- Email: [email protected]
The Bispectral Index Scale: Its Use in the Detection of Brain Death
The Bispectral Index Scale: Its Use in the Detection of Brain Death D. Escudero, J. Otero, G. Muñiz, J.A. Gonzalo, C. Calleja, A. González, A. Martı´nez, D. Parra, R. Yano, and F. Taboada ABSTRACT Objective. To evaluate the Bispectral Index Scale (BIS) monitor as a method of brain death (BD) detection. Patients and Methods. We performed an observational prospective study in an intensive care unit (ICU) of a university hospital of 19 patients hospitalized nonconsecutively in the ICU with serious neurologic pathology and evolution toward BD. A BIS monitor, XP model, and the sensor “BIS Quatro” were used to continuously record values: suppression ratio (SR), quality of the signal index, and electromyographic (EMG) activity. Results. The BD diagnosis was made through neurological clinical exploration and electroencephalogram (EEG) in all the cases. Additionally, transcranial Doppler was used in 13 patients. Coincident with clinical worsening, it was observed that there was a gradual decrease of the BIS value, together with a rise in the SR. In all the patients in which the BD diagnosis was confirmed, the BIS showed values of 0 and suppression rates of 100. Only one patient showed interferences, due to EMG activity, the same problem was detected when a conventional EEG was performing. After using a neuromuscular blocker, the values of BIS and SR were 0 and 100, respectively. Conclusions. The BIS is a noninvasive, simple, and easy to interpret method. All the patients with BD diagnosis except for one had a BIS value of 0 and TS of 100, showing a perfect correlation with the other diagnostic methods. The BIS cannot be used on its own for the confirmation of the BD, but it is a useful tool to detect the beginning of brain herniation.
T
HE DIAGNOSIS of brain death (BD) diagnosis is carried out through a clinical neurological exploration.1– 4 Together with the clinical diagnosis there are a series of instrumental tests that can be used. The Spanish legislation guidelines perfectly define the circumstances that oblige the use of an instrumental diagnosis.5 The Bispectral Index Scale (BIS) is a parameter originated by a mathematical analysis of data taken from the electroencephalogram (EEG), which is highly complex and multivariate (latency, amplitude, bispectral). Initially, the BIS was used in surgery to control the grade of hypnotic depth of anesthesia. Nowadays, its use is beginning to spread to the intensive care unit (ICU) in order to control the sedation levels, the management of the barbiturate coma, and even the prognosis index for patients with cerebral injury (both traumatic and secondary).6 –9 The BIS has a scale of values from 0 to 100. A BIS of 100 represents an awake individual, while a BIS of 0 represents complete
electrical silence (cortical suppression). Values between 40 and 60 indicate an adequate grade of sedation.
PATIENTS AND METHODS This prospective study in an ICU of a university hospital evaluated a population of patients with a high probability of evolution toward BD based upon clinical criteria. The criteria used were a lower Glasgow Coma Score (GCS) as well as the finding on cranial computed tomography scan of large and catastrophic lesions. The treatment and monitoring of the patients was done according to standard procedures. No patient received a pentobarbital infusion From Intensive Care Unit, Central University Hospital of Asturias, Asturias, Spain. Address reprint requests to Dra Dolores Escudero, Intensive Care Unit, Central University Hospital of Asturias, C/ Celestino Villamil s/n 33006 Oviedo, Asturias, Spain. E-mail: dolores. [email protected]
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.08.054
Transplantation Proceedings, 37, 3661–3663 (2005)
3661
3662 treatment. Nineteen patients were in the ICU from December 2003 to May 2004.
BIS Monitoring BIS and electromyographic (EMG) activity were recorded continuously using and BIS XP monitor (Aspect Medical Systems, Newton, Mass, USA) and a sensor “BIS Quatro” situated on the forehead and in the temporal area. Several parameters were continuously followed: the Suppression Ratio (SR), which is percentage of time over the last 63 seconds recorded in which the EEG is isoelectric; the Quality of Signal Index, and EEG with a direct visualization and speed of 25 mm per second using a scale of 25 V per division.
Definition of BD The clinical exploration and instrumental diagnosis were adjusted to the scientific recommendations in the subject and diagnostic protocols from the Spanish legislation. The EEG was performed according to the recommendations of the American Electroencephalographic Society.10 In the studies with a transcranial Doppler, the anterior and posterior circulation was evaluated. The presence of “oscillating flow” and “systolic spikes” was accepted as sonographic outlines of cerebral circulatory arrest, following the Task Force of Neurosonology in the BD guidelines.11
RESULTS
The study was performed in 19 patients (nine women and 10 men) admitted to the ICU. The mean age was of 60.3 years (30 to 75). Four patients with head injury, seven subarachnoidal hemorrhage, six intracerebral hemorrhage, and two, ischemic strokes from thrombosis in the middle cerebral artery. The GCS at the time of admission to the ICU was of 4.5 ⫾ 1.5 (3 to 8). In 13 patients, the GCS when admitted was ⱕ5. Both ischemic stroke patients had a National Institute of Health Stroke Score at the time of admission of 30 and 21, respectively. The mean stay in the ICU was 5.56 days (1 to 17). All patients developed a BD situation. With family authorization, 17 (89.4%) became organ donors. Together with the neurological exploration, all the patients underwent an EEG, and thirteen (68.4%) a transcranial Doppler. In all patients, coinciding with the clinical worsening and increased intracranial pressure (ICP), the BIS value decreases progressively, at the same time as an increase in the RS. We have examined whether the BIS detects the moment of brain herniation in advance, since its values fell down to 0 immediately after the patient showed an autonomic storm. When the BIS was compared with the other diagnostic methods, it showed an excellent correlation, without discrepancies with various techniques. Using clinical exploration as the “gold standard,” the BIS sensitivity was 94.7%. In all the studied patients in whom the BD diagnosis was confirmed, the BIS showed values of 0 and a suppression rate of 100, except one case that could be considered “transient false-negative.” It was a 30-year-old woman with a subarachnoidal hemorrhage, caused by an
ESCUDERO, OTERO, MUÑIZ ET AL
aneurysm in the posterior inferior cerebellar artery. Initially, and ICP of 70 mmHg was detected; afterward she developed a syndrome of intracranial hypertension refractory to the usual treatment. On the third day of admission, the patient was diagnosed with BD. During maintenance as a potential organ donor, administration of fluids was carried out as well as an infusion of norepinephrine. The patient showed a sinus tachycardia (140 bpm), which provoked a pulsated movement in the muscles of the neck and face. Under these conditions, the BIS value was 21 with an SR of 30. EMG activity from electrode placement over the frontal and temporal muscles can falsely elevate the BIS. When doing a conventional EEG, there was also an intense contamination by the EMG, which forced the use of muscle relaxants. After the use of the relaxant, the BIS and TS values were 0 and 100, respectively, and the EEG was recorded as isoelectric. DISCUSSION
The BIS is a simple, noninvasive, and easy to interpret method. In all our-patients, coinciding with clinical worsening and increased ICP, there was a progressive decrease in the BIS value, rapidly detect a brain herniation since the values fell to 0 immediately after the autonomic storm, before cerebral circulatory arrest. When the diagnosis of BD was confirmed, all patients had a BIS of 0 and an SR of 100, except for one referred to as “transient false-negative” due to EMG contamination. This problem is well known appear relatively often in the analysis of a conventional EEG.12 The EEG signals are recorded in a band of 0.5–30 Hz, while the EMG signals are found in a 30 to 300 Hz band. BIS uses EEG signals up to 47 Hz. Therefore, EMG activity of low frequency may overestimate the BIS, especially when there is no EEG activity as happens in BD. This fact justifies the described patient as “transient false-negative.” In these cases it is necessary to administer a muscle relaxant. This problem has been noted in similar clinical cases by other authors.13,14 When comparing the BIS results with the clinical exploration, the sensitivity was 94.7%. Once BD has been confirmed there were no further increases in the BIS. Our results mainly coincide with the ones in the only published series about BIS for detection of brain death.15 In conclusion, BIS monitoring detects in advance situations EEG inactivity, which can optimize the time dedicated to the diagnosis of BD, and therefore facilitate organ procurement for transplantation. BIS values of 0 and suppression rate of 100 may be considered an alarm signal that warns of the onset of brain herniation. Since the BIS provides a regional study of brain electrical activity, it obviously cannot be used exclusively as a confirmatory test for BD. REFERENCES 1. Escudero D, Otero J: Avances clı´nicos y legales en el diagnóstico de muerte encefálica durante la década de los trasplantes en España. Nefrologı´a XXI:30, 2001
THE BISPECTRAL INDEX SCALE 2. Escudero AD: Diagnóstico clı´nico de muerte encefálica. Prerrequisitos y exploración neurológica. Med Intensiva 24:106, 2000 3. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Practice parameters for determining brain death in adults (Summary statement). Neurology 45:1012, 1995 4. Wijdicks EFM: The diagnosis of brain death. N Engl J Med 344:1215, 2001 5. Real Decreto 2070/1999, de 30 de Diciembre, por el que se regulan las actividades de obtención y utilización clı´nica de órganos humanos y la coordinación territorial en materia de donación y trasplante de órganos y tejidos. BOE 3/2000 de 04-01-2000, p 179 6. Johansen JW, Sebel PS: Development and clinical application of electroencephalographic bispectrum monitoring. Anesthesiology 93:1336, 2000 7. De Deyne C, Struys M, Decruyenaere J, et al: Use of continuous bispectral EEG monitoring to assess depth of sedation in ICU patients. Intensive Care Med 24:1294, 1998 8. Gilbert TT, Wagner MR, Halukurike V, et al: Use of bispectral electroencephalogram monitoring to assess neurologic status in unsedated critically ill patients. Crit Care Med 29:1996, 2001
3663 9. Azim N, Wang CY: The use of bispectral index during a cardiopulmonary arrest: a potential predictor of cerebral perfusion. Anaesthesia 59:610, 2004 10. Henry C, Goldie WD, Hughes JR, et al: American Electroencephalographic Society. Guideline three: minimum technical standards for EEG recording in suspected cerebral death. J Clin Neurophysiol 11:10, 1994 11. Ducrocq X, Hassler W, Moritake K, et al: Consensus opinion on diagnosis of cerebral circulatory arrest using Dopplersonografy. Task Force Group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology. Journal of the Neurological Sciences 159:145, 1998 12. Wee AS: Scalp EMG in brain death electroencephalogram. Acta Neurol Scand 74:128, 1986 13. Bruhn J, Bouillon TW, Shafer SL: Electromyographic activity falsely elevates the bispectral index. Anesthesiology 92:1485, 2000 14. Myles PS, Cairo S: Artifact in the bispectral index in a patient with severe ischemic brain injury. Anesth Analg 98:706, 2004 15. Vivien B, Paqueron X, Le Cosquer P, et al: Detection of brain death onset using the bispectral index in severely comatose patients. Intensive Care Med 28:419, 2002
T
HE DIAGNOSIS of brain death (BD) diagnosis is carried out through a clinical neurological exploration.1– 4 Together with the clinical diagnosis there are a series of instrumental tests that can be used. The Spanish legislation guidelines perfectly define the circumstances that oblige the use of an instrumental diagnosis.5 The Bispectral Index Scale (BIS) is a parameter originated by a mathematical analysis of data taken from the electroencephalogram (EEG), which is highly complex and multivariate (latency, amplitude, bispectral). Initially, the BIS was used in surgery to control the grade of hypnotic depth of anesthesia. Nowadays, its use is beginning to spread to the intensive care unit (ICU) in order to control the sedation levels, the management of the barbiturate coma, and even the prognosis index for patients with cerebral injury (both traumatic and secondary).6 –9 The BIS has a scale of values from 0 to 100. A BIS of 100 represents an awake individual, while a BIS of 0 represents complete
electrical silence (cortical suppression). Values between 40 and 60 indicate an adequate grade of sedation.
PATIENTS AND METHODS This prospective study in an ICU of a university hospital evaluated a population of patients with a high probability of evolution toward BD based upon clinical criteria. The criteria used were a lower Glasgow Coma Score (GCS) as well as the finding on cranial computed tomography scan of large and catastrophic lesions. The treatment and monitoring of the patients was done according to standard procedures. No patient received a pentobarbital infusion From Intensive Care Unit, Central University Hospital of Asturias, Asturias, Spain. Address reprint requests to Dra Dolores Escudero, Intensive Care Unit, Central University Hospital of Asturias, C/ Celestino Villamil s/n 33006 Oviedo, Asturias, Spain. E-mail: dolores. [email protected]
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.08.054
Transplantation Proceedings, 37, 3661–3663 (2005)
3661
3662 treatment. Nineteen patients were in the ICU from December 2003 to May 2004.
BIS Monitoring BIS and electromyographic (EMG) activity were recorded continuously using and BIS XP monitor (Aspect Medical Systems, Newton, Mass, USA) and a sensor “BIS Quatro” situated on the forehead and in the temporal area. Several parameters were continuously followed: the Suppression Ratio (SR), which is percentage of time over the last 63 seconds recorded in which the EEG is isoelectric; the Quality of Signal Index, and EEG with a direct visualization and speed of 25 mm per second using a scale of 25 V per division.
Definition of BD The clinical exploration and instrumental diagnosis were adjusted to the scientific recommendations in the subject and diagnostic protocols from the Spanish legislation. The EEG was performed according to the recommendations of the American Electroencephalographic Society.10 In the studies with a transcranial Doppler, the anterior and posterior circulation was evaluated. The presence of “oscillating flow” and “systolic spikes” was accepted as sonographic outlines of cerebral circulatory arrest, following the Task Force of Neurosonology in the BD guidelines.11
RESULTS
The study was performed in 19 patients (nine women and 10 men) admitted to the ICU. The mean age was of 60.3 years (30 to 75). Four patients with head injury, seven subarachnoidal hemorrhage, six intracerebral hemorrhage, and two, ischemic strokes from thrombosis in the middle cerebral artery. The GCS at the time of admission to the ICU was of 4.5 ⫾ 1.5 (3 to 8). In 13 patients, the GCS when admitted was ⱕ5. Both ischemic stroke patients had a National Institute of Health Stroke Score at the time of admission of 30 and 21, respectively. The mean stay in the ICU was 5.56 days (1 to 17). All patients developed a BD situation. With family authorization, 17 (89.4%) became organ donors. Together with the neurological exploration, all the patients underwent an EEG, and thirteen (68.4%) a transcranial Doppler. In all patients, coinciding with the clinical worsening and increased intracranial pressure (ICP), the BIS value decreases progressively, at the same time as an increase in the RS. We have examined whether the BIS detects the moment of brain herniation in advance, since its values fell down to 0 immediately after the patient showed an autonomic storm. When the BIS was compared with the other diagnostic methods, it showed an excellent correlation, without discrepancies with various techniques. Using clinical exploration as the “gold standard,” the BIS sensitivity was 94.7%. In all the studied patients in whom the BD diagnosis was confirmed, the BIS showed values of 0 and a suppression rate of 100, except one case that could be considered “transient false-negative.” It was a 30-year-old woman with a subarachnoidal hemorrhage, caused by an
ESCUDERO, OTERO, MUÑIZ ET AL
aneurysm in the posterior inferior cerebellar artery. Initially, and ICP of 70 mmHg was detected; afterward she developed a syndrome of intracranial hypertension refractory to the usual treatment. On the third day of admission, the patient was diagnosed with BD. During maintenance as a potential organ donor, administration of fluids was carried out as well as an infusion of norepinephrine. The patient showed a sinus tachycardia (140 bpm), which provoked a pulsated movement in the muscles of the neck and face. Under these conditions, the BIS value was 21 with an SR of 30. EMG activity from electrode placement over the frontal and temporal muscles can falsely elevate the BIS. When doing a conventional EEG, there was also an intense contamination by the EMG, which forced the use of muscle relaxants. After the use of the relaxant, the BIS and TS values were 0 and 100, respectively, and the EEG was recorded as isoelectric. DISCUSSION
The BIS is a simple, noninvasive, and easy to interpret method. In all our-patients, coinciding with clinical worsening and increased ICP, there was a progressive decrease in the BIS value, rapidly detect a brain herniation since the values fell to 0 immediately after the autonomic storm, before cerebral circulatory arrest. When the diagnosis of BD was confirmed, all patients had a BIS of 0 and an SR of 100, except for one referred to as “transient false-negative” due to EMG contamination. This problem is well known appear relatively often in the analysis of a conventional EEG.12 The EEG signals are recorded in a band of 0.5–30 Hz, while the EMG signals are found in a 30 to 300 Hz band. BIS uses EEG signals up to 47 Hz. Therefore, EMG activity of low frequency may overestimate the BIS, especially when there is no EEG activity as happens in BD. This fact justifies the described patient as “transient false-negative.” In these cases it is necessary to administer a muscle relaxant. This problem has been noted in similar clinical cases by other authors.13,14 When comparing the BIS results with the clinical exploration, the sensitivity was 94.7%. Once BD has been confirmed there were no further increases in the BIS. Our results mainly coincide with the ones in the only published series about BIS for detection of brain death.15 In conclusion, BIS monitoring detects in advance situations EEG inactivity, which can optimize the time dedicated to the diagnosis of BD, and therefore facilitate organ procurement for transplantation. BIS values of 0 and suppression rate of 100 may be considered an alarm signal that warns of the onset of brain herniation. Since the BIS provides a regional study of brain electrical activity, it obviously cannot be used exclusively as a confirmatory test for BD. REFERENCES 1. Escudero D, Otero J: Avances clı´nicos y legales en el diagnóstico de muerte encefálica durante la década de los trasplantes en España. Nefrologı´a XXI:30, 2001
THE BISPECTRAL INDEX SCALE 2. Escudero AD: Diagnóstico clı´nico de muerte encefálica. Prerrequisitos y exploración neurológica. Med Intensiva 24:106, 2000 3. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Practice parameters for determining brain death in adults (Summary statement). Neurology 45:1012, 1995 4. Wijdicks EFM: The diagnosis of brain death. N Engl J Med 344:1215, 2001 5. Real Decreto 2070/1999, de 30 de Diciembre, por el que se regulan las actividades de obtención y utilización clı´nica de órganos humanos y la coordinación territorial en materia de donación y trasplante de órganos y tejidos. BOE 3/2000 de 04-01-2000, p 179 6. Johansen JW, Sebel PS: Development and clinical application of electroencephalographic bispectrum monitoring. Anesthesiology 93:1336, 2000 7. De Deyne C, Struys M, Decruyenaere J, et al: Use of continuous bispectral EEG monitoring to assess depth of sedation in ICU patients. Intensive Care Med 24:1294, 1998 8. Gilbert TT, Wagner MR, Halukurike V, et al: Use of bispectral electroencephalogram monitoring to assess neurologic status in unsedated critically ill patients. Crit Care Med 29:1996, 2001
3663 9. Azim N, Wang CY: The use of bispectral index during a cardiopulmonary arrest: a potential predictor of cerebral perfusion. Anaesthesia 59:610, 2004 10. Henry C, Goldie WD, Hughes JR, et al: American Electroencephalographic Society. Guideline three: minimum technical standards for EEG recording in suspected cerebral death. J Clin Neurophysiol 11:10, 1994 11. Ducrocq X, Hassler W, Moritake K, et al: Consensus opinion on diagnosis of cerebral circulatory arrest using Dopplersonografy. Task Force Group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology. Journal of the Neurological Sciences 159:145, 1998 12. Wee AS: Scalp EMG in brain death electroencephalogram. Acta Neurol Scand 74:128, 1986 13. Bruhn J, Bouillon TW, Shafer SL: Electromyographic activity falsely elevates the bispectral index. Anesthesiology 92:1485, 2000 14. Myles PS, Cairo S: Artifact in the bispectral index in a patient with severe ischemic brain injury. Anesth Analg 98:706, 2004 15. Vivien B, Paqueron X, Le Cosquer P, et al: Detection of brain death onset using the bispectral index in severely comatose patients. Intensive Care Med 28:419, 2002