BJA Education, 21(4): 154e161 (2021)
doi: 10.1016/j.bjae.2020.12.001
Matrix codes: 1E06,
2A04, 3J02
Accidental awareness under general anaesthesia:
Incidence, risk factors, and psychological
management
M.C. Kim1,*, G.L. Fricchione1,2 and O. Akeju1
1
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA and 2Benson-Henry Institute
for Mind Body Medicine and the McCance Center for Brain Health, Harvard Medical School, Boston, MA,
USA
*Corresponding author. mckim@partners.org
Keywords: acute; intraoperative awareness; post-traumatic; stress disorders; traumatic
Learning objectives
By reading this article, you should be able to:

Describe the known risk factors for accidental
awareness under general anaesthesia (AAGA).

Recall the stress disorders associated with AAGA.

Detail the American Psychiatric Association’s
practice guidelines for psychopharmacological
and psychotherapeutic interventions for post-
traumatic stress disorder (PTSD).

Recount recommendations for management of
patients with AAGA.
Meerim Cindy Kim MD is an attending anaesthetist at Massachu-
setts General Hospital, and an instructor in anaesthesia at Harvard
Medical School. Her major clinical and research interests are
anaesthesia for neurosurgery and EEG monitoring for anaesthesia.
Gregory Fricchione MD is associate chief of psychiatry at the
Department of Psychiatry, Massachusetts General Hospital. He is
also the director for the Division of Psychiatry and Medicine and
Benson-Henry Institute for Mind Body Medicine at the McCance
Center for Brain Health.
Oluwaseun Akeju MD MMSc is the anaesthetist-in-chief at the
Massachusetts General Hospital and the Henry Isaiah Dorr Associate
Professor of Research and Teaching in Anaesthetics and Anaesthesia
at Harvard Medical School.
Accepted: 2 December 2020
© 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
For Permissions, please email: permissions@elsevier.com
Advance Access Publication Date: 21 January 2021
Key points

Patients that experience distress during AAGA are
prone to PTSD.

Evidence-based therapeutic management strate-
gies for AAGA-induced PTSD have been con-
strained by the relatively low incidence of AAGA.

Treatment with antidepressants in combination
with cognitive behavioural therapy is frequently
used to treat PTSD.
Accidental awareness during general anaesthesia (AAGA) is a
rare but severe complication of anaesthetic care. Despite ad-
vances in physiological monitoring and an improved under-
standing of the neural mechanisms underlying anaesthesia,
the incidence of AAGA has remained steady for several de-
cades.1 At present, there is a disparity between reports of
AAGA from patients (1e2 in 1000 general anaesthetics) and
from anaesthesia care providers (1 out of 15,000 general an-
aesthetics).2 The 5th National Audit Project (NAP5) of the
Royal College of Anaesthetists, the largest patient-centred
report on AAGA to date, examined more than 400 individual
experiences of AAGA and found considerable variation in the
incidence of AAGA across anaesthetic techniques.3
The long-term health-related consequences of AAGA can
be devastating. We note that 43% (15/35) of patients with
history of definite or possible AAGA in three major AAGA trials
including the B-Unaware (Anaesthesia Awareness and the
Bispectral Index) trial, the BAG-RECALL (BIS or Anaesthesia
Gas to Reduce Explicit Recall) trial, and the MACS (Michigan
154
 Accidental awareness under general anaesthesia

Table 1
Summarizes the key findings and limitations of 5 major AAGA trials. BIS (Bispectrial index), CI (Confidence interval), ARR (Absolute risk
reduction), NMB (Neuromuscular Blockade), NNTB (Number-needed-to-treat in order to benefit one person), MAC (Minimum alveolar
concentration).

Trials Number Target Incidence of Study design Statistical finding Findings/Limitations

of population AAGA (95% CI)
patients

B-Aware 2463 High risk for BIS group: 1/
Multicentre, randomised
(2004)15 AAGA 1225 (0.17%) controlled trial e BIS-
Routine care guided protocol (target
group: 40e60) vs routine care
11/1238 (0.91%) group

43% of patients
received propofol infusion

Brice interview

Committee of three
experienced anaesthetists
independently coded each
report as ‘awareness’,
‘possible awareness’, or
‘no awareness’
Fisher’s exact test,
BIS significantly reduced
P¼0.03 the incidence of AAGA.
ARR 0.14%e1.4%16
Unclear if statistical
NNTB difference was attributable
697 to7016 to BIS itself or to increased
vigilance towards AAGA
given constant monitoring
of BIS values compared
with routine care group.

Included 37 patients’
reports of memories
related to AAGA event.

Aftermath of AAGA and
long-term psychological
effects were not
mentioned.

The anxiety and
depression scores at 30
days postoperatively
between AAGA vs no
awareness groups were
similar for anxiety (P¼0$06)
and depression (P¼0.27).

Patients with confirmed
awareness reported lesser
satisfaction with care than
those without confirmed
awareness at both the 24 h
and 30 day interviews
(P<0.0001 for both).

B- 1941 High risk for BIS group: 2/
Single-centre RCT e No difference
Single-centre study failed
Unaware AAGA 974 (0.21%) BIS-guided protocol ARR to show statistical
(2008)4 MAC group: (target 40e60) vs target -0.57%e0.56%16 difference.
2/967 (0.21%) MAC protocol (0.7e1.3) NNTB
Included 16 patients’

Only Inhaled ∞ to 17916 reports of memories
anaesthetics were used related to AAGA event.

Brice interview
The study coordinator

Committee of three offered all patients who
experienced reported such memories
anaesthetist referral for counselling.
independently coded each
Aftermath of AAGA and
report as ‘awareness’, long-term psychological
‘possible awareness’, or effects were not
‘no awareness’ mentioned.

BAG- 5713 High risk for BIS group: 8/
Multicentre, No difference
Despite being a
RECALL AAGA 2861 (0.28%) international, ARR multicentre, international
(2011)5 MAC group: randomised controlled e0.49%e0.02%16 study, failed to show
2/2852 trial e BIS-guided proto- NNTB statistical difference.
(0.0.07%) col (target 40e60) vs ∞ to 467316
Every patient who reported
target MAC protocol AAGA were offered referral
(0.7e1.3) to a psychologist.

Only Inhaled
Aftermath of AAGA and
anaesthetics were used long-term psychological

Brice interview effects were not

Committee of three mentioned.
experienced anaesthetist
independently coded each
report as ‘awareness’,
‘possible awareness’, or
‘no awareness’

MACS 18,836 of All surgical
Multicentre, No difference
Study was terminated after
(2012)6 30,000 patients international, prespecified interim
goal randomised controlled analysis determined no
reached trial e BIS-guided proto- significant difference
col (target 40e60) between two groups.
(continued on next page)

BJA Education - Volume 21, Number 4, 2021 155

Accidental awareness under general anaesthesia

Table 1 (continued )

Trials Number Target Incidence of Study design Statistical finding Findings/Limitations

of population AAGA (95% CI)
patients

vs target MAC protocol

(0.7e1.3).

Included patients who
received propofol and
dexmedetomidine
infusion

Brice interview

NAP5 300 Individuals ~1:19,000 in all
Voluntary anonymous The incidence of
Largest survey conducted
(2014)3 who anaesthetics survey of AAGA in UK certain/probable on AAGA, based out of UK
experienced ~1:8600 when and Ireland and possible and Ireland.
AAGA and NMB was used
Relied on spontaneous accidental
141 reports of AAGA of
volunteered to ~1:8600 in self-reports of AAGA by awareness cases certain/probable and
report their cardiothoracic patients via a secure on- was ~1:19,600 possible cases were
experience anaesthesia line portal for 1 yr anaesthetics examined.

Incidences were
Psychological experience
~ 1:670
estimated using reports of AAGA was reported:
Caesarean
of accidental awareness half described AAGA in
section
as the numerator, and a neutral way, the other half
parallel national experienced distress.
anaesthetic activity Distress was likely in
survey to provide setting of paralysis.
denominator data.
Long-term psychological

Each case was effects were identified.
reviewed by a panel of 41% of AAGA patients
experts and classified on experienced moderate to
type of report and degree severe long-term sequelae.
of evidence
Early reassurance and
active early support may
be the best prospect of
mitigating impact of AAGA
and structured pathway is
proposed.

AAGA, accidental awareness under general anaesthesia; ARR, ; BIS, bispectral index; MAC, ; NMB, ; NNTB.

Awareness Control Study) trial, met the Diagnostic and Statis-
tical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria
for the diagnosis of post-traumatic stress disorder (PTSD).4e7
It is important to understand the risk factors that predis-
pose to AAGA. This knowledge is expected to guide our clinical
practice, given that 73.6% (81/110) of the certain/probable re-
ports of AAGA cases examined by NAP5 were considered
preventable.8 Because studies of AAGA have typically focused
on risk factors and prevention strategies, insights into the
pathophysiology of AAGA-induced stress disorders are
limited. Studies to inform evidence-based management of
AAGA-induced stress disorders have also been limited by the
relatively low-frequency occurrence of AAGA.
This review explores the psychological implications of
AAGA and summarises current recommendations for man-
agement of AAGA. The American Psychiatric Association’s
practice guidelines for psychopharmacological and psycho-
therapeutic interventions that have been extrapolated to pa-
tients who have experienced AAGA are discussed. Lastly,
current recommendations for anaesthetists on the immediate
management of patients who have experienced AAGA are
addressed.
Incidence
Although the reported incidence of AAGA has been consistent
at 1e2 out of 1000 general anaesthetics for the past decades,
there are substantial variations between subspecialties and
groups of patients. It is well established that the incidence of
AAGA is significantly higher in paediatric, obstetric, and cardiac
anaesthesia.9e11 Interestingly, the incidence of AAGA is also
heavily skewed towards women. A review of litigations related
to AAGA in the UK showed that 117 out of 159 (74%) of AAGA
claims were from women, and two thirds were related to ob-
stetric care.12 Similarly, in the USA, closed claims data of AAGA
revealed that 61 out of 79 (77%) claims were also from women.13
These numbers indicate that there may be a sex susceptibility to
AAGA or possibly, a reporting bias. Genetic predisposition to
AAGA has also been suggested. For example a secondary anal-
ysis of 26,490 patients in the B-Unaware trial, BAG-RECALL trial,
and MACS trial revealed that patients with a history of AAGA
were five times more likely to experience AAGA again (relative
risk¼5.0; 95% CI, 1.3e19.9).14 Table 1 summarises the key find-
ings and limitations of five major studies of AAGA.
The incidence of AAGA in NAP5 (~1 out of 19,600) was
remarkably lower than in previous reports. Patients in the
NAP5 study actively sought to report their personal experi-
ence of AAGA via a secure online portal. The authors of NAP5
argued that the occurrence of AAGA reported to NAP5 may be
more relevant in clinical practice, as patients chose to report
the event spontaneously. Even if differences in the incidence
of AAGA from NAP5 and the Brice interview cannot be
explained easily, the importance of patient-reported and
thoroughly investigated incidences of AAGA should not be
undervalued.17

156 BJA Education - Volume 21, Number 4, 2021

 Accidental awareness under general anaesthesia

a Primary brain regions involved b Fear conditioning

in regulation of fear and threat responses Fear
R (signals to hypothalamus
and brainstem)
Conditioned
stimulus CORONAL
CeM SECTION
dmPFC ACC CeL
ITC

vmPFC BA
LA
Midline
OFC
Amygdala
Amygdala Hippocampus
Unconditioned
stimulus

c Regulatory relationships between the mPFC, d Connectivity of the amygdala and associated
hippocampus, and amygdala fear or panic response

Lateral hypothalamus increased heart rate;

increased blood pressure
Dorsal vagal nerve bradycardia; ulcer disease
Amygdala
mPFC Parabrachial nerve panting; respiratory distress

Basal forebrain arousal; hypervigilance;

attention
Nucleus reticularis increased startle response
pontis caudalis

Hippocampus Central gray area freezing; decreased

social interaction
Paraventricular nerve corticosteroid release

Fig 1 Schematic diagram of neural circuitry Involved in fear conditioning and post-traumatic stress disorder. A, Primary brain regions involved in regulating fear
and threat responses are the amygdala, the hippocampus, and the medial prefrontal cortex, which comprises dorsal (dmPFC) and ventral (vmPFC) subdivisions;
the orbitofrontal cortex (OFC); and the anterior cingulate cortex (ACC). B, Amygdala-specific circuits that are involved in fear conditioning. The sensory infor-
mation representing the conditioned stimulus (e.g. previously neutral stimulus such as driving a car) is integrated within the amygdala with the unconditioned
stimulus information (e.g. a traumatic event such as an explosion in a car). The amygdala is central in the neural circuit involved in regulating fear conditioning. In
general, input to the lateral nucleus (LA) of the amygdala leads to learning about fear, whereas the central amygdala (lateral [CeL] and medial [CeM] subdivisions)
is responsible for sending output signals about fear to the hypothalamus and brainstem structures. The intercalated cell masses (ITC) are thought to regulate
inhibition of information flow between the basal nucleus (BA) and central amygdala. C and D, Interactions between components of the mPFC and the hippo-
campus constantly regulate the amygdala’s output to subcortical brain regions activating the fear reflex. The mPFC (in particular, the vmPFC) is classically thought
to inhibit amygdala activity and reduce subjective distress, while the hippocampus plays a role both in the coding of fear memories and also in the regulation of
the amygdala. The hippocampus and mPFC also interact in regulating context and fear modulation. Figure 1 adapted from Ross et al.21

Risk factors The anaesthetic drug type, or perhaps the use of anaes-
thetic drugs that are typically reserved for emergencies,
To obtain comparator data, NAP5 used information from a
increased the risk of AAGA. Ketamine, etomidate and thio-
nationwide activity survey as denominator data for AAGA
pental were used most often in the AAGA activity survey
cases. The NAP5 investigators reported a 10-fold increase in
cohort, with ratios of 17.2, 14.3, and 8.2, respectively, whereas
the incidence of AAGA in obstetric patients and a 2.5-fold in-
propofol’s ratio of use was 0.9. The incidence of AAGA
crease in cardiothoracic patients. It appeared that female sex
increased from 1 out of 135,000 general anaesthetics to 1 out of
increased susceptibility as 91 out of 141 (65%) cases of AAGA
8200 general anaesthetics when neuromuscular blocking
involved female patients. Obese patients were three times
drugs were used. Importantly, monitoring and reversal of
more likely to experience AAGA, and the use of total intra-
neuromuscular block were less frequent in those with AAGA.
venous anaesthesia was overrepresented in patients who
Processed electroencephalogram (pEEG) monitoring was used
experienced AAGA (18% in AAGA cases vs 8% overall).

BJA Education - Volume 21, Number 4, 2021 157

Accidental awareness under general anaesthesia
in only 2.8% of all general anaesthetics in the activity survey,
and AAGA occurred despite use of pEEG monitor in 6 out of 141
(4.3%) cases of AAGA. However, it is unclear whether the
anaesthetists had access to the raw EEG or spectrogram for
anaesthetic state monitoring. Owing to limited usage, the
NAP5 investigators were not able to derive a meaningful sta-
tistical analysis between pEEG use and AAGA.
The patient’s experience of accidental
awareness during general anaesthesia
Spontaneous reports of AAGA did not occur routinely after the
precipitating event. Only 47 out of 141 (33%) reports were
made on the day of the surgery and less than half within the
first 24 h. Interestingly, only 35 out of 141 (25%) reports were
made to the anaesthetist who took care of the patient. Many
patients first reported AAGA during preparations for a sub-
sequent procedure, as patients became understandably
anxious about having general anaesthesia. These findings
highlight the need to perform postoperative checks on pa-
tients and may explain the disparity between patients’ and
anaesthetists’ reports of AAGA. Twelve patients (11%) sub-
mitted a formal complaint to the hospital, and 8 (6%) initiated
legal action.
Patients’ experiences of AAGA varied. NAP5 found that in
47% of AAGA cases, the recall of AAGA was described in a
neutral way, involving few isolated aspects of the experience,
such as auditory and tactile memory. However, the other 53%
of the AAGA events were associated with distress. The pri-
mary causes of distress were paralysis and pain. Not sur-
prising, all forms of distress were strongly associated with
long-term psychological consequences, such as flashbacks,
insomnia, fear of future surgery, and PTSD.
Psychophysiological mechanisms of PTSD
The alert, non-stressed brain benefits from a topedown
management system, such that the medial prefrontal cortex
(mPFC) down-regulates amygdala-driven fear conditioning
through axonal stimulation of inhibitory g-aminobutyric
interneurones in the basolateral region of the amygdala.18 In
contrast, the stressed brain is marked by a diminished ca-
pacity of the mPFC and the hippocampus to act as checkpoints
on the excitatory flow that emerges from the amygdala. This
leads to a bottomeup system, characterised by more reflexive
and habitual responses by the primitive brain circuits in the
limbic system.19 Neuroimaging data on PTSD neurocircuitry
supports the importance of the inhibitory control of the mPFC
over the amygdala by showing that a diminution in mPFC
function is associated with the heightened amygdala activity
seen in PTSD.20 To our knowledge, changes in neural structure
and functional connectivity have not yet been investigated in
subjects with AAGA compared with matched controls using
neuroimaging. Figure 1 illustrates the neural circuitry
involved in fear conditioning and PTSD.
General anaesthesia and neural circuitry of PTSD
Inhibition of long-term potentiation of the g-aminobutyric
acid type A receptor in the hippocampus and other parts of the
medial temporal lobe memory system e amygdala and the
hippocampal region including perirhinal, entorhinal, and
parahippocampal cortices e are associated with amnesia
during anaesthesia.22 AAGA may result in a net effect
158 BJA Education - Volume 21, Number 4, 2021
summarised by a failure to downregulate glutamatergic and
norepinephrine pathways emanating from the amygdala.
Moreover, painful stimuli may further increase amygdala ac-
tivity. A putative downstream effect of increased amygdala
output leads to activation of hypothalamic and brainstem
circuits underlying high arousal fighteflightefreeze and
behavioural inflammatory response syndromes. Hence, the
amygdalar activity surge during AAGA may lay down a per-
manent emotionally traumatic memory (PTSD) through exci-
totoxic long-term potentiation. 23
Psychological assessment and diagnosis
Patients who experience AAGA are often traumatised. Pa-
tients in the NAP5 study described feelings of panic, extreme
fear, dissociation, suffocation, and fear of dying. In some, the
distress persisted with long-term symptoms of post-
traumatic stress. The distress of AAGA may emerge soon af-
ter the event, qualifying it as an acute stress disorder (ASD).
The presence of nine symptoms or more from the five
categories of intrusion, negative mood, dissociation, avoid-
ance, and arousal is required to make the diagnosis of ASD,
with symptoms beginning or worsening after the traumatic
event(s) occurred. The diagnosis of ASD ranges between 3
days and 1 month after exposure to the traumatic event. Sleep
disturbance (e.g. difficulty falling or staying asleep, restless
sleep), irritable behaviour, and angry outbursts (with little or
no provocation) that are typically expressed as verbal or
physical aggression toward people or objects are seen in ASD.
In addition, patients may display hypervigilance, concentra-
tion difficulties, and an exaggerated startle response.
Post-traumatic stress disorder is diagnosed when these
symptoms last for more than 1 month after a traumatic event.
Some patients do not initially present with PTSD, making the
diagnosis challenging. The exposure scenario for PTSD is the
same as in ASD. However, the traumatic event is persistently
re-experienced with upsetting memories, nightmares, flash-
backs, distress after traumatic reminders, and physical reac-
tivity after exposure to trauma reminders.
The Psychological Sequelae of Surgery Study (Psych SOS)
was a prospective 2 yr cohort study involving participants of
three AAGA prevention trials: B-Unaware trial, BAG-RECALL
trial, and MACS trial. 24 The study confirmed that experi-
encing AAGA substantially increased the risk of PTSD. The
risk factors for post-surgical PTSD included poor social sup-
port; history of PTSD; prior mental health treatment; dissoci-
ation related to the surgery; perceiving that one’s life was in
danger during surgery; and intraoperative awareness. Recog-
nising these risk factors during patient screening can be
useful for promoting early diagnosis and treatment referrals.
Management
To our knowledge, there are no specific treatment guidelines
for AAGA. Instead, treatment recommendations have been
extrapolated from our current understanding of general PTSD.
The American Psychiatric Association published treatment
guidelines for ASD and PTSD in 2004 with updates in 2014. 25
There is no evidence-based psychopharmacological recom-
mendation that prevents ASD and PTSD in patients at risk.
Treatment with selective serotonin reuptake inhibitors (SSRIs)
can be used for both ASD and PTSD. SSRIs are recommended
as first-line medication for PTSD because they can reduce
symptoms of re-experiencing, avoidance, numbing, and
 Accidental awareness under general anaesthesia

Table 2
Summarises the key findings and limitations of the meta-analyses on management of PTSD. RCTs (Randomised controlled trials), SMD
CI, confidence interval; PTSD, post-traumatic stress disorder; RCTs, Randomised controlled trials; SMD, Standardised mean difference.

Meta-analysis Method Data Findings Limitations

Psychological RCTs that involved 4190 patients
Patients with PTSD
Network meta-analysis
interventions psychological 66 trials benefit from assumes included trials
Gerger and interventions for adults Intervention categories psychological are drawn from the same
colleagues26 with PTSD 1. Cognitive behavioural interventions. population.
therapy
There is no evidence that
Did not examine possible
2. Cognitive therapy one intervention is moderating effects of
3. Eye movement superior than another. patient characteristics,
desensitisation such as type of trauma,
4. Exposure therapy veterans, or civilian,
5. Other psychological chronicity of symptoms.
interventions
6. Supportive therapies
7. Stress management

Pharmacological RCTs that involved any 6189 patients
Interventions pharmacological 51 trials
Cipriani and intervention or placebo as Pharmacological
colleagues27 oral therapy for adults medications:
with PTSD Desipramine, fluoxetine,
paroxetine, phenelzine,
risperidone, sertraline,
venlafaxine, phenelzine,
mirtazapine, olanzapine,
brofaromine,
amitriptyline, topiramate,
imipramine, nefazodone,
NK1R antagonist,
guanfacine, tiagabine,
prazosin, bupropion,
divalproex, citalopram,
lamotrigine, nefazodone
Comparison of RCTs that compares 922 patients
psychotherapeutic, outcomes and 12 RCTs
pharmacological acceptability of 23 direct comparisons
and combination psychotherapeutic and between
treatment pharmacological psychotherapeutic and
Merz and treatments and their pharmacological
colleagues28 combination in adults treatments or their
with PTSD combinations
Outcome analysis:
1. Comparative benefit
between 2 treatment
approaches to PTSD
symptom improvement
2. Comparative
acceptability of the
treatment approaches,
as indicated by patient
drop-out rates before
treatment termination

Desipramine, fluoxetine,
paroxetine, phenelzine,
risperidone, sertraline,
and venlafaxine were
more effective than
placebo.

Phenelzine was better
than many other active
treatments and was the
only drug, which was
significantly better than
placebo in terms of
decreasing drop-out rates
(odds ratio¼7.50; 95% CI,
1.72 to 32.80).

Divalproex had overall
the worst ranking.

Psychotherapeutic
treatments showed
greater benefit than
pharmacological
treatments in both
network (SMD, 0.83; 95%
CI, 1.59 to 0.07) and
pairwise (SMD, 0.63; 95%
CI, 1.18 to 0.09, 3 RCTs)
meta-analyses.

However, combined
treatments were
associated with better
outcomes than
pharmacological
treatments in long-term
network meta-analysis
(SMD, 0.96; 95%
CI, 1.87 to 0.04), but not
in the pairwise meta-
analysis, which included
2 RCTs (SMD, 1.02; 95%
CI, 2.77 to 0.72).

No evidence of
differences in
acceptability of all 3
approaches.

Network meta-analysis
assumes included trials
are drawn from the same
population.

Most trials did not report
adequate information
about randomisation and
location concealment.

Findings only apply to
acute phase of PTSD.

Evidence seems to support
the use of
psychotherapeutic
approach as first-line
treatment for PTSD, but
combined treatment of
both psychotherapeutic
and pharmacological
treatments was superior in
the long term.

Study included few (12)
comparative RCTs for the
short-term analyses, and
even fewer (6) RCTs for
long-term analyses. Scar-
city of long-term findings
limit conclusions.

hyperarousal. SSRIs are also effective for psychiatric disorders
that frequently coexist with PTSD (e.g. depression, panic dis-
order, social phobia, and obsessive-compulsive disorder).
They may reduce symptoms such as suicidality, impulsivity,
and aggression that complicate the management of PTSD.
They also are generally well tolerated, although with
continued use, adverse effects may occur on discontinuation.
Other antidepressants can also be beneficial. Benzodiazepines
may reduce acute anxiety and help with sleep, but they have
not been establised to prevent ASD or PTSD, or treat the core
symptoms of PTSD. Caution is warranted given their potential
for abuse. Anticonvulsants such as divalproex, carbamaze-
pine, topiramate, and lamotrigine may help treat re-
experiencing symptoms of nightmares and flashbacks. The

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Accidental awareness under general anaesthesia
atypical antipsychotic medications including olanzapine,
quetiapine, and risperidone may be helpful in some patients.
These drugs may be also indicated for patients with comorbid
psychotic disorders or when first-line approaches have been
ineffective in controlling symptoms. Alpha2-adrenergic ago-
nists and a1-adrenergic blockers may also provide symptom-
atic relief.
Early supportive psychotherapeutic interventions, along
with psychoeducation and case management that encourage
reliance on inherent resilience and good sound judgement,
can be very beneficial after acute trauma. This is because they
promote engagement in ongoing care and can lead to the use
of appropriate treatments. Patients diagnosed with ASD and
PTSD may also benefit from cognitive behavioural therapy
with an exposure component. Eye movement desensitisation
and reprocessing, which includes a brief, interrupted
exposure-based therapy, directed eye movements, along with
recall and venting of traumatic memories in the setting of
relaxation response elicitation, may also be helpful. Stress
inoculation, imagery rehearsal, and prolonged exposure
techniques may reduce PTSD-associated anxiety and avoid-
ance symptoms. Present-centred and trauma-focused group
therapies may also reduce the severity of symptoms. Psy-
chological debriefing is not recommended as there is no evi-
dence to suggest it is effective in preventing PTSD.
There have been three recent meta-analyses of data on the
management of PTSD. The first focused on psychological in-
terventions for adults with PTSD.26 The second focused on
pharmacological treatment.27 The third compared outcomes
and acceptability of psychotherapeutic and pharmacological
treatments and their combination in adults with PTSD.28 Ac-
cording to these meta-analyses, patients with PTSD clearly
benefit from psychological interventions, although there is no
evidence that one intervention is superior to another. Desipra-
mine, fluoxetine, paroxetine, phenelzine, risperidone, sertraline,
and venlafaxine were more effective than placebo for symp-
tomatic PTSD. Thus, evidence supports a choice of psychother-
apeutic approaches as first-line treatments for PTSD. It is notable
that treatment combining both psychotherapy and psycho-
pharmacology was superior in the long term. Table 2 summa-
rises the key findings and limitations of these meta-analyses.
The NAP5 awareness support pathway emphasises the
importance of: (i) face-to-face postoperative meeting with
patients that experience AAGA; (ii) early consultation with a
psychiatrist or psychologist and early assessment of flash-
backs, nightmares, new level of anxiety, and depressed mood;
and (iii) active follow-up at 2 weeks to assess for new or
ongoing needs for treatment referrals.
The NAP5 was a large-scale survey that characterised the
incidence of AAGA in the UK and Ireland. Thus, extrapolating
the findings of NAP5 outside of the UK and Ireland warrants
careful consideration.29 This is because cultural and societal
norms, which can fundamentally shape patients’ expecta-
tions of care may vary between different populations.
Conclusions
Accidental awareness under general anaesthesia is associated
with ASD and PTSD in patients who experience distress, such
as paralysis and pain during the event. However, evidence-
based therapeutic management strategies for ASD and PTSD
have been constrained by the relatively low incidence of
AAGA. Thus, treatment strategies are based on extrapolations
from patients with PTSD that is not associated with AAGA.
160 BJA Education - Volume 21, Number 4, 2021
Because significant depression affects 30e50% of patients
diagnosed with PTSD, drug treatment with antidepressants in
combination with cognitive behavioural therapy can be
especially helpful.30 All reports of AAGA should be taken very
seriously and institutional guidelines should be in place to
follow the NAP5 awareness support pathway. Anaesthetists
should be aware of the risk factors for AAGA and choose their
anaesthetic plan carefully, especially regarding use of neuro-
muscular blocking drugs and TIVA. Future prevention
research might study the effects of targeted psychological
therapies in patients at risk for post-surgical PTSD.
Declaration of interests
The authors declare that they have no conflicts of interest.
MCQs
The associated MCQs (to support CME/CPD activity) will be
accessible at www.bjaed.org/cme/home by subscribers to BJA
Education.
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