Acta Anaesthesiologica Scandinavica:Volume 40(9)October 1996pp 1073-1086
Awareness in anaesthesia: Incidence, consequences and
prevention
[Review Article]
Heier, T.; Steen, P. A.
Department of Anesthesiology, Ullevaal University Hospital, Oslo, Norway.
Address: Tom Heier MD, PhD; Department of Anesthesiology; Ullevaal University Hospital; N-0407 Oslo, Norway
Awareness has been a concern since the first time ether anaesthesia was demonstrated by William Morton in
1846. The patient was reported to be half-awake during the operation, and later expressed that he had
experienced pain. In 1847 a female patient was reported to be aware of the instrument movements in the
surgeon's hands (1), and in the early 1900s the surgeon George Washington Crile called attention to the fact
that the anaesthetized brain was not unresponsive. "It may be an unpleasant thought that although our patient
is unconscious from general anaesthesia, the nerve impulses inaugurated by operative injury of the nerves
reach the brain, making a reactive opposition to the surgeon, an attempt to get off the table and escape from
the injuries the surgeon is inflicting." (2) With the use of curare in the 1940s "the signs of anaesthesia"
disappeared, and many were reluctant to use the drug because of the possibility of having a completely
paralysed, but conscious patient. "Care must therefore be taken to deaden sensation and ensure
unconsciousness" (3). In 1959 Cheek demonstrated by use of hypnosis that patients under the influence of
general anaesthetics may retain intraoperative auditory information (4). The possibility of awareness during
anaesthesia and surgery is still a major concern (5-22).
Depth of anaesthesia vs. awareness
The original descriptions of anaesthesia were based on observed physiological responses to increasing doses
of inhaled anaesthetics (23-25). Prys-Roberts defined pain as conscious perception of noxious stimuli, and
anaesthesia as a state in which the patient neither perceives nor recalls such stimuli, and thus does not
experience pain (26). In 1993 Kissin refined the definition of anaesthesia as consisting of several different
components: anxiolysis, analgesia, hypnosis, muscle relaxation, and suppression of somatic (motor) and
autonomic (haemodynamic, sudomotor, hormonal) responses to noxious stimulation (27). These various endpoints should not be regarded as a result of one single anaesthetic action (27). Studies both on intravenous and
inhaled anaesthetics suggest that they represent different pharmacological actions, with different underlying
mechanisms of action. This is most obvious with opioid drugs. The morphine and fentanyl potency (expressed
as ED50, the concentration eliminating the measured response in 50% of the animals) ratios in rats between
blockade of the response to noxious stimulation and loss of the righting reflex (measure of consciousness in
animal studies) are different, which is not consistent with a unitary nonspecific mechanism of anaesthetic action
(28). Additionally, in rats, both reserpine and thiopental antagonize the effect of opioids on the movement
response to noxious stimulation, while a synergistic effect exists on the righting reflex (29, 30). For thiopental,
etomidate, and diazepam the dose-response curves for loss of righting reflex, blockade of noxious stimulationinduced movement response, and suppression of cardic acceleration response to noxious stimulation vary ( 31),
again suggesting different mechanisms of action for different components of anaesthesia. Similarly, in mice, the
ratio of ED50 for movement response to tail-clamp (MAC) to ED50 for the righting reflex varies between
different inhaled anaesthetics (32).
In patients, MAC was originally defined as the minimal alveolar concentration of an inhaled anaesthetic
required to prevent purposeful movement of head or extremities upon surgical skin incision in 50% of patients
in the near steady-state situation (MAC-incision) (33). In a recent clinical study the concentration of isoflurane
needed to prevent voluntary response to verbal commands as a fraction of MAC was significantly less than for
nitrous oxide (0.38% MAC vs. 0.64 MAC) (34). Although this difference may reflect the stimulatory effect of
nitrous oxide on the sympathetic nervous system (35-37), multiple mechanisms of action for different end-points
of anaesthesia seem to be involved. This may not be apparent during everyday clinical anaesthesia because
inhaled anaesthetics affect all components of anaesthesia more uniformly than opioids (38, 39). It is also
suggested that different anaesthetics may induce the same anaesthetic end-point by different mechanisms of
action (40-43). This view is supported by results obtained on isolated single-neuron preparations, where various
inhaled anaesthetics had differential effects on the discharge activity (44).
General anaesthetics are compounds with widely diverse chemical structures (45). The only physiochemical
common characteristic is their lipid solubility. Traditionally, they were considered nonspecific, acting by
perturbation of the lipid bilayer of the cell membrane in nerve cells (41). Consistent with the view that
anaesthetics exert their effects by different mechanisms of action, new data suggest that these drugs act on
sensitive proteins in the CNS (41). Unlike with local anaesthetics, impulse conductance in myelinated neuronal
fibres is not affected by clinical doses of general anaesthetics, reinforcing the view that excitatory synaptic
transmission is disrupted during anaesthesia (43, 46-48). Thin unmyelinated nerve fibres in CNS may, however,
be as sensitive to inhaled anaesthetics as excitatory synapses (46, 48), and isoflurane induces hyperpolarization
of neuronal cell body/dendrite, which may contribute to the depression of neuronal excitability ( 48, 49). Although
the mechanisms of action of general anaesthetics are only partly known, recent data suggest that both
cholinergic and amino acid-mediated neurotransmitter systems are involved (45, 50-53).
Hypnosis consists of amnesia and unconsciousness (16) which should be considered different components of
anaesthesia, as amnesia may be induced by drugs that do not affect consciousness significantly (54-56). In this
context, amnesia can be defined as loss of learning and memory functions (12) which appear related to longterm potentiation (LTP), a phenomenon characterized by a long-lasting (days to weeks) postsynaptic response
to a brief tetanic stimulation (57, 58). LTP is mostly studied in the hippocampus, which is associated with
memory functions (58), and is related to stimulation of the NMDA glutamate postsynaptic receptor (50, 59, 60),
which stimulates the production of nitric oxide. It is speculated that inhibition of nitric oxide production creates
anaesthesia (51, 52). Ketamine impairs LTP by blocking the NMDA receptor (60), in contrast to other
anaesthetics (volatile, barbiturates) which enhance inhibition (GABA as transmitter) of this excitatory synapse
(50) either by reducing presynaptic transmitter release, or by postsynaptic hyperpolarization (48, 50).
It is suggested that the state of consciousness is determined by neuronal activity in the brain stem reticular
formation which connects with every part of the brain and spinal cord, and receives afferent impulses from all
sensory modalities (61). General anaesthetics may induce unconsciousness by enhanced inhibition or
suppression of excitatory responses of the reticular formation neurons evoked by somatosensory stimuli (62).
One MAC halothane thus significantly reduces acetylcholine release in the medial pontine reticular formation,
probably the primary region for normal sleep regulation. Direct application of acetylcholine in this part of the
brain induces a REM sleep-like state in intact unanaesthetized animals (63), and brain stem mechanisms
involved in the generation of naturally occurring sleep may play a key role when anaesthetics induce
unconsciousness (64).
No clear clinical end-point can serve as a basis for rational administration of drugs to achieve
unconsciousness, and presently absence of recall of events is the only objective criterion for unconsciousness
(16). Several studies suggest that a consciousness transition zone exists during the induction and emergence
from anaesthesia (10, 14, 34, 65, 66). At low brain concentrations of anaesthetics the patient responds to verbal
commands and has conscious (explicit) recall of the event. At higher concentrations the patient may remember
the event if offered a cue (cued conscious recognition). At even higher concentrations the ability for explicit
memory is lost, but the patient may still respond to auditory impulses such as verbal commands (wakefulness),
or retain information as unconscious (implicit) memory, only revealed by psychologic testing and hypnosis (12,
67, 68).
It is not known if memory of events during anaesthesia and surgery can be completely prevented. It is
speculated that implicit memory, especially of auditory impulses, may take place independent of depth of
anaesthesia (10, 69), since auditory impulses can be detected in the brain stem despite an isoelectric EEG ( 70).
In the absence of surgical stimulation, however, isoflurane 0.2 MAC prevented explicit learning, and isoflurane
(71) or desflurane 0.6 MAC (72) prevented both explicit and implicit learning in humans. The concentration
required to eliminate memory functions in the presence of surgical stimuli is not known, but it is reasonable to
believe that it is higher, as noxious stimuli may increase the level of consciousness (34, 73).
Depth of anaesthesia depends on two antagonizing factors: the anaesthetic, which induces different
anaesthesia components to a varying degree depending on the specific drug used; and the surgical stimulation,
which may activate the sympathetic nervous system and increase the patient's level of consciousness and the
somatic and autonomic reactivity (73, 74). Adequate depth of anaesthesia requires a sufficient amount of the
agent to secure unconsciousness and other components of anaesthesia as needed for that particular surgical
procedure, without jeopardizing vital organ functions. Ideally, depth of anaesthesia should be assessed in
relationship to each anaesthetic component separately, tested by specific stimuli (16, 27).
Based on the above discussion, awareness during general anaesthesia can be defined as a degree of
consciousness, revealed by the occurrence of explicit or implicit memory of intraoperative events.
Intraoperatively, eye opening or movements indicate impending awareness (12). During such an episode
information may be stored temporarily into short-term memory (STM), and may or may not be stored
permanently into long-term memory (LTM) (10). Both explicit and implicit memory are stored in LTM (10).
Postoperatively, an interview will reveal explicit awareness. Detection of implicit awareness requires
psychological testing, which is impractical during routine anaesthesia. Some patients have dreams during
anaesthesia, implying a mental state in the transition zone between explicit and implicit awareness ( 12, 19). To
ensure that the dreaming has not occurred postoperatively, the episode should be revealed shortly after
conclusion of anaesthesia.
Incidence of awareness
There is a great variability in the reported incidence of awareness during anaesthesia and surgery, due to
several reasons:
1. The incidence is dependent on the diagnostic criteria use to identify awareness. For explicit memory the
incidence may be zero (75). If any movement response during surgery suggests impending awareness, a
frequency as high as 100% may be observed (76). If dreaming suggests awareness, the frequency is in the
range 0-60% (Table 1 and 2). Response to verbal commands during surgery (wakefulness) was observed in
70% of the patients in one study (77).
Table 1. Incidence of awareness during anaesthesia for general surgery
Table 2. Incidence of awareness during anaesthesia in special groups
2. Different combinations of drugs used in anaesthetic practice depress consciousness to a varying extent.
3. The need of the patients for anaesthetics may depend on the intensity of the noxious stimuli.
4. The pharmacokinetics and pharmacodynamics of a particular anaesthetic agent vary between patients,
leading to varying dose requirements to obtain the same level of unconsciousness.
5. Certain surgical procedures require light anaesthesia, increasing the risk of patient awareness.
Incidence of conscious (explicit) awareness with different anaesthetics (Table 1)
Inhaled anaesthetics
When nitrous oxide 60-70% alone was used for maintenance of routine anaesthesia, a technique used in the
60s and 70s, the reported incidence of conscious awareness was 0-7% (78-84). In investigations where either
volatile anaesthetics, opioids or ketamine are added to nitrous oxide 50-70% the incidence is <2% (85-89),
although occasionally higher percentages may be reported from studies including only few individuals ( 90, 91).
Recently, in a study of more than 3400 patients, Jordening and Pedersen found that the incidence was 0.2%
for nitrous oxide 60-70% combined with fentanyl and droperidol in diazepam-premedicated patients (92).
Similar results were obtained in a study of 1000 patients by Liu et al. in 1991, where unfortunately the
anaesthetic techniques used were not described in detail (93). Only a few case reports are available of
conscious awareness during routine anaesthesia with volatile agents administered in inspired doses >1% (92,
94-96). At least one of those was caused by a vaporizer leakage (96). These findings are consistent with studies
showing that inhaled anaesthetics are relatively more potent than nitrous oxide on consciousness compared to
pain suppression (34).
Intravenous agents
Awareness with propofol as a sole anaesthetic is described (97), but the dosage was not higher than that
recommended in the presence of nitrous oxide (12 mg·kg-1·h-1 (98). No conscious awareness was reported
when propofol as recommended by the manufacturer was administered in conjunction with alfentanil and
topical application of lidocaine for laryngoscopy procedures in 15 patients (99). In a recent retrospective study
of 1727 patients 0.3% experienced conscious awareness during total intravenous anaesthesia with propofol (612mg·kg-1·h-1) and alfentanil (40-80 µg·kg-1·h-1) (100). In 2 of those 5 cases less than the intended doses of
propofol were administered inadvertently. Zero percent and 3% conscious awareness was observed in two
studies including 11 and 32 female patients, respectively, undergoing breast or gynaecological surgery with
midazolam (0.15mg·kg-1·h-1)and alfentanil (1 µg·kg-1·h-1) (77, 101). In a study of 24 orthopaedic patients 13%
experienced conscious awareness when ketamine was administered as a sole anaesthetic ( 85). The frequency
of conscious awareness was 8% during bronchoscopy in 130 patients with thiopental-oxygen-succinylcholine
anaesthesia (102).
Incidence of conscious (explicit) awareness in special groups (Table 2)
Cardiac surgery
There are several case reports of documented awareness during ketamine-diazepam (103), ketamine-nitrous
oxide (104), high-dose opioid-oxygen (105, 106), and cyclopropane (107) anaesthesia. In a series of 30 patients,
23% had explicit awareness during high-dose fentanyl anaesthesia with or without halothane or nitrous oxide
supplementation (108). Maunuksela (109) compared pethidine-nitrous oxide, droperidol-fentanyl and halothane
anaesthesia, and observed an explicit awareness frequency of 5%, 13%, and 0%, respectively. In a large
survey including 700 patients 1.1% experienced explicit awareness (110). The awareness episodes occurred
mostly secondary to DC-shocks during cardiopulmonary bypass, or other painful procedures such as sternal
split, aortic root dissection and electrocauterization (108, 109). This tendency to conscious awareness during
cardiac surgery is not completely eliminated by adding an amnesic drug like diazepam (111).
Caesarean section
The pre-delivery part of caesarean section requires light anaesthesia. In one study, all 6 patients anaesthetized
with 75% nitrous oxide in oxygen as the sole anaesthetic pre-delivery experienced conscious awareness (112).
When pentothal 4mg·kg-1+ nitrous oxide 50-70% was used, the reported frequency of explicit awareness varies
between 2 and 12% (113-115). When this anaesthetic regimen was supplemented by fentanyl 100 µg or
morphine 0.2mg·key-1+ diazepam 0.1 mg·kg-1 postdelivery 1.5-8% experienced awareness (116, 117).
Several authors report no conscious awareness when 0.5% halothane is added to 50% nitrous oxide after
tracheal intubation in studies including 30 to 245 patients (75, 76, 113, 115), while 3% could recall intraoperative
event when 1% enflurane was added (118). In 1991 Lyons and Macdonald reported an incidence of awareness
of 1.3% and 0.4% when retrospectively evaluating 3000 caesarean section patients who received either
thiopental 4mg·kg-1+50-70% nitrous oxide with halothane 0.5%(terminated postdelivery) or thiopental 6mg·kg 1
+50-70% nitrous oxide with isoflurane 1% until end of surgery (119).
Trauma surgery
Surgery for major trauma in haemodynamically unstable patients will frequently require light anaesthesia.
Conscious awareness was experienced by 4 of 37 patients during emergency surgery with ketamine for
induction and volatile anaesthetics for maintenance (120), and by 6 of 14 patients who received no anaesthetics
for tracheal intubation and during the first approximately 20 min of surgery as they were
unconscious/haemodynamically unstable on arrival (120).
Incidence of unconscious (implicit) awareness during anaesthesia (Table 1 and 2)
The use of recall as a measure of cognitive processing during anaesthesia has led to the conclusion that
awareness is a rare event. This might be erroneous as it does not take into account that memories may be
inaccessible for conscious recall (6). The frequency of 'dreams', which may indicate unconscious intraoperative
awareness, is much higher than recall of intraoperative events. However, it is difficult postoperatively to
ascertain that the episode really occurred during anaesthesia (19, 81).
In nonobstetrical patients the reported incidence of dreaming during unsupplemented nitrous oxide anaesthesia
is 3-57% (78, 81, 83, 84, 88). When either inhaled anaesthetics, opioids or ketamine are added to nitrous oxide
the incidence varyies from 0 to 16% (81, 84, 85, 89, 91). Total intravenous anaesthesia (propofol or midazolam, in
conjunction with alfentanil, administered as continuous infusions), is associated with a dreaming frequency of
0-9% (77, 99, 101). Eight of 24 (33%) orthopaedic patients anaesthetized with ketamine as a sole agent
experienced dreaming (85). This is in contrast to an incidence of 0.9% in a recent study of 1000 nonobstetrical
patients interviewed 20-36 hours postoperatively, where unfortunately the anaesthetic techniques were not
specified (93).
In obstetrical patients the reported incidence of dreaming was 31% during unsupplemented nitrous oxideoxygen anaesthesia in 150 patients (114), 4-11% when nitrous oxide 70% was supplemented with opioid and
diazepam after delivery of the infant (116, 117), and 5-8% when supplemented by inhaled anaesthetics (118,
119). In one study none of 129 patients had unpleasant dreams during nitrous oxide 70% + 0.5% halothane
anaesthesia (75).
Adequate responses to verbal commands during anaesthesia, without any conscious memory of the event,
may also suggest implicit or unconscious memory (34). When neuromuscular blocking agents are used during
anaesthesia the incidence may be investigated using the isolated forearm technique with a tourniquet applied
to one upper extremity before administration of the neuromuscular blocking agent, enabling the patient to move
the arm. Seventy-two percent of 32 nonobstetrical patients during total intravenous anaesthesia with
midazolam-fentanyl (77), and more than 90% of 30 (76) and 74 (118) patients during nitrous oxide plus
halothane or enflurane for caesarean section, responded one or several times to verbal commands without
recall of the event. The real incidence of implicit awareness during anaesthesia may therefore be high.
Intensity of noxious stimulation vs. the incidence of awareness
There are no data available on the relationship between the intensity of noxious stimulation and the level of
consciousness during anaesthesia. However, surgical manipulation and tracheal intubation are strong
stimulants of the sympathetic nervous system, and therefore considered to increase the level of consciousness
during anaesthesia (8, 73, 74). This is consistent with the observation that conscious awareness during cardiac
surgery frequently occurs during sternotomy or other painful procedures (105, 107, 109). Similarly, in a study of
160 premedicated patients 3 incidents of conscious awareness (2%) occurred during tracheal intubation after
induction with phenoperidine, droperidol, thiopentone and succinylcholine (121).
Influence of patient-related differences in pharmacokinetics on awareness
Patient-related factors, such as age, smoking, acute or chronic use of alcohol or drugs such as opiates or
amphetamines, may increase the anaesthetic dose needed to obtain a certain level of unconsciousness,
especially during opioid-based anaesthesia (8, 122-128). Patients with a compromized circulation require less
anaesthetics as a larger proportion of their cardiac output is delivered to the brain than in healthy individuals
(129).
In conclusion, the incidence of awareness depends on the diagnostic criteria used, and varies with different
anaesthetic techniques. If the frequency of response to verbal commands during isolated forearm studies is
indicative, the incidence may be very high.
Consequences of awareness
Awareness during surgery may affect the patient adversely, but may also have a potential for patient benefit
with programmed passive learning during anaesthesia.
Conscious awareness - adverse effects
In 1993 Moerman et al. (130) interviewed 26 patients who had experienced awareness with explicit recall of
intraoperative events. Most patients felt panic and helplessness related to the inability to move or call for help,
and some had frightening sensations of impending death, being left unattended, or that pain might be
experienced. Seventy percent suffered significant aftereffects, including day-time anxiety, sleep disturbances
and nightmares, and 3 needed psychotherapeutic help. Ninety percent of the patients who experienced pain
during the awareness episode suffered after-effects. Similar findings are observed in other studies (92, 119, 130,
131) and case reports (132-139), also describing patients disabled after the incident.
Sometimes the conscious awareness incident is less obvious. In these patients, a syndrome of traumatic
neurosis may occur (5, 135), characterized by anxiety, irritability, preoccupation with death, and repetitive
nightmares. The patients are reluctant to talk about their problems, as they are unable to connect them with the
anaesthesia episode and fear being considered insane. Strikingly, in many patients the symptoms subside
when fragments of their nightmares are connected to events occurring during surgery (5).
Unconscious awareness - adverse effects
Intraoperative events or auditory information presented to patients under general anaesthesia may be
remembered subconsciously (4-6, 108, 140-144), but the connection to the event is subtle and cannot be recalled.
Consequently, the influence of implicit memory on postoperative behaviour is not well studied clinically. Case
reports suggest that operating room conversation, especially rude remarks related to the patient, may
adversely influence the postoperative course without the patient's conscious knowledge (4, 6). The connection
to the intraoperative event may be revealed by hypnosis (5, 6, 143, 144), based on the assumption that memory
formed in one state may be recalled better in the same than in a different state (state-dependent memory)
(145). An analogy between the state of general anaesthesia and that of hypnosis has been considered. These
studies (5, 6, 143, 144) were not controlled or blinded, and may be of limited value, as confabulations cannot be
excluded (146). Also, the period of dreaming may have occurred postoperatively during recovery from
anaesthesia, rather than during surgery (147).
Drugs with amnesic effects used as premedicants or during anaesthesia may influence the patient's ability to
recall intraoperative events, without eliminating the ability of implicit memory (54, 56, 81, 148-150). It has also
been suggested that a patient can have a conscious awareness episode, but be unable to recall the incident
postoperatively, if the anaesthesia is subsequently deepened (151), or if the retrieval process is blocked by
psychological or physiological mechanisms (152). Therefore, conclusive evidence in the literature of
unconscious memory of intraoperative events adversely affecting postoperative behavior is essentially lacking.
Learning during anaesthesia
For implicit memory formation, auditory perception must still be functioning during anaesthesia, and
physiological studies suggest this is the case (10, 69, 70). In unstimulated volunteers, implicit memory is
suppressed at 0.45 MAC isoflurane (153), slightly higher if nitrous oxide is administered simultaneously (154).
Implicit memory during anaesthesia considered adequate for surgery has been demonstated by some
investigators (155-158), while others have failed (71, 72, 159-163). This discrepancy may at least in part be
explained by the great variability in anaesthetic techniques. Since unconsciousness during anaesthesia is
considered a graded phenomenon (10, 14, 34, 65, 66), factors known to influence the depth of anaesthesia,
especially the anaesthetic technique used and the level of surgical stimulation, must be similar when results
from different studies are compared.
Subconscious memory building during anaesthesia is also studied with a variety of tests, but it is not known
which test is most sensitive to learning ability during anaesthesia (12). Priming is greater when the target
material and the implicit test are presented in the same sensory modality, i.e. both auditory (12, 164). The
salience of the information presented during anaesthesia might be important and insignificant stimuli may not
be memorized (6). Consequently, differences in tests and procedures may also explain varying results (12). In
unstimulated volunteers, 1.5-2 times the concentration of desflurane or propofol required to prevent response
to verbal commands, suppressed memory of emotionally charged information (165). The drug concentration
needed to suppress such information during surgical stimulation is not known.
If implicit memory occurs during anaesthesia, learning processes may take place, and learning skills may even
be improved by the relaxed state achieved during anaesthesia, analogous to the increased responsiveness to
verbal suggestions observed during hypnosis (12, 166). In prospective double-blind experiments with volatile
anaesthetics, it appears that intraoperative suggestions influence postoperative behaviour (i.e. the number of
times a suggested body part is touched) (156, 167, 168). These studies have been criticized for the lack of preanaesthesia baseline assessment of the behaviour tested (169). Bethune et al. (158) and Jansen et al. (170)
could not replicate these results when a pre-operative behaviour assessment was included in patients
anaesthetized with either methohexitone or propofol.
Both a reduction (171-174) and no effect (175-179) on duration of hospital stay has been reported for patients
presented during anaesthesia with positive suggestions predicting a rapid and comfortable post-operative
recovery. There is no clear explanation for the variability in the results. The level of consciousness affected by
the anaesthetics and the surgical stimulation may have varied (71, 173). One of the positive studies (171) has
been criticized for using an inappropriate control group (179), but statistical arguments can also be used the
other way. The number of patients included in the referred studies were relatively small, and the complexity of
factors influencing the duration of hospital stay (type of surgery, surgical skills, intrinsic patient and illness
variability, and discharge policy), may easily obscure any effect of positive suggestions. The fact that some
studies show effect of intraoperative positive suggestions at all may therefore be considered strong evidence of
a real effect, not precluded by reports of no benefits (12). Studies with a high statistical power, which require
inclusion of a large number of patients, standardized anaesthetic and surgical techniques and exclusion of
patients having complications secondary to surgery, are unfortunately lacking (173).
Some authors find reduced postoperative analgesic requirements after intraoperative positive suggestions ( 180184), others not (185-187). Most investigators only recorded requests for intramuscular opiates, which probably
is an unreliable measure of the patient's real needs (188), but both positive (183, 184) and no effect (186, 187)
have also been reported with patient-controlled analgesia.
In conclusion, there is solid evidence that implicit memory function exists during anaesthesia, based on
experimental studies with doses of anaesthetics less than those required for surgery. During anaesthesia for
surgery the picture is more obscure. The situation is multifactorial and the depth of anaesthesia is influenced
both by the anaesthetic used and the intensity of the surgical stimulation. No conclusive evidence exists on the
presence or lack of influence on behavior, active learning, hospital stay, or need for postoperative analgesics.
Prevention of awareness
Most anaesthesiologists would probably agree that if anaesthesia is deep enough (isoelectric EEG) there will
be no conscious or unconscious awareness. As the margin of safety of most anaesthetic agents is narrow,
administration of high doses of anaesthetics is not always compatible with safe conduct of anaesthesia. We are
constantly balancing positive and negative effects of the anaesthetic agents, and since at present a reliable
monitor for consciousness is not available, we might have to accept some incidents of awareness to avoid
higher morbidity and mortality from deep levels of anaesthesia.
Patient - anaesthesiologist relationship
The first step toward prevention of awareness is probably the anaesthesiologist's acceptance and awareness
of this potentially disabling experience!
The ASA has recommended considering informing the patient of the possibility of awareness, especially when
intentionally light anaesthesia is anticipated (189). In one survey, 50% of the patients expressed concern about
the possibility of being awake during surgery (190). Preoperative assurance that qualified personnel are
watching the patient continuously might be beneficial should an awareness situation occur. The
anaesthesiologist should also see the patient the day before surgery to relieve any patient anxiety, since
increased sympathetic activity may increase the potential for awareness during anaesthesia ( 74).
While the patient is asleep the anaesthesiologist should take precautions that patient related remarks by
operating room personnel do not occur. There are case reports showing that conscious or unconscious
memory formation of salient information may take place during otherwise adequate anaesthesia ( 4, 6, 130).
Avoidance of unintentional light anaesthesia
The endtidal gas concentrations of inhalational anaesthetics should ideally be monitored, and the vaporizer
checked at regular intervals.
Pumps for intravenous anaesthetics must have volume and pressure alarms, and the infusions should
preferably be administered via separate iv lines.
Patient characteristics known to increase the anaesthetic requirements during opioid-based anaesthesia, such
as cigarette smoking, chronic alchohol or drug abuse, should be accounted for in the choice and dosage of
anaesthetic agents (123, 125, 126).
Administration of drugs with known amnesic qualities as premedicant or during anaesthesia, i.e. scopolamine
or benzodiazepines, has been recommended (12, 189), but they may not block all implicit memory formation
during anaesthesia (54, 56, 81, 148-150).
In order to prevent pollution in the operating room, anaesthetic gases are frequently avoided during induction of
anaesthesia. The hypnotic drugs used normally redistribute quickly, and the brain concentration may be less
than optimal when tracheal intubation is performed. Tracheal intubation is a very potent stimulus, and very high
anaesthetic concentrations are needed to prevent movement responses secondary to the procedure, if muscle
relaxants are not used (191). Consequently, awareness episodes are likely to occur in association with tracheal
intubation (121, 130, 192). In an attempt to secure unconsciousness during tracheal intubation, it is adviseable to
combine an opioid with the hypnotic, and administer an extra dose of the hypnotic drug just prior to this
procedure (189).
Administration of intentional light anaesthesia
A minimum of anaesthetics, i.e. 4-5mg/kg pentothal and nitrous oxide 50%, is often administered during the
first stage of a caesarean section. The addition of low doses of volatile anaesthetics reduce the frequency of
awareness significantly, without adversely affecting the newborn (75).
In hypovolaemic trauma, patients' awareness episodes may occur during induction of anaesthesia or surgery,
even if the patient is unconscious on arrival at the operating room (120). The preferred anaesthetic drug in this
situation is ketamine, due to its stimulatory effects on the sympathetic nerve system. However, awareness
episodes are described also during ketamine anaesthesia (85, 86, 120).
Assessment of anaesthesia depth
At present there is no monitor available that can determine if the patient is unconscious or not during
anaesthesia (193). Depth of anaesthesia is clinically judged by the observation of somatic (patient movements)
and autonomic reflexes (increased heart rate and blood pressure, tearing and pupil dilation). There are only a
few case reports of awareness during surgery in unparalyzed patients where somatic reflexes were absent ( 92,
94, 194). Consequently, the observation of movement responses is the best clinical measure available for
detecting impending awareness during surgery. In the presence of muscle relaxants adequacy of anaesthesia
is most often assessed by the observation of autonomic reflexes, although a firm relationship to awareness is
not established (193).
Use of muscle relaxants
Muscle relaxants are used for tracheal intubation and to obtain surgical relaxation, but most surgical
procedures do not require complete neuromuscular blockade. Consequently, the ability of limb movement may
be preserved during most surgery, although the precise relationship between degree of neuromuscular
blockade and limb movement ability is not determined. As muscle relaxation depends both on the degree of
neuromuscular blockade and the anaesthetic depth (195, 196), the dosage of muscle relaxants needed to obtain
a certain level of muscle relaxation gradually decreases with increasing concentrations of anaesthetics ( 196).
This is specifically shown for volatile inhaled anaesthetics (196), which block stimulatory impulses on alpha
motor neurons in the spinal medulla (197), and potentiate the effect of muscle relaxants at the neuromuscular
junction (198-202).
A nerve stimulator should be used whenever muscle relaxants are given, enabling the anaesthesiologist to
titrate the administration according to surgical needs (203). If the patient moves in response to noxious stimuli,
more anaesthetics should be administered, not a muscle relaxant.
When deep neuromuscular blockade is required during surgery, the activity of muscle groups known to be
more resistent to the effect of muscle relaxants, i.e. diaphragm, larynx, facial or neck muscles ( 204-206), should
be observed, and surface EMG monitoring from facial or neck muscles may be helpful (207, 208).
Inhaled vs. nitrous oxide-opioid or total iv anaesthesia
Awareness has been observed with both inhaled, nitrous oxide-opioid and total iv anaesthesia (see incidence
section). There are at least three reasons why volatile anaesthetics may be less associated with awareness
than other anaesthetic regimens in patients who cannot move in response to noxious stimuli:
A. a. There is significant interindividual variability in the pharmacokinetics of intravenous anaesthetics (209-214),
and during routine anaesthesia the plasma drug concentration cannot adequately be predicted from the dose
administered. As an example, the plasma concentration obtained during a constant rate infusion of propofol
(6.5mg·kg-1 8 patients varied between 2.5 and 5 µg·ml-1 (213). Even with a computer-controlled infusion pump,
using population-based pharmacokinetic data for drug delivery, the plasma concentration can deviate
significantly from the target (211), and online plasma drug concentration determination is not yet available.
Awareness might therefore occur during intense noxious stimulation in patients who pharmacodynamically
require a high brain drug concentration, but pharmacokinetically achieve a low concentration from a given
dose.
B. For volatile anaesthetics the brain drug concentrations can be adequately estimated intraoperatively in
normoventilated patients, using continuous endtidal concentration measurements (215). Therefore, anaesthetic
depth can probably more adequately be adjusted according to the patient's needs than during total intravenous
anaesthesia.
C. b. Volatile inhaled anaesthetics more potently suppress consciousness (MAC-awake relative to MACincision) than nitrous oxide (34). An anaesthetic regimen based on a combination of nitrous oxide and opioids
may therefore be associated with a higher frequency of awareness than other anaesthetic regimen. Some
clinical studies suggest that this is the case (90, 91).
D. c. The interindividual variability in drug concentration needed to prevent movement response to noxious
stimulation may be less with volatile than with nitrous oxide-opioid or total intravenous anaesthesia (9, 16, 209211). This must now be questioned as a recent study found no difference in the interindividual variability in the
concentration of anaesthetics required to obtund the response to command for desflurane (MAC-awake) and
propofol (Cp50-awake) (216).
Summary
Awareness during anaesthesia is a state of consciousness that is revealed by explicit or implicit memory of
intraoperative events. Although large clinical surveys indicate an incidence of explicit awareness of <0.3%
during anaesthesia for general surgery, this adverse effect should be a great concern, because patients may
be permanently disabled by the experience of being awake during surgery. Prevention of awareness during
anaesthesia starts with an appropriate preoperative visit to the patient. The anaesthetic delivery machines must
be properly checked before and during anaesthesia. The anaesthetic depth should be assessed by observation
of movement responses, and consequently a minimum of muscle relaxants used. Because the anaesthetic
depth can be controlled by determination of endtidal drug concentration, volatile inhaled anaesthesia may be
associated with a lower frequency of awareness than other anaesthetic regimens.
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Keywords:
Anesthesia: general; anesthetics: volatile, intravenous; complications: awareness; memory: explicit,
implicit; monitoring: EEG, evoked potentials, peripheral nerve stimulation; neuromuscular blockade.