Note: The following is expanded from an article, "Anesthesia, Effects on Cognitive Functions", by J.F. Kihlstrom, L.J. Couture, D.L. Schacter, & R.L. Cork which appears in the Encyclopedia of Neuroscience, 2^nd Ed., edited by G. Adelman (Amsterdam: Elsevier Science Publishers, 1998).

What is surgical anesthesia? Surgical anesthesia is intended to render the patient insensitive to pain. In a typical clinical procedure, known as balanced anesthesia, the patient is premedicated with a sedative intended to relieve pre-operative anxiety and facilitate the induction of anesthesia itself (often this is a benzodiazepine such as diazepam or midazolam; otherwise, a barbiturate such as thiopental or nonbenzodiazepine such as propofol may perform this function). Sedation is followed by the induction of general anesthesia by intravenous injection of a sedative, narcotic (e.g., morphine, fentanyl, alfentanyl), or ketamine. In addition, a nondepolarizing curare-like derivative (e.g., vecuronium, d-turbocurarine) or a depolarizing drug (e.g., succinylcholine) is administered to induce muscle paralysis. After intubation and connection to a ventilator for artificial respiration, general anesthesia may be maintained by a mixture of oxygen and nitrous oxide, often in combination with a volatile agent (e.g., halothane, enflurane, or isoflurane) or intravenous drug. At the conclusion of the surgery, muscle relaxation is reversed (e.g., by neostigmine or other anticholinesterase), and normal (unassisted) breathing is restored. In addition, the patient may be given an analgesic agent (e.g., morphine) to manage any acute pain experienced postoperatively.

Another method, commonly used in office procedures and outpatient surgery, is known as "conscious sedation". In this procedure, the patient is sedated by barbiturates (e.g., sodium pentothal) or benzodiazepines (e.g., Valium), and receives a local or regional anesthetic (e.g., Novocain). Because no general anesthetic is involved, the patient never loses consciousness. He or she remains awake and able to move during the procedure, and can interact with the medical team, but feels no pain. Because of the amnesic properties of most sedative drugs, the patient may have no memory of the procedure after it is over.

Some surgical procedures are appropriately performed with only local or regional anesthesia. Examples include the use of Novocain for routine dental work, or epidural blocks in obstetrics. Without sedation or anesthesia, the patient remains fully aware during the procedure, and retains conscious memory for the events of surgery. In neurosurgery, for example, patients are not commonly anesthetized because the brain has no afferent neurons to conduct pain messages.

How was anesthesia discovered? Anesthesia for surgery was introduced in America only in the 1840s. Before this time, surgical patients were simply expected to withstand the pain of the procedure. Alternatively, they were intoxicated with alcohol or opiates (e.g., laudanum). Humphry Davy (1778-829), a famous English chemist, discovered through self-experimentation that nitrous oxide relieved headache and dental pain, but his report went unnoticed in the medial community; it did, however, led to the use of "laughing gas", and later ether, for entertainment at parties!

The first demonstration of surgical anesthesia was by Horace Wells (1815-1848), an American dentist who had observed the effects of nitrous oxide at a traveling medicine show. Wells had some of his own teeth extracted painlessly under nitrous oxide, but during his first pubic demonstration, in Boston in 1845. Despite the fact that the patient reported no awareness or memory of pain, the demonstration was judged a failure, and Wells mocked, because the patient screamed and struggled throughout the procedure. However, Wells's failure was observed by another dentist, William Morton, who began experimenting with ether. In 1846, Morton demonstrated the surgical removal of a tumor in a patient who showed no signs or reports of pain. (Click on the picture above left to see an enlarged painting of this event.) By 1847, ether and chloroform were firmly established as general anesthetics on both sides of the Atlantic. Except for childbirth: physicians worried about the effects of chemical analgesics on the fetus, and also worried that the absence of pain would impair the bonds between mother and child.

Later, it was discovered that morphine lessened the amount of chloroform needed to produce complete anesthesia. In the early 20^th century ether and chloroform werereplaced by halogenated hydrocarbons such as halothane (sometimes, a mixture of nitrous oxide and oxygen, or intravenous narcotics such as fentanyl, are used instead of a volatile agent). In 1942, Griffith and Johnson administered curare to reduce reflexive responses to surgical incisions (and artificial respiration to maintain breathing). This yielded the "balanced anesthesia" procedure still in use today: a "cocktail" of drugs to induce loss of consciousness, eliminate pain, and calm the operative area.

Originally, general anesthesia was considered to be a purely "empirical" treatment, whose effectiveness had been demonstrated but whose mechanism of action was unknown. For this reason, anesthesia was initially ignored by established medical practitioners, who for professional reasons did not want to employ any technique whose scientific basis was not understood.

How does anesthesia work? We still do not know exactly how general anesthesia works, but modern neuroscientific research has at least suggested a number of plausible hypotheses. The most commonly accepted theory is that general anesthetics operate directly on the central nervous system to temporarily inhibit synaptic transmission (the chemical means by which neural impulses are transmitted between adjacent neurons). This results in a general loss of consciousness that affects sensory awareness in all modalities and at all body loci.

Beyond this general statement, one "nonspecific" theory holds that anesthetics impair the operation of the sodium pump, preventing depolarization of postsynaptic neurons. A more recent "dual-process model" suggests that anesthetics simultaneously inhibit the actions of excitatory neurotransmitters such as glutamate and acetylcholine and enhance the actions of inhibitory neurotransmitters such as GABA and glycine. The specific physiological mechanism by which anesthesia is achieved probably differs for each different class of anesthetic agents.

Am I really unaware during general anesthesia? General anesthesia is sometimes called a "controlled coma", as indexed by four features: (1) the lack of motor response to instructions; (2) suppression of autonomic and skeletal responses to intraoperative stimuli such as incisions; (3) absence of retrospective awareness of pain; and (4) postoperative amnesia for surgical events such as conversations among the medical team.

Of course, anesthesia is a complex procedure and on occasion things can go wrong. In cases of inadequate anesthesia the patient may be aware of the surgery as it goes on.Preoperative sedation may reduce anxiety, and the analgesic administered as part of the "balanced" cocktail may reduce worry; but the muscle relaxant, also administered as part of "balanced" anesthesia, prevents the patient from communicating that he or she is still awake until after the procedure is over. Fortunately, the incidence of surgical awareness is very low (well under 1%), and even then it is most common in procedures such as Caesarian section, trauma surgery, and some cardiac procedures, where the standard of care permits only a light plane of anesthesia to begin with.

Is there unconscious processing during anesthesia?  By definition, adequately anesthetized patients rarely show any conscious recall or recognition of surgery. Nevertheless, there is some evidence that surgical events may be processed to some degree even by adequately anesthetized patients, resulting in the encoding of memory traces of experience that can affect postsurgical experience, thought, and action.

Prima facie evidence for information processing during general anesthesia is provided by studies of classical conditioning in animals: conditioned fear responses can be acquired during anesthesia, and displayed after recovery. This evidence is mitigated, however, by the empirical fact that conditioned responses can be established in almost any organism that has a nervous system, including decorticate animals. This primitive form of learning should not be confused with the higher cognitive processes involved in intelligent perception, memory, and thought.

Other evidence indicates that adequately anesthetized patients continue to show event-related potentials (ERPs) to auditory and tactile stimulation (ERPs are specific electrical responses of the brain to environmental stimuli). In fact, ERPs constitute one way in which the patient's status is monitored during surgery. However, the ERP is very complex: for example, the first 10 milliseconds of the auditory ERP reflect brainstem activity, those arising with 10-100 msec the activity of the primary auditory cortex, and those observed after 100 msec the activity of the cortical association areas. Only the early components of the ERP are clearly unaffected by anesthetic agents (these are the only components routinely monitored during surgery); the later, perceptual-cognitive components exhibit dose-related suppression of activity. To date, there have been few studies of the fate of later components of the cognitive ERP, such as the P300 response to the omission of an expected event, or the N400 response to semantic anomalies.

In the absence of definitive studies of cognitive ERPs, on-line evidence of complex mental activity comes primarily from studies using the "isolated forearm technique", in which muscle relaxant is prevented from affecting one arm by means of a tourniquet. In some (but not all) cases, the patient retains the ability to make a motor response with the spared limb in accordance with instructions from the anesthetist, but this is usually confined to the earliest stages of surgery, where the plane of anesthesia is the lightest. However, most adequately anesthetized patients have no conscious recollection of having been given these instructions, or of responding.

Is there any memory for surgical events? Evidence of information processing during anesthesia is often sought in evidence of memory afterwards. Of course, a failure to remember surgical events is part and parcel of the definition of adequate anesthesia. However, recent studies of both brain-damaged patients and intact subjects supports a distinction between explicit memory, which requires the conscious recollection of a previous episode; and implicit memory, as revealed by a change in task performance that is attributable to such an event. Explicit and implicit memory are dissociable. For example, amnesic patients typically fail to recall or recognize the items studied in a list of words; however, they generally show priming effects attributable to the study episode when they are asked to identify words presented under degraded conditions, or to words as completions of stems or fragments. By definition, adequate general anesthesia abolishes explicit memory for surgical events; but the possibility remains that some degree of implicit memory may be spared.

Although the evidence is still rather mixed, recent studies employing procedures derived from the laboratory study of normal and pathological memory suggest that a dissociation between explicit and implicit memory may be obtained under certain conditions of adequate anesthesia. For example, patients (maintained on nitrous oxide-oxygen and, in some cases, halothane) who were presented a list of low-frequency words during surgery showed no memory for the list on a post-operative recall test; but when encouraged to guess on a recognition test, showed greater accuracy than control subjects. In another study, patients anesthetized with the inhalant isoflurane were presented with a list of extremely low-frequency words. They were unable to remember these words following recovery; however, they did rate these items as more familiar than carefully matched control words. This effect was not observed when the anesthetic was switched to the intravenous narcotic fentanyl, suggesting that different kinds of anesthetic agents have different effects on memory.

In one widely cited study of general anesthesia, patients anesthetized with the inhalant isoflurane who were read paired associates (e.g., bread-butter) during their surgery. When tested in the recovery room, they showed no subsequent free recall, cued recall, or recognition of the items. However, when presented with the initial word of each pair and asked to report the first word that came to mind, they were more likely to produce the item with which the cue had been paired during surgery, compared to control pairs that had not been presented. This phenomenon, known as repetition priming, shows that implicit memory has been spared, even if the patients lacked explicit memory for the surgical events. The recognition and familiarity findings of the earlier studies may also have been due to spared implicit memory. Again, however, the identical study performed with patients who received anesthesia by the intravenous narcotic, sufentanyl. This finding strengthens the hypothesis that different classes of anesthetic agents, operating through different physiological mechanisms, have different effects on implicit memory.

Since these early studies, several other well-designed studies have failed to find evidence of spared implicit memory in adequately anesthetized patients. For this reason, the fate of implicit memory for events occurring during general anesthesia remains controversial, especially among anesthetists. However, a recent "meta-analysis" of the literature by Philip Merikle and Meredyth Daneman, two Canadian psychologists (published in Consciousness & Cognition, a scientific journal, in 1996) reviewed 44 studies involving 2,517 patients showed clear evidence that repetition priming is relatively spared under such conditions; however, there was little evidence for spared semantic priming. Thus, unconscious perception during anesthesia may be limited to relatively simple perceptual operations, and may not extend to more complicated cognitive analyses.

As its name implies, conscious sedation does not entail a general loss of consciousness on the part of the patient. Nevertheless, the centrally acting drugs do produce a dense amnesia for the surgery and surrounding events. Once again, however, this amnesia tends to dissociate explicit and implicit memory. In a study of midazolam, for example, subjects showed a profound deficit in recognition memory, but intact levels of priming on a test of perceptual identification. And in a study of propofol paralleling the isoflurane and sufentanyl studies of general anesthesia, patients who studied paired associates during surgery showed poor postoperative cued recall, but intact priming when asked to generate free associations. Thus, the drugs involved in conscious sedation seem to impair explicit memory, while sparing implicit memory.

The distinction between general anesthesia and conscious sedation underscores the fact that "general anesthesia" is not a single, monolithic construct. It seems likely that the various types of anesthetics in current use have different psychological effects as well. Detailed study of the cognitive effects of the various classes of anesthetic agents, coupled with a more detailed psychopharmacological theory of anesthetic effects, may yield important insights into the biological substrates of conscious and nonconscious cognitive processes.

What are the implications of implicit memory?  The preservation of some information-processing functions during adequate general anesthesia, as revealed by findings of spared implicit memory is mostly of theoretical interest to psychologists and neuroscientists. Nevertheless, the possibility that something "gets in" during anesthesia, even unconsciously, has some potential practical implications. For example, a few studies have obtained evidence that at least some patients respond positively to hypnosis-like therapeutic suggestions administered during anesthesia, showing speeded postoperative recovery, diminished requests for pain medication, and the like, although the patients do not remember receiving the suggestion.

The "psychosomatic" effects of intraoperative suggestion, if confirmed, would also count as evidence of information processing during anesthesia, as well as of implicit memory. The meta-analysis by Merikle and Daneman found no evidence for the effectiveness of therapeutic suggestions given intra-operatively, although the evidence is sparse. It may be that such suggestions are helpful, and unlikely that any harm comes from them. For this reason, some surgeons and anesthetists offer their patients with tapes containing soothing music and therapeutic suggestions, to be played during surgery. No harm comes from this procedure, and clinical research may yet determine that they are helpful.

Some physicians resist evidence of spared implicit memory during general anesthesia because it seems to imply that the patients in question are not adequately anesthetized. In their view, any post-operative memory implies intra-operative awareness, and thus a failure of anesthesia. However, this reaction is inappropriate, because memory does not necessarily imply awareness. The implicit memories observed following general anesthesia are unconscious memories, resulting from unconscious perceptual activities that are themselves severely limited in scope. Far from implying that ostensibly anesthetized patients are in fact aware of surgical events as they occur, priming effects merely indicate that some extremely limited perceptual processing of the surgical environment goes on outside of awareness.

Figure 1. "First Operation Under Ether", painted 1882-1894 by Robert C. Hinkly, on display in the Fancis A. Countway Library of Medicine, Harvard Medical School.

Figure 2. Adapted from Kihlstrom, J.F., Schacter, D.L., Cork, R.L., Hurt, C.A., & Behr, S.E., "Implicit and explicit memory following surgical anesthesia", Psychological Science, 1, 303-306 (1990).

Figure 3. Adapted from Cork, R.C., Heaton, J.F., Campbell, C.E., & Kihlstrom, J.F., "Is there implicit memory after propofol sedation?", British Journal of Anaesthesia, 76, 492-498 (1996).
 
 

Comprehensive coverage of the continuing debate over cognition during surgical anesthesia is provided by the proceedings of international symposia dedicated to the topic, which have been held about every three years since 1989. Four such volumes have appeared to date:

Bonke, B., Fitch, W. , & Millar, K. (Eds.). (1990). Awareness and memory during anaesthesia. Amsterdam: Swets & Zeitlinger.

Sebel, P.S., Bonke, B., & Winograd E. (Eds.). (1993). Memory and awareness in anesthesia II. Englewood Cliffs, N.J.: PTR Prentice Hall.

Bonke, B., Bovill, J.G., & Moerman, N. (Eds.). (1996). Memory and awareness in anaesthesia III. Assen, the Netherlands: Van Gorcum.

Jordan, C., Vaughan, D.J.A., & Norton, D.E.F. (2000). Memory and awareness in anaesthesia IV. London: Imperial College Press.

Cork, R.L., Couture, L.J., & Kihlstrom, J.F. (1997). Memory and recall. In J.F. Biebuyck, C. Lynch, W.M. Zapol, M. Maze, & L.J. Saidman (Eds.), Anesthesia: Biologic foundations (pp. 451-467). New York: Lippincott-Raven.

Polster, M.R. (1994). Drug-induced amnesia: Implications for cognitive neuropsychological investigations of memory. Psychological Bulletin, 114, 477-493.

Hindmarch, I., Jones, J.G., & Moss, E. (1987). Aspects of recovery from anaesthesia. London: Wiley.

Jones, J.G. (Ed.). (1989). Depth of anaesthesia. Bailliere's Clinical Anaesthesiology: International Practice and Research (Vol. 3, No. 3). London: Bailliere Tindall.

Pernick, M.S. (1985). A calculus of suffering: Pain, professionalism, and anesthesia in 19^th-century America. New York: Columbia University Press.

Rey, R. (1998). The history of pain. Cambridge, Ma.: Harvard University Press.

Rosen, M. & Lunn, J.N. (1987). Consciousness, awareness and pain in general anaesthesia. London: Butterworths.

John F. Kihlstrom, PhD

Copyright © 2000 Institute for the Study of Healthcare Organizations & Transactions

Last modified:03.26.2004 11:02 PM