Brazilian consensus on anesthetic depth monitoring

Introduction

One of the most important gains in anesthesia was the recent admission that light anesthesia, awakening, intraoperative awareness, and memory are all real problems with deleterious psychological consequences for a significant portion of patients.¹ On the other hand, deep anesthesia appears to be associated with increased morbidity and mortality.²

Maintaining the adequate level of anesthesia depth is critical. Very superficial or deep depth levels can be disastrous in both the short and long run. The patient expects that the procedure be absolutely painless and throughout the surgery he is asleep, without any perception or memory of what happened during that period. It is important to emphasize that this concept is applied to general anesthesia, and a patient should always be well informed if the anesthetic approach is a regional anesthesia with sedation, a situation that may have awakening episodes not associated with pain or immobility.

Accidental intraoperative awareness (AIA) is the undesirable outcome of insufficient anesthesia. Consciousness research takes into account the ability of an individual to present responses to stimuli and/or commands.

Cerebral monitoring is necessary in current clinical practice of anesthesiology. Avoiding excess anesthetic doses is of great importance, not only because there is the possibility of reducing the immediate adverse effects of anesthetics, such as cardiovascular and respiratory depression, but also to prevent cognitive impairment in patients with low neuronal reserve. AIA is the most feared anesthetic complication regarding the improper administration of anesthetic agents. Autonomic signs are not able to guide the adjustment of drugs, as there are many components of the clinical context that interfere with autonomic function.

This paper aims to evaluate concepts related to anesthetic depth monitoring, as well as to show the current evidence and present recommendations for the use of intraoperative monitoring of brain electrical activity. The recommendations may be adopted, modified, or rejected according to clinical needs and possible restrictions.

Concepts

In order to prevent unintentional awakening and deep anesthesia damage, the advancement in the field of brain monitoring and more adequate understanding of the neurobiological processes involving consciousness and memory were necessary. For a proper understanding of this approach, some concepts are important:

(a) Awareness-a term with broad meaning. For neuroscience, it translates the relationship between the individual and the environment, his responses to external stimuli and self-perception. It has two components: level of consciousness and content of consciousness.³ (b) Level of consciousness (arousal/wakefulness)-refers to the wakefulness or asleep state. There is an integration of certain nuclei present in brain stem, hypothalamus, and basal ganglia that will inhibit or stimulate the cortex and thalamus, regulating the sleep-wake cycle.⁴ (c) Content of consciousness (awareness)-refers to the set of information established in functional bases of cortical and thalamic-cortical system. While the subcortical structures interact to keep the cortex awake and stimulated, specific regions of the cortex have a role to process the contents of consciousness.⁵ The level of consciousness may not be related to the content of consciousness. A comatose patient has a reduced level and content of consciousness. Patients in a vegetative state have their sleep-wake cycles intact, but compromised content of consciousness, not being able to interact voluntarily, recognize people, or process information⁶ (Fig. 1).

Figure 1
Components of consciousness: level and content of consciousness.

(d) Memory-it is the acquisition, development, conservation, and retrieval of information. They are classified according to the duration, function, and content.⁷ (e) Declarative or explicit memory-refers to information voluntarily or spontaneously redeemed. (f) Non-declarative implicit memory-refers to information that is not voluntarily or spontaneously redeemed, able to generate behavioral changes.⁸ (g) Amnesia-deficit in the formation or retrieval of memories. Anesthetics may affect both explicit and implicit memory, but explicit memory appears to be more susceptible to drug-induced amnesia.⁹

Clinical monitoring of anesthetic depth

Some physiological parameters are used to measure anesthetic depth and guide the anesthetic choice and dose titration. Blood pressure, heart rate, breathing pattern changes, somatic and skeletal motor activities, sweating, lacrimation, pupil diameter, and vasomotor skin reflexes are used.¹⁰ However, depending on patient's clinical condition and on drugs used, these parameters may have poor representation in assessing anesthetic depth.¹¹

Tachycardia, hypertension, sweating, and lacrimation are usually considered inadequate analgesia signs. However, sympathetic stimulation is not always a result of the painful stimuli perception. There are situations in which the parasympathetic can be predominantly stimulated, such as in the autonomic response due to nociceptive stimuli in the esophagus. In this case, vagal fibers are predominantly involved, triggering a slow heart rate.¹⁰

The presence of movement in response to painful stimuli has been one of the methods for assessing the potency of anesthetic agents. Although the motor response is mediated by spinal reflexes, its presence is an important sign of inadequate anesthesia, which makes the patient susceptible to the risk of intraoperative awakening and awareness.¹⁰

During surgery under general anesthesia, it is the motor response that makes it possible to know whether the patient is able to voluntarily meet the commands and respond to painful stimuli. When a neuromuscular blocking agent is used, it prevents the motor response to voluntarily comply with commands, or the motor reflex response to painful stimuli.

The use of neuromuscular blocker is related to AIA, which rarely occurs when it is not used.¹²

To preserve motor responses of surgical and pharmacologically paralyzed patients, the isolated forearm technique (IFT) is a standard alternative. It consists of the isolation of a forearm with a pneumatic cuff inflated before the intravenous neuromuscular blocker injection, preventing drug action in the temporarily ischemic limb.¹²

The occurrence of motor response with IFT is rated in five levels:

Level 0: No response or spontaneous movement. Level 1: Random movements unrelated to any stimulation. Level 2: Movements in response to tactile stimuli, including painful movements (2a: movement not localized, 2b: movement that tracks stimulus). Level 3: Movement in direct response to verbal command. Level 4: Movement in response to questions or response options. Level 5: Spontaneous and purposeful movements, showing the patient's intention to communicate.

Although the most frequently found response levels are 0 and 3, it is observed that even if AIA does not occur in level 3, which was demonstrated in a study by Kerssens et al.,¹³ where hemodynamic parameters were not correlated with the presence or absence of response, but the EEG parameters such as BIS and SEF 95%, which showed better integration between their values and the clinical observation by the IFT.¹³

Electrical monitoring of anesthetic depth

Raw electroencephalogram (EEG) has characteristic frequency bands, classified according to fluctuation bands as: Gamma, Beta, Alpha, Theta, Delta and Slow ( Fig. 2). ^14and15

Figure 2
Frequency bands.

When assessed without processing, they hamper the analysis of intraoperative parameters related to anesthetic depth. With increased anesthetic depth, high amplitude electrical activity is observed at low frequencies and may have surge suppression or no activity (isoelectrical) patterns with higher doses of anesthetics (Fig. 3).¹⁶

Figure 3
Deep anesthesia standards (isoelectrical or burst suppression).

The pattern of electrical activity usually shows frequencies up to 70 Hz and amplitudes of ±50 µV. This activity is superimposed on electromyography, which has amplitudes and similar frequencies but with greater representation in values greater than 50 Hz. However, equipments developed to assess anesthetic depth show, independently, indexes related to electromyography, evaluated in different frequency bands (e.g., BIS: 70-110 Hz and CSM: 75-85 Hz). Each of the anesthetic depth evaluation equipment has its own algorithm with several windows and bands of different analyses.^17,18and19

BIS Vista(r) (Aspect Medical Systems, Newton, MA)

For the calculation of the indices related to equipment, frequencies up to 47 Hz (nervous system and electromyography) and 70-110 Hz are used for electromyography (EMG), where the signal is picked up at 2-s windows (epochs). The indices are:

(a) Bilateral bispectral

BIS number is obtained from the weighted analysis of 4 subparameters: burst suppression ratio, Quazi suppression, beta relative power, and fast/slow synchronization (Fig. 4), where a multivariate statistical model is applied using a nonlinear function. The delay time is 7.5 s and the refresh rate is 1 s.¹⁹

Figure 4
Subparameters generating BIS.

(b) Suppression rate

Burst suppression is defined as intervals greater than 0.5 s, in which the EEG voltage is below ±5 µV in the last 60 s. Thus, normal suppression rate is equal to zero.^14and19

(c) Electromyographic power

This variable is calculated as the sum of all RMS (root mean square) in the range of 70-110 Hz, normalized to 0.01 µVRMS and expressed in decibels (dB). For example, if RMS (70-110 Hz) = 1 µV; pEMG = 20 log(1/0.01) = 40 dB. The display range, shown in a bar graph, is between 30 and 55 dB. It is an important parameter, as it measures the electrical activity in the facial nerve nucleus (bulb-pontine region). During general anesthesia, the values are typically below 30 dB. Values above 30 during general anesthesia represent high activity in the facial nerve nucleus¹⁹ (Fig. 5).

Figure 5
Electromyography (EMG) in red.

(d) Asymmetry

It represents power variation between the right and left sides of the brain, with a white spectral signalizing the higher power side. In adults, variations up to 20% are considered normal¹⁹ (Fig. 6).

Figure 6
Asymmetry in white, signaling to the left.

(e) Spectral edge frequency 95% (SEF 95%)

SEF 95% is the frequency below which 95% of the power is in the range up to 30 Hz. However, spectral analysis (spectrogram) has shown to be of great importance for its ability to highlight the alpha-hypersyncronization (thalamocortical) and slow fluctuation (corticocortical) (Fig. 7), characteristics of adequate depth of anesthesia in adults.²⁰

Figure 7
SEF 95% bilateral and bilateral spectrogram with alpha hypersynchronization.

Characteristics of monitoring equipment available in Brazil

The raw signal of electrical activity is picked up by surface electrodes (non-invasive), adapted according to points defined in neurology by the system 10/10 with referential montages (Fig. 8).¹⁵ Table 1 shows the main features of each equipment.^{18, 19,21and22}

Figure 8
Positioning of the sensors according to the manufacturer: A, BIS; B, Entropy; C, CSM; and D, SEDLine.

Table 1
Main parameters of each equipment.

Equipment	Anesthesia/limits	TS/limits	EMG/limits	Asymmetry	SEF 95%	Spectrogram	Delay time
BIS bilateral view	40–60	±5 µV	70–110 Hz	Yes	Yes	Yes	7.5 s
SEDLine-PSI bilateral	25–50	NA	NA	No	Yes	Yes	6.4 s
Entropy response	40–60	NA	NA	No	No	No	Variable
CSM	40–60	±3.5 µV	75–85 Hz	No	No	No	15 s

• NA, not available.

Description of the evidence collection method

The search strategy used for this recommendation was by research in OvidMedline, Ovid Embase, and Cochrane Library:{Cochrane Database of Systematic Reviews (CDSR); Cochrane Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects (DARE)}. The references were crossed with the collected material for identification of items with better methodological design, followed by critical evaluation of its contents and classification according to the strength of the evidence.

The searches were made between June and September 2015. The clinical monitoring survey began in year 1990. For BIS, Entropy, PSA 4000 (Patient State Analyzer), and CSM (Cerebral State Monitor), the survey used was from 2000. The review was limited to prospective studies, preferably systematic reviews with relevance to the topic discussed.

The descriptors used in the search were: monitoring intraoperative; and/or consciousness monitors/ and or sedation monitor/ and or sedation measurement/and or anesthesia, general/and or anesthesia, intravenous/ and or anesthetics, inhalation/ and or perioperative period/ and or perioperative evaluation/ and or signal processing/ and or computer-assisted/ and or intraoperative complications/ perioperative care/ and or monitoring, physiologic/ and or electroencephalography/ and or mental recall/ and or wakefulness/ and or consciousness/ and or perception/ intraoperative awareness/ or awareness/ and or deep sedation/ and or conscious sedation/ and or depth of anesthesia monitor/ and or postoperative period/ and or EEG or EMG/ and or BIS/ and or Entropy/ and or PSA 4000/CSM.

The quality of evidence and strength of recommendation adopted for these consensus decisions was from GRADE (Grading of Recommendations, Assessment, Development and Evaluation), according to the following descriptions:

Quality of evidence:

A-High: Level of evidence from well-planned and conducted randomized clinical trials, with parallel groups, adequate controls, adequate data analysis, and consistent findings, targeting the clinical outcome of interest to the physician and the patient. B-Moderate: Evidence from randomized controlled trials with important problems in conducting, inconsistent results, assessment of a surrogate endpoint rather than an outcome of interest to the physician and patient, assessment imprecision, and publication biases. C-Low: Results from cohort studies and case control, highly susceptible to bias. D-Very low: Results from uncontrolled observational studies and unsystematic clinical observations.

Strength of recommendation:

1-Strong: The advantages clearly outweigh the disadvantages; or else, the disadvantages outweigh the advantages. 2-Weak: There is uncertainty between advantages and disadvantage.

Strategies and recommendations

Because the aim of this study was to evaluate the impact of monitoring the brain electrical activity in general anesthesia on different outcomes, we considered the following topics:

Anesthetic consumption

Excessive administration of anesthetic agents is often used unnecessarily. This effect occurs because the depth of anesthesia is usually guided by somatic and autonomic clinical signs. However, these signs do not have reliable measures to ensure unconsciousness.²³ Some studies have shown that proper monitoring of anesthetic depth could reduce excessive administration of anesthetic agents, reducing recovery time from anesthesia, nausea and vomiting, headache, and cognitive dysfunction, especially in the elderly.^23and24

The monitoring of anesthetic agent measurements, especially of inhaled gases, has become routine because of the units incorporated into multiparameter monitors. Studies using the quantification of expired gas concentrations showed significant reduction in the total consumption of agents, compared to clinical monitoring.^25and26 However, it does not guarantee the absence of consciousness and, when compared with the assessment instruments of brain electrical activity, it results in increased anesthetic consumption.^27,28and29

There is a close relationship between inhaled anesthetic agent titration and electrical activity monitoring.^{25, 26,30and31} Thus, consciousness monitors began to be used to guide anesthetic administration.

The studies chosen for this evaluation have high scientific consistency; Grades A and B, were selected from among those with low evidence of bias, despite the impossibility of blindness by the professional using the monitor in the study. The inclusion criteria included comparison of anesthetic depth monitoring, such as BIS, Entropia, PSA 4000, and CSM, compared with clinical signs or fractional expired anesthetic gases. Agents used in the studies were propofol, desflurane, sevoflurane or isoflurane.^{25, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60and61}

The studies showed that these monitors, especially BIS, when properly used, provide reduction of anesthetic consumption.^{38, 39, 51, 55, 62, 63, 64,65and66}

Recent meta-analysis by Cochrane²³ showed that in 10 studies with intravenous anesthesia involving 672 participants, there was a significant reduction in propofol consumption when the anesthetic depth was guided by the BIS. The mean reduction was 1.32 mg kg h^-1 (95% CI -1.91 to -0.73). The same meta-analysis showed that in 14 studies of balanced anesthesia, involving 985 participants, there was a significant reduction in anesthetic consumption with an average decrease of 0.65 MAC (95% CI -1.01 to -0.28). Regarding analgesic consumption, the studies evaluated fentanyl, remifentanil, and sufentanil consumptions, showing reduced consumption. Only in the study by Hachero et al.,⁴⁰ a significant increase was found in the use of fentanyl with BIS control. The combining results showed no significant difference in the use of narcotics.

Recommendation

The use of devices to monitor anesthetic depth, such as BIS, Entropia, PSA 4000, and CSM, is associated with reduced inhaled and intravenous anesthetic consumptions, as well as reduced anesthetic recovery time, compared to the method of clinical signs and symptoms monitoring (1A and 1B).

Intraoperative awakening

Studies have shown variability in the incidence of intraoperative awakening due to different survey methods and differences in the studied population. Some studies with populations considered to be at higher risk reported an intraoperative awakening incidence of 1:100, especially when repeated questionnaires are used.⁶⁷ Others reported very low incidence of 1:15,000 when the report is done spontaneously by the patient, as in the project NAP 5.⁶⁸

While it seems reasonable that the monitoring of brain electrical activity can prevent intraoperative awakening, the available evidence shows results that depend on the population, on the anesthetic technique, and on the evaluated monitoring.

It is worth noting the populations that are at increased risk of intraoperative awakening. There are three situations commonly associated with this event: (i) the patient does not tolerate adequate doses of anesthetic (e.g., critical patients); (ii) there is inadequate anesthesia masking signals (use of neuromuscular blockers); (iii) the nature of the operation or the patient's condition requiring different doses.^67and69

Other risk factors for intraoperative wake include the ASA status (indicating patients with more comorbidities),^70and71 use of total intravenous anesthesia, history of depression, absence of premedication, previous history of awakening,⁷² and emergency operation.⁷¹

Some studies have investigated the impact of using BIS in the incidence of intraoperative awakening. Myles et al.,⁷³ showed a significant reduction of the event in a high-risk population (absolute risk reduction of 0.73%) with BIS, compared to standard care. It is noteworthy that the incidence of memory was high in the control group in this study: 0.89%. However, it has not been confirmed in later studies, such as the B-Unaware³⁰ and Bag-Recall.³¹ These studies compared the incidence of intraoperative awakening in high-risk patients randomized into two groups: the use of BIS between 40 and 60 versus MAC maintenance between 0.7 and 1.3. There was no difference between the groups; however, the study power was calculated based on an incidence of 1% and 0.5%, respectively. Zhang et al.⁷⁴ conducted a similar investigation with total intravenous anesthesia, showing that the incidence of explicit memory decreased significantly with BIS monitoring (0.65-0.14%).

B-Unaware³⁰ was the first study to assess the use awareness monitoring to reduce intraoperative awakening. It surveyed 1941 patients and found an incidence of intraoperative awakening of 0.21% (95% CI, 0.08-0.53) without reducing the event using BIS.

As estimated by the study Bag-Recall,³¹ it would be necessary to study 3333 high-risk patients in order to prevent one episode of awareness using BIS. The results of the Bag-Recall study do not support the superiority of BIS protocol over end-tidal anesthetic-agent concentration protocols to prevent intraoperative awakening even in high-risk patients. This study sought to correct some flaws of the B-Unaware study, such as being multicenter, international, having a larger sample, and discarding low-risk criteria such as factors for inclusion of patients. However, the study had several limitations that may not be ruled out, such as considering the results in patients receiving potent inhalation anesthetic agents, unable to extrapolate them to other agents. Furthermore, the study used only one of the commercially available technologies for monitoring awareness.

Mashour et al.²⁵ evaluated 21,601 patients and did not demonstrate increased efficacy of using monitoring (BIS), compared to the use of anesthetic protocols to reduce the incidence of intraoperative awakening with explicit memory (0.08 vs. 0.12%, p = 0.48). However, post hoc analysis has demonstrated that the use of BIS may be superior to the absence of monitoring to reduce intraoperative awakening. These data are consistent with those described by the Cochrane systematic review; ⁷⁵ however, there was no benefit in anesthesia recovery.

According to the analysis and review of the literature, we observed that the recommendations of the American Society of Anesthesiologists Task Force on intraoperative awakening⁷⁶ corroborate the current studies.

Recommendation

To prevent intraoperative awakening, the use of brain electrical activity monitors is suggested for high-risk patients under balanced general anesthesia (2B). For patients under total intravenous anesthesia, as it is a risk factor for intraoperative awakening, the use of brain electrical activity monitoring is highly recommended (1A).

Morbidity and mortality

If on one hand the maintenance of inadequate anesthesia is associated with intraoperative awakening and its serious consequences, on the other hand, a general anesthesia deeper than necessary to keep the patient unconscious has been considered a marker of severity, especially in elderly and critically ill patients. However, studies evaluating the association between anesthetic depth and mortality are secondary analyses of outcomes designed for another purpose, or are multivariate analysis of institutional databases that, despite having a large observational sample, collide in the weakness of the multivariate model conclusions, which are legitimate proponents of hypotheses, but lack robust prospective studies for causal confirmation of the findings.

The study by Monk et al.⁷⁷ identified the BIS cumulative time < 45 (relative risk = 1.244 h^-1; p = 0.0121) as an independent predictor of mortality in up to one year after the operation. However, it was not confirmed in another study with similar design and presence of cancer as a covariate. ⁷⁸ Patients without cancer showed no increased mortality, even with considerably low cumulative levels of BIS.

Secondary analysis of the B-Aware study⁷⁹ evaluating intraoperative awakening showed no difference in mortality between the group undergoing anesthesia guided by BIS and the standard care group. However, in the analysis of the subgroup monitored with BIS, there was higher mortality within four years in the group with deep anesthesia (BIS < 40 for more than 5 min). A similar result was found in the secondary analysis of patients undergoing cardiac surgery in the study B-Unware.⁸⁰ BIS levels < 45 were associated with higher mortality, along with other severity criteria, such as transfusion, ICU stay, and use of tranexamic acid. The authors hypothesize that low BIS values are an epiphenomenon, that is, they are not responsible for the primary outcome, as in the analysis of patients undergoing non-cardiac surgery in the same study; this association could not be related.⁸¹

Sessler et al.⁸² found that the combination of intraoperative variables, with hypotension, low levels of BIS, and low levels of inhaled anesthetics concentration (Triple Low), is associated with more fragile patients, susceptible to complications. This study linked the association of low MAP (<75 mmHg), low MAC (<0.8), and low levels of BIS (<45) with increased 30-day mortality. The generated hypothesis was that these combined variables are markers of a profile of patients "sensitive" to perioperative stress rather than potential therapeutic targets that may be involved in reducing adverse events. Kertai et al.,⁸³ using the "Triple Low" criteria, found that these variables were not independent predictors when clinical and surgical variables are included in the statistical model.

Evidence of mortality and low levels of BIS association or "Triple low" are conflicting. Nevertheless, they indicate that susceptible patients deserve special care, with the possibility of optimization of results in the short, medium and long run. Willingham et al.,⁸⁴ in a retrospective observational study including 13,198 patients from three clinical trials: B-Unaware, BAG-RECALL and Michigan Awareness Control Study, showed that the risk of mortality at 30 and 90 days postoperatively was increased by approximately 10% for every 15 cumulative minutes in the triple low state, suggesting that this is not an epiphenomenon. Randomized, prospective, controlled studies in progress, such as the Balanced trial (www.anzctr.org.au, ACTRN12612000632897),⁸⁵ comparing the effects of different levels of anesthetic depth in mortality up to one year, probably will clarify the influence of the depth of anesthesia and postoperative mortality.

Recommendation

Electrical nervous activity evaluated mostly by the BIS (disregarding other possible components, such as suppression rate, spectrogram or both), alone or in combination with other variables such as MAP and CAM percentage, has a weak association with mortality (2B).

Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD)

In the elderly population, cognitive changes such as delirium and POCD after anesthetic-surgical procedures have older age as the main risk factor.⁸⁶

POD is an acute onset syndrome characterized by changes in consciousness and floating variation in memory, attention, cognitive, and perceptual disorders.⁸⁷

COPD is a subtle disorder of thought processes that can influence isolated areas of cognition, such as verbal memory, visual memory, language comprehension, visual-spatial abstraction, attention or concentration.⁸⁸

POD is the most important factor for COPD in hospitalized geriatric patients.⁸⁷

The brain of an elderly person requires lower doses of anesthetic agents compared to that of a young person and is more likely to present burst suppression in the EEG.⁸⁹ Brain monitors, such as the BIS, allow adequate anesthetic depth, dose titration, and minimizes the residual effects on cognition.^{76, 90, 91, 92,93and94}

There is correlation between surface anesthesia and post-traumatic stress syndrome and between deep anesthesia and cognitive dysfunction.⁹⁴ Randomized controlled trials show reduced incidence of POD when patients are monitored with BIS.^{90, 91,92and93}

Chan et al., in a randomized study with patients aged 60 years or more, comparing patients monitored with BIS or routine care, found that the BIS group (40-60) showed reduced risk of developing delirium in the immediate post-operative period and POCD in the evaluation at three months.⁹¹

Recommendation

Monitoring the depth of anesthesia with BIS monitor facilitates anesthetic titration, decreases brain exposure, especially in the elderly, to high doses of the anesthetic agents, and thus can contribute to reduce POD (1A) and POCD (2A and 2B).

References

• ¹
  Aceto P, Perilli V, Lai C, et al. Update on post-traumatic stress syndrome after anesthesia. Eur Rev Med Pharmacol Sci. 2013;17:1730-7.
• ²
  Monk TG, Saini V, Weldon BC, et al. Anesthetic management and one-year mortality after noncardiac surgery. Anesth Analg. 2005;100:4-10.
• ³
  Mashour GA, Orser BA, Avidan MS. Intraoperative aware- ness from neurobiology to clinical practice. Anesthesiology. 2011;114:1218-33.
• ⁴
  Purdon PL, Pierce ET, Mukamel EA, et al. Electroencephalogram signatures of loss and recovery of co nsciousness from propofol. PNAS. 2013;110:E1142-51.
• ⁵
  Koch C, Mormann F. The neurobiology of consciousness. In: Mashour GA, editor. Consciousness, awareness, and anesthesia. 1st ed. Cambridge: Cambridge University Press; 2010. p. 24-46.
• ⁶
  Laureys S. The neural correlate of (un)awareness: lessons from the vegetative state. Trends Cogn Sci. 2005;9:556-9.
• ⁷
  Izquierdo I. Memória. 2nd ed. São Paulo: Artmed Editora; 2011. p. 11.
• ⁸
  Kerssens C, Alkire M. Memory formation during general anes- thesia. In: Mashour GA, editor. Consciousness, awareness, and anesthesia. 1st ed. New York: Cambridge University Press; 2010. p. 47-73.
• ⁹
  Moore J, Kelz M. Brain anatomy of relevance to the anes- thesiologist. In: Mashour GA, Lydic R, editors. Neuroscientific foundation of anesthesiology. 1st ed. New York: Oxford Univer- sity Press; 2011. p. 7-16.
• ¹⁰
  Guinard B. Monitoring analgesia. Best Pract Res Clin Anaesthe- siol. 2006;20:161-80.
• ¹¹
  Nunes RR. Componentes da atividade anestésica-uma nova visão. Rev Bras Anestesiol. 2003;53:145-9.
• ¹²
  Pandit JJ, Russell IF, Wang M. Interpretations of response using the isolated forearm technique in general anaesthesia: a debate. Br J Anaesth. 2015;115 Suppl. 1:i32-45.
• ¹³
  Kerssens C, Klein J, Bonke B. Awareness: monitoring versus remembering what happened. Anesthesiology. 2003;99:570-5.
• ¹⁴
  Rampill IJ. A primer for EEG signal processing in anesthesia. Anesthesiology. 1998;89:980-1002.
• ¹⁵
  Montenegro MA, Cendes F, Guerreiro MM, et al. EEG na prática clínica. 2nd ed. Rio de Janeiro: Revinter; 2012.
• ¹⁶
  Brown EM, Lydic R, Schiff ND. General anestesia, sleep and coma. N Engl J Med. 2010;363:2638-50.
• ¹⁷
  Zouridakis G, Papanicolaou AC. A concise guide to intraopera- tive monitoring. Boca Raton: CRC Press; 2001.
• ¹⁸
  Jensen EW, Litvan H, Revuelta M, et al. Cerebral state index during propofol anesthesia. Anesthesiology. 2006;105:28-36.
• ¹⁹
  Nunes RR, Chaves IMM, Alencar JCG, et al. Bispectral index and other processed parameters of electroencephalogram: an update. Rev Bras Anestesiol. 2012;62:105-17.
• ²⁰
  Purdon PL, Pierce ET, Mukamel EA, et al. Electroencephalogram signatures of loss and recovery of consciousness from propofol. PNAS. 2013:E1142-51.
• ²¹
  Drover DR, Lemmens HJ, Pierce ET, et al. Patient state index. Tritation of delivery and recovery from propofol, alfentanil and nitrous oxide anestesia. Anesthesiology. 2002;97:82-9.
• ²²
  Nunes RR, Almeida MP, Sleigh JW. Spectral entropy: a new method for anesthetic adequacy. Rev Bras Anestesiol. 2004;54:404-22.
• ²³
  Punjasawadwong Y, Phongchiewboon A, Boonjeungmonkol N. Bispectral index for improving anaesthetic delivery and post- operative recovery (Review). Cochrane Database Syst Rev. 2014;6:CD003843.
• ²⁴
  Hudson AE, Hemmings HC. Are anaesthetics toxic to the brain? Br J Anaesth. 2011;107:30-7.
• ²⁵
  Mashour GA, Shanks A, Tremper KK, et al. Prevention of intraoperative awareness with explicit recall in an unselected surgical population: a randomized comparative effectiveness trial. Anesthesiology. 2012;117:717-25.
• ²⁶
  Avidan MS, Mashour GA. Prevention of intraoperative awareness with explicit recall: making sense of the evidence. Anesthesiol- ogy. 2013;118:449-56.
• ²⁷
  Ahmad S, Yilmaz M, Marcus RJ, et al. Impact of bispec- tral index monitoring on fast tracking of gynecologic patients undergoing laparoscopic surgery. Anesthesiology. 2003;98: 849-52.
• ²⁸
  Basar H, Ozcan S, Buyukkocak U, et al. Effect of bispectral index monitoring on sevoflurane consumption. Eur J Anaesthe- siol. 2003;20:396-400.
• ²⁹
  Recart A, Gasanova I, White PF, et al. The effect of cerebral monitoring on recovery after general anesthesia: a compar- ison of the auditory evoked potential and bispectral index devices with standard clinical practice. Anesth Anal. 2003;97: 1667-74.
• ³⁰
  Avidan MS, Zhang L, Burnside BA, et al. Anesthesia awareness and the bispectral index. N Engl J Med. 2008;358:1097-108.
• ³¹
  Avidan MS, Jacobsohn E, Glick D, et al. Prevention of intraoper- ative awareness in a high-risk surgical population. N Engl J Med. 2011;365:591-600.
• ³²
  Aime I, Verroust N, Masson-Lefoll C, et al. Does monitoring bispectral index or spectral entropy reduce sevoflurane use? Anesth Analg. 2006;103:1469-77.
• ³³
  Anez C, Papaceit J, Sala JM, et al. The effect of encephalogram bispectral index monitoring during total intravenous anesthesia with propofol in outpatient surgery. Rev Esp Anestesiol Reanim. 2001;48:264-9.
• ³⁴
  Assare H, Anderson RE, Jakobsson J. Sevoflurane requirements during ambulatory surgery: a clinical study of bispectral index and auditory evoked potential guided anaesthesia. Ambul Surg. 2002;9:207-11.
• ³⁵
  Boztug N, Bigat Z, Akyuz M, et al. Does using the bispectral index (BIS) during craniotomy affect the quality of recovery? J Neurosurg Anesthesiol. 2006;18:1-4.
• ³⁶
  Bruhn J, Kreuer S, Bischoff P, et al. Bispectral index and A-line AAI index as guidance for desflurane-remifentanil anaesthesia compared with a standard practice group: a multicentre study. Br J Anaesth. 2005;94:63-9.
• ³⁷
  Chiu CL, Ong G, Majid AA. Impact of bispectral index mon- itoring on propofol administration in patients undergoing cardiopulmonary bypass. Anaesth Intensive Care. 2007;35: 342-7.
• ³⁸
  Ellerkmann RK, Soehle M, Kreuer S. The Entropy Module(r) and Bispectral Index(r) as guidance for propofol-remifentanil anaes- thesia in combination with regional anaesthesia compared with a standard clinical practice group. Anaesth Intensive Care. 2010;38:159-66.
• ³⁹
  Gan TJ, Glass PS, Windsor A, et al. Bispectral Index monitoring allows faster emergence and improved recovery from propofol, alfentanil and nitrous oxide anesthesia. BIS Utility Study Group. Anesthesiology. 1997;87:808-15.
• ⁴⁰
  Hachero A, Alamo F, Caba F, et al. - Influence of bispectral index monitoring on fentanyl requirements during total intravenous anesthesia for major gynecological surgery. Rev Esp Anestesiol Reanim. 2001;48:364-9.
• ⁴¹
  Ibraheim O, Alshaer A, Mazen K, et al. Effect of bispec- tral index (BIS) monitoring on postoperative recovery and sevoflurane consumption among morbidly obese patients under- going laparoscopic gastric banding. Middle East J Anesthesiol. 2008;19:819-30.
• ⁴²
  Kamal NM, Omar SH, Radwan KG, et al. Bispectral index moni- toring tailors clinical anesthetic delivery and reduces anesthetic drug consumption. J Med Sci. 2009;9:10-6.
• ⁴³
  Kreuer S, Biedler A, Larsen R, et al. Narcotrend moni- toring allows faster emergence and a reduction of drug consumption in propofol-remifentanil anesthesia. Anesthesiol- ogy. 2003;99:34-41.
• ⁴⁴
  Kreuer S, Bruhn J, Stracke C, et al. Narcotrend or bispectral index monitoring during desflurane-remifentanil anesthesia: a comparison with a standard practice protocol. Anesth Analg. 2005;101:427-34.
• ⁴⁵
  Leslie K, Myles PS, Forbes A, et al. Recovery from bispectral index-guided anaesthesia in a large randomized controlled trial of patients at high risk of awareness. Anaesth Intensive Care. 2005;33:443-51.
• ⁴⁶
  Luginbuhl M, Wuthrich S, Petersen-Felix S, et al. Different benefit of bispectral index (BIS) in desflurane and propofol anes- thesia. Acta Anaesthesiol Scand. 2003;47:165-73.
• ⁴⁷
  Masuda T, Yamada H, Takada K, et al. Bispectral index mon- itoring is useful to reduce total amount of propofol and to obtain immediate recovery after propofol anesthesia. Masui. 2002;51:394-9.
• ⁴⁸
  Morimoto Y, Oka S, Mii M, et al. Efficacy of bispectral index monitoring in improving anesthetic management, economics, and use of the operating theater. Masui. 2002;51:862-8.
• ⁴⁹
  Muralidhar K, Banakal S, Murthy K, et al. Bispectral index-guided anaesthesia for off-pump coronary artery bypass grafting. Ann Cardiac Anaesthesia. 2008;11:105-10.
• ⁵⁰
  Myles PS, Leslie K, McNeil J, et al. Bispectral index monitoring to prevent awareness during anaesthesia: the B- Aware randomised controlled trial. Lancet. 2004;363:1757-63.
• ⁵¹
  Nelskyla KA, Yli-Hankala AM, Puro PH, et al. Sevoflurane titra- tion using bispectral index decreases postoperative vomiting in phase II recovery after ambulatory surgery. Anesth Analg. 2001;93:1165-9.
• ⁵²
  Paventi S, Santevecchi A, Metta E, et al. Bispectral index mon- itoring in sevoflurane and remifentanil anesthesia. Analysis of drugs management and immediate recovery. Minerva Anesthe- siol. 2001;67:435-9.
• ⁵³
  Puri GD, Murthy SS. Bispectral index monitoring in patients undergoing cardiac surgery under cardiopulmonary bypass. Eur J Anaesthesiol. 2003;20:451-6.
• ⁵⁴
  Samarkandi AH, Abdel-Meguid ME, Abdullah KM, et al. Bis- pectral index monitoring and titration of anaesthetics during off-pump coronary artery bypass surgery. Egypt J Anaesth. 2004;20:357-61.
• ⁵⁵
  Song D, Joshi GP, White PF. Titration of volatile anesthetics using bispectral index facilitates recovery after ambulatory anesthe- sia. Anesthesiology. 1997;87:842-8.
• ⁵⁶
  Struys MM, De Smet T, Versichelen LF, et al. Comparison of closed-loop controlled administration of propofol using Bispec- tral Index as the controlled variable versus ''standard practice'' controlled administration. Anesthesiology. 2001;1:6-17.
• ⁵⁷
  Tufano R, Palomba R, Lambiase G, et al. The utility of bispec- tral index monitoring in general anesthesia. Minerva Anestesiol. 2000;66:389-93.
• ⁵⁸
  White PF, Ma H, Tang J, et al. Does the use of electroencephalo- graphic bispectral index or auditory evoked potential index monitoring facilitate recovery after desflurane anesthesia in the ambulatory setting? Anesthesiology. 2004;100:811-7.
• ⁵⁹
  Wong J, Song D, Blanshard H, et al. Titration of isoflurane using BIS index improves early recovery of elderly patients undergoing orthopedic surgeries. Can J Anaesth. 2002;49:13-8.
• ⁶⁰
  Zhang C, Xu L, Ma YQ, et al. Bispectral index monitoring prevent awareness during total intravenous anesthesia: a prospective, randomized, double-blinded, multi-center controlled trial. Chin Med J. 2011;124:3664-9.
• ⁶¹
  Zohar E, Luban I, White PF, et al. Bispectral index monitoring does not improve early recovery of geriatric outpatients under- going brief surgical procedures. Can J Anaesth. 2006;53:20-5.
• ⁶²
  Bannister CF, Brosius KK, Sigl JC, et al. The effect of bispectral index monitoring on anesthetic use and recovery in children anesthetized with sevoflurane in nitrous oxide. Anesth Analg. 2001;92:877-81.
• ⁶³
  Bhardwaj N, Yaddanapudi S. A randomized trial of propofol consumption and recovery profile with BIS-guided anesthesia compared to standard practice in children. Paediatr Anaesth. 2010;20:160-7.
• ⁶⁴
  Chan MTV, Cheng B, Gin T, et al. Cognitive dysfunction after anesthesia: a randomized controlled trial. J Neurosurg Anes- thesiol. 2010;22:408-9.
• ⁶⁵
  Kerssens C, Gaither JR, Sebel PS. Preserved memory func- tion during bispectral index-guided anesthesia with sevoflurane for major orthopedic surgery. Anesthesiology. 2009;111: 518-24.
• ⁶⁶
  Messieha ZS, Ananda RC, Hoffman WE, et al. Bispectral Index System (BIS) monitoring reduces time to discharge in children requiring intramuscular sedation and general anesthesia for out- patient dental rehabilitation. Pediatr Dent. 2004;26:256-60.
• ⁶⁷
  Leslie K, Davidson AJ. Awareness during anesthesia: a problem without solutions? Minerva Anestesiol. 2010;76:624-8.
• ⁶⁸
  Pandit JJ, Andrade J, Bogod DJ, et al. 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: summary of main findings and risk factors. Br J Anaesth. 2014;113:549-59.
• ⁶⁹
  Ghoneim MM, Block RI, Haffarnan M, et al. Awareness during anaesthesia: risk factors, causes and sequelae: a review of reported cases in the literature. Anesth Analg. 2009;108:527-35.
• ⁷⁰
  Sebel PS, Bowdle TA, Ghoneim MM, et al. The incidence of awareness during anaesthesia: a multicenter United States study. Anesth Analg. 2004;99:833-9.
• ⁷¹
  Errando CL, Sigl JC, Robles M, et al. Awareness with recall during general anaesthesia: a prospective observational evaluation of 4001 patients. Br J Anaesth. 2008;101:178-85.
• ⁷²
  Aranake A, Gradwohl S, Ben-Abdallah A, et al. Increased risk of intraoperative awareness in patients with a history of aware- ness. Anesthesiology. 2013;119:1275-83.
• ⁷³
  Myles PS, Leslie K, McNeil J, et al. Bispectral index monitoring to prevent awareness during anaesthesia: the B- Aware randomised controlled trial. Lancet. 2004;363:1757-63.
• ⁷⁴
  Zhang C, Liang MA, Ya-qun MA, et al. Bispectral index moni- toring prevent awareness during total intravenous anesthesia: a prospective, randomized, double-blinded, multi-center con- trolled trial. Chin Med J. 2011;124:3664-9.
• ⁷⁵
  Punjasawadwong A, Y, Phongchiewboon Bunchungmongkol for anaesthetic N. Bispectral index improving delivery and postoperative recovery. Cochrane Database Syst Rev. 2014;6:CD003843.
• ⁷⁶
  Practice Advisory for Intraoperative Awareness and Brain Function Monitoring. A report by the American Society of Anesthesiologists Task Force on Intraoperative Awareness. Anes- thesiology. 2006;104:847-64.
• ⁷⁷
  Monk TG, Saini V, Weldon BC, Sigl JC. Anesthetic management and one-year mortality after noncardiac surgery. Anesth Analg. 2005;100:4-10.
• ⁷⁸
  Lindholm ML, Traff S, Granath F, et al. Mortality within 2 years after surgery in relation to low intraoperative bispectral index values and preexisting malignant disease. Anesth Analg. 2009;108:508-12.
• ⁷⁹
  Leslie K, Myles PS, Forbes A, Chan MT. The effect of bispec- tral index monitoring on long-term survival in the B-aware trial. Anesth Analg. 2010;110:816-22.
• ⁸⁰
  Kertai MD, Pal N, Palanca BJ, et al. Association of periopera- tive risk factors and cumulative duration of low bispectral index with intermediate-term mortality after cardiac surgery in the B-Unaware Trial. Anesthesiology. 2010;112:1116-27.
• ⁸¹
  Kertai MD, Palanca BJ, Pal N, et al. Bispectral index monitoring, duration of bispectral index below 45, patient risk factors, and intermediate-term mortality after noncardiac surgery in the B- Unaware Trial. Anesthesiology. 2011;114:545-56.
• ⁸²
  Sessler DI, Sigl JC, Kelley SD, et al. Hospital stay and mortality are increased in patients having a ''triple low'' of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia. Anesthesiology. 2012;116:1195-203.
• ⁸³
  Kertai M, White WD, Gan TJ. Cumulative duration of ''triple low'' state of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia is not associated with increased mortality. Anesthesiology. 2014;121:18-28.
• ⁸⁴
  Willingham MD, Karren E, Shanks AM, et al. Concurrence of intraoperative hypotension, low minimum alveolar concentra- tion, and low bispectral index is associated with postoperative death. Anesthesiology. 2015;123:775-85.
• ⁸⁵
  Short TG, Leslie J, Chan MTV, et al. Rationale and design of the balanced anesthesia study: a prospective randomized clinical trial of two levels of anesthetic depth on patient outcome after major surgery. Anesth Analg. 2015;121:357-65.
• ⁸⁶
  Nunes RR, Lopes CGD. Delirium e distúrbio cognitivo no pós- operatório. In: Pires OC, Albuquerque MAC, Fernandes CRF, et al., editors. Educação Continuada em Anestesiologia, vol. 7. Rio de Janeiro: Sociedade Brasileira de Anestesiologia (SBA); 2015. p. 47-54.
• ⁸⁷
  Ahmed S, Laurent B, Sampson EL. Risk factors for inci- dent delirium among older people in acute hospital medical units: a systematic review and meta-analysis. Age Ageing. 2014;43:326-33.
• ⁸⁸
  Bryson GL, Wyand A. Evidence-based clinical update: general anesthesia and the risk of delirium and postoperative cognitive dysfunction. Can J Anesth. 2006;53:669-77.
• ⁸⁹
  Purdon PL, Pavone KJ, Akeju O, et al. The ageing brain: age-dependent changes in the electroencephalogram during propofol and sevoflurano general anaesthesia. Br J Anaesth. 2015:i46-57.
• ⁹⁰
  Sieber FE, Zakriya KJ, Blute MR, et al. Sedation depth during spinal in elderly patients undergoing hip fracture repair. Mayo Clin Proc. 2010;85:18-26.
• ⁹¹
  Chan MT, Cheng BC, Lee TM, et al. CODA Trial Group. BIS-guided anesthesia decrease postoperative delirium and cog- nitive decline. J Neurosurg Anesthesiol. 2013;25:33-42.
• ⁹²
  Radtke FM, Franck M, Lendner J, et al. Monitoring depth of anaesthesia in a randomized trial decreases the rate of postop- erative delirium but not postoperative cognitive dysfunction. Br J Anaesth. 2013;110:i98-105.
• ⁹³
  Whitlock EL, Torres BA, Nan Lin, et al. Postoperative delirium in a substudy of cardiothoracic surgical patients in the BAG- RECALL clinical trial. Anesth Analg. 2014;118:809-17.
• ⁹⁴
  Shepherd J, Jones J, Frampton GK, et al. Clinical and cost effectiveness of depth of anaesthesia monitoring (E- Entropy, Bispectral Index and Narcotrend): a systematic review and eco- nomic evaluation. Health Technol Assess. 2013;17:1-263.

Publication Dates

• Publication in this collection
  Nov-Dec 2015

History

• Accepted
  03 Nov 2015