British Journal of Anaesthesia, xxx (xxx): xxx (xxxx)

doi: 10.1016/j.bja.2023.04.016
Advance Access Publication Date: xxx
Editorial

EDITORIAL

Depth of anaesthesia monitoring: time to reject the index?

Timothy J. McCulloch1,2,* and Robert D. Sanders1,2,3,4
1
Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia, 2Department of
Anaesthetics, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, NSW, Australia, 3Institute of Academic
Surgery, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, NSW, Australia and 4NHMRC Clinical Trials
Centre, University of Sydney, Sydney, NSW, Australia

*Corresponding author. E-mail: Tim.McCulloch@sydney.edu.au

Summary
Depth of anaesthesia monitors can fail to detect consciousness under anaesthesia, primarily because they rely on the
frontal EEG, which does not arise from a neural correlate of consciousness. A study published in a previous issue of the
British Journal of Anaesthesia showed that indices produced by the different commercial monitors can give highly
discordant results when analysing changes in the frontal EEG. Anaesthetists could benefit from routinely assessing the
raw EEG and its spectrogram, rather than relying solely on an index produced by a depth of anaesthesia monitor.

Keywords: anaesthesia; awareness; consciousness; depth of anaesthesia index; electroencephalography; monitoring

Anaesthetists currently have access to a variety of depth of
anaesthesia (DOA) monitors that process the EEG to produce a
numerical index intended to guide dosing of anaesthetic
agents. Definitive evidence that these monitors reduce the risk
of awareness under anaesthesia is lacking; however, clinical
experience is that DOA monitor indices usually increase on
emergence from anaesthesia. It is therefore likely that, in any
individual patient, failure to deliver adequate anaesthetic
agents during surgery will lead to a rise in the index, poten-
tially alerting the anaesthetist in time to prevent a serious
episode of awareness. This prima facie evidence is the basis for
recommendations that DOA monitoring be used when the risk
of awareness is increased, such as TIVA with a neuromuscular
blocking agent1 and lower-dose inhalational anaesthesia.2
Currently available DOA monitors are known to have
serious limitations, despite their apparent successful imple-
mentation into clinical practice. For pragmatic reasons, these
monitors are all based on the frontal EEG, which is problem-
atic, as there is no theoretical basis for using the frontal EEG to
monitor for (un)consciousness.3,4 The prefrontal cortex is
important for a conscious brain’s executive functions, but
DOI of original article: 10.1016/j.bja.2022.12.026.
accumulating data suggest this brain region is not central for
producing consciousness itself,5 although other evidence
suggests it may be important for the conscious perception of
external sensory stimuli.6 Casey and colleagues7 recently
showed that during anaesthesia and sleep, correlates of
consciousness more likely reside in deeper structures, such as
the anterior and posterior cingulate cortex. However, given the
current state of knowledge, features of the frontal EEG asso-
ciated with loss of responsiveness during general anaesthesia
are just thatdassociations.8 Whilst there are features of the
frontal EEG typically seen with anaesthesia-induced loss of
responsiveness, those features are not present in all patients
and are not seen with all classes of anaesthetic agents.
In a previous issue of the British Journal of Anaesthesia, Hight
and colleagues9 reported the behaviour of DOA monitors when
processing frontal EEG recordings collected previously from a
group of patients undergoing cardiac surgery. They first
identified episodes of apparent lightening of anaesthesia,
defined on the basis of spectral analysis revealing changes
similar to the spectral changes often seen just before emer-
gence from general anaesthesia. There was substantial varia-
tion in the behaviour of DOA monitors when presented with
these EEG recordings. In many cases, the various monitors

© 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
For Permissions, please email: permissions@elsevier.com

1
 2 - Editorial
produced indices that changed in opposite directions (i.e. over
the same time period within the same patient, some indices
increased, whilst others decreased), and there was poor
concordance in whether the indices were within their rec-
ommended clinical range for general anaesthesia. It is con-
cerning that the same EEG signal can result in such disparate
output from a group of devices all purporting to monitor the
same phenomenon. They cannot all be right! There was no
clear winner, as none of the individual monitors displayed an
increased index for every EEG episode of apparent lightening
of anaesthesia.
The EEG features used by Hight and colleagues9 to define
apparent lightening of anaesthesia were an increase in the
dominant frequency within the alpha band and a simulta-
neous decrease in delta power. This pattern has been re-
ported during emergence from propofol anaesthesia,10 and
increased alpha frequency has also been shown with
decreasing volatile anaesthetic concentration.11 Analysing
the EEG spectrum using the methods of Hight and colleagues9
has not been extensively validated as a method for detecting
inadequate anaesthetic dosing. In a previous paper, based on
the same set of EEG recordings, these authors cautiously
stated that these spectrogram patterns, ‘ … might sometimes
represent inadequate hypnotic effect of anaesthesia’.12
Therefore, it cannot be concluded with any certainty that a
DOA monitor whose index did not rise was necessarily failing
to detect inadequate anaesthesia. In 12 of the 52 cases in the
current study, all five DOA monitors produced an index
designated as either within the clinical range or deeper than
the clinical range. This result could be interpreted as showing
that all five monitors failed to detect inadequate anaesthesia,
but the alternative must also be considered that at least some
of those events were not actually episodes of inadequate
anaesthesia.
Another caveat when interpreting the results of Hight and
colleagues9 is that failure of the monitors to agree on whether
the EEG should be scored as outside the recommended clinical
range for anaesthesia is not necessarily a significant discor-
dance. For example, if one monitor’s index is a single point
above the limit for the recommended clinical range and an-
other’s index is a single point below, this could arguably be
considered a trivial disagreement.
The EEG records used by Hight and colleagues had been
recorded digitally for a previous study.12 These recordings
were converted back to an analogue electrical signal and then
fed to the DOA monitors being tested. A similar methodology
was first reported by Eagleman and colleagues,13 who devised
a ‘playback’ system to test the performance of DOA monitors
using EEG recordings from elderly patients during induction,
maintenance, and emergence from general anaesthesia. In
contrast to the results of Hight and colleagues, Eagleman and
colleagues13 found that the DOA monitors all performed
similarly well, despite the fact that elderly patients frequently
do not exhibit typical EEG spectrograph patterns.14
Storing EEGs and playing them back to DOA monitoring
algorithms is an intriguing technique that has potential for
wider application. We could significantly increase the knowl-
edge gained from studies on EEG and DOA by routinely storing
and sharing digital EEG recordings. For example, two studies
have demonstrated a spectacular failure of the BIS® monitor
to detect consciousness in awake volunteers who were given
neuromuscular blocking agents.15,16 Whether the other DOA
monitors would also fail under these experimental conditions
is not known, and regrettably, there are no digital recordings of
the EEGs of those brave volunteers who allowed themselves to
undergo awake paralysis.
This latest finding by Hight and colleagues adds to the
existing evidence that available DOA monitors are not ideal.
This is not to say these monitors are not useful. The manu-
facturers’ claims that there is a very low risk of awareness
with recall if their index is within the recommended range are
borne out by decades of clinical use during which case reports
of complete failure have been uncommon. Nevertheless,
there are convincing reports of intraoperative recall of surgical
procedures when a DOA index had been falsely
reassuring.17e19 Whilst these concerning events appear to be
uncommon, isolated forearm studies indicate awareness
without recall (during otherwise acceptable levels of general
anaesthesia) is not uncommon,20 and DOA monitors do not
reliably detect these episodes of consciousness.8,21 It appears
that modern anaesthesia practice is effective at minimising
the risk of awareness with recall whilst still allowing aware-
ness without recall. If this is considered a problem for our pa-
tients, it is difficult to envisage how the problem will be
overcome until monitors can be developed that more directly
respond to consciousness itself.
It is remarkable that despite widespread clinical use, the
data behind the decisions to designate a clinical range (40e60
in the case of BIS) remain unclear. In the seminal study by
Glass and colleagues,22 the effective bispectral index for 95% of
the population to be unresponsive to verbal command was 51
(95% confidence interval [CI]: 47e52), whilst for explicit recall it
was 64 (95% CI: 52e69). Neither of these results provide con-
fidence in an upper limit of 60. Based on a case in the seminal
B-Aware trial, the authors suggested that an upper limit of
bispectral index monitoring of 55 be considered.23 Given the
challenges from data provided by studies of intraoperative
isolated forearm monitoring, awake but paralysed volunteers,
and the B-Aware study, is it time to reject these indices or at
least reconsider the relevant range?
We agree with the recommendations from professional
bodies that DOA monitoring be used when there is a presumed
increased risk of awareness.12 However, clinicians do need to
be aware that these monitors are not completely reliable, and
it is possible for patients to be aware despite a reassuring in-
dex. We consider it critical that the index is interpreted in the
context of the raw electroencephalogram and spectrogram,
although we acknowledge that trials showing this is a superior
approach are lacking. Anaesthetists do not use HR alone as a
metric of cardiac function, and the DOA index alone is not
adequately informative. We concur with the suggestion of
Hight and colleagues9 that clinicians familiarise themselves
with the spectrogram signatures that frequently accompany
emergence from anaesthesia. Unfortunately, not all monitors
currently display a raw EEG spectrogram.
Beyond the EEG spectrogram, there are other lines of
enquiry that could lead to advances in EEG analysis to help
with titration of anaesthetics. Recent advances include the use
of deep learning algorithms to classify EEG correlates of
different anaesthetic states,24 better phenotyping of general
anaesthesia to understand the neurophysiology underlying
different states of consciousness and incorporating better
spatial resolution of the surface EEG,7 and incorporating
evoked responses into EEG analysis.24,25 However, none of
these technologies are, at present, ready for clinical use.
As a final caveat, any information derived from the frontal
EEG has the inherent limitation that the signal might not arise
from a true neural correlate of consciousness. Nonetheless,

the frontal EEG is what we have available at present, and it
behoves us to maximise its utility by interpreting all the
available informationdnot just the index.
Authors’ contribution
Concept: RDS, TJM
Writing of the paper: TJM, RDS
Declarations of interest
RDS is an editor of the British Journal of Anaesthesia. TJM has no
conflicts to declare.
References
1. Checketts MR, Alladi R, Ferguson K, et al. Recommenda-
tions for standards of monitoring during anaesthesia and
recovery. Anaesthesia 2016; 71: 85e93
2. APSF Committee on Technology. APSF-endorsed statement
on revising recommendations for patient monitoring during
anesthesia 2022. Available from: https://www.apsf.org/wp-
content/uploads/newsletters/2022/3701/APSF3701-2022-
02-a03-StatementPatientMonitoring.pdf. [Accessed 20
March 2023]
3. Sanders RD, Gaskell A, Sleigh J. Can use of frontal EEG
monitoring increase intraoperative connected conscious-
ness? Br J Anaesth 2018; 121: 191e3
4. Sanders RD, Mostert N, Lindroth H, Tononi G, Sleigh J. Is
consciousness frontal? Two perioperative case reports
that challenge that concept. Br J Anaesth 2018; 121: 330e2
5. Koch C, Massimini M, Boly M, Tononi G. Neural correlates
of consciousness: progress and problems. Nat Rev Neurosci
2016; 17: 307e21
6. Sergent C, Corazzol M, Labouret G, et al. Bifurcation in
brain dynamics reveals a signature of conscious process-
ing independent of report. Nat Commun 2021; 12: 1149
7. Casey CP, Tanabe S, Farahbakhsh Z, et al. Distinct EEG
signatures differentiate unconsciousness and disconnec-
tion during anaesthesia and sleep. Br J Anaesth 2022; 128:
1006e18
8. Gaskell AL, Hight DF, Winders J, et al. Frontal alpha-delta
EEG does not preclude volitional response during anaes-
thesia: prospective cohort study of the isolated forearm
technique. Br J Anaesth 2017; 119: 664e73
9. Hight D, Kreuzer M, Ugen G, et al. Five commercial ‘depth
of anaesthesia’ monitors provide discordant clinical rec-
ommendations in response to identical emergence-like
EEG signals. Br J Anaesth 2023; 130: 536e45
10. Purdon PL, Pierce ET, Mukamel EA, et al. Electroencepha-
logram signatures of loss and recovery of consciousness
from propofol. Proc Natl Acad Sci U S A 2013; 110: E1142e51
Editorial - 3
11. Hight D, Voss LJ, Garcia PS, Sleigh J. Changes in alpha
frequency and power of the electroencephalogram during
volatile-based general anesthesia. Front Syst Neurosci 2017;
11: 36
12. Kaiser HA, Peus M, Luedi MM, et al. Frontal electroen-
cephalogram reveals emergence-like brain activity
occurring during transition periods in cardiac surgery. Br J
Anaesth 2020; 125: 291e7
13. Eagleman SL, Drover CM, Li X, MacIver MB, Drover DR.
Offline comparison of processed electroencephalogram
monitors for anaesthetic-induced electroencephalogram
changes in older adults. Br J Anaesth 2021; 126: 975e84
14. Purdon PL, Pavone KJ, Akeju O, et al. The ageing brain:
age-dependent changes in the electroencephalogram
during propofol and sevoflurane general anaesthesia. Br J
Anaesth 2015; 115: i46e57
15. Messner M, Beese U, Romsto € ck J, Dinkel M,
Tschaikowsky K. The bispectral index declines during
neuromuscular block in fully awake persons. Anesth Analg
2003; 97: 488e91
16. Schuller PJ, Newell S, Strickland PA, Barry JJ. Response of
bispectral index to neuromuscular block in awake volun-
teers. Br J Anaesth 2015; 115: i95e103
17. Vassiliadis M, Geros D, Maria K. Awareness despite low
spectral entropy values. Anesth Analg 2007; 105: 535
18. Rampersad SE, Mulroy MF. A case of awareness despite an
‘adequate depth of anesthesia’ as indicated by a bispectral
index monitor. Anesth Analg 2005; 100: 1363e4
19. Avidan MS, Jacobsohn E, Glick D, et al. Prevention of
intraoperative awareness in a high-risk surgical popula-
tion. N Engl J Med 2011; 365: 591e600
20. Sanders RD, Tononi G, Laureys S, Sleigh JW. Unrespon-
siveness s unconsciousness. Anesthesiology 2012; 116:
946e59
21. Sanders RD, Gaskell A, Raz A, et al. Incidence of connected
consciousness after tracheal intubation: a prospective,
international, multicenter cohort study of the isolated
forearm technique. Anesthesiology 2017; 126: 214e22
22. Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P.
Bispectral analysis measures sedation and memory ef-
fects of propofol, midazolam, isoflurane, and alfentanil in
healthy volunteers. Anesthesiology 1997; 86: 836e47
23. Myles PS, Leslie K, Mcneil J, Forbes A, Chan MTV. Bispec-
tral index monitoring to prevent awareness during
anaesthesia: the B-Aware randomised controlled trial.
Lancet 2004; 363: 1757e63
24. Lee M, Sanz LRD, Barra A, et al. Quantifying arousal and
awareness in altered states of consciousness using inter-
pretable deep learning. Nat Commun 2022; 13: 1064
25. Casey CP, Tanabe S, Farahbakhsh Z, et al. Dynamic causal
modelling of auditory surprise during disconnected con-
sciousness: the role of feedback connectivity. Neuroimage
2022; 263, 119657