Seminars in Anesthesia, Perioperative Medicine and Pain (2006) 25, 211-218

Awareness during general anesthesia: concepts and

controversies
Stuart A. Forman, MD, PhD
From the Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston,
Massachusetts.
KEYWORDS:
Awareness;
Recall;
General anesthesia;
Mechanism;
Electroencephalography;
Risk factors

Unintended awareness with recall is estimated to occur during about 1 in every 750 general anesthetics.
Patients experiencing intraoperative awareness may develop symptoms of post-traumatic stress disorder. To understand how awareness during general anesthesia occurs, its risk factors, strategies for
prevention, and the potential role of various drugs used during anesthesia, I begin with a brief review
of research on how and where anesthetics suppress different central nervous system functions. I critique
the major clinical studies on intraoperative awareness, discussing a number of uncertainties arising from
limitations in the scientific methods applicable in this setting. Controversies in this topic are due in part
to inconsistent and inadequate data on the impact of awareness events on patients, and divergent views
about the value of encephalographic monitoring. I also outline strategies for preventing intraoperative
awareness and managing cases when they occur.
2006 Elsevier Inc. All rights reserved.

In 1845, Horace Wells attempted to demonstrate nitrous

oxide anesthesia to physicians at Massachusetts General
Hospital in Boston, but his patient moved and cried out.
Surgeons observing the procedure considered Wells demonstration a failure, although the patient had no recall of his
operation. A year later, when W.T.G. Morton demonstrated
the use of ether in the same venue, surgeons observing the
procedure considered it a groundbreaking success. Nonetheless, Mortons patient, Gilbert Abbot, reported that he
had been aware during his surgery, while experiencing no
pain.1 These two early cases demonstrate the often contradictory goals that create a challenge for anesthetists: the
surgeons primary requirement of an anesthetic is that the
patient be immobile, whereas patients want to be oblivious
of their surroundings and the trauma inflicted on their bod-

Address reprint requests and correspondence: Stuart A. Forman, Department of Anesthesia and Critical Care, CLN-3, Massachusetts General
Hospital, Fruit Street, Boston, MA 02114.
E-mail: saforman@partners.org.

0277-0326/$ -see front matter 2006 Elsevier Inc. All rights reserved.
doi:10.1053/j.sane.2006.09.004

ies. From a patients perspective, Wells anesthetic may be

considered more successful than Mortons!
During general anesthesia, distinct neural functions are
dynamically suppressed to varying degrees. If the anesthetic
dosage is sufficiently light and/or the patient is resistant to
the drug effects, awareness and recall of intraoperative
events may occur. It may be particularly difficult for anesthetists to discern that a patient is aware when muscle
relaxants are used to provide optimal surgical conditions.
Awareness during general anesthesia is a problem that is
receiving increased attention from patients, clinicians, and
researchers. In 2004, the Joint Commission on Accreditation of Hospital Organizations (JCAHO) issued a Sentinel
Alert encouraging greater attention to this problem.2
This review aims to explain how and why awareness
during general anesthesia occurs. We begin by summarizing
research on the multiple actions of general anesthesia,
which are mediated by different parts of the central nervous
system. We will review clinical research on awareness during
general anesthesia, with an emphasis on recognizing high-risk
patients and strategies for preventing this problem. Controver-

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Seminars in Anesthesia, Perioperative Medicine and Pain, Vol 25, No 4, December 2006

sies regarding clinical data on the incidence and impact of

awareness events, and the value of anesthetic-depth monitoring
during general anesthesia will also be discussed.

Anesthetic actions and anatomic substrates

To non-anesthetists, it seems surprising that patients can be
aware during a general anesthetic, because the uninformed
view is that general anesthesia is an all-or-nothing affair.
Until recently, this view was also held by many anesthetists
and researchers, who simply defined anesthesia as a state
where experimental subjects were unresponsive to stimuli.
This concept also extended to hypotheses on the mechanism
of general anesthesia; the Unitary Hypothesis, first proposed
by Claude Bernard in the 19th century and a foundation for
research well into the 20th century, proposed that all general
anesthetic drugs act via a common mechanism. We now
know that both of these ideas are vast oversimplifications.
General anesthetics affect a wide variety of neural functions, suppressing different neural circuits at different concentrations. Although there is no established consensus defining general anesthesia, the most important therapeutic
actions of all general anesthetics include suppression of
memory, awareness (consciousness), and movement. Suppression of these three central nervous system (CNS) functions occurs at different anesthetic concentrations. In addition, each of these anesthetic-sensitive actions is controlled
by different neural circuits in the CNS, which are also
anatomically distinct (Figure 1). There is now convincing
evidence that movement in response to pain (the MAC
endpoint) is suppressed by anesthetic effects that are almost
entirely within the spinal cord,3,4 whereas inhibition of
awareness and memory are due to effects on different brain
circuits.
Different general anesthetics also act via distinct mechanisms at the molecular level. Many intravenous and volatile anesthetics affect the CNS by enhancing the activity of
gamma-aminobutyric acid type A (GABAA) receptors,
which are the dominant inhibitory neurotransmitter-activated ion channels in the brain. Other general anesthetics,
notably nitrous oxide and ketamine, do not affect GABAA
receptors, but inhibit excitatory neurotransmission associated with glutamate and acetylcholine receptors.5,6 Other
molecular targets, some not yet identified, also contribute to
the therapeutic and toxic actions of general anesthetics.

Assessment of anesthetic depth: how do we

know how much is enough?
Anesthetic depth can be defined by the intensity of stimulus
that elicits a response from the patient (see Figure 1). Surgical anesthesia is traditionally defined by suppression of
movement in response to surgical pain. Movement after an
incision is suppressed in half of subjects at the Minimum

Figure 1 A functional-anatomic model of general anesthesia.

(Top) The figure depicts the brain and spinal cord as separate, in
order to emphasize the fact that different anesthetic actions are
mediated by different regions of the nervous system. (Bottom)
Critical neural functions that are suppressed by general anesthesia
are listed below the corresponding CNS structure and arranged
according to the concentration of anesthetic (increasing from bottom to top) required for suppression. The standard anesthesia
potency scalars MAC, MAC-Awake, and MAC-BAR are depicted
in rank order. The distance below the corresponding lines at these
concentrations correlates with the probability of suppression of
neural functions. Note that sensory transduction (including pain),
transmission, and primary sensory perception are intact, even at
high anesthetic concentrations. At low anesthetic concentrations,
painful peripheral stimuli can cause cortical arousal, increasing
MAC-awake. Reducing peripheral inputs with peripheral nerve or
neuraxial blocks will have a converse action. Analgesic drugs will
attenuate the effects of pain on the cortex, whereas others, including some beta agonists, can directly activate the cortex and thereby
increase MAC-awake.

(actually Median) Alveolar Concentration (MAC).7 Deeper

planes of general anesthesia may suppress autonomic responses to extremely painful stimuli, which is quantified for
some drugs as MAC-BAR (MAC-Blockade of Autonomic
Reflexes). Perceptive awareness, functionally defined as the
ability to perceive non-painful stimuli, interpret them, and
respond appropriately, is suppressed at MAC-Awake,8
which is about one-third of MAC for volatile agents and for
N2O is about 2/3 MAC (0.7 atm).9 Memory implies both
the acquisition and retention of information for later recall.6
With the inhaled anesthetics, amnesia is produced at lower
concentrations than hypnosis.9
Ensuring adequate anesthesia delivery would be easier if
every patient was equally sensitive to anesthetic drugs.
However, there is large patient-to-patient variability. Some
factors underlying these variations are known. For both
MAC and MAC-Awake endpoints, older patients as a group
require less anesthetic than younger patients, and core temperature influences sensitivity to anesthetics in a predictable
fashion.10 Chronic exposure to neuro-depressants (eg, alco-

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Awareness During General Anesthesia

hol, barbiturates, benzodiazepines, some anti-seizure drugs,

and opiates) may induce resistance to general anesthetics,
whereas acute exposure to neuro-modulators (eg, cocaine
versus alcohol) can shift anesthetic requirements upward or
downward. Identifying these factors is helpful, but precisely
predicting individual sensitivity to anesthetics remains impossible, because there are many additional factors (including genetic variations) that are currently unknown and not
revealed by routine pre-anesthetic evaluation.
Moreover, adequate anesthetic depth is a moving target.
Factors such as anxiety and pain alter patients sensitivity to
anesthetics, so that MAC and MAC-Awake measured in
volunteers may not be valid for many surgical patients.
Increased surgical pain increases MAC and also increases
MAC-awake via ascending spinothalamic and thalamocortical activation. Painful stimuli also may reverse memory
suppression induced with light anesthesia.11 In contrast,
neuraxial blockade reduces spinothalamo-cortical stimulation, reducing MAC (tested in cranial nerves) and decreasing benzodiazepine and volatile anesthetic requirements for
sedation.12,13 Pharmacologic interventions that are common
during anesthesia may also influence CNS activity and
therefore the depth of anesthesia. Direct thalamocortical or
cortical stimulation may occur in the presence of epinephrine, ephedrine, dopamine, and other adrenergic stimulants
that cross the blood brain barrier.14 MAC-awake may also
be reduced in the presence of beta-blockers.15
Assessment of patient responses to various stimuli was
the common practice up through the 1960s, when general
anesthesia was delivered almost exclusively via inhalation
of a few volatile agents, with or without nitrous oxide, to
spontaneously breathing patients. The introduction and
widespread use of muscle relaxants as adjuncts to general
anesthesia dramatically changed clinical practice and created new unexpected problems.
First, muscle relaxants produce an immobile patient and
optimal surgical conditions, while enabling anesthetists to
use lighter anesthesia and avoiding the cardiovascular
depression associated with high doses of volatile agents.
This represents a fundamental shift in the therapeutic use of
volatile and IV anestheticsthese drugs are now primarily
used to provide hypnosis and amnesia, not immobility.
Secondly, neuromuscular blockade makes assessment of
anesthetic depth much more difficult. Motor responses to
stimuli are absent when muscle relaxants are used, unless
measures have been taken to prevent total paralysis. One
rarely used method to assess perceptive awareness during an
anesthetic with relaxants is the Isolated Forearm Technique
(IFT), where a tourniquet applied before relaxants are administered prevents paralysis of one hand.16,17
When muscle relaxants are used, autonomic responses
such as heart rate, blood pressure, pupil size, and sweating
are observed by anesthetists to assess patient responses to
various stimuli. However, autonomic signs have repeatedly
been proven to be unreliable indicators of anesthetic depth
and they are often modified by patient position, surgical

213
Table 1
1)
2)
3)
4)
5)

The Modified Brice Interview21

What is the last thing you remember before surgery?

What is the first thing you remember after surgery?
Do you remember anything happening during surgery?
Did you have any dreams during surgery?
What was the worst thing about your surgery?

events, neuraxial blockade, and a variety of medications that

do not affect consciousness. Monitors that use electroencephalographic signals to estimate depth of anesthesia have
been developed. These devices are described in another
article (G. Mashour), and their utility in preventing awareness during general anesthesia is discussed below.
Assessment of memory formation, by definition, cannot
occur during a general anesthetic. A further challenge is that
memory can be either explicit (episodic) or implicit (somatic). Implicit memory is inferred when patients perceive,
but cannot consciously retrieve information, whereas their
subsequent performance on specially designed tests shows
the influence of that information.18 Accurate assessment of
explicit versus implicit memory is usually based on recall of
validated word lists and performance on exclusion versus
inclusion tests using post-exposure word lists.18,19 This testing requires considerable planning and effort.

Types of awareness during general anesthesia

events
The converging issues of variable patient sensitivity, dynamic changes in anesthetic requirements, and the difficulty
in assessing anesthetic depth in paralyzed patients inevitably results in some patients receiving too much anesthesia
and others receiving too little. Thus, there is a wide range of
experiences reported by patients following general anesthesia. Most clinical cases of awareness during general anesthesia
are elicited using a post-anesthesia structured interview, which
is sometimes repeated at intervals after surgery.20,21 For a
variety of reasons, patients rarely report such experiences to
their anesthetists without prompting, so it is critical that
anesthetists habitually perform post-operative interviews
that incorporate specific questions designed to elicit reports
of awareness (Table 1). Intraoperative awareness can be
characterized by duration, the experience of pain and/or
anxiety, and whether explicit recall is present. Without
question, the most disturbing cases are those of prolonged
awake paralysis, where patients are aware, experiencing
pain and anxiety, and able to remember these experiences. It
appears that most cases of awareness with explicit recall are
brief, and usually no pain is experienced. In addition, a large
number of cases fall into the category of awareness without
explicit recall. In these, patients report only vague memories, which may or may not be associated with intraoperative events. Finally, some case series include dreams or

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dream-like experiences which have been judged to be associated with intraoperative events.20,22,23
Awareness during general anesthesia can also be classified as preventable or not.22 Most cases where the details of
the case are available have been deemed preventable. In
cases where light anesthesia with paralysis was not intentionally used, awareness during general anesthesia is often
associated with drug administration errors, mis-labeled drug
syringes, empty vaporizers, leaky gas delivery circuits, dysfunctional or misused drug infusion pumps, and intravenous
lines that stopped running. Another frequent preventable
scenario is during difficult airway cases, where the hypnosis
provided by an induction bolus of intravenous anesthetic
wears off while the anesthetist is struggling to ventilate the
patient or intubate the patients airway.

Incidence of awareness during general

anesthesia
The root of many controversies about intraoperative awareness is uncertainty about its incidence, compounded by the
variable definitions of these events and the methodology
used to detect them. Scientists and psychologists interested
in how awareness occurs during general anesthesia have
devised scientific tests that are difficult to apply in the OR
setting. Unlike these carefully controlled experiments used
to determine MAC-awake and amnestic potencies of anesthetics, clinicians conducting studies of intraoperative
awareness in patients provide no specific stimuli for clinical
patients to remember. Instead, recent large clinical studies
attempting to estimate the incidence of awareness during
general anesthesia rely on multiple post-anesthetic interviews, usually using a modified Brice interview (Table 1).21
In these studies, intraoperative awareness is often broadly
defined and sub-classified, adding a significant degree of
subjectivity to the results. Thus, the only way to confirm
definite awareness is if patients accurately recall conversations or music that they hear in the OR during the period
of awareness. Unconfirmed, but probable cases of awareness include hearing voices or feeling discomfort associated
with intubation or surgery, whereas possible cases are
those that are more vague and dream-like.24 Because some
patients have developed psychological symptoms without
explicit recall, it is inferred, but difficult to prove, that they
have implicit recall of intraoperative events or that the
trauma of the experience results in memory suppression.25
Given all these caveats, one large study in Sweden reported
an incidence of definite awareness of 0.06%20 and a 2004
study in US academic centers reported an incidence of
awareness with recall of 0.13%.26 These two research
groups may have assessed awareness cases differently. The
incidence of other types of patient experiences are higher
than for explicit awareness, which is consistent with the fact
that memory formation is usually suppressed at anesthetic
concentrations that enable perceptive awareness.

There are other uncertainties that arise from the methods

used in many clinical studies. Patients do not report all cases
of intraoperative awareness in the post-anesthesia care unit;
positive responses increase during second and third interviews days to weeks later. This contrasts with carefully
controlled studies on volunteers, which show that retention
of memories formed under the influence of inhaled anesthetics monotonically degrades with time after the experiment is conducted.11 One possible explanation is that
awareness experiences reported days after surgery may represent patient memories formed in the post-anesthesia care
unit rather than in the operating room. Alternatively, patients may be reticent to report negative experiences such as
awareness while still dependent on the care of hospital staff.
The Hawthorne effect27 may influence these studies in several ways. Anesthetists may alter their anesthetic technique
subtly when they know that intraoperative awareness will be
monitored. In addition, patients may be more prone to give
positive responses to questions about intraoperative awareness, simply because they are asked.

Risk factors for awareness during general

anesthesia
The factors that influence the risk of awareness during
general anesthesia include those associated with the anesthetic technique, the type of surgery, and the patient.1 A
critical factor is the use of neuromuscular blockade. When
muscle relaxants are not used during general anesthesia,
patients can move, and the absence of movement suggests
that the patient is adequately anesthetized, or if aware, not
suffering. Another significant risk is light anesthesia techniques, particularly cardiac anesthesia without hypnotic
agents and N2O-narcotic-relaxant, which has been associated with up to 4% awareness. It is therefore expected that
the highest risk surgeries are those associated with light
anesthesia, which is often intentionally used to prevent the
hemodynamic consequences of high concentrations of volatile or intravenous agents. These include cardiac surgery
(1-1.5% awareness), trauma surgery (11-43% awareness),
and Cesarean section under general anesthesia (0.4%),
where light anesthesia is used to minimize newborn depression. Patient-related factors include chronic alcohol, antiepileptic, opiate, or other sedative drug use (associated with
higher anesthetic requirements), history of awareness during general anesthesia, limited cardiovascular reserve, or
ASA Class IVV (low tolerance for adequate anesthesia).26

Psychological harm and awareness during

general anesthesia
After experiencing intraoperative awareness, some patients
have developed post-traumatic stress disorder (PTSD),25,28,29
which is considered the most harmful consequence. Symptoms

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Awareness During General Anesthesia

Table 2 What to do if your patient experiences awareness

during general anesthesia
1) Get as much information about your patients experience
as possible. Record the detailed account in their chart.
2) Verify your patients story.
3) Acknowledge and apologize for your patients suffering
(without admitting guilt) and be sympathetic to the
patient. Explain what happened to the patient and answer
all of their questions.
4) Inform the surgeon(s) and nurse(s) involved in the case,
the departmental QA committee, and a hospital lawyer.
5) Make daily follow-up visits while your patient is
hospitalized and volunteer to be available for phone
consultations after they leave the hospital.
6) If your patient experiences symptoms of PTSD, refer them
to a knowledgeable psychiatrist.

include depression, anxiety attacks, sleep disorders, flashbacks

to the experience, and nightmares. Although rare, PTSD has
also been diagnosed in patients who have no explicit recall of
intra-operative events, but who develop symptoms suggestive
of intraoperative awareness, such as recurrent dreams about
being buried alive or burying friends or family members alive.
A patients understanding of their experiences can affect the
psychological impact of awareness during general anesthesia.
Patients may think that their awareness during general anesthesia experiences are impossible (uninformed healthcare
workers may also deny this possibility), leading them to become confused or question their own sanity. In a number of
cases, when a patients experience is validated and explained
by a physician, their symptoms of PTSD diminish or stop. In
others, patients remain victims for prolonged periods of
time.29
Compared to the estimates of awareness during general
anesthesia incidence, we know even less about the incidence
of PTSD. A follow-up to Sandins Swedish incidence
study20 by Lennmarken et al.29 suggests that half or more of
the patients who experienced awareness with recall developed long-term psychological problems despite having had
3 weeks of contact and repeated offers of psychological
support from the research team immediately after their surgery. It remains controversial whether repeated debriefing is
helpful or harmful to people following traumatic experiences. There are data suggesting that PTSD is worsened
when recall of traumatic events is associated with a stress
response (thus repeated debriefing may worsen things). One
preliminary report suggests that PTSD may be attenuated by
early administration of beta-blockers, effectively uncoupling memory from the stress response.30

Medicolegal consequences of awareness

during general anesthesia
A small fraction of patients who experience awareness during general anesthesia initiate legal action against their

215
anesthesia providers. Most of these are women,31 who also
disproportionately complain of PTSD symptoms. In the
ASA closed claims database from 1971 to 2001, the percentage of claims against anesthetists for intraoperative
awareness grew from 1% to 3%,32 and it is likely to continue growing. Cases of intraoperative awareness, especially
with explicit recall, are difficult to defend, because it is
assumed that a general anesthetic is supposed to make
patients unconscious. As of 2001, reported awards to patients for awareness with recall ranged from $1000 to
$600,000, but the median award for psychological damages
from intraoperative awareness was small ($18,000) in comparison to that for other anesthesia-related injuries
($100,000).
In the event that your patient experiences or claims to
have had awareness during general anesthesia, there are
several actions which can potentially reduce the psychological harm to the patient and the probability of legal action
against caregivers.1 These are summarized in Table 2.

Strategies to prevent awareness during

general anesthesia
Ghoneim33 has suggested a number of preventive measures
to help avoid intraoperative awareness. Table 3 includes
many of Ghoneims recommendations and a few others.

Table 3 Prevention of awareness during general anesthesia

and its consequences
1) Check equipment carefully before use.
2) Premedicate with amnestic. They synergize with
anesthetics to prevent awareness. Also, if awareness
occurs, psychological trauma is less likely without recall.
3) Avoid muscle relaxants and minimize their use when
needed.
4) Avoid light induction doses. Re-bolus with intravenous
hypnotic during multiple intubation attempts. Consider
using inhalation induction technique.
5) Supplement N2O/narcotic with volatile or propofol, if
possible.
6) Assure agent delivery using End-tidal gas monitors.
Check drug infusion pumps frequently.
7) Consider beta-blockers, which may reduce MAC-Awake
and may also decrease the likelihood of PTSD.30
8) Consider earplugs or headphones to reduce patient
awareness of noises in the OR.
9) Inform high-risk patients about awareness during
general anesthesia, and consider doing so for all
patients.
10) Routinely ask your post-op patients questions designed
to detect awareness (see Table 1).
11) Educate yourself about awareness during general
anesthesia.
12) Consider EEG-based monitoring in high-risk cases.

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Seminars in Anesthesia, Perioperative Medicine and Pain, Vol 25, No 4, December 2006

To use electroencephalographic awareness

monitors or not
Perhaps the most visible controversy regarding intraoperative awareness surrounds decisions about the use of EEG
monitors for anesthetic depth. A follow-up study to the
Swedish awareness survey by Ekman et al34 reported that
routine use of BIS (Aspect Medical Systems, Natick, MA)
monitoring reduced intraoperative awareness by nearly
80%. However, the use of historical controls and uncertainty about whether methodology in the two groups was
identical make this result questionable. An accompanying
editorial35 (written by a physician who developed the BIS
monitor36 and is a paid consultant to Aspect Medical Systems) suggests that this result is bolstered by its agreement
with another. In the B-Aware trial,37 randomization to
BIS/No BIS was applied to high risk patients and the
incidence of explicit awareness reports was 80% lower in
patients with BIS-guided anesthesia. Interestingly, in the
B-Aware trial, the incidence of probable and possible
awareness reports was not reduced when BIS monitoring
was used, suggesting that these types of reports are unrelated to intraoperative anesthetic depth. It also remains uncertain whether the real-world utility of BIS monitoring in
the hands of most anesthetists is as good as these studies
suggest. In a US multi-center study,26 there was a higher
rate of intraoperative awareness with recall among BISmonitored patients compared with those who had no BIS
monitor. This implies that the physicians using the monitor
either applied the device incorrectly or they failed to appropriately use the information the monitor provides.
On a purely economic basis, one cannot justify routine
BIS monitoring in the general OR population. With a perpatient cost of $20 for BIS disposables and an assumed
average malpractice payout of $50,000, the BIS monitor
would pay for itself if a malpractice payout is made for one
in every 2500 cases However, monetary compensation is
awarded to patients in only 1 to 2 per 100 harmful events,32
so the incidence of intraoperative awareness with recall
would need to be 2-4% to produce malpractice savings.
Some additional cost-savings may be achieved if one routinely uses the monitor to titrate anesthesia, which has been
shown to reduce both the use of anesthetic agents and the
incidence of post-operative nausea and vomiting in outpatient settings.35
In high-risk patients (see above), where the incidence of
intraoperative awareness is 0.5% to 2% or higher (ie,
trauma), my opinion is that patients should be informed of
the risk of intraoperative awareness, and the use of awareness monitoring is justified.
Currently available electroencephalographic monitoring
is not a panacea for the problem of intraoperative awareness. Remember that BIS only reduces the incidence of
awareness with recall, and not other more frequent types of
patient awareness reports.37 Furthermore, to make the BIS
monitor most effective, anesthetists should limit general

anesthetic drugs to those agents for which the monitors

utility is verified (propofol and volatile inhalants). Sebel35
has pointed out that no other monitors used routinely during
anesthesia are economically justifiable, nor have any of
them been shown to reduce the incidence of harmful events
during surgery and anesthesia.
In the end, decisions regarding routine use of monitors
depend on the cost of avoiding harm versus the value that
the anesthetist and patients place on avoiding that harm. At
present, many anesthetists and most trial juries apparently
do not value the psychological harm associated with intraoperative awareness as much as the physical harm associated with other anesthesia mishaps. There are interesting
analogs in these value judgments to the issues regarding
adequate treatment of patients pain, another form of subjective suffering. Because the cost of additional monitoring
is not born directly by them, patients cost-benefit analysis
will likely be quite different from that of caregivers and
insurers.

Anesthetic drugs, awareness, and

electroencephalographic monitoring
Opioids
Opioids alone do not suppress awareness. Patients receiving large opioid doses may be unresponsive to pain, but
they will respond to loud noises and remain aware of their
surroundings. As a consequence, opioids do not alter the
incidence of awareness when added to nitrous oxide, and
they do not alter basal BIS measurements.
Nonetheless, opioids may reduce the amount of cortical
arousal associated with peripheral pain (Figure 1), and
therefore, may reduce the possibility that surgical pain will
cause patients to awaken. Furthermore, the psychological
trauma associated with awareness and pain is greater than
that of awareness without pain.

Nitrous oxide and ketamine

Propofol, barbiturates, etomidate, and halogenated volatile anesthetic agents all modulate GABAA receptor activity
and shift the cortical EEG to lower frequencies.6 BIS and
other EEG-based monitors provide strong correlation with
hypnosis for this group of general anesthetics. In contrast,
nitrous oxide and ketamine (xenon and cyclopropane, too)
do not modulate GABAA receptors, but they do produce
hypnosis. These anesthetics are associated with unchanged
or increased high frequency EEG signals and a high reported incidence of dreaming during anesthesia.38 Furthermore, BIS and other EEG monitors do not accurately predict
the depth of anesthesia with these drugs. Research may yet
discover new correlates of consciousness that will lead to

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Awareness During General Anesthesia

development of more universally applicable monitors for

anesthetic depth.
Another feature of anesthesia with nitrous or ketamine is
potent analgesia, presumably due to NMDA receptor inhibition in the spinal cord. Thus, like opioids (see above),
these drugs suppress cortical arousal during painful stimulation, which may reduce the probability of awareness.

Nitrous oxide-volatile mixtures

MAC for nitrous oxide and volatile anesthetics is additive; in other words, a mixture of 0.5 MAC N2O plus 0.5
MAC volatile suppresses movement in response to pain
like 1 MAC volatile. However, studies suggest that the
hypnotic activities of nitrous oxide and volatile anesthetics
are sub-additive.39,40 Thus, a mixture of 0.5 MAC-awake
N2O plus 0.5 MAC-awake volatile anesthetic is not as
hypnotic as 1 MAC-awake volatile. This suggests that
N2O has an action which antagonizes the hypnosis induced
by volatile anesthetics, perhaps via direct cortical arousal
(see above).

Market influences on medicine and science

The injection of marketable technology into the intraoperative awareness story has engendered further controversy
and uncertainty. Many researchers publishing studies on the
impact of awareness monitors have received support from
or have financial interests in the companies manufacturing
these devices. While this is not surprising, financial linkages
are known to influence the reported outcomes of scientific
studies and clinical trials.41 Marketing efforts for awareness
monitors have emphasized both patients horror stories
and the malpractice risk to physicians. Corporate strategy
has also evolved toward strategic alliances with makers of
anesthesia delivery/monitoring equipment, which has effectively frozen out potential competition. Testing in the US of
an awareness monitor based on auditory evoked potentials
stopped in 2003 for this reason.
Some representatives of the American Society of Anesthesiologists leadership, perhaps feeling that market-driven
publicity about awareness during general anesthesia42 tarnishes our specialty in the eyes of patients, have positioned
themselves in opposition to the makers of awareness monitors. ASA has published a pamphlet on intraoperative
awareness that addresses patient concerns with assurances
that anesthesiologists are caring professionals, states that
EEG monitoring cannot prevent awareness, and cites the
need for more research. A recent ASA Taskforce produced
a Practice Advisory for Intraoperative Awareness and Brain
Function Monitoring, concluding that there is insufficient
evidence to justify a standard, guideline, or absolute requirement that these devices be used to reduce the incidence
of awareness . . ..43 The report goes on to state that the
decision to use a brain function monitor should be made on

217
a case-by-case basis by the individual practitioner for selected patients . . ..
Although the central conclusion of the ASA Taskforce is
difficult to refute, it represents a temporizing strategy that
awkwardly justifies ignoring available awareness monitoring devices until further efficacy data is provided. This
stance provides no solace to patients who have either experienced intraoperative awareness or are concerned about its
occurrence. In my view, it undermines the assertion that
anesthesiologists (or at least their public advocates) care
about and are actively encouraging measures to reduce the
incidence of this problem.

Summary and recommendations

As the ASA Taskforce report states, it is up to you to decide
what is best for your patient. Anesthesia providers should
educate themselves thoroughly about intraoperative awareness and pre-anesthetic evaluation should routinely include
assessment of patients risk for this problem. Strategies to
reduce the chance of awareness (Table 3) should be applied
whenever possible, unless these increase the risk of other
unfavorable outcomes. Postoperatively, patients should be
asked questions designed to elicit reports of awareness experiences (Table 1). When intraoperative awareness is suspected, the responsible anesthesia providers, their departmental administrators, and quality assurance team members
should activate a series of interventions aimed at defining
the nature of the event and its causes, while minimizing its
impact by providing supportive care to patients (Table 2).
Patients assessed to be at high risk for intraoperative awareness should be informed about their status and anesthetic
plans should explicitly incorporate approaches to reduce
this risk, including the use of EEG-based monitoring when
feasible.

References
1. Ghoneim MM: Awareness during anesthesia, in Ghoneim MM (ed):
Awareness During Anesthesia. Oxford, Butterworth-Heinemann,
2001, pp 1-22
2. JCAHO: Joint Comission on Accreditation of Hospital Organizations
Sentinel Event Alert, Report No. 32, 2004
3. Antognini JF, Carstens E: Macroscopic sites of anesthetic action: brain
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