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Introduction
Awareness during general anaesthesia is a result of an inadequate
depth of anaesthesia (DoA) and the incidence is approximately 1-2%
in patients at high risk (1-5). Traditional clinical signs of depth of ana-
esthesia can be unreliable and various DoA monitors are commerci-
ally accessible but not all of them are validated to the same extent (6-
7). In previous studies, monitors like Bispectral Index (BIS) andAudi-
tory evoked potentials (AEP) have been questioned in different con-
texts (3, 8-14). A reliable way of measuring DoA is sought (15-18)
and thus, an improvement or further development of alternative means
for monitoring DoA is needed.
The latencies and amplitudes of the brainstem waves of AEP are
called the auditory brainstem response (ABR). ABR measures the
electrical activity of the subcortical nerve cells generated by neuronal
activity in the auditory pathways in the brainstem, within the first 10
milliseconds (ms) following acoustic stimulation. The wave pattern
consists of seven positive peaks, wave I is starting at the eight cranial
nerve and extending into medulla (wave II). Wave III represents
neuron activity at the level of auditory pons, and wave IV in the supe-
rior olivary complex (SOC). Wave V is believed to originate from the
inferior colliculus (19-20).
Available information about DoA and traditional ABR is limited. A
recent and further development of a digital ABR by SensoDetect AB
(Lund, Sweden), called SensoDetect Brainstem Evoked Response
Audiometry (SD-BERA), has been developed as a diagnostic tool for
psychiatric diseases, but has never been evaluated during general anaes-
thesia. Previous studies using traditional, analogue ABR show contra-
dictory results regarding the effects from general anaesthesia (8, 15, 21-
25). Therefore, the aim of this study was to investigate brainstem audi-
tory-evoked potentials during general anaesthesia using SD-BERA.
Method
This prospective exploratory study was performed at Lund University
Hospital during spring of 2012. After approval by the Regional Ethics
Committee (Dnr: 2012/97, Lund, Sweden), seven consenting adult
patients scheduled for elective orthopaedic surgery with American
Society of Anesthesiologists (ASA) physical status I and II were assig-
ned. Patients were excluded if they had known or suspected neurolo-
gic disorder, or known or suspected hearing disabilities.
Standard monitoring of vital parameters was started, and electrodes
for monitoring with BIS and SD-BERA were placed before the induc-
tion of the anaesthesia. The surface electrodes were attached to the
skin over the mastoid bones behind both ears, with a ground electrode
placed on the forehead and a reference electrode placed on the vertex.
The attachment surface was prepared with disinfectant and scrub
before placement to optimize electrode contact and the stimuli were
presented through TDH-50P-headphones. Absolute impedance and
interelectrode impedance were measured before and after the experi-
ments to verify that electrode contact was maintained (below 5000Ω)
during the whole procedure. No active participation from the patients
was required. Patients were instructed to close their eyes and relax
after the headphones were applied to reduce myogenic artefacts. After
a calm environment was achieved in the theatre, a stopwatch was star-
ted simultaneously with SD-BERA to match time with events in pro-
tocol and SD-BERA data. BIS were noted for the first time and sti-
muli were presented through the headphones to create a baseline in
alert state.
Stimuli were presented and evoked potentials recorded using SD-
BERA (SensoDetect, Lund, Sweden). A series of 1300 clicks of
acoustic stimuli was used. The sound was a square-shaped click tone
used in a standard ABR. The intensity of the tones did not exceed 70
dB. Divergent responses to stimuli, defined as the 10% of the 1300
responses with the largest range in volt, and the 10% with the narro-
west range, were excluded as outliers. This was done to remove arte-
facts, for instance breathing, coughs, and movements. The remaining
1040 responses were used to establish an average wave pattern. An
algorithm was also applied to filter specific artefacts like cardiac acti-
vity, and the frequency of adjacent electrical equipment (50Hz).
The anaesthesia apparatus Dräger PrimusTM (Dräger Medical)
with carbon dioxide absorber was used to perform the chosen anaes-
Sykepleievitenskap .Omvårdnadsforskning .Nursing Science
23
CATHARINA LARSSON, EMMA LARSSON, FREDRIK ÅHLANDER, JOHN JAHR OG ANDERS JOHANSSON
Monitoring depth of anaesthesia
using auditory brainstem response:
an exploratory clinical study
Catharina Larsson, CRNA, MSc, Emma Larsson, CRNA, MSc, Fredrik Åhlander, MD, John Jahr, MD, PhD, Anders Johansson,
RNAIC, associate professor*.
ABSTRACT
Purpose: Various depth-of-anaesthesia monitors are available, but their trustworthiness is questioned.The aim of this study was to investigate
brainstem auditory-evoked potentials during general anaesthesia using a specific audiometry method named SensoDetect Brainstem Evoked
Response Audiometry (SD-BERA).
Methods: Seven patients with American Society of Anaesthesiologists physical status I and II scheduled for elective orthopaedic surgery were
assigned. Brainstem auditory evoked responses were recorded at different stages of anaesthesia. Bispectral index and end-tidal tension of
Sevoflurane were measured at the same time.
Results: The index (%) from pre-anaesthesia to anaesthesia were significantly reduced 100 [0-0] vs. 53 [49-72], respectively (p=0.0156). At
extubation the index were set back to normal level with a significant increase from anaesthetized state, 102 [78-135] (p=0.0156). No signifi-
cant difference could be observed between pre-anaesthesia and at extubation (p=0.6875).
Conclusion: The findings imply that SD-BERA has a potential to measure depth of anaesthesia.
KEY WORDS: Anaesthesia, Brainstem Evoked Response Audiometry
thetic procedure and to monitor end tidal Sevoflurane concentration
(PETsevo). For the BIS monitoring a BISTM MONITOR Model A-
2000TM (Aspect Medical Systems, Newton, MA, USA) was used.
The chosen anaesthetic procedure was performed according to a
previously published study (26). Patients were monitored with 3-lead
ECG, SpO2, inspiratory oxygen partial pressure (FiO2) and sevoflu-
rane expiratory partial pressure (PETsevo) as analyzed by the ventila-
tor.At the induction, all patients were pre-oxygenated with 100% oxy-
gen for 3–4 minutes with fresh gas flow of 5 l/min. Anaesthesia was
induced with 2 µg/kg Fentanyl and 1.5–3.0mg/kg Propofol. Muscle
relaxant drugs used were Suxamethonium or Rocuronium bromide.
Manual ventilation was assisted with 100% oxygen until tracheal intu-
bation was performed. The Sevoflurane tension was regulated to 3%
on the vaporizer, and after five minutes, the fresh gas flow was adju-
sted to 1.0 l/min with an unchanged Sevoflurane tension throughout
the anaesthesia. Extra doses of Fentanyl (50-100 µg) were administe-
red if the mean arterial blood pressure (MAP) increased > 20% above
the initial baseline level. Hypotension was treated by head lowering,
crystalloid or colloid infusion and/or 5-10 mg Ephedrine intrave-
nously. All patients received 3-5 ml kg-1h-1of glucose 2.5 % with
sodium (70 mmol C-1), chloride (45 mmol C-1) and acetate (25 mmol
C-1) intravenously. Neuromuscular blockade was monitored.
During the anaesthesia, the recording with SD-BERA and parame-
ters as BIS and PETsevo were read simultaneously at specific time
points and documented. The time points were defined as: Baseline
(alert state, pre-anaesthesia =A), Anaesthetised I (ciliary reflex
gone=B), Anaesthetised II (preceding first incision=C) and Extuba-
tion (D). The stimuli generate an ABR during two minutes, which is a
mean of a continuous recording during this period of time. The ABR
closest to the time point of interest was chosen. BIS and PETsevo
were measured at the same time for depicting anaesthesia.
Statistical analysis
All recorded ABR waves were analysed in retrospect using GraphPad
Prism. The aberrations in the recordings were confirmed by a comp-
uterized algorithm patented by SensoDetect. The wave pattern was
analysed with respect to amplitudes and the data derived from the ana-
lysed amplitudes was indexed (SD-BERA Index) to specific values in
percent. The alert state for each patient was established at an indivi-
dual baseline set to 100%.
The data are presented as median and interquartile range, and ana-
lysed using the non-parametric Friedman test to examine the diffe-
rence between the matched data in the different time-points (A-D). A
Wilcoxon matched pair test was also applied to detect differences bet-
ween any matched data in the different time-points. A P-value < 0.05
was considered to indicate statistical significance.
Results
A total of seven patients fulfilled the inclusion criteria and were enrol-
led in the study. The indexes derived from the brainstem activity and
BIS for each patient at the different time points (A-D) are presented in
table 1. However, one of the seven patients did not fulfil all the measu-
rement with BIS, because of BIS-monitoring failure.
The index and end-tidal sevoflurane concentrations (PetSevo) for all
the patients with the dispersion degree at the time points (A-D) is dis-
played in Table 2. At extubation (time point D) the median index was
set back to values round the baseline (time point A).
Measures from SD-BERA differed between anaesthetic (B and C) and
non-anaesthetic states (A and D), measures demonstrated statistical
differences between A:B (p=0.0156), A:C (p=0.0156), B:D
(p=0.0156) and C:D (p=0.0156) and no difference could be observed
between measures B:C (p=1.000) and A:D (p=0.6875), respectively.
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VÅRD I NORDEN 4/2013. PUBL. NO. 110 VOL. 33 NO. 1 PP 0–0
Table 1. Individual index for each patientʼs brainstem
auditory response (SD-BERA) and BIS, at the different time
points A-D (N=7 SD-BERA and N=6 BIS).
Gender (age/yr)
Female (20)
SD-BERA (%)
BIS
Female (28)
SD-BERA (%)
BIS
Female (57)
SD-BERA (%)
BIS
Male (22)
SD-BERA (%)
BIS
Male (23)
SD-BERA (%)
BIS
Male (34)
SD-BERA (%)
BIS
Male (37)
SD-BERA (%)
BIS
A
100
-
100
97
100
97
100
98
100
98
100
98
100
98
B
57
-
52
65
49
36
79
65
72
31
53
80
47
32
C
68
-
45
33
54
27
67
30
74
34
53
35
50
32
D
102
-
173
92
56
97
135
91
130
97
78
98
80
97
Table 2. Indexes for SD-BERA, BIS and end-tidal sevoflurane
concentrations (PetSevo) at presented time points: Baseline
(alert state, pre-anaesthesia =A), Anaesthetised I (ciliary
reflex gone =B), Anaesthetised II (preceding first incision
=C) and Extubation (D). Values are expressed as median and
[interquartile range], N=7 SD-BERA, N=6 BIS and N=7
PetSevo.
SD-BERA
(Index %)
BIS
(Index)
PetSevo
(%)
A
100
[86-105]
98
[97-98]
0
[0.0]
B
53
[49-72]
50.5
[31.75-68.75]
0
[0.0]
C
54
[50-68]
32.5
[29.25-34.25]
2.1
[1.8-2.3]
D
102
[78-135]
97
[91.75-97.25]
0.4
[0.2-0.5]
Discussion
The main finding in the present study is a significant difference in
amplitudes of waveV between anaesthetised (time point B and C) and
defined alert state (time point A and D) (Table 2).This finding is con-
sistent with some of the existing literature and implies that SD-BERA
has a potential to measure depth of anaesthesia measuring differences
in the waveV amplitude (15, 21). Many studies has focused on the dif-
ferences in latencies with contradicting results (8, 24-25), but in this
study we focused on amplitudes and demonstrate significant changes
in wave V.
Interestingly, there is a wide distribution in individual indexes
around the baseline at extubation (Table 1 and 2). To our knowledge,
there is no existing data that indicates such variations (rebound effect)
in the context of using anaesthetic agents in humans. This phenome-
non may be explained in pharmacological or psychological terms. In
pharmacological terms it is known that a rebound effect could arise
following discontinuation of sedative substances (27). Furthermore,
the chosen anaesthetic procedure used sevoflurane for maintenance
after induction with propofol. Young-Shin and colleagues compared
emergency agitation between sevoflurane and propofol in adults and
the results demonstrates that 45% of the patients in the sevoflurane
group developed emergency agitation compared to 10% when using
propofol (28). It can´t be ruled out that this phenomenon occurred
during the present phase of extubation in the current study and that
this phenomenon is demonstrated with the values above 100%, detec-
ted by the SD-BERA. Further research has to be done to clarify this
issue.
According to other interferences with anaesthetic agents it is sugge-
sted that ABR are not influenced by central or peripheral muscle rela-
xants. To present authors this knowledge is only demonstrated in a few
animal studies. However, ABR is a commonly used method to deter-
mine hearing sensitivity in animals, using either isoflurane or keta-
mine anaesthesia. In an animal study designed by Ruebhausen et al.,
they concluded that hearing thresholds obtained with isoflurane were
on average elevated across a broad frequency range compared to
ketamine (29). This significant effect, generated from different anaes-
thetic agents, demonstrates a substantial difference between general
anaesthetics on ABR sensitivity. Therefore, potential mechanisms and
further implications for ABR during general anaesthesia to detect
DoA, had to be evaluated and discussed.
Table 1 depicts the observed relationship between SD-BERA and
BIS, including all time points. Validity is difficult to quantify in this
context, as there is no accepted gold standard measure of anaesthetic
depth (7). To be able to validate DoA monitoring, Bruhn and collea-
gues highlight the importance of comparing the actual instrument
with the states of unconsciousness and the plasma concentration of the
anaesthetic drug (7). In the present study PETsevo is utilized; howe-
ver, a more reliable and precise measurement would have been to use
arterial Sevoflurane tensions (Pasevo), as in the presented reference by
Enekvist et al (27). This may be considered in future studies. However,
BIS and PETsevo were used for depicting anaesthesia in correlation
with SD-BERA, demonstrating adequate levels according to used and
excepted values.
There are some important limitations of the present study. An ABR
is an average of two minutes of data recording and the SD-BERA
index will be an approximation if the patient is not in a steady state.
However, the aim of the present study was to explore the potential of
the method. In order to validate the method in further studies, more
exact time points should be chosen and eventually a real-time analysis
approach should be performed. The operative setting in which electro-
encephalographic data were collected could have affected the out-
come. Artefacts are a critical issue for the method. Interference of
other instruments used in the operating room, as well as the surgery
itself could potentially affect the outcome, as well as artefacts of
neuronal origin such as suppression of cortical activity during general
anaesthesia. Another limitation is that we don’t measure body tempe-
rature among the patients, even though studies indicate affected brain-
stem response in association with hypothermia. However, it’s been
reported that the body temperature must decrease below 28 ºC to
affect the ABR (30-33).
A possibility for decreasing the dispersion degree in time point D
would be if the extubation procedure occurred more standardised, in a
manner that the patients surely would be back at a similar alert state.
Another limitation is the small number of participants, but conside-
ring the design where intra-individual responses were studied, it was
still possible to achieve convincing results.
The fact that the technique is able to detect consistent differences of
amplitudes at certain time points during the procedure is promising. In
consideration to present and previous studies, further research is nee-
ded focusing on the use of SD-BERA to find further traits that can
support the results of this study, but also investigate if SD-BERA has
a potential of a more detailed quantification of DoA. Furthermore,
future research may show the potential to DoA in context with intrave-
nous agents alone. According to studies, BIS thresholds do not appear
to be independent of the combinations of anaesthetic agents adminis-
tered (10-13). Baas and colleagues also presents limitations with AEP
in association with opioids and peripheral analgesics, which as well
may motivate to further investigation of these findings in the same
context with SD-BERA (34).
Conclusion
The findings in this study imply that SD-BERA has a potential to
measure depth of anaesthesia.
Catharina Larsson, CRNA, MSc1, Emma Larsson, CRNA, MSc1,
Fredrik Åhlander, MD2, John Jahr3, MD, PhD, Anders Johansson,
RNAIC, associate professor1*.
1Department of Health Sciences, Faculty of Medicine, P.O. Box 157,
221 00 Lund, Sweden
2Clinical Memory Research Unit, Department of Clinical Sciences
Malmö, Lund University, Malmö, Sweden
3Department of Intensive- and Perioperative Care, Lund University
Hospital, S-221 85, Lund, Sweden
*Corresponding author: Anders Johansson, Department of Health
Sciences, Faculty of Medicine, P.O. Box 157, 221 00 Lund,
SwedenSweden. Phone: +46 46 2221930,
E-mail: anders.johansson@med.lu.se
Acknowledgements
Special thanks to the staff at Department of Perioperative Care at
Lund University Hospital for assistance to make this study viable.
We would also like to thank SensoDetect for support and inspiration
and declare that the authors have no conflict of interest.
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