The purpose of general anesthesia is to render surgical patients unconscious, and thus insensitive to pain and oblivious to events occurring during the procedure. For this reason, anesthesia -- like sleep and coma -- often enters into philosophical and scientific discussions of consciousness. How do we know that the patient is unconscious? Appearances to the contrary notwithstanding, are there reasons to think that anesthetized patients are actually conscious after all? Assuming that they are actually unconscious, is it possible for them to acquire and retain unconscious memories of pain and surgical events? What can the biological mechanisms of general anesthesia tell us about the neural correlates of consciousness?
Up until the middle of the 19th century, anesthesia was not a feature of surgery. Instead, patients were simply required to withstand the pain of the procedure, perhaps with the aid of alcohol, opiates (such as laudanum), a bite-board, and physical restraints.
In the early 1840s, James Elliotson and James Esdaille, two Scottish surgeons, successfully employed "Mesmerism", otherwise known as "animal magnetism", a forerunner to modern hypnosis, as an anesthetic agent in many surgical operations. Unfortunately, Mesmerism was in ill repute in scientific medicine. And their timing was bad: just as they were beginning to publish their results, the first chemical anesthetics were documented.
Humphrey Davy (1778-1829), the pioneering electrochemist, discovered the effects of nitrous oxide on headache and dental pain during his research on respiratory physiology; but his report went unnoticed in the medical community and the substance was quickly consigned to use at "laughing gas" parties.
In 1845, Horace Wells, an American dentist, successfully used nitrous oxide for anesthesia during a dental extraction. But when he attempted to repeat the demonstration before an audience of physicians and surgeons, the demonstration failed.
But on October 16, 1846, William
Morton, another dentist, employed ether in the
surgical removal of a tumor with no signs or reports of pain
in the patient. That event is now celebrated in hospitals and
medical schools throughout the world as "Ether Day". The
event is also immortalized in two
paintings: the one on the left,
by Robert Hinckley (1896), hangs in the
Countway Medical Library at Harvard Medical School; the
one on the right, by Warren and Lucia
Prosperi (2001), hangs in the "Ether Dome", the actual
surgical theatre where the operation took place.
Actually, ether had been used successfully for dental anesthesia as early as 1842, and that same year Crawford Long, a physician in Georgia, actually used ether in surgery. However, in the 19th century dentistry wasn't considered "real" medicine; and Long did not publish his results until 1849, so Morton got priority for his discovery (still, Morton was a dentist; and Long had the major teaching hospital of Emory University named for him!).
Morton died in 1868, and his tombstone in Cambridge's Mount Auburn Cemetery carries the following epitaph, composed by Bigelow:
Soon thereafter, in 1847, chloroform was
introduced by Simpson as an alternative to ether, which had
an unpleasant odor and other side effects.
Anesthesia was also extended from surgery to obstetrics,
although some physicians had qualms about dangers to the
neonate. Some religious authorities claimed that
anesthesia violated God's will that women give birth in pain
(see Genesis). Queen Victoria essentially
ended the debate in 1853 when she received chloroform for
the birth of her eighth (!) child, Prince Leopold. The first
American woman to give birth under chloroform was Fanny
Longfellow, wife of Henry Wadsworth Longfellow.
Nevertheless, some professionals and others continued to
debate a "calculus of suffering" by which some individuals,
and some conditions, were deemed more worthy of anesthesia
than others. And even in the 20th (and 21st) century,
the subjective nature of pain led both healthcare
professionals and political policymakers to disparage many
claims of "pain and suffering" as mere malingering.
For interesting histories of pain and pain control, see
- A Calculus of Suffering by Martin Pernick (1985).
- Pain: A Political History by Keith Wailoo (2014).
The story of Morton and Ether Day is told in "The Great Moment" (1944), a biopic directed by Preston Sturges.
The stories of Freud' and Halsted'
relationship to cocaine are told in two books:
Both books were reviewed by Frederick Crews in "Physician, Heal Thyself", published in two parts in the New York Review of Books (09/29/2011 and 10/13/2011).
Halsted became addicted during a program of self-experimentation on the anesthetic properties -- very common in medical research at the time. He managed to control his addiction, however, engaging in cocaine "binges" during vacations and other free time. More or less: Halsted was treated for his cocaine addiction with morphine (it was widely believed at the time that the two drugs were antagonists) -- and he promptly became a morphine enthusiast - -if not quite an addict -- as well.
Freud also experimented with cocaine in work
leading up to the publication of "On Coca" (Uber Coca,
1884), and other papers that, for some reason, didn't make
it into the Standard Edition of the Complete
Psychological Works of Sigmund Freud -- perhaps
because they were deemed "neurological" in nature.
In a reversal of Halsted's experience, but again based on
the belief that morphine and cocaine were physiological
antagonists, Freud advocated the use of cocaine for the
treatment of morphine addiction! Despite
Freud's advocacy, his principal case, his physician
colleague Ernst Fleischl, was a disaster.
Freud himself was not averse to the
recreational use of cocaine.
Ernest Jones, Freud's biographer (some would say hagiographer), dismisses the whole "cocaine episode" of 1884-1887 as an aberration. On the other hand, Crews, a vigorous critic of Freud and psychoanalysis, points out that the cocaine episode foreshadowed the problems with Freud's later psychotherapeutic work:
Already by 1886, then, Freud was displaying premature certainty, impatience with methodological safeguards, truculence, and a belief that he was destined for great things. Those weren't traits that blossomed after he developed psychoanalysis and felt a need to defend it. They were the very engine of invention.
At no point in either campaign did he place the safety and welfare of patients ahead of ambition. When cocaine was found to be tragically addictive for physicians and patients who had followed his thoughtless advise, he fought back desperately in 1887, bending the truth in order to exculpate himself. And when, after decades of claiming that psychoanalysis is the sovereign remedy for psychoneuroses, he allowed that he had "never been a therapeutic enthusiast", he didn't apologize; by then his fame as the Columbus of the unconscious was secure.
Freud's triumph in reaching that pinnacle without the aid of any confirmed discoveries or cures may be the most amazing chapter in the entire history of self-promotion.... Without cocaine, the polite and unhappy young doctor of April 1884 might never have become so reckless, so adamant, so sex preoccupied, and so convinced of his own importance that the contagion was caught by millions. Cocaine, along with nicotine, was Freud's drug of choice -- but in the century to come, the opiate of the educated classes would be psychoanalysis.
Throughout the 20th century, the techniques
for delivering and maintaining anesthesia were improved.
Modern anesthetic technique is known as balanced anesthesia, because it employs a "cocktail" of different drugs to achieve the goals of general anesthesia: sedation, loss of consciousness (sometimes referred to as "narcosis" or "hypnosis"), amnesia; and muscle relaxation.
There are also a number of alternatives to
There's even a turn toward no anesthesia
at all. That is, no general anesthesia, so that the
patient is wide awake during even major procedures that, in the past, would have involved general
anesthesia. In awake surgery
patients receive local or regional anesthesia to block pain, and conscious sedation to alleviate anxiety, but otherwise they're wide
awake during surgery, can watch the proceedings (though it's not clear
now much they'll remember, given
that they often receive
sedatives that are themselves amnestic agents),
and interact with the surgical team. Of
course, there are some downsides. The patient might
hear the surgeon comment on some problem encountered during
the procedure. Or, for that matter, the patient might
get bored and engage the anesthetist in
conversation. Medical students take courses in
doctor-patient communication, but, at
least until now, they've not been trained for anything
like this. Still, why "awake"
surgery might become more common.
Regional anesthesia is less expensive than general
anesthesia, there are fewer complications
and side effects, and faster recovery times. And, of
course, general anesthesia is always
available if patients change their minds. See
Under the Knife, with Eyes and Ears Wide Open" by Jan
Hoffman, New York Times, 03/26/2017)..
Since the 19th century, modern "scientific" medicine has generally disdained purely "empirical" treatments that are known to be efficacious, even though their scientific bases are not known. Nevertheless, general anesthesia has been universally adopted despite the fact that its underlying mechanisms remain a matter of considerable mystery.
Based on our understanding
of the molecular and cellular bases of neural activity, it
seems plausible that general anesthetics could temporarily
and reversibly disrupt neural activity in one of several
To complicate things further, the various classes of anesthetic agents appear to have somewhat different mechanisms of action. For example, many intravenous "hypnotic" drugs -- including propofol, barbiturates such as thiopental, and benzodiazepines such as diazepam -- appear to interact with gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, to increase the time that chloride ion channels are open, resulting in a hyperpolarization of cell membranes. However, ketamine, another intravenous anesthetic, interacts with excitatory N-methyl-D-aspartate (NMDA) receptors instead. Natural and synthetic opioid anesthetics such as fentanyl, of course, act on opioid receptors, inhibiting presynaptic release of neurotransmitters such as acetylcholine and substance P. However, even in high doses these drugs do not, by themselves, induce loss of consciousness. For this purpose, they are often combined with nitrous oxide and oxygen. Nitrous oxide, for its part, has effects on NMDA receptors similar to those of ketamine. Current evidence is broadly consistent with anesthetic action on both synaptic excitation and inhibition, with the contribution of each process varying from agent to agent.
The molecular and cellular mechanisms by which inhaled anesthetics such as isoflurane achieve their effects have been subject of intense investigation and debate. According to the Myer-Overton rule known since the late 19th century, there is a strong correlation between the potency of an anesthetic gas and its solubility in lipids. One early suggestion was that the expansion of nerve cell membranes effectively closed the ion channels by which sodium enters the cell to induce an action potential.
However, It is now believed that the inhalants bind directly to specific pockets of relevant proteins rather than altering the lipid bilayer itself. In this way, they might create a dynamic block of the "lock and key" channels involved in synaptic excitation; some anesthetics also intensify synaptic inhibition. Although the general view is that anesthetics act on the postsynaptic side, there are some indications that they inhibit presynaptic neurotransmitter release as well.
The concept of balanced anesthesia implies that there are likely to be a number of separate mechanisms working together to produce analgesia (lack of pain), a sleep-like loss of consciousness (sometimes referred to as "hypnosis"), immobility (voluntary responses to surgical stimuli, as opposed to the spinal reflexes suppressed by muscle relaxants such as vecuronium), and amnesia (lack of memory for surgical events). According to one proposal, inhalants such as isoflurane, which induce both immobility and amnesia, achieve these effects by different routes: immobility by acting on GABA receptors in the spinal cord, and amnesia by suppressing activity in the hippocampus.
As it happens, the specific proteins affected by inhaled anesthetics are receptors for GABA, among other neurotransmitters. Thus, the inhaled anesthetics may share a mechanism with the intravenous anesthetics after all. Along the same lines, the inhaled anesthetics share some pharmacological properties, such as tolerance, withdrawal, and cross-tolerance, with alcohol and sedative hypnotics such as barbiturates; this suggests that there may be a common mechanism uniting the inhaled and the intravenous anesthetics as well. On the other hand, there are now a number of anesthetic agents that violate the Meyer-Overton rule, and it is known some gases can bind to the proteins implicated in anesthesia yet not cause anesthesia. Although much attention has focused on GABA, Hans Flohr has implicated NMDA instead. Both nitrous oxide and ketamine act as antagonists on NMDA receptors, blocking glutamate, an excitatory neurotransmitter -- as does xenon, a newly developed anesthetic. Even if the intravenous anesthetics share a final common pathway with some inhaled anesthetics, other inhalants may achieve the same effects by rather different means.
suggest a "dual-process" theory, in which general
anesthesia occurs by virtue of one or another of two
Some theorists have sought to solve the mystery of anesthesia by invoking another mystery, namely quantum theory. Roger Penrose, a British mathematical physicist, and Stuart Hameroff, an American anesthesiologist, have famously speculated that consciousness is a product of certain processes described by quantum theory.
Anyway, within the
context of the quantum theory, Hameroff has
proposed that these processes take place in
microtubules -- proteins found in the walls of
neurons that are shaped like hollow tubes.
Although the conventional view is that
microtubules serve a structural function,
supporting the structure of the cell, it is also
true that they are built out of proteins -- and
certain proteins are known to be the site of
anesthetic activity. Penrose and Hameroff contend
that consciousness is actually a product of
processes occurring in this microtubular
cytoskeleton, which are in turn magnified by the
The Penrose-Hameroff theory of both consciousness and anesthesia has attracted a great deal of interest, and something like it has been endorsed by Eccles, but at this stage it remains highly speculative, and has been criticized on both logical and empirical grounds.
The quantum theory of consciousness has been criticized as excessively speculative, but its status might actually be worse than that -- an instance of what the Nobel physics laureate Murray Gell-Mann has called "quantum flapdoodle". The basic problem is that there is no reason to think that the "micro" (really, subatomic) world of quantum mechanics has anything to do with the "macro" world of classical physics -- that is, the real world in which human experience, thought, and action actually take place. For example, in the Unconscious Quantum (1995), Victor Stenger calculated that quantum mechanics operates only when a system's mass (m), speed (v), and distance (d) are on the order of Planck's constant (h). Because the properties of neurotransmitters exceed this limit, Stenger argues that quantum mechanics cannot provide a useful description of what is going on in the nervous system.
Or, as I like to put it, whether the strings of string theory vibrate in 10 or 11 or 26 dimensions, apples still fall, planets still revolve around their suns, the universe still expands -- and people still think and behave.
success of general anesthesia is marked by three
these terms, anesthesia is almost always
successful, with far fewer than 1% of surgical
patients report any awareness during
In general surgery, intraoperative awareness and postoperative recall are usually attributable to light anesthesia, machine malfunction, errors of anesthetic technique, and increased anesthetic requirements -- for example, on the part of patients who are obese or abuse alcohol or drugs. The incidence of surgical recall arises in special circumstances, such as trauma, cardiac, or obstetrical surgery, where cardiovascular circumstances dictate lighter planes of anesthesia. Even then, the incidence of surgical recall is remarkably low -- in part because even in the absence of anesthesia, the benzodiazepines often used for sedation are themselves amnestic agents.
In fact, modern anesthetic practice may underestimate the incidence of intraoperative awareness by interfering with postoperative memory. That is to say, an inadequately anesthetized patient may be aware of surgical events at the time they occur, but be unable to remember them later because of sedative-induced anterograde amnesia.
However low, the possibility of surgical awareness means that, in addition to monitoring various aspects of vital function during the operation, the anesthetist must also monitor the patient's state of consciousness, or anesthetic depth. This task would be made easier if psychology and cognitive science could reach consensus on the neural or behavioral correlates of consciousness. In the absence of such criteria, anesthesiologists have often been forced to improvise.
One set of standards simply relies on measures of anesthetic potency. Research has determined the minimum alveolar concentration (MAC) of inhalant which prevents movement in response to surgical stimulation in 50% of patients; MAC-aware is the concentration required to eliminate awareness of the stimulation. As a rule, MAC-aware is roughly half of MAC, suggesting that some of the movement in response to surgical stimulation is mediated by subcortical structures, and does not necessarily reflect conscious awareness. Similar standards for adequate anesthesia, based on blood plasma levels, have been worked out for intravenous drugs such as propofol.
It should be noted that the operational definition of MAC-Aware means that 50% of patients will be aware of surgical events despite the presence of anesthetic -- although a dose amounting to about 1.3 MAC does seem to do the trick.
Nevertheless, it is important to supplement knowledge of dose-response levels with more direct evaluations of the patient's conscious awareness. Unfortunately, many obvious clinical signs of consciousness -- such as talking or muscle movement in response to surgical stimulation are obviated by the use of muscle relaxants.
To make things worse, the use of muscle relaxants in balanced anesthesia makes it possible to perform surgery under lighter doses of anesthetic agents -- increasing the risk of intraoperative awareness and postoperative recall at the same time as they decrease the risk of anesthetic morbidity. In fact, it was recognized early on that the use of muscle relaxants increased the risks further, by preventing inadequately anesthetized patients from communicating their intraoperative awareness to the surgical team -- a situation reminiscent of Harlan Ellison's science-fiction classic, I Have No Mouth and I Must Scream (1967).
Of course, the simple fact that anesthesia impairs conscious recall does not mean that anesthetized patients lack on-line awareness of what is going on around them. In principle, at least, they could experience an anterograde amnesia for surgical events similar to that which occurs in conscious sedation. Or, perhaps, a retrograde amnesia. In either case, the possibility remains open that the patient is aware during surgery, but forgets it completely thereafter.
In the absence of a reliable and valid physiological index of conscious awareness -- something that is not likely to be available any time soon -- what is needed is some kind of direct behavioral measure of awareness, such as the patient's self-report. In balanced anesthesia, of course, such reports are precluded by the use of muscle relaxants.
But a variant on balanced anesthesia known as the isolated forearm technique (IFT), developed by Tunstall (1977), actually permits surgical patients to directly report their level of awareness in response to commands and queries. Because muscle relaxants tend to bind relatively quickly to receptors in the skeletal musculature, if the flow of blood is temporarily restricted to one forearm by means of a tourniquet, the muscles in that part of the body will not be paralyzed. And therefore, the patient can respond to the anesthetist's instruction to squeeze his or her hand, or raise their fingers -- that is, if they are aware of the command in the first place.
Interestingly, response to the IFT is not highly correlated with ostensible clinical signs of consciousness. Nor does it predict postoperative recollection of intraoperative events. In one study (King et al., 1993), more than 40% of patients receiving general anesthesia for caesarian section responded positively to commands; yet only about 2% had even fragmentary recollections of the procedure. On the assumption that a patient who responds discriminatively to verbal commands is clearly conscious to some extent, the IFT indicates that intraoperative awareness is somewhat greater than has previously been believed. On the other hand, discriminative behavior also occurs in the absence of perceptual awareness, as in cases of "subliminal" perception, masked priming, and blindsight. Estimates of intraoperative awareness may indeed be suppressed by an anterograde amnesia, which effectively prevents patients from remembering, and thus reporting, any awareness that they experienced during surgery.
The IFT is a useful tool for the anesthesiologist, but there are other, less direct, ways of monitoring surgical awareness that are more popular.
Traditionally, some anesthesiologists have relied on presumed autonomic signs of conscious pain and stress, such as the PRST score based on four factors:
In modern practice, most methods for monitoring the depth of anesthesia involve the central nervous system.
One common monitoring technique employs event-related potentials (ERPs, also known as evoked potentials, or EPs) elicited in the EEG by weak somatosensory, auditory, or even visual stimulation. The ERP, which is obtained by averaging the brain's response to repeated stimulation, consists of three components:
Adequate anesthesia reduces the amplitude of the various peaks and troughs in the ERP, as well as the latency of various components representing brainstem response and early and late cortical responses. Of course, the late "cognitive" components of the ERP would be expected to disappear entirely during adequate anesthesia. An AEP index of consciousness reflects the degree to which the late "cognitive" components of the ERP are suppressed, and the three "mid-latency" components of are delayed with respect to their normal occurrence between 20 and 45 milliseconds after the stimulus.
Another EEG index of consciousness is based on the EEG power spectrum, derived by a fast Fourier transform (don't ask) of the raw EEG signal. To make a long story short, the EEG can be broken up into four basic bands based on frequency.
of the raw EEG is provided by
bispectral analysis, a proprietary
algorithm (meaning that it is a patented
trade secret!) which employs a
complicated set of transformations to
yield a bispectral index (BIS)
based on a number of features of the
EEG, such as the amount of
high-frequency activation (indicating
wakefulness) and periods of "flat line"
EEG (indicating the lack thereof).
ranges from close to 100 in subjects who
are normally awake, to values well under
60 in patients who are adequately
anesthetized, and is clearly correlated
with brain-imaging measures of cortical
Although most physiological indices of anesthetic depth have been validated against such criteria as movement in response to painful surgical stimulation, they have also been compared to various aspects of memory performance. In one study, a 0.2% end-tidal concentration (a measure related to MAC) of isoflurane produced a substantial impairment of performance on a continuous recognition test even over retention intervals as short as 8 seconds, while a 0.4% end-tidal concentration reduced recognition after 32 seconds to zero. Another study showed similar effects for low and high doses of propofol. In a study comparing midazolam, isoflurane, alfentanyl, and propofol, a 50% reduction in recall was associated with an average BIS score of 86, while an average BIS of 64 yielded reductions of 95%.
proprietary device making use of processed
EEG yields "stages" of
anesthesia, analogous to sleep
stages, ranging from A (fully awake)
to F (a absence of brain activity).
2008, a group of anesthesia researchers at McGill University
introduced McSleepy, an automated system for delivering
anesthetics. Given information about a patient's weight and
age, McSleepy calculates the amount of anesthetic to be delivered,
and then monitors the patient's level of consciousness.
Depending on measurements of the bispectral index, muscle
responsiveness (as an index of muscle relaxation), and heart rate
and blood pressure (as proxies for pain), will add or withhold
In 2010, McSleepy hooked up with DaVinci, a surgical robot (where the surgeon operates a set of joysticks, but the actual cutting is done by a machine), to perform the first intercontinental surgery -- a prostatectomy. The patient was in Italy, but the anesthesia was monitored and delivered by McSleepy, and the surgery itself was done by DaVinci, all controlled from McGill.
A note is in order
about the side-effects of
general anesthesia. There is some
evidence that general anesthesia
can lead to post-operative
delirium (POD), including
similar to those seen
in the amnesic
are occurrences of postoperative
(POCD), which lasts
much longer and
includes a wider range
of problems in
deeper the anesthesia,
as measured by BIS or
similar indices, the
patients are especially
at risk for both POD and
less risk to
brain. But the
risks at any age have to
be balanced against the fact
that most modern
surgeries wouldn't be
possible at all
anesthesia, and those
would also be pretty
(ask any Civil War
For more details,
Dangers of Going
Under" by Carina
04/2014; and "The
Risks of Going
Under" by Andrea
While adequate general anesthesia abolishes conscious recollection of surgical events by definition, it is possible that unconscious (or, for that matter, conscious) intraoperative perception may lead to unconscious postoperative memory that influences the patient's subsequent experience, thought, and action outside of phenomenal awareness.
In fact, clinical lore within anesthesiology includes the "fat lady syndrome", in which an overweight patient's postoperative dislike of her surgeon is traced to unkind remarks he made about her body while she was anesthetized. Nevertheless, documented cases are hard to find.
In the late 1950s and early 1960s David Cheek, a Los Angeles physician and hypnotherapist, described a number of patients who, when hypnotized, remembered meaningful sounds that occurred in the operating room -- particularly negative remarks. Cheek claimed to have corroborated these reports, and attributed unexpectedly poor postoperative outcomes to unconscious memories of untoward surgical events. Unfortunately, the interview method he employed, hypnotic "ideomotor signaling", is highly susceptible to experimenter bias, and information that would corroborate such memories is not always available. Accordingly, the possibility cannot be excluded that patients' postoperative "memories", recovered through this technique, are confabulations.
Despite these methodological problems, Cheek's suggestion was subsequently supported by Bernard Levinson, who as an experiment staged a bogus crisis during surgery. After the anesthesia had been established (with ether), the anesthesiologist, following a script, asked the surgeon to stop because the patient's lips were turning blue. After announcing that he was going to give oxygen, and making appropriate sounds around the respirator, he informed the surgeon that he could carry on as before. One month later, Levinson hypnotized each of the patients -- all of whom had been selected for high hypnotizability and ability to experience hypnotic age regression -- and took them back to the time of their operation. Levinson reported that four of the ten patients had verbatim memory for the incident, while another four became agitated and anxious; the remaining two patients seemed reluctant to relive the experience. Levinson's provocative experiment suggested that surgical events could be perceived by at least some anesthetized patients, and preserved in memory -- even if the memories were ordinarily unconscious, and accessible only under hypnosis.
Despite Levinson's report, unconscious perception during general anesthesia remained largely unexplored territory until the matter was revived by Henry Bennett. Inspired by the apparent success of Cheek's "ideomotor signaling" technique for revealing unconscious memories, Bennett gave anesthetized surgical patients a tape-recorded suggestion that, when interviewed postoperatively, they would perform a specific behavioral response, such as lifting their index finger or pulling on their ears. Although no patient reported any conscious recollection of the suggestion, approximately 80% of the patients responded appropriately to the experimenter's cue. Bennett, following Cheek, suggested that unconscious memories were more likely to be revealed with nonverbal than with verbal responses.
At about the
same time, Evans and Richardson
reported that intraoperative
suggestions, delivered during
general anesthesia, led to improved
patient outcome on a number of
variables, including a significantly
shorter postoperative hospital stay.
Again, the patients had no conscious
recollection of receiving these
suggestions. Although this study was
not concerned with memory per se,
the apparent effects of suggestions
on post-surgical recovery certainly
implied that the suggestions
themselves had been processed, if
unconsciously, at the time they
As it happens, subsequent studies have failed to confirm the findings of either Bennett et al. or Evans and Richardson. And more recently, a double-blind study inspired by Levinson's report, in which non-patient volunteers received sub-anesthetic concentrations of either desflurane or propofol, failed to obtain any evidence of memory for a staged crisis. Nevertheless, these pioneering studies, combined with an increasing interest in consciousness and unconscious processing within the wider field of psychology and cognitive science stimulated a revival of interest in questions of awareness, perception, and memory during and after surgical anesthesia, which have been carried out with progressively improved paradigms.Of particular importance to this revival was the articulation, in the 1980s, of the distinction between two different expressions of episodic memory -- explicit and implicit. To review:
In one of the first controlled studies of implicit memory following surgical anesthesia, Kihlstrom et al. worked with patients receiving isoflurane anesthesia for elective surgery. Through earphones, these patients were played an auditory list of 15 paired associates consisting of a familiar word as the cue and its closest semantic associate as the target -- e.g, ocean-water. The stimulus tape was presented continuously from the first incision to the last stitch, for an average of 67 repetitions over an average of 50 minutes. In the recovery room, the patients were read the cue terms from the stimulus list, as well as a closely matched set of cues from a control list of paired associates, and asked to recall the word with which each cue had been paired on the list read during surgery: this constituted the test of explicit memory. For the test of implicit memory, they were read the same cues again, and asked simply to respond with the first word that came to mind. The subjects recalled no more target words from the presented list than from a control list, thus showing that they had very poor explicit memory for the experience. On the free-association test, however, they were more likely to produce the targeted response from the presented list, compared to control targets, thus displaying a priming effect. Compared to explicit memory, which was grossly impaired (as would be expected with adequate anesthesia), implicit memory was relatively spared.
Despite this early success, subsequent studies employing similar paradigms produced a mix of positive and negative results.
For example, Cork et al. precisely replicated the procedure employed by Kihlstrom et al. with another group of patients receiving sufentanyl, and found that explicit and implicit memory were equally impaired. Although the two studies, taken together, suggested the interesting hypothesis that different anesthetic agents might have different effects on implicit memory, a more parsimonious conclusion might have been that the isoflurane effects were spurious.
In a debate at the Second International Symposium on Memory and Awareness in Anesthesia, held in 1992, experimental psychologists and anesthesiologists agreed that memory for events during anesthesia had not yet been convincingly demonstrated by an overwhelming body of research.
Over the next few years, however, the literature began to settle, so that in 1996 a comprehensive quantitative review by Merikle and Daneman of 44 published studies concluded that adequately anesthetized patients can, indeed, show postoperative memory for unconsciously processed intraoperative events.
Although the more recent literature continues to contain a mix of positive and negative results, there are simply too many positive findings, from too many different implicit memory paradigms, to be ignored. At the same time, the literature contains enough negative studies, and other anomalous results, to warrant further investigation.
For example, in their 1996 review Merikle and Daneman concluded that the evidence for unconscious processing during general anesthesia was not limited to "indirect" measures of implicit memory, and extended to "direct" measures of explicit memory as well. This is a surprising statement, given that adequately anesthetized patients lack conscious recollection by definition. However, these authors included in their survey only the few tests of explicit memory that encouraged guessing, and excluded the many studies that discouraged guessing. While guessing yields a more exhaustive measure of conscious recollection, it is also true that guessing can be biased, unconsciously, by priming itself. Therefore, it is likely that some of the "explicit" memory identified by Merikle and Daneman is, in fact, contaminated by implicit memory. In support of this idea, a study employing the "process dissociation" procedure confirmed that postoperative memory was confined to automatic priming effects, and not conscious recollection.
A persisting issue is whether postoperative implicit memory might be an artifact of fluctuations in anesthetic depth which occur naturally during surgery. To some extent, this question was addressed in a new review of the literature, by Deeprose and Andrade (2006), which included 24 studies that employed formal (rather than clinical) assessments of anesthetic depth by means of the isolated forearm technique, auditory evoked potentials, or processed EEG (such as the Bispectral Index, spectral edge frequency, or Narcotrend). This review yielded mixed evidence generally favoring the hypothesis that perceptual priming was often spared during anesthesia. But no evidence that semantic priming was also preserved. There was more repetition priming observed in studies that employed a relatively light plane of anesthesia, compared to studies that employed deeper planes, but in all cases the anesthesia was clinically adequate, so there is no question that the preserved priming occurred only in patients who were in some sense "awake" during presentation.
In what is perhaps the best of these studies, Iselin-Chaves and her colleagues (2005, 2006). Instead of adopting the usual format of a comparison of explicit and implicit memory (e.g., comparing stem-cued recall with stem-completion), these investigators opted to use only a stem-completion test. However, they employed Jacob's Method of Opposition and Process-Dissociation Procedure to separate out the automatic (unconscious) and controlled (conscious) contributions to task-performance. In their experiment, 48 patients anesthetized with isoflurane or propofol (but without sedative premedication) were presented with a list of 40 words, each word repeated 40 consecutive times. There was also an unanesthetized control group.
within 36 hours of surgery, each
patient performed a
stem-completion test under
Inclusion and Exclusion
instructions. The patients
produced 17% of targets under
both conditions. That is,
they produced the same number of
targets when they were
instructed to exclude any they
consciously remembered, as they
did when there were instructed
to include those that they
consciously remembered. By
contrast, the controls produced
49% of the targets under the
Inclusion instructions, and only
15% of the targets under the
Obviously, most of the patients'
stem-completion performance was
mediated by automatic priming,
while most of the controls'
performance was mediated by
During surgery, depth of anesthesia was monitored by the bispectral index, and individual test items were classified according to the average BIS score obtained during their presentation. For the patients, conscious recollection did not vary with BIS score -- after all, even "light" anesthesia is enough to impair explicit memory. But the automatic component, representing unconscious priming, was much larger than the controlled component, representing conscious recollection.
This study has been criticized for its reliance on average BIS scores, which leave open the possibility that the spared priming reflected conscious processing occurring during natural fluctuations of anesthetic depth. In response, Iselin-Chaves and her colleagues (2006) re-analyzed their data, classifying each target in terms of the maximum BIS score obtained during its presentation. The results were very much the same, except -- not surprisingly -- less priming was observed for items presented under the vary deepest levels of anesthesia. Still, it has to be pointed out that considerable priming occurred for items presented during "adequate" anesthesia, and that "adequate" anesthesia was sufficient to take the conscious, controlled component of task-performance almost to zero. There was priming for items presented during anesthesia, and this priming was spared even when explicit memory was grossly impaired.
Most work on implicit memory employs tests of repetition priming, such as stem- or fragment-completion, in which the target item recapitulates, in whole or in part, the prime itself -- for example, when the word ashtray primes completion of the stem ash-. Repetition priming can be mediated by a perception-based representation of the prime, which holds information about the physical properties of the item, but not about its meaning. But there are other forms of priming, such as semantic priming, where the relationship between prime and target is based on "deeper" processing of the prime -- for example, when the prime cigarette primes completion of the stem ash- with -tray as opposed to -can. Semantic priming requires more than physical similarity between prime and target, and must be mediated by a meaning-based representation of the prime. The distinction between repetition and semantic priming is sometimes subtle. For example, in the isoflurane study described earlier, the paired associates presented as primes were linked by meaning, but because both elements of the pair were presented at the time of study, the priming effect observed could have been mediated by a perception-based representation, rather than a meaning-based one. The point is that implicit memory following surgical anesthesia is fairly well established when it comes to repetition priming, but conclusions about semantic priming are much less secure. Fewer studies have employed semantic priming paradigms, and relatively few of these studies have yielded unambiguously positive results. If semantic priming occurs at all following general anesthesia, it is most likely to occur for items presented at relatively light levels of anesthesia, as indicated by indices such as BIS. At deeper planes of anesthesia, implicit memory -- if it occurs at all -- is likely to be limited to repetition priming.
Priming effects are evidence of implicit memory, but they can also serve as evidence of implicit perception -- a term coined to refer to the effect of an event on experience, thought, and action, that is attributable to a stimulus event, in the absence of (or independent of) conscious perception of that event. Implicit perception is exemplified by "subliminal" perception of degraded stimuli, as well as neurological syndromes such as "blindsight" and neglect. In general anesthesia, the patients are presumably unaware of the priming events at the time they occurred. For that reason, evidence of implicit memory following general anesthesia is also evidence of implicit perception.
Link to the
website for the 8th
symposium on Memory and
Awareness in Anesthesia, to
be held in 2011 at the
Medical College of
brief history of this
symposium (several of the
symposium proceedings have
The distinction between perception-based and meaning-based priming may have implications for the use of intraoperative suggestions to improve post-surgical outcome. As noted earlier, a positive report by Evans and Richardson helped stimulate this line of research to begin with. If subjects unconsciously retain information about surgical events, it might indeed be possible for them to benefit from therapeutic suggestions offered to them while they were anesthetized. On the other hand, if implicit memory following anesthesia is limited to repetition priming, implying that the anesthetized patient's state of consciousness does not permit semantic analysis of the intraoperative message, it is hard to see how such suggestions could have any effects at all.
fact, as noted earlier, attempts
to replicate the Evans and
Richardson study have been
largely unsuccessful, and the
Evans and Richardson study
itself has been criticized on a
number of grounds:
double-blind. As an
additional feature, all
provided an objective
measure of the amount of
pain they experienced: if
the therapeutic suggestions
worked, patients who
received them would be
expected to request less
medication than those who
As it happened, there
were no significant differences
between the three groups of
patients in terms of either
post-operative pain reports,
requests for morphine, or
nausea. In other words,
suggestions had no more effect
on postoperative outcome than
suggestions of the same sort --
or, for that matter, the pre-
and intraoperative reading of
Intraoperative suggestions will do no harm, and patients may derive some "placebo" benefit from the simple knowledge that they are receiving them during surgery. To the extent that intra-operative suggestions do some good, the limitations on information processing during anesthesia may mean that any positive effects are more likely to be mediated by their prosody, and other physical features, than by their meaning: a soothing voice may be more important that what the voice says. If anesthesiologists want patients to respond to the specific semantic content of therapeutic messages, such messages are probably better delivered while patients are awake, during the pre-operative visit that is already established as the standard of care.
General anesthesia is sometimes referred to as a controlled coma, and indeed anesthetized patients superficially resemble comatose patients:
coma, general anesthesia
underscores two basic
surgical patients seem
to lack both these
This page last revised 03/27/2017.