Volume 115, Number S1, July 2015

British Journal of Anaesthesia 115 (S1): i1i3 (2015)

doi:10.1093/bja/aev224

EDITORIALS

J. Kurata1,, * and H. C. Hemmings Jr2,

1
Department of Anesthesiology and Pain Clinic, Tokyo Medical and Dental University Hospital of Medicine,
1-5-45 Yushima, Bunkyo City, Tokyo 113-8519, Japan, and
2
Departments of Anesthesiology and Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York,
NY 10065, USA

*Corresponding author. E-mail: jkmane@tmd.ac.jp

The 9th International Symposium on Memory and Awareness in

Anesthesia (MAA9) was held in Tokyo, Japan on June 2023, 2014,
attracting over 70 delegates from around the world. It was chaired
by Jiro Kurata, from the Tokyo Medical and Dental University, and
was jointly sponsored by the British Journal of Anaesthesia to support research activities in the elds of awareness during anaesthesia, neurobiological mechanisms of general anaesthesia,
consciousness, and memory. This topic complements the recently published National Audit Project NAP5 survey of accidental
awareness under general anaesthesia conducted in the UK in
2012 and published in the British Journal of Anaesthesia last
year.13 The present British Journal of Anaesthesia special issue on
Memory and Awareness in Anaesthesia was planned by Hugh
Hemmings, a co-organizer of MAA9, to present the most current
ndings and views on topics from selected presentations during
the meeting, in addition to submissions in response to an open
call for papers. All the MAA9 abstracts are also included in this
special on-line-only issue. Details of the MAA9 programme can
be found at the conference website (http://maa9.umin.jp/).
The scope of previous MAA symposia has ranged from the
neuroscience of anaesthetic action, memory, and consciousness
to the clinical aspects of awareness during anaesthesia. The
MAA9 followed this tradition, while emphasizing the clinical aspects: epidemiology, diagnosis, prevention, and treatment of intraoperative awareness, with a conference slogan of Minding the
Mind of Subconscious Self. Although anaesthesiology has devoted tremendous efforts to studies of anaesthetic pharmacology
and the mechanisms of anaesthetic-induced unconsciousness,

which can be approached in a relatively direct manner through

behavioural analyses, it has paid much less attention to subconscious processes of mind. At least part of memory is formed in
the subconscious domain of mind,4 and for this reason could
be resistant to clinical ranges of general anaesthetics aimed to
produce elimination of conscious behaviour. The MAA9 was programmed to propose that anaesthesiology should now approach
the next stage, the care for the subconscious mind.
Detection of intraoperative awareness during anaesthesia
has historically been a major focus of research and technology
development in anaesthesiology. Currently, there are several
kinds of anaesthetic depth monitors, in addition to real-time
or simulated monitors of anaesthetic concentrations, available
in most operating theatres. Behaviour-based standardization of
mathematically processed EEG, cortical evoked potentials, or
both has attempted to turn probability of awareness into an
anaesthetic depth index, or a vital sign for consciousness. In recent years, such indices for anaesthetic depth have been tested
for efcacy in detecting intraoperative awareness compared
with anaesthetic concentration monitors, which is summarized
in the review by Mashour,5 along with some of the controversial
and established aspects of intraoperative awareness. Despite
such efforts, titrated administration of anaesthetics, using either
an anaesthetic depth or a concentration monitor, has not
been successful in decreasing the incidence of intraoperative
awareness with recall. No single reliable anaesthetic technique
or monitor is yet available to eliminate awareness with recall
during general anaesthesia.

Chair of the 9th International Symposium on Memory and Awareness in Anesthesia (MAA9); Co-Editor, Special Issue on Memory and Awareness in
Anaesthesia.
Co-Editor, Special Issue on Memory and Awareness in Anaesthesia.
The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
For Permissions, please email: journals.permissions@oup.com

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Memory and awareness in anaesthesia

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Editorials

intraoperative awareness can have signicant negative psychological impact on patients, which suggests that a more systematic
response and follow-up care are necessary.20
Amongst the irreplaceable roles of the MAA conferences has
been, and hopefully will continue to be, an investigation into subconscious processing of information during anaesthesia. Now
that we have abundant, if not sufcient, evidence for anaesthetic-induced unconsciousness, we should investigate further the
science of subconsciousness. The next meeting, MAA10, will continue this conversation around the clinical and basic science of
memory and awareness in anaesthesia, to be chaired by Professor Sinikka Mnte in Helsinki, Finland in 2017. Until the details
of MAA10 are ofcially announced, the MAA9 facebook page
(http://www.facebook.com/maa9.jp/) will remain a source of information on the development of MAA10. Please leave a comment on this page if you have suggestions or would like to be
included in the mailing list for MAA10.
We sincerely hope that this special issue, marking the up-todate knowledge and insights on memory and awareness in anaesthesia, will help to promote further scientic inquiries and
technological development to eliminate the most dreadful
complication of general anaesthesia: intraoperative awareness.
Caring for the whole human existence, conscious and subconscious, should continue to be the core mission of anaesthesiology. Finally, we would like to thank all the authors of these
excellent articles, all the attendees, support staff, and sponsors
of the MAA9, and Oxford University Press for realizing this special
issue.

Authors contributions
Wrote, edited, and approved the nal version; contributed equally to the work: J.K. and H.C.H.

Declaration of interest
J.K. is a member of the International Advisory Panel, Editorial
Board of Anaesthesia and an Associate Editor of Journal of Anesthesia. H.C.H. is an Editor of the British Journal of Anaesthesia and an
Editor of Anesthesiology.

Funding
Grants-in-Aid for Scientic Research (no. 26460695 to J.K.), Japan;
National Institutes of Health, Bethesda, MD, USA (H.C.H.).

References
1. Pandit JJ, Andrade J, Bogod DG, et al. 5th National Audit Project
(NAP5) on accidental awareness during general anaesthesia:
summary of main ndings and risk factors. Br J Anaesth
2014; 113: 54959
2. Cook TM, Andrade J, Bogod DG, et al. 5th National Audit Project
(NAP5) on accidental awareness during general anaesthesia:
patient experiences, human factors, sedation, consent, and
medicolegal issues. Br J Anaesth 2014; 113: 56074
3. Pandit JJ, Andrade J, Bogod DG, et al. 5th National Audit Project
(NAP5) on accidental awareness during general anaesthesia:
protocol, methods, and analysis of data. Br J Anaesth 2014;
113: 5408
4. Veselis RA. Memory formation during anaesthesia: plausibility of a neurophysiological basis. Br J Anaesth 2015; 115
(Suppl. 1): i13i19
5. Mashour GA, Avidan MS. Intraoperative awareness: controversies and non-controversies. Br J Anaesth 2015; 115
(Suppl. 1): i20i26

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A signicant concern is the increasing reliance on EEG-based

monitors of anaesthetic depth to titrate administration of anaesthetic agents. Some of the issues with using processed indices of
the EEG rather than the raw waveform are addressed in the review by Hagihira,6 along with editorial commentary by Veselis.7
Purdon and colleagues8 report profound age-dependent changes
in the EEG that also have important implications for depth-of-anaesthesia monitors relying on processed EEG signals. Greater
sensitivity to anaesthetics evident in the increased susceptibility
to burst suppression in the elderly7 is supported by animal studies that demonstrate delayed emergence and increased sensitivity to anaesthetics in old rats.9 This is highlighted in an editorial
by Hudson and Proekt.10 Age-dependent changes in the EEG response to anaesthesia also occur in children, as demonstrated
for sevourane by Akeju and colleagues;11 this phenomenon
has implications for EEG-based monitors of anaesthetic depth
in both the young and the elderly. The impact of the unique
pharmacological prole of ketamine on its EEG signature is
described in a study by Pal and colleagues,12 who show that ketamine, like other general anaesthetics, suppresses high-frequency
activity and promotes a breakdown in cortical coherence.
Reasons for failure of general anaesthesia in suppressing
memory and awareness could include technical problems or mishaps, such as an inadvertent discontinuation or a low concentration of general anaesthetic agent. Neuromuscular blocking
agents, which are non-hypnotics, could also conceal conscious
behaviour and affect reliability of EEG-based depth-of-anaesthesia monitors. These issues are highlighted in two studies by
Thomsen and colleagues13 14 from a Danish registry of patients
with documented butyrylcholinesterase ( plasma cholinesterase)
deciency, showing that prolonged paralysis due to impaired
elimination of esterase-dependent neuromuscular blockers (succinylcholine or mivacurium) markedly increased the likelihood
of awareness during emergence from anaesthesia, particularly
when neuromuscular function monitoring was not used. The importance of not withholding neuromuscular function monitoring
when paralytic drugs are used during anaesthesia is highlighted
in the editorial by Avidan and Stevens.15 An important limitation
of EEG-based depth-of-anaesthesia monitors is described by
Schuller and colleagues16 in a fascinating study of volunteer
anaesthetists who underwent intentional awake paralysis
using the isolated forearm technique to show that the bispectral
index monitor itself cannot always distinguish anaesthesia
from paralysis, the implications of which are highlighted in an
editorial by Schneider and Pilge.17 Use of the isolated forearm
technique as a monitor of depth of anaesthesia and as a research
tool into mechanisms of anaesthesia is presented in a thoughtprovoking debate and review by Pandit and colleagues.18
Not all known cases of intraoperative awareness with recall,
however, can be explained by such logical causes. Should we
now question the ability of general anaesthetics to produce unconsciousness and amnesia reliably? Targeting only conscious
behaviour might not necessarily provide reliable protection of
patients from traumatic memory of physical or psychological
injuries during surgery and anaesthesia. The mechanisms of
memory formation are reviewed by Veselis,4 while Pryor and colleagues19 used functional magnetic resonance imaging to show
that propofol suppresses emotional memory formation through
a hippocampal mechanism. Implicit memory formation during
anaesthesia remains understudied and poses a signicant problem that could be relevant to post-traumatic stress disorder, and
possibly, postoperative delirium and cognitive dysfunction. A
report from the Anesthesia Awareness Registry of the American
Society of Anesthesiologists indicates that explicit recall of

Editorials

14.

15.
16.

17.

18.

19.

20.

of neuromuscular monitoring in patients with butyrylcholinesterase deciency. Br J Anaesth 2015; 115 (Suppl. 1): i78i88
Thomsen JL, Nielsen CV, Palmqvist DF, Gtke MR. Premature
awakening and underuse of neuromuscular monitoring in a
registry of patients with butyrylcholinesterase deciency.
Br J Anaesth 2015; 115 (Suppl. 1): i89i94
Avidan MS, Stevens TW. The diving bell and the buttery. Br J
Anaesth 2015; 115 (Suppl. 1): i8i10
Schuller PJ, Newell S, Strickland PA, Barry JJ. Response of bispectral index to neuromuscular block in awake volunteers.
Br J Anaesth 2015; 115 (Suppl. 1): i95i103
Schneider G, Pilge S. Restrict relaxants, be aware, and know
the limitations of your depth of anaesthesia monitor. Br J
Anaesth 2015; 115 (Suppl. 1): i11i12
Pandit JJ, Russell IF, Wang M. Interpretations of responses
using the isolated forearm technique in general anaesthesia:
a debate. Br J Anaesth 2015; 115 (Suppl. 1): i32i45
Pryor KO, Root JC, Mehta M, et al. Effect of propofol on the
medial temporal lobe emotional memory system: a functional
magnetic resonance imaging study in human subjects. Br J
Anaesth 2015; 115 (Suppl. 1): i104i113
Kent C, Posner K, Mashour G, et al. Patient perspectives
on intraoperative awareness with explicit recall: report
from a North American anaesthesia awareness registry. Br J
Anaesth 2015; 115 (Suppl. 1): i114i121

British Journal of Anaesthesia 115 (S1): i3i5 (2015)

doi:10.1093/bja/aev223

What about ? Relationship between pain and EEG

spindles during anaesthesia
R. A. Veselis1,2
1

Department of Anesthesiology and Critical Care Medicine, Memorial SloanKettering Cancer Center, 1275 York Avenue,
New York, NY 10065-6007, USA, and
2
Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA
E-mail: veselisr@mskcc.org
The prodigy childrenof the EEG frequencyspectrumthese days are
and .13 As we wrestle with weighty concepts of consciousness,
memory, and anaesthetic effects thereon, the rst objective measure of brain activity is being scrutinized more closely for clues about
the underlying machinery. The most basic grammar used to communicate in EEG language refers to the different frequencies in
the EEG signal. This has its roots in the historical order of interest
in different EEG oscillations, documented as letters from the beginning portion of the Greek alphabet.4 Rhythms of different frequencies were noticeable to the naked eye in analog EEG signals, and
those most noticeable attracted our interest rst. This is somewhat
akin to contemporary astrophysicists still using references to the
constellations. There is nothing inherently wrong with this, as
long as one is aware of the history and is careful to avoid imbuing
mechanisms of action too closely to descriptive labels.
One important caveat with this analogy is that whereas the
borders between constellations are well dened, they are not so
with EEG frequencies. The frequency at which becomes , the
border of which embodies sleep spindles, is somewhat ill dened.

Thus, one persons (fast or high) might be anothers (slow or

low) . Current interest in rhythms centres on memory processes, but it should be remembered that has been related
to many other aspects of cognition (including movement) in
the past.5 Likewise, is studied to understand the processes
of consciousness, closely related to information transfer in the
brain.3 6 Thus, is of interest in how anaesthetics affect consciousness, or in other words, how anaesthetics work.7 In fact,
the denition of has been extended to higher frequency bands
to capture more of the EEG bandwidth as recording methods and
capacity for data storage and analysis improve.8 As with , ()
has been subdivided into various frequency bands, with sigma
a less frequently used term basically analogous to sleep spindles. Both refer to similar frequencies in the EEG, approximately
1214 Hz, though, again, these boundaries are porous.9 10 Greek
letter labels may be good shorthand, but the underlying principles of communication, network activity, and information content, and the underlying neurobiology that produces these
oscillations are really the important principles to focus on.

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6. Hagihira S. Changes in the electroencephalogram during anaesthesia and their physiological basis. Br J Anaesth 2015; 115
(Suppl. 1): i27i31
7. Veselis RA. What about ? Relationship between pain and EEG
spindles during anaesthesia. Br J Anaesth 2015; 115 (Suppl. 1):
i3i5
8. Purdon PL, Pavone KJ, Akeju O, et al. The aging brain: Age-dependent changes in the electroencephalogram during propofol and sevourane general anaesthesia. Br J Anaesth 2015; 115
(Suppl. 1): i46i57
9. Chemali JJ, Kenny JD, Olutola O, et al. Ageing delays emergence from general anaesthesia in rats by increasing anaesthetic sensitivity in the brain. Br J Anaesth 2015; 115
(Suppl. 1): i58i65
10. Hudson AE, Proekt A. Some heightened sensitivity. Br J
Anaesth 2015; 115 (Suppl. 1): i5i8
11. Akeju O, Pavone KJ, Thum JA, et al. Age-dependency of sevourane-induced electroencephalogram dynamics in children. Br J Anaesth 2015; 115 (Suppl. 1): i66i76
12. Pal D, Hambrecht-Wiedbusch VS, Silverstein BH, Mashour GA.
Electroencephalographic coherence and cortical acetylcholine
during ketamine-induced unconsciousness. Br J Anaesth 2015;
114: 97989
13. Thomsen JL, Nielsen CV, Eskildsen KZ, Demant MN, Gtke MR.
Awareness during emergence from anaesthesia: signicance

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