­ported P K values ranging from 0.74 for blood concen­tration of propofol to 0.86 for BIS. As such, the authors concluded that no significant differences in performance could be demonstrated between these various indica­tors of anaesthetic depth.

Another study reported significant association between response to command and memory when continuous infusion of propofol was used as the induction anaesthetic. [30] Wide ranges of mean arterial pres­sure and heart rate values have been reported during various intraoperative periods and awareness has been found to occur even in the absence of tachycardia or hypertension. [10]

Nevertheless, the Task Force recommends that clinical techniques and conventional monitoring are valu­able and should be used to assess intraoperative con­sciousness. The importance of monitoring the respira­tion when the patient is not under any neuromuscular paralysis cannot be stressed enough. The Guedel's Stage 3 plane III level of anaesthesia must ideally be achieved before surgery commences so as to ensure adequate anaesthetic depth.

b)Brain electrical activity monitoring:

Most of the devices designed to monitor brain elec­trical activity for assessing the anaesthetic effect record EEG activity from electrodes placed on the forehead. Systems can be further divided into those that process spontaneous EEG and electromyographic activity and those that acquire evoked responses to auditory stimuli.

I. Spontaneous electroencephalographic ac­tivity monitors:

(1) Bispectral index: (Aspect Medical systems, MA)

The BIS converts a single channel of frontal EEG into an index of hypnotic level. To compute the BIS, several variables derived from the EEG time domain and frequency domain are combined into a single index of hypnotic level. Targeting a range of BIS values 40­60 is advocated to prevent awareness during anaes­thesia while allowing a reduction in the administration of anaesthetic agents. [31]

Several randomized controlled studies have com­pared outcomes with BIS guided anaesthetic adminis­tration versus standard clinical practice without BIS. In the B-Aware study that included 2500 patients at high risk of intraoperative awareness, explicit recall occurred in 0.17% of patients when BIS monitors were used as compared to 0.91% in patients treated by routine clini­cal practice. [7]

Another nonrandomized comparison of the use of BIS monitoring versus a cohort of historic controls in a group of 12,771 patients found explicit recall oc­curring in 0.04% of BIS monitored patients versus 0.18% of the historic controls. [32] Other studies con­ducted to determine BIS values associated with intra­operative awareness reported no statistically significant difference when BIS was used (0.18%) as compared to when BIS was not used (0.1%). [1]

A more recent study was conducted to determine whether a BIS protocol was better than a protocol based on a measurement of end tidal anaesthetic gas(ETAG) for decreasing anaesthetic awareness in high risk patients. 2000 patients were randomly assigned to BIS-guided anaesthesia (target BIS range of 40-60) or ETAG-guided anaesthesia (target ETAG range of 0.7 to 1.3 MAC). The patients were assessed for awareness postoperatively at 0-24 hrs, 24-72 hrs and at 30 days following surgery. It was found that intraop­erative awareness occurred even when BIS values and ETAG concentrations were within target ranges and the authors did not support the routine use of BIS moni­tors as a part of a standard practice during general ana­esthesia. [33] Several intraoperative events unrelated to ti­tration of anaesthetic agents can produce rapid changes in BIS values(eg cerebral ischaemia, hypoperfusion, gas embolism, unrecognized haemorrhage, inadvertent blockage of anaesthetic drug delivery). [34],[35],[36],[37] There are other case reports that suggest that routine intraopera­tive procedures (eg. activation of electromagnetic de­vices, patient warming or cooling) may interfere with BIS functioning. [38],[39],[40],[41] Mychaskiv et al, demonstrated the failure of BIS as a reliable monitor of the depth of ana­esthesia. [42] Their patient had the horrifying experience of both hearing the sternal saw as well as feeling his chest being cut open during cardiac surgery. This recall of intraoperative events occurred at a BIS of 47 with nitrous oxide and sevoflurane anaesthesia. Other au­thors have also reported incidences of intraoperative awareness despite monitored values of BIS indicating an adequate depth of anaesthesia. [43]

(2) Entropy: (GE Healthcare Technologies Waukesha, WI)

Entropy describes the irregularity, complexity or unpredictability characteristics of a signal. A single sine wave represents a completely predictable signal (en­tropy=0) whereas noise from a random number gen­erator represents entropy =1. State entropy (SE) is an index ranging from 0-91 (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 0-100 (awake) computed over a frequency range from 0.8-47 Hz containing the higher electromyographic dominated frequencies and will therefore respond to increased electromyographic ac­tivity resulting from inadequate analgesia. Correlational studies report the following P k values for loss of con­sciousness: for RE, 0.83-0.97; for SE, 0.81-0.90. No clinical trials however are available that conclusively show that entropy monitoring reduces the incidence of intraoperative awareness.



(3) Narcotrend (Monitor Technik, Germany)

The Narcotrend is derived from a system devel­oped for the visual classification of the EEG patterns associated with various stages of sleep. After artefact exclusion and Fourier transformation, the original elec­tronic algorithm classified the frontal EEG according to: A (awake), B (sedated), C (light anaesthesia), D (general anaesthesia), E(general anaesthesia with deep hypnosis), F (general anaesthesia with increasing burst suppression). In a recent iteration of the software, the alphabetical scale has been translated into a dimension­less index scaled from 0 (deeply anaesthetized) to 100 (awake).Reported mean Narcotrend values are as fol­lows: after induction-72-80 and at emergence-80. [44]

There are few studies on the reliability of Narcotrend as an aid to reduce awareness. Russel used the 'isolated forearm technique' to check for the pres­ence of intraoperative consciousness during general anaesthesia. [45] This study concluded that the Narcotrend was unable to differentiate reliably between conscious and unconscious patients during general anaesthesia when neuromuscular blocking agents were used.

(4) Patient State Analyser (Physiometrix, North Billerica, MA)

The patient state index (PSI) is derived from a four channel electroencephalograph. The derivative of the Patient State Index 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 lower levels of consciousness and se­dation. The reliability of PSI is however debatable. Sneider et al, studied the ability of PSI and BIS to de­tect awareness in 40 patients subjected to anaesthesia with sevoflurane-remifentanil / propofol-remifentanil combination. They concluded that despite significant differences between mean values at responsiveness and nonresponsiveness for BIS and PSI, neither measure was sufficient to detect awareness in an individual pa­tient. [46] A subsequent study has however shown PSI to be a useful indicator of the level of hypnosis under gen­eral anaesthesia. [47]

(5) SNAP index (Everest Biomedical Instruments, Chesterfield, MO)

The SNAP II calculates a "SNAP index" from a single channel of EEG. The index calculation is based on a spectral analysis of EEG activity in the 0-18 Hz and 80-420 frequency ranges and a burst suppression algorithm. 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) component.

(6) Cerebral State Monitor (Danmeter A/S, Odense, Denmark)

This is a hand held device that analyses a single channel EEG and presents a Cerebral State "Index" scaled from 0-100. It also provides EEG suppression percentage and a measure of electromyographic activ­ity (75-85 Hz). No literature is available that has ex­amined the impact of these two monitors on the inci­dence of intraoperative awareness.

II. Evoked brain electrical activity monitors:

Auditory Evoked Potential Monitor (Danmeter)

Auditory evoked potentials are the electrical re­sponses of the brain stem, the auditory radiation and the auditory cortex to auditory sound stimuli in the form of clicks delivered via headphones. The brainstem re­sponse is relatively insensitive to anaesthetics whereas early cortical responses called midlatency auditory evoked potentials (MLAEPs) change in a predictable manner with increasing concentrations of volatile and intravenous anaesthetics. Increasing anaesthetic con­centrations lead to an increased latency and reduced amplitude of the various waveform components. From a mathematical analysis of the AEP waveform, the de­vice generates a AEP index (AAI) that provides a cor­relate of anaesthetic concentration. This AEP index is scaled from 0-100 and the AAI corresponding with a low probability of consciousness is <25. Randomized controlled trials comparing MLAEP monitoring to stan­dard clinical anaesthesia practices without MLAEPs reported reduced times to eye opening or orientation. [48] Another study reported a P k value of 0.99 for aware­ness after LMA insertion. [49]


   Present Status Of Brain Function Monitors Top


The use of a brain function monitor is dedicated to the assessment of effects of anaesthetics on the brain and correlation with the depth of anaesthesia. Although we are familiar with the effects of anaesthetics, our knowledge of their exact site and mechanism of action still remains limited. Surface electrodes for cortical EEG measurements are un­likely to reveal drug action at the level of critical memory centres like the hippocampus. Also, the measured values by these monitors do not have a uniform sensitivity across different anaesthetic drugs and types of patients. Thus it is possible that pa­tients can have awareness despite apparently low BIS values. The incidence of awareness depends on the type of surgery, the anaesthetics used and the timing of and technique of evaluating awareness and recall. [50] Moreover, artefacts can be introduced by the use of cautery, lasers, patient warmers etc. As such the clinical applicability of these monitors in the prevention of intraoperative awareness has not been established. Although isolated reports of a decrease in the frequency of awareness in high risk cases are available, there is still insufficient evidence to justify a standard guideline for the use of these monitors to reduce the risk of awareness during general anaes­thesia. Another important consideration is the extra financial burden imposed by the use of these moni­tors. Routine awareness monitoring with a propri­etary device in most patients undergoing anaesthe­sia would add about £30 million to UK healthcare costs. [51] Although no figures are available for India, the economic aspect may be an important consider­ation. Hence, inspite of a large variety of brain func­tion monitors being available, the consultants par­ticipating in the Practice Advisory for Intraoperative Awareness do not support the use of a brain electri­cal activity monitor to decrease the risk of intraop­erative awareness for all patients. They recommend its use for patients with conditions that place them at higher risk such as trauma surgery, caesarean, total intravenous anaesthesia and patients requiring smaller doses of general anaesthetics. The Advisory recom­mends that intraoperative monitoring of the depth of anaesthesia for the purpose of minimizing the occur­rence of awareness should rely on multiple modali­ties including clinical techniques (e.g.reflex move­ment) and conventional monitoring systems (e.g.ECG, blood pressure, end tidal anaesthetic ana­lyzer and capnography). Ensuring adequate delivery of anaesthetics assumes even more importance when neuromuscular blocking drugs are used.


   Recommendations For Management Of Post Anaesthesia Awareness Top


Measures that have been recommended should this adverse event occur include the following:

1) Providing a postoperative structured interview and a questionnaire to the patient so as to define the nature of the intraoperative awareness episode, after it has been reported.

2) Offering postoperative counselling or psycho­logical support.

No studies are available that demonstrate an im­provement in the patient's well being following the use of questionnaires or interviews when intraoperative awareness has occurred. However, the Task Force does recommend that a detailed account of the patient's experience be obtained. He or she should be reassured and some explanation for what has happened and why should be given (eg. the necessity to administer light anaesthesia due to cardiovascular instability). Details of the incident should be placed in the patient's records so as to guide the anaesthesiologist for management of future anaesthetics. The patient should be offered psy­chological or psychiatric support. The details of the in­terview should be recorded in the patients chart and the surgeon, patient's nurse, hospital lawyer and physician's insurer should be notified. During the hos­pital stay, the patient should be visited daily to look for psychological sequelae like sleep disturbances, day time anxiety etc. Following discharge, contact by telephone should be maintained till the patient is fully recovered. Early referral to the psychiatrist or psychologist should be done whenever necessary so as to reduce the inci­dence of post traumatic stress disorder. Finally an oc­currence report regarding the event should be com­pleted for the purpose of quality management.

Intraoperative awareness is an alarming compli­cation both for the patient and anaesthesiologist alike. Although the incidence is rare, yet it can have consid­erable potential for severe emotional distress in the patient as well as professional, personal and financial consequences for the anaesthesiologist. It may be caused by a poor technique or equipment malfunction but its occurrence does not necessarily indicate these problems. While a few simple measures may go a long way in reducing its incidence, further research needs to be directed towards eliminating this unexpected anaes­thetic problem. Finally, a sympathetic approach and good psychological support will help reduce the patient's trauma following this adverse event.



 
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29.Leslie K, Sessler DI, Smith WD, Larson MD, Ozaki M, Blanchard D, Crankshaw DP. Prediction of movement dur­ing propofol/nitrous oxide anaesthesia: performance of con­centration, electroencephalographic, pupillary and haemodynamic indicators. Anesthesiology 1996; 84:52-53.  Back to cited text no. 29  [PUBMED]  [FULLTEXT]  
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35.Hayashida M, Chinzei M, Komatsu K, Yamamoto H, Tamaii H, Orii R, Hanaoka K, Murakami A. Detection of cerebral hypoperfusion with bispectral index during paediatric cardiac surgery. Br J Anaesth 2003; 90: 694-8.  Back to cited text no. 35      
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42.Mychaskiv G H, Horowitz M, Sachdev V, Heath BJ. Ex­plicit intraoperative recall at a bispectral index of 47. AnesthAnalg 2001;92:808-9.  Back to cited text no. 42      
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45.Russel 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.  Back to cited text no. 45      
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47.Pricep LS, Gugins LD, John ER, Chabot RJ, Howard B, Merkin H, Tom HL, Wolter S, Rausch L, Kox WJ. The Patient State Index as an indicator of the level of hypnosis under general anaesthesia. Br J Anaesth 2004; 92: 393-9.  Back to cited text no. 47      
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