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Revista Brasileira de Anestesiologia

Print version ISSN 0034-7094On-line version ISSN 1806-907X

Rev. Bras. Anestesiol. vol.59 no.1 Campinas Jan./Feb. 2009 



When the bispectral index (Bis) can give false results*


Cuando el índice bispectral (BIS) puede suministrar valores falsos



Leonardo Teixeira Domingues Duarte, TSAI; Renato Ângelo Saraiva, TSAII

IAnestesiologista do Hospital Sarah Brasília
IICoordenador de Anestesiologia da Rede Sarah de Hospitais de Reabilitação

Correspondence to




BACKGROUND AND OBJECTIVES: The bispectral index (BIS) is a multifactorial parameter derived from the electroencephalogram (EEG), which allows monitoring of the hypnotic component of anesthesia. It was obtained from the algorithm based on the analysis of a large number of EEGs from volunteers and patients undergoing sedation and general anesthesia with different anesthetic agents. The use of BIS to monitor the depth of anesthesia reduces the incidence of intraoperative awakening and recall, among other benefits. The objective of this review was to present clinical situations in which the BIS gives false results, either elevated or decreased, due to conditions related to the patient or anesthetic actions unforeseen when the algorithm was elaborated.
CONTENTS: The bispectral index can be altered and influenced in different clinical situations in which abnormal EEG patterns are present; the effects of different anesthetics and other drugs not included when the algorithm was elaborated; interference from electrical equipment; as well as peculiarities of the monitor.
CONCLUSIONS: Although the BIS algorithm underwent several changes since its first version, the anesthesiologist should be aware of situations that cause false BIS readings to avoid complications, may it be secondary to anesthetic overdose or underdosing, which might cause intraoperative awakening and recall.

Key Words: ANESTHESIA: General; MONITORING: bispectral index, awareness.


JUSTIFICATIVA Y OBJETIVOS: El índice bispectral (BIS) es un parámetro multifactorial derivado del electroencefalograma (EEG), que permite la monitorización del componente hipnótico de la anestesia. Fue obtenido a partir de algoritmo derivado del análisis de un gran número de EEG de voluntarios y pacientes sometidos a sedaciones y anestesia general con diferentes agentes anestésicos. Además de otros beneficios, el uso del BIS para la monitorización de la profundidad de la anestesia, reduce el aparecimiento del despertar y memoria intraoperatoria. Esa revisión tuvo el objetivo de presentar situaciones clínicas en que el BIS denota valores no verdaderos, que están falsamente elevados o reducidos, debido a condiciones del paciente o a acciones de anestésicos no previstos cuando se elaboró su algoritmo.
CONTENIDO: Los valores del BIS pueden sufrir la alteración y el influjo en múltiples situaciones clínicas en que existen estándares anormales del EEG; efecto de diferentes anestésicos y otros fármacos no incluidos en la elaboración de su algoritmo; interferencia por equipos eléctricos; o debido a peculiaridades del monitor.
CONCLUSIÓN: A pesar de que el algoritmo del BIS haya sufrido diversas alteraciones desde su primera versión, esas situaciones que determinan variaciones falsas de los valores del BIS, deben ser reconocidas por el anestesiólogo para evitar complicaciones, sean a causa de la sobredosis anestésica, o por subdosis que podrán causar el despertar y la memoria intraoperatoria.




The bispectral index (BIS) is a multifactorial parameter derived from the electroencephalogram (EEG) that allows monitoring of the hypnotic component of anesthesia1. It is a dimensionless number that varies from 0 to 100. In non-anesthetized patients the bispectral index varies from 90 to 100. On the other hand, total suppression of cortical electrical activity results in a BIS of zero. A BIS between 40 and 60 is associated with a low probability of intraoperative awakening and awareness2.

Monitoring of the bispectral index allows the reduction of anesthetics, maintenance of adequate levels of hypnosis, and prevents both extremely deep anesthesia levels and awakening and formation of implicit and explicit memory during general anesthesia1,2. In fact, in 1996 the FDA recommended the use of BIS to monitor the depth of anesthesia to reduce the incidence of intraoperative awakening and recall. It also allows faster awakening and reduces the length of stay in the post-anesthetic recovery room, which reduces costs2.

The bispectral index was obtained from an algorithm derived from the analysis of a large number of EEGs of volunteers and patients under sedation and general anesthesia with different anesthetics3. Although the BIS algorithm was modified several times to improve its performance and decrease the interference of artifacts, its results can still be changed and influenced by different clinical situations and anesthetics that were not included during its elaboration4.

During surgery, the anesthesiologist needs to know whether the depth of anesthesia, composed of hypnosis, amnesia, and analgesia, is adequate in all moments of the nociceptive stimulation. However, those qualities cannot be discriminated just through parameters derived from the EEG. Despite the efficacy of BIS in reducing intraoperative recall2, its occurrence even when the monitor is used is still reported in the literature. Thus, the BIS is not 100% specific in predicting intraoperative awakening and recall, which is one of the limitations of this monitoring. Even though it is not realistic to expect that any monitor will not show false-negative results, there are reports in the literature of cases in which the patient had intraoperative recall despite BIS values characteristics of hypnosis and adequate anesthetic depth. A precise correlation between sedation scales and BIS values recorded during anesthesia is not consistently present. Electrical equipment, specific clinical conditions, abnormal EEG patterns, and neuromuscular blockers (NMB) can interfere with BIS monitoring.

The objective of this review was to present clinical situations in which BIS results are erroneously elevated or decreased by conditions related to the patient or anesthetic effects not foreseen when the algorithm was elaborated. The anesthesiologist should recognize those situations to avoid errors in anesthetic management.

Monitor-Related Situations

To use the BIS to monitor the depth of hypnosis based on the levels recorded, the monitor should be predictably influenced by different anesthetics and show good inter- and intra-patient reproducibility. In fact, a study suggested different placements of BIS electrodes (frontal and occipital) in the same patient showed strong correlation between readings5. However, in two recent studies the concomitant use of older BIS versions and the BIS-XP, the most recent version of the monitor, gave different results6. The results of the XP monitor (version 4.0) were significantly lower than that of the A-2000 monitor (version 3.4) (33 x 40) 7. Besides, the concomitant use of two BIS-XP monitors in the same patient showed that different readings in 10% of the cases, suggesting different anesthesia depths8. The monitors showed a concordance coefficient of 0.65. The results of this study suggest that the BIS-XP does not have consistent intra-patient reproducibility8.

One should emphasize that the performance of a BIS model will not be necessarily the same as other models. The most recent algorithm of the BIS monitor (BIS XP version 4.0) may have resulted in lower BIS scores than those of older models for the same level of hypnosis. This difference is secondary to the inclusion in more recent models of mechanisms that reduce the level of noise, interferences, and electromyographic activity, resulting therefore in lower BIS values. Anyway, one should not forget that the model of BIS monitor can influence the interpretation of the results.

All monitors currently available need different times to calculate and update the index in response to changes in the depth of anesthesia. The time to update BIS records can range from 14 to 155 seconds9. The latency of the bispectral index may indicate a limitation of the efficacy of this monitor on the prevention of intraoperative recall and in the transition from alertness to unconsciousness.

Falsely elevated BIS can occur when electrode impedance is elevated due to erroneous placement or reduced adherence10. The bispectral index requires specific electrodes that, although they are comfortable, easy to use, and guarantee low impedance when capturing the EEG signal, they are very expensive. Thus, the use of ECG electrodes has been suggested as a lower cost alternative11. However, although their use is feasible, after adaptation of specific models of monitor11, it is problematic. First, impedance to the EEG signal can remain elevated and very variable, even with adequate skin preparation10. Second, depending on monitor model, it might be impossible to connect them to the monitor.

Electromyographic (EMG) activity and neuromuscular blockers (NMB) can influence significantly BIS monitoring. Elevated EMG activity increases BIS, while the subsequent administration of NMBs reduces it12. Electromyographic activity represents artifacts superimposed on the frequency band of EEG signals used by the algorithm of the monitor to determine BIS values. Since the frequency limits range of EMG (30 to 300 Hz) and ECG (0.5 to 30 Hz) signals are very close, low frequency EMG signals can be erroneously interpreted as high frequency EEG signals, leading to a false elevation of BIS13. Therefore, EMG frequencies can simulate the component of EEG frequency associated with being awake and superficial anesthesia (30 - 47 Hz). From this moment on, the BIS interprets erroneously EMG signals, making patients in deep anesthesia seem more awake than they really are. In this situation, the administration of NMBs decreases BIS values by reducing artifacts, revealing their real value.

The evolution of BIS algorithm includes a reduction in the impact of EMG contamination, both in sedation ranges and anesthesia. A correlation between the EMG and the false elevation of BIS does not exist. The anesthesiologist should be attentive and verify signal quality (SQI), EMG activity, and the tendency of BIS values regarding the clinical status of the patient before making any decisions.

Anesthetic Effects and Other Drugs

Different situations in which BIS values did not coincide with the clinical status of sedation or did not correlate with the expected anesthetic effects have been described in the literature.

Nitrous oxide (N2O) has weak cortical action. This effect is not detected by the BIS algorithm14. Inhalation of 50% N2O does not change BIS and does not reduce the level of consciousness15. At the 70% concentration, the response to vocal commands is lost, but BIS remains unchanged15. The addition of N2O to volunteers receiving target-controlled infusion of propofol decreased the probability of response to a range of stimuli at any level of BIS16. When 55 to 63% of N2O was added to anesthesia with propofol and remifentanil it did not change BIS, but it prevented movements during laryngoscopy and tracheal intubation17. Based on those results, N2O seems to have a small role on the hypnotic state, but it seems to work predominantly as analgesic. One should be attentive because BIS monitoring might not be sensitive enough to give an adequate measurement of the depth of sedation and hypnosis when N2O is used as a single agent. In those cases, clinical monitoring of sedation is the best option14.

One study reported paradoxal reduction of BIS 6 minutes after interruption of N2O, from 95 - 81 to 30 - 5015. The EEG recorded simultaneously showed an increase in the activity of low frequency ä and è waves, similar to the pattern seen in deep anesthesia. This result can be attributed to a withdrawal and suppression phenomenon unique to the sudden interruption of N2O.

Ketamine, on the doses of 0.25 to 0.5, can block the response capacity of patients, but it does not reduce the BIS18. This drug increases â activity associated with reduction in ä power19. This EEG pattern was reflected on the paradoxal increase in BIS values20. When used during sedation in combination with propofol, ketamine increased hypnosis without affecting BIS levels20.

Different inhalational anesthetics can cause peculiar changes in the EEG. As a consequence, BIS values are not the same with equipotent concentrations of different anesthetics. The bispectral index was significantly greater with halothane than with equipotent doses of sevoflurane21 or isoflurane22. This indicates that the BIS algorithm, which was not described for halothane, does not reflect the hypnotic effects of this anesthetic. Therefore, when BIS is used to monitor anesthesia with halothane, one should be careful to avoid inadvertent anesthetic overdose.

On the other hand, while BIS was more elevated during anesthesia with halothane than with sevoflurane21,23 in adults and children, it had similar behavior during anesthesia with sevoflurane or halothane in newborns23.

A case in which the inspired fraction of isoflurane was increased from 0.9% to 1.26%, causing a paradoxal increase in BIS, has been reported24. This paradoxal awakening reaction was, in reality, due to an increase in á and â waves in the EEG. The bispectral index returned to baseline levels after reducing the concentration of isoflurane.

A report using the A1000 monitor resented two volunteers whose BIS remained unchanged, between 35 and 40, despite the progressive increase in propofol plasma concentration25. On the other hand, the EEG recorded simultaneously indicated burst suppression. The authors speculated that BIS levels of 35 to 40 would represent the uncertainty range between the beta ratio and burst suppression in which the BIS algorithm would be less sensitive to the effects of propofol25.

The effects of opioids on BIS also require attention. In comparison to intravenous and inhalational anesthetics, opioids cause minimal electrophysiological changes in the cerebral cortex. Subcortical structures are involved with the mechanism of action of opioids that are not detected by the EEG. Combined with a constant target concentration of propofol, a progressive increase or reduction in the dose of remifentanil does not change BIS26. On the other hand, the addition of fentanyl, sufentanil, remifentanil, or alfentanil to the target-controlled infusion of propofol results in loss of consciousness with lower concentrations of propofol, but the associated values of BIS are higher27,28. Studies have demonstrated that even high doses of remifentanil do not change BIS during continuous infusion with propofol26. The bispectral index is not accurate when fentanyl associated or not with propofol29 or midazolam30 is used during coronary bypass surgeries.

Those results demonstrated clearly that the hypnotic effects of propofol are increased by opioids, but monitoring with BIS does not show this effect, which can lead to inadvertent anesthetic overdose. However, despite requiring attention, BIS monitoring during anesthesia with propofol and opioids is in fact very useful. When this combination is balanced during surgery, it produces BIS values that can be used as a baseline from which an elevation in the response to surgical stimuli will indicate awakening due to a deficiency of the analgesic component of anesthesia; in this case, one should increase the dose of the opioid.

Unexpected variations in BIS during general anesthesia in response to the administration of different drugs were described. A case report referred to the elevation of BIS above 70 in response to beta-adrenergic stimulation resulting from the administration of isoproterenol31. The increase in BIS did not seem to be related with surgical stimulation and the patient did not have intraoperative recall. The administration of successive doses of methylene blue to increase methemoglobinemia caused simultaneous sudden and severe reduction in BIS followed by recovery to the levels before the administration of the drug32. Other causes for the reduction in BIS were not identified and, consequently, the temporal relationship between the administration of the drug and the reduction in BIS favors the theory that there might be an interaction between methylene blue and the electroencephalographic monitoring.

Interference from Electrical Equipment

The bispectral index also demonstrated to be somewhat weak when artifacts are present. Different electrical devices, besides the electric scalpel, can affect BIS monitoring. During cardiac surgeries a rise in BIS up to 90 during the use of the atrial pacemaker, which decreased when the pacemaker was turned off, was seen31. The quality of the electroencephalographic signal was low when the pacemaker was turned on, and electrical interference was responsible for the artifact observed in BIS.

However, the signal quality bar does not show the artifact every time. False elevations in BIS, when the thermal blanket was turned on and placed directly on the face of the patient, have been reported34. The bispectral index returned to 35 to 60 when the device was turned off. Similarly, BIS increased suddenly during shoulder arthroscopy when the oscillations produced by the shaver started35. Besides, an ENT system created an electromagnetic field around the head of the patient leading to an increase in BIS36. Those electrical devices can cause vibrations or minimal frequency on BIS electrodes, simulating EEG waves found in superficial anesthesia or during alertness. Those signal interferences were not identified by the monitor as interferences. Therefore, once more, conditions for inadvertent anesthetic overdose are created.

Changes in BIS Secondary to Abnormal EEG Patterns

There are different reports and situations in which the BIS shown by the monitor does not coincide with the clinical state of sedation, due to the pathophysiology of brain function or limitations in the performance of the monitor. One report described an awake patient with a BIS of 4737. On the other hand, sometimes painful stimulation during surgery in the presence of inadequate anesthesia results in EEG suppression. One study demonstrated a significant reduction in BIS immediately after peritoneal irrigation in abdominal surgeries38. Administration of fentanyl before abdominal irrigation abolished this abnormal BIS response, which did not change during irrigation. These data show that stimulation during peritoneal irrigation can cause a paradoxal response characterized by a reduction in EEG-derived parameters38. One should be attentive for the development of this paradoxal response to avoid inappropriate superficiality of the anesthetic plane.

Some individuals have a specific genetically-determined EEG variant, which manifests with low voltage39.This is a normal variant that affects 5 to 10% of the population and it is not associated with any cerebral dysfunction. Since the BIS algorithm was developed in volunteers with normal EEG, this abnormal EEG pattern is not recognized by the monitor. For this reason, it is important to confirm the BIS in all patients before anesthetic induction.

However, a low voltage EEG can also be induced by drugs. A fast and paradoxal reduction in BIS was seen during the elimination phase of remifentanil in six patients40. The same effect was reported with inhalational anesthetics during the elimination of sevoflurane and isoflurane41. In those two reports, the EEG showed very low voltage (< 15 µV), which was interpreted by the monitor as burst suppression.

In electroconvulsive therapy, after recovering consciousness, patients have a peculiar EEG pattern characterized by very slow ä waves, resembling deep planes of anesthesia. Therefore, the BIS reflects this postictal state (which is independent of the anesthetic used) with very slow levels, from 45 to 5742. The case of a patient with spontaneous eyes opening who had a BIS of 7 has also been reported.

The BIS algorithm was developed using data from individuals with normal EEG and, consequently, neurologic disorders that manifest with abnormal EEG patterns will, most likely, affect BIS monitoring. Although recent studies using the bispectral index in patients with brain lesions reported good correlation with sedation scales43, unusual situations during BIS monitoring in patients with neurologic disorder have been reported.

One study showed that slowing of the EEG associated with dementia changed awaken BIS44. In patients with dementia secondary to Alzheimer's and multiple brain infarcts the BIS, while awaken, was lower than that of elderly individuals in the same age range used as control (89 x 95) 44. Reduced BIS levels in individuals with dementia correlate with the Mini Mental State Examination. Despite the results of this study, further studies are needed to confirm the usefulness of BIS to detect dementia.

Children with cerebral palsy had significantly lower BIS than normal children, both during anesthesia maintenance with sevoflurane and during awakening from anesthesia45. One report described BIS behavior in a patient in permanent vegetative state who underwent dental surgery46. Baseline BIS was reduced (74 to 85) due to neurologic damage, but it was reduced even further after the administration of sevoflurane. However, similar to normal individuals, at the end of the surgery BIS rose to 98 - 100. This report demonstrates that BIS cannot differentiate integrated and non-integrated cortical activity. In normal individuals, elevate BIS reflects the great cortical activity manifested by being conscious. However, in individuals with neurological lesions, elevated BIS does not indicate, necessarily, integrated cortical activity.

Besides those situations, the BIS algorithm is also very vulnerable to artifacts when EEG signals are absent (brain death) or profoundly depressed (severe hypothermia). In two individuals with confirmed brain death, BIS rose from 0-5 to 38 due to synchronization of the electrocardiogram signal with the BIS, which interpreted ECG signals as EEG activity47.

Clinical Conditions That Cause Changes in BIS

Different clinical situations that lead to a reduction in cardiac output and, consequently, brain perfusion, cause a reduction in BIS. This was seen in a patient with asystole who was successfully resuscitated48. An isoelectric EEG pattern occurred 10 minutes after the beginning of asystole. When thoracic compressions were instituted, leading to an increase in brain perfusion, a low-voltage, high-frequency EEG pattern developed. With the return of the cardiac rhythm, which restored blood flow to the brain, the EEG signal returned to normal.

A parallel reduction in BIS down to zero with isoelectric EEG is associated with cardiac arrest secondary to hypovolemia49. As blood pressure is restored to normal levels and brain perfusion is resumed, BIS increased to the levels seen before the complication48. Changes in bispectral index can occur even before the development of hemodynamic changes50. This can probably be explained by the changes induced in anesthetic pharmacokinetics. On the other hand, during hemodynamic changes variations in BIS are secondary to changes in brain perfusion.

Although the BIS was not designed or validated to detect brain lesion, BIS monitoring can help detect it. The bispectral index can reflect, besides global encephalic ischemia, focal ischemia. In surgeries of the carotid artery, BIS is reduced during arterial clamping and it returns to normal when blood flow is reestablished51.

Hypothermia is another factor that should be considered during BIS monitoring. In patients anesthetized with isoflurane on cardiopulmonary bypass with hypothermia, it was estimated that BIS decreased 1.12 units for each Celsius degree reduction in body temperature52. This is secondary to the linear reduction in the need of anesthetics as well as a reduction in brain activity.

Hypoglycemia (down to 72 causes a small increase in the frequency of low frequency ä and è waves53. Reduction in glucose levels to 54 causes a diffuse increase in ä and è waves. At 32, the increase in ä and è waves is associated with a reduction in á waves, a pattern very similar to that of general anesthesia53. In fact, BIS as low as 45 in patients with hypoglycemic coma, which rose after blood glucose levels were restored to normal, has been reported54.



Although the BIS algorithm has changed since its first version, false variations in BIS still occur, and they should be recognized by the anesthesiologist to avoid complications during general anesthesia due to anesthetic overdose or low doses, which can lead to intraoperative wakening and recall, and their consequences.

The bispectral index should be seen as additional datum of general anesthesia monitoring and interpreted in the context of other clinical data and monitors.



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Correspondence to:
Dr. Leonardo Teixeira Domingues Duarte
Rua 09 Norte, Lote 03/1.703 — Águas Claras
71908-540 Taguatinga, DF

Submitted em 6 de março de 2008
Accepted para publicação em 13 de outubro de 2008



* Received from Hospital Sarah Brasília, DF

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