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Monitoring and Prevention of Awareness in TraumaAnesthesiaV Borzova, C Smith

Citation

V Borzova, C Smith. Monitoring and Prevention of Awareness in Trauma Anesthesia. The Internet Journal ofAnesthesiology. 2009 Volume 23 Number 2.

Abstract

OBJECTIVES

Review the incidence of awareness in trauma

Discuss the risk factors and consequences ofawareness in trauma

Formulate a rational plan for prevention ofawareness in trauma

Review the management of awareness duringanesthesia

INTRODUCTION

Intraoperative awareness is defined as patient'sconsciousness during a procedure performed under generalanesthesia with subsequent recall of the events. 1 Awareness

during general anesthesia has received increased attentionamong the medical profession and lay public in recent years.The Joint Commission on Accreditation of HealthcareOrganizations issued a Sentinel Event Alert in 2004 aimed atreducing the risks and managing the impact of anesthesiaawareness. 2 Introduction of technologies capable of

quantifying the depth of anesthesia, most notably theBispectral Index monitor (BIS), has given cliniciansadditional tools to monitor intraoperative levels ofconsciousness. Prospective, randomized multicenter studieslooking at the incidence of intraoperative awareness 3 and

use of BIS monitoring as a way to prevent it, 4 5 have been

conducted. The American Society of Anesthesiologists(ASA) incorporated the results of these and additionalstudies and developed a Practice Advisory for IntraoperativeAwareness and Brain Function Monitoring to assistanesthesiologists in minimizing the risks of awareness undergeneral anesthesia. 6 The Practice Advisory acknowledged

that certain patient characteristics (substance use or abuse,

limited hemodynamic reserve, ASA physical status 4 or 5),certain surgical procedures (trauma and cardiac surgery,Cesarean delivery) as well as anesthetic techniques (rapidsequence induction, reduced anesthetic doses especially inthe presence of paralysis) place patients at increased risk ofintraoperative awareness. The purpose of this article is toreview the Practice Advisory and other available literaturewith special emphasis on monitoring and prevention ofawareness in trauma patients.

INCIDENCE

The incidence of intraoperative awareness is estimated to be0.1-0.2% in the general surgical population (Table 1). 7

Figure 1

Table 1. Incidence of awareness during general anesthesia

Cardiac surgery and Cesarean deliveries have a higherincidence of recall 8 9 with awareness as high as 11-43%

reported in major trauma patients. 10 However, in a 1999

study of 96 trauma patients, only one patient had auditoryrecall. 11 In a prospective, nonrandomized multicenter study

of 19,575 patients, a total of 25 awareness cases were

Monitoring and Prevention of Awareness in Trauma Anesthesia

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identified (0.13% incidence). 12 There were 46 additional

cases (0.24%) of possible awareness and 1183 cases (6.04%)of possible intraoperative dreaming. 16 Awarenessaccounted for 2% of 1,977 general anesthesia claims from1990 to 2001 including 56 claims for recall and 9 claims forawake paralysis. 13 A median payment of $34,049 (United

States $) was made in 52 percent of recall claims.Interestingly, there were no reports of awareness in traumaclaims. 14 This discrepancy may be due to improvements in

trauma resuscitation, thus permitting the administration ofadequate doses of anesthetic agents to trauma patients. 15

CONSEQUENCES

Awareness is a serious complication of anesthesia. It is oftendescribed by patients as their worst hospital experience. 11Patients report paralysis, pain, perception of surgicalmanipulations and ability to hear conversations. Auditoryperception and the sensation of paralysis are the mostfrequently reported sequelae, followed by the sensation ofpain. 15 Feelings of panic, helplessness and pain are not

uncommon. Some patients may develop post-traumaticstress disorder. Psychiatric complications are more likely ifpain accompanies the awareness. 16 However, as noticed in

Practice Advisory, “in some circumstances, intraoperativeawareness may be unavoidable to achieve other criticallyimportant anesthetic goals”. 1

ETIOLOGY AND RISK FACTORS

In a prospective, open, cross-sectional study of the incidenceof awareness in 2612 elective surgery patients, the doses ofisoflurane and propofol were significantly lower in patientswith awareness. 8 (Table 2) In the study, a large proportionof the patients with awareness were found to have a historyof major depression and also had preoperative symptoms ofdepression and anxiety. 8 Female gender and anesthetictechniques using intraoperative opioid and neuromuscularblocking agents without a volatile anesthetic was associatedwith a higher frequency of malpractice claims for awarenessin the ASA Closed Claims Project. 17 Accidental paralysis of

patients prior to induction of anesthesia due to intravenousinfusion errors involving succinylcholine drips or syringeswaps when a muscle relaxant was injected instead of asedative, opioid or hypnotic agent is a common cause ofawake paralysis. 18 In a multicenter US trial, (Table 3)

awareness was associated with increased ASA physicalstatus (odds ratio, 2.41; 95% confidence interval, 1.04–5.60for ASA status III–V compared with ASA status I–II). 3 Ageand gender did not influence the incidence of awareness.

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Table 2. Risk Factors for Awareness

Figure 3

Table 3. Causes of Awareness

The presence of conditions that may decrease anestheticrequirement such as hypotension, hypothermia, acidemia,alcohol intoxication, and severe anemia did not reliablyprevent awareness during surgery for major trauma when theprimary anesthetic agent was discontinued for 20-80 min in6 severely injured patients. 14 However, 1 patient with abody temperature of 30.5 o C did not suffer awarenessduring surgery despite the absence of any anesthetic agentfor over 4 hours. 14

The ASA Practice Advisory proposed a systematic approachfor monitoring and prevention of intraoperative awareness. 1It recommends the identification of risk factors associatedwith intraoperative awareness (Table 4, Fig 1).


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Figure 4

Table 4. Identifying patients at risk for intraoperativeawareness with recall. Modified from Reference 1.

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Fig 1

Causes and consequences of awareness. FROM GhoneimMM: Awareness during anesthesia. Anesthesiology2000;92:597-602. Figure 1 on page 598. [PUBLISHER TOOBTAIN PERMISSION]

Patients identified to be at risk for intraoperative awarenessshould be informed of their risks. 19 The most frequent

identifiable cause of awareness during general anesthesia islow or no concentrations of the primary anesthetic agent.Therefore, anesthesia providers should adhere to thechecklist protocol for anesthesia machines and equipment toassure that the desired anesthetic drugs and doses will bedelivered. The proper functioning of intravenous access,infusion pumps, and their connections, including thepresence of appropriate backflow check valves should beinsured. Care should be taken to avoid accidental paralysisprior to induction due to infusion errors or syringe swapsinvolving paralytic medications. Midazolam was noticed tobe associated with lower frequency of intraoperativeawareness in one double -blinded randomized clinical trial. 20

The decision to administer benzodiazepines or scopolamineprophylactically should be made on case-by-case basis forselected patients. Benzodiazepines and scopolamine can alsobe administered intraoperatively in an effort to preventawareness if a patient wakes up unexpectedly duringsurgery.

PREVENTION OF AWARENESS

The problem with awareness during general anesthesia isthat the recall component can only be detectedpostoperatively by interviewing the patient. The question iswhether monitoring the anesthetic depth will preventawareness and what tools do we have to monitor theanesthetic depth. Clinical signs such as purposeful or reflexmovement, response to commands, eyelash reflex, pupillarydiameters, perspirations, and tearing are valuable but notreliable measures of anesthetic depth. Standard ASAmonitoring assessing blood pressure, heart rate, respiratoryrate and end-tidal anesthetic concentrations should be usedroutinely, but also lack specificity. There are reports ofawareness in the absence of elevated blood pressure andheart rate. 11,21 Use of neuromuscular blocking agents andcardiovascular medications such as beta-blockers can masksomatic and autonomic signs of the depth of anesthesia.(Table 5)


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Figure 6

Table 5. Prevention of awareness during general anestehsia.Modified from Ghonheim, 2000. Reference 23

Concentration-effect relations of inhalational agents providea guide to the depth of anesthesia. Minimal values of 0.8-1.0MAC of volatile anesthetics almost always preventawareness. 21 However, different physiological conditions

(aging, substance abuse, pregnancy, hypoxemia, anemia) andindividual variability in anesthetic requirements can affectthe minimal values of volatile agent or plasma concentrationof intravenous anesthetics necessary to prevent recall.Confounding variables that affect the minimal values ofvolatile agent or plasma concentration of intravenousanesthetic to prevent recall include gender, age, and thearousing effect of surgery and emotionally charged material.19,23,25 The synergistic effect of drugs such asbenzodiazepines, opioids, scopolamine, and other anestheticswith the volatile agents is difficult to quantify because oftheir varying effects and sites of action. In the 1984 and1999 studies of awareness in trauma, the standard anestheticprotocol specifically excluded the use of benzodiazepinesand scopolamine. 14,15

BRAIN FUNCTION MONITORS

Monitoring the state of hypnosis during general anesthesiausing commercially available technology has becomepossible since the introduction of the Bispectral Index (BIS)in 1996. 22 More recently, a number of other brain function

monitors processing either spontaneous (Cerebral StateMonitor, Entropy, Narcotrend, Patient State Index- Sedline,SNAP) or auditory evoked electrical activity (AEPMonitor/2 ) have been introduced and marketed forassessment of depth of anesthesia. Anesthetic drugs inducedose dependent changes in the electroencephalogram (EEG).(Table 6)

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Table 6. Brain Function Monitors

The BIS measures depth of anesthesia by analyzing the EEGto generate a score or index from 0 to 100. 23 The index was

derived utilizing a composite of multiple advanced EEGsignal processing techniques including bispectral analysis,power spectral analysis, and time domain analysis. (Figs 2and 3)

.

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Fig 2

EEG changes with increasing doses of anesthesia includeincreased amplitude and decreased frequency. Note thetransition from small amplitude, fast frequency in the awakestate (BIS = 90-100) to large amplitude, slow frequency withgeneral anesthesia (BIS < 60). From Kelley S: Monitoringconsciousness using the bispectral index during anesthesia.A pocket guide for clinicians. Second edition. Reproducedwith permission from Dr Kelley, Aspect Medical Systems.


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Fig 3

Analysis of a typical EEG segment. Processed EEGparameters of anesthetic effects are 95% spectral edgefrequency, median frequency, and relative delta power.Reproduced with permission from Dr Kelley, AspectMedical Systems, reference 27

The index represents the progression of consciousness frombeing awake (Index = 100) to no brain activity or isoelectricEEG with BIS value of 0. (Fig 4)

.

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Fig 4

Signal processing used for BIS. EEG epochs are digitizedand analyzed to look for key EEG features using 3 primarypaths: 1. power spectral analysis, 2. bispectral analysis, and3. time-based analysis. A scaled value is generated based onstatistical modeling. There are 4 key EEG features tocharacterize anesthetic effect: 1. degree of beta frequencyactivation, 2. amount of low frequency synchronization, 3.presence of nearly suppressed periods within the EEG, and4. presence of isoelectric periods within the EEG.Reproduced with permission from Dr Kelley, AspectMedical Systems , reference 27.

A BIS value between 40-60 is considered suitable forsurgical anesthesia and reflects a decreased cerebralmetabolic rate and a low probability of consciousness. 24 (Fig

5 and 6)

.

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Fig 5

The BIS index reflects reduced cerebral metabolic rateproduced by most anesthetics. Using PET scanning, therewas a significant correlation between BIS and decreasingbrain metabolic activity as measured by glucose metabolism.Reproduced with permission from Dr Kelley, AspectMedical Systems , reference 27.

.


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Fig 6

Logistic regression of probability of consciousness versusBIS for propofol, midazolam, and isoflurane. As BISdecreases below 70, the probability of explicit recalldecreases. With BIS < 60, there is an extremely lowprobability of consciousness. Reproduced with permissionfrom Dr Kelley, Aspect Medical Systems, Kelley SD.Reference 27 [modified from Glass, reference 28]

The cerebral state monitor is a small handheld EEG monitorfor determining depth of anesthesia. The entropy monitormeasures the degree of entropy, or disorder, in the EEG.Entropy falls with increasing concentration of anesthetic.Entropy calculated in the frequency domain is the basis forthe commercially available Entropy monitor which computes2 parameters- state entropy and response entropy and theirdifference. 25 State entropy is calculated in the frequency

band dominated by the EEG signal (0.8-32 Hz, hypnoticcomponent of anesthesia), whereas response entropy iscalculated from 0.8 to 47 Hz (extended frequency responsedominated by EMG activity). The Sedline uses derivedquantitative 4 channel EEG as a function of hypnotic state togive a patient state index. 26 (Fig 7 and 8)

Figure 13

Fig 7

Primary steps in the development of the patient state indexalgorithm (Sedline) required the use of 3 databases: 1.normal EEGs and artifacts, 2. EEGs during generalanesthesia with a variety of agents, and 3. EEGs in healthyvolunteers during general anesthesia with stepwise increasesand decreases anesthetic concentration. FROM Drover DD,Lemmens HJ, Pierce ET, et al:Patient state index. Titrationof delivery and recovery from propofol, alfentanil, andnitrous oxide anesthesia. Anesthesiology 2002;97:82-9.[PUBLISHER TO OBTAIN PERMISSION] figure 2 onpage 87


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Figure 14

Fig 8

EEG processing with the patient state index (Sedline). EEGrecordings are collected from 2 anterior, a midline central,and a midline posterior scalp location. Artifacts are detectedand rejected. EEG data is frequency transformed intosubbands and total power. The patient state index isgenerated as a numeric value from 0 to 100. FROM DroverDD, Lemmens HJ, Pierce ET, et al: Patient state index.Titration of delivery and recovery from propofol, alfentanil,and nitrous oxide anesthesia. Anesthesiology 2002;97:82-9[PUBLISHER TO OBTAIN PERMISSION] . figure 3 onpage 88

The patient state index is based on EEG power, frequency,and phase information from anterior-posterior relationshipsof the brain, as well as coherence between bilateral regionsof the brain. Compared with single channel monitoring, theSedline provides more information with greater capacity fordetecting subtle changes in brain function including densityspectral array and raw real-time 4-channel EEG data. TheAEP Monitor/2 uses auditory event potentials together withEEG extraction to monitor level of consciousness. Auditoryevoked responses have previously been shown to correlate

well with level of consciousness and BIS. 27 With the AEP

Monitor/2, acoustic stimulation is provided and the evokedresponse is measured. (Fig 9)

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Fig 9

Auditory evoked potential (AEP) response. The brainstemresponse waves (BAEP) occur within the first 10 ms afterthe click stimulus. These responses are relative insensitive togeneral anesthetics. The middle latency waves (MLAEP)occur 10 to 80 ms after the click stimulus – the AAI Monitorextracts the middle latency auditory potentials in the 20 – 80ms window. They show graded changes with generalanesthetics over the clinical concentration range. The latecortical changes (LLAEP) occur 80 ms after the clickstimulus and later. These potentials disappear at sedativeconcentrations of general anesthetics. From: AEP Monitor /2 Directions for Use for Version 1.6. Danmeter A/S,Kildemosevej 13, DK-5000, Odense C, Denmark.Reproduced with permission from Danmeter A/S

Brainstem response waves occur within the first 10 ms afterthe click stimulus. These responses are relatively insensitiveto general anesthetics. The middle latency waves (earlycortical response) occur 10 to 80 ms after the click stimulus.The monitor extracts the middle latency response in the 20 –


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80 ms window. They show graded changes with generalanesthetics over the clinical anesthetic concentration range.The late cortical changes occur 80 ms after the click stimulusand later. These potentials disappear at sedativeconcentrations of general anesthetics. An index in the rangeof 100 – 0 is calculated. (Fig 10)

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Fig 10

The AAI index of the AEP Monitor. The AAI index iscalculated in the 20-80 ms window of the auditory evokedpotential (middle latency AEP) since the brainstem and longlatency AEPs do not correlate well with level ofconsciousness. Latency and amplitude changes in theMLAEP are weighted equally. The AAI is a linearcombination of contributions from the MLAEP and EEG.The recommended AAI values for surgical anesthesia are15-25. From: AEP Monitor / 2 Directions for Use forVersion 1.6. Danmeter A/S, Kildemosevej 13, DK-5000,Odense C, Denmark. Reproduced with permission fromDanmeter A/S.

In clinical trials, only use of the BIS monitor was associatedwith decreased awareness. 4,5 The B-aware prospective,randomized, double-blinded, multicenter trial of 2,503 high-awareness risk patients (trauma, cardiac surgery, rigidbronchoscopy, Cesarean delivery) revealed that BIS -guidedanesthesia reduced the incidence of awareness with recall by82%. 4 In another study, routine use of BIS monitoringdecreased the incidence of awareness in general surgicalpatients by 77% comparing to historical controls. 5 In bothstudies, two patients experienced awareness despite usingBIS. Interestingly, all four patients recalled events duringperiods of significant stimulation (sternal split, tracheal

intubation) when BIS values were near or greater than 60.Thus, periods of intense stimulation should be watchedcarefully and interventions should be undertaken promptly toprevent awareness. In a subsequent meta-analysis of 20studies with 4056 participants, the authors concluded thatBIS guided anesthesia reduced the incidence ofintraoperative awareness with recall in surgical patients athigh risk of awareness (odds ratio 0.20, 95% confidenceinterval 0.05 to 0.79). 28

BIS monitoring was used by Lubke et al in acute traumapatients undergoing general anesthesia (etomidate induction,isoflurane and fentanyl maintenance) to determine whetherthe probability of memory declines with increasing depth ofthe hypnotic state. 15 These authors found that auditoryinformation processing (implicit memory) occurred at BISlevels between 40 and 60. There was one instance ofauditory recall at these levels of general anesthesia. 15

One of the limitations of brain function monitors is that thenumerical index can be influenced by different factors.Pacemakers and forced-air warmers among other medicaldevices can increase BIS values by producing anelectromechanical artifact. 27 Ketamine may increase BISdue to its unique pattern of EEG activation. 29 Transient

paradoxical response to increased isoflurane concentrationhas been reported. 30 Excessive muscle tone from forehead

muscles may increase BIS and is known aselectromyographic (EMG) artifact. Neuromuscular blockingagents can alleviate EMG artifact and result in decreasedBIS. Rapid changes in BIS values were reported withcerebral ischemia, gas embolism, unrecognized hemorrhage,and hypoglycemia (Figure 11). 31

Fig 11. Influence of artifacts (electromagnetic- EMG,electromechanical) and reduced cerebral metabolism(cardiac arrest, hypoperfusion, hypothermia) on bispectralindex. From Kelley S: Monitoring consciousness using thebispectral index during anesthesia. A pocket guide forclinicians. Second edition. Reproduced with permissionfrom from Dr Kelley, Aspect Medical Systems.

Preexisting patient conditions can influence BIS values asreported in a volunteer with genetically determined low-voltage EEG signals. 32 BIS values should be interpreted

with caution in patients with neurological disorders. Despitethese limitation, monitoring BIS provides a better measureof the hypnotic state compared with autonomic responsesand better measure of pharmacodynamic effect of ananesthetic agent compared with end-tidal or target plasma


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concentrations.. 33 Moreover, BIS guided anesthesia has been

shown to decrease the incidence of awareness, decreaserecovery time (time to eye opening, response to verbalcommand, extubation and orientation) and shorten durationof postanesthesia care unit stay. 4,5,33

MANAGEMENT OF AWARENESS

Anesthesia awareness cannot always be prevented. If apatient unexpectedly becomes conscious during the surgery,the practitioner can consider using benzodiazepines and/orscopolamine. 23 However, there are no studies thatevaluated efficacy of this approach in reducing theoccurrence of awareness. Once an episode of intraoperativeawareness has been reported, practitioners mustacknowledge and manage the patient with compassion anddiligence. The details of the event should be discussed withthe patient as well as possible reasons for its occurrence.(Table 7)

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Table 7. Management of awareness. Modified fromGhonheim, 2000. Reference 23

The patient should be assured of credibility of this account.Finally, counseling and psychological support should beoffered including referral to a psychiatrist or psychologist.20,23 Pain, anxiety and delayed neurotic symptoms weremore common if awareness occurred in conjunction withneuromuscular blockade. 7 The delayed neurotic symptomsresolved within 3 weeks in all patients after repeateddiscussion and information. 7 Future studies are needed toexamine the impact of these interventions on patient’s well-being.

SUMMARY AND CONCLUSIONS

In summary, intraoperative awareness is a serious problemaffecting 0.1-0.2% of the general surgical population.Patients at high risk of awareness, such as those withhypotension or limited cardiovascular reserve should beidentified preoperatively and informed of the risk, ifpossible. Steps to ensure the proper delivery of anesthetics

should be undertaken. Multiple modalities includingstandard ASA monitors and clinical observations of reflexesand movements in nonparalyzed patients should be routinelyemployed. Use of complete neuromuscular blockade shouldbe avoided when possible. The decision to usebenzodiazepines, scopolamine and BIS monitoring should bemade on case-by-case basis in selected patients. We feel thatbrain function monitoring such as BIS should be routine inhigh risk surgical patient populations such as previousepisode of awareness, patients with limited hemodynamicreserve, cardiac surgery, reduced anesthetic doses duringparalysis, and somatosensory or evoked potentialmonitoring. If intraoperative awareness is reportedpostoperatively, patients should be offered support andpsychological counseling.

References

1. Practice Advisory for Intraoperative Awareness and BrainFunction Monitoring. A report by the American Society ofAnesthesiologists Task Force on Intraoperative Awareness.Anesthesiology 2006;104:847-64.2. Preventing, and managing the impact of, anesthesiaawareness. Joint Commission on Accreditation of HealthcareOrganizations. Sentinel Event Alert. Issue 32, October 6,2004.3. Sebel PS, Bowdle TA, Ghoneim MM, Ramjil IJ, PadillaRE, Gan TJ, Domino KB. Incidence of awareness duringanesthesia: A multicenter United States study. Anesth Analg2004; 99:833-9.4. Myles PS, Leslie K, McNeil J, Forbes A, Chan MTV.Bispectral Index monitoring to prevent awareness duringanesthesia: the B-Aware randomized controlled trial. Lancet2004; 363:1757-63.5. Ekman A, Lindholm ML, Lennmarken C, Sandin R.Reduction in the incidence of awareness using BISmonitoring. Acta Anesthesiol Scand 2004;48:20-6.6. Myles P, Williams D, Hendrata M, Anderson H, WeeksA. Patient satisfaction after anaesthesia and surgery: resultsof a prospective survey of 10 811 patients. Br J Anaesth2000; 84:6-10.7. Liu WHD, Thorp TAS, Graham SG, Aitkenhead AR:Incidence of awareness with recall during generalanaesthesia. Anaesthesia 1991;46:435-78. Lyons G, Macdonald R. Awareness during cesareansection. Anesthesia 1991: 46:62-64.9. Dowd NP, Cheng DCH, Karski JM, et al: Intraoperativeawareness in fast-track cardiac anesthesia. Anesthesiology1998;89:1068-7310. Bogetz M, Katz J. Recall of surgery for major trauma.Anesthesiology 1984; 61(1):6-9.11. Lubke GH, Kersens C, Phal H, Sebel PS. Dependence ofexplicit and implicit memory on hypnotic state in traumapatients. Anesthesiology 1999; 90:670-80.12. Sebel PS, Lang E, Rampil I, et al: A multicenter study ofbispectral EEG analysis for monitoring anesthetic effect.Anesth Analg 1997;84:891-913. Liability associated with awareness during anesthesia.ASA Newsletter, June 2006, Vol 70.14. Sharar SR, Tsai YK, Posner KL, Domino KB, CheneyFW. Do liability and patient injuries for anesthetic care ofacute trauma differ from those of non-trauma care?: Aclosed claim analysis. Internet source.


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15. Moerman N, Bonke B, Oosting J: Awareness and recallduring general anesthesia. Facts and feelings.Anesthesiology 1993;79:454-6416. Macleod AD, Maycock E. Awareness during anaesthesiaand post-traumatic stress disorder. Anaesth Intens Care1992; 20:378-82.17. Domino KB, Posner KL, Caplan RA, Cheney FW:Awareness during anesthesia. A closed claims analysis.Anesthesiology 1999;90:1053-6118. Osborne GA, Webb RK, Runciman WB: Patientawareness during anaesthesia: an analysis of 2000 incidentreports. Anaesth Intens Care 1993;21:653-419. Ghoneim MM: Awareness during anesthesia.Anesthesiology 2000;92:597-60220. Miller DR, Blew PG, Martineau RJ, Hull KA:Midazolam and awareness with recall during totalintravenous anesthesia. Can J Anesth 1996; 43: 946-53.21. Ghoneim MM, Block RI: Learning and memory duringgeneral anesthesia. An update. Anesthesiology1997;87:387-41022. Johansen JW, Sebel PS. Development and clinicalapplication of electroencephalographic bispectrummonitoring. Anesthesiology. 2000; 93:1336– 44.23. Kelley SD. Monitoring level of consciousness duringanesthesia and sedation.http://www.aspectmedical.com/resources/handbook/default.mspx24. Glass PSA, Bloom M, Kearse L, et al: Bispectralanalysis measures sedation and memory effects of propofol,midazolam, isoflurane, and alfentanil in healthy volunteers.Anesthesiology 1997;86:836-4725. Weil G, Passot S, Servin F, Billard V: Does spectralentropy reflect the response to intubation or incision during

propofol-remifentanil anesthesia? Anesth Analg2008;106:152-926. Drover DD, Lemmens HJ, Pierce ET, et al:Patient stateindex. Titration of delivery and recovery from propofol,alfentanil, and nitrous oxide anesthesia. Anesthesiology2002;97:82-927. Plourde G, Joffe D, Villemure C, Trahan M: The P3awave of the auditory event-related potential revealsregistration of pitch change during sufentanil anesthesia forcardiac surgery. Anesthesiology 1993;78:498-50928. Punjasawadwong Y, Boonjeungmonkol N,Phongchiewboon A. Bispectral index for improvinganaesthetic delivery and postoperative recovery. CochraneDatabase of Systematic Reviews 2007, Issue 4. Art. No.:CD003843. DOI: 10.1002/14651858.CD003843.pub2.29. Hans P, Dewandre P.-Y,Brichant JF,Bonhomme V:Comparative effects of ketamine on Bispectral Index andspectral entropy of the electroencephalogram undersevoflurane anaesthesia. Br J Anaesth 2005:94(3):336-40.30. Detsch O, Schneider G, Kochs E, Hapfelmeier G,Werner C: Increasing isoflurane concentration may causeparadoxical increase in the EEG bispectral index in surgicalpatients. Br J Anaesth 2000:84(1):33-7.31. Vivien B, Langeron O, Riou B: Increase in BispectralIndex (BIS) while correcting a severe hypoglycemia. AnesthAnalg 2002;95:1824-25.32. Schnider TW, Luginbuhl M, Petersen-Felix S, Mathis J:Unreasonably low Bispectral Index values in a volunteerwith genetically determined low-voltageelectroencephalographic signal. Anesthesiology1998;89:1607-8.33. Flaishon R, Sebel PS, Sigl J: Recovery of consciousnessafter thiopental or propofol. Anesthesiology 1997;86:613-9


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Author Information

Vera V. Borzova, MD, FAAPResident in Anesthesia, Department of Anesthesia, MetroHealth Medical Center, Case Western Reserve University School ofMedicine

Charles E. Smith, MD, FRCPCProfessor of Anesthesia, Department of Anesthesia, MetroHealth Medical Center, Case Western Reserve University Schoolof Medicine

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