Explicit recall of intraoperative events during general anesthesia occurs in approximately 0.2% of nonobstetric and noncardiac cases, while evidence for unconscious implicit memory remains conflicting.
Awareness during general anesthesia is a rare but potentially devastating complication that highlights the need for vigilant anesthetic management and potential monitoring strategies.
(Ghoneim) Professor.(Block) Associate Professor.Received from the Department of Anesthesia, College of Medicine, University of Iowa, Iowa City, Iowa. Submitted for publication November 20, 1996. Accepted for publication March 27, 1997.Address reprint requests to Dr. Ghoneim: Department of Anesthesia, College of Medicine, University of Iowa, Iowa City, Iowa 52242.Dennis M. Fisher, M.D., EditorIn 1992, we published a review article in Anesthesiology on learning and consciousness during general anesthesia. 1 Since then, there has been a steady flow of publications and two international conferences on the subject; one in 1992 in Atlanta, Georgia, and another in 1995 in Rotterdam, the Netherlands. In 1992, the issue of preservation of unconscious information-processing capability by the anesthetized patient was debated because of the mixed results of studies at that time. We and others 2,3 thought that with improvement in the quality of work in this area, the issue of whether unconscious retention of intraoperative events is a reliable, replicable phenomenon might be resolved in a few years. Unfortunately, this has not happened. With conflicting reports and contradictory statements being published, we chose to update the reader on this and related subjects with particular emphasis on problems and difficulties in this area, and to provide some comments that we hope will be useful for future studies.Here we address the following issues.1. Explicit or conscious memory or “awareness”;2. Studies of anesthetized patients using implicit tests of memory;3. Postoperative motor behavior after presentation of suggestions during anesthesia;4. Studies of the efficacy of administration of therapeutic suggestions during anesthesia;5. Studies of healthy volunteers;6. Effects of anesthetics on animal learning and memory; and7. Reports of cases of psychosomatic disorders after anesthesia and surgery.In each area, we discuss in particular the studies that have been published since 1992, within the context of the earlier literature, followed by comments and critiques. We use the term consciousness as defining a state of awareness of the outside world and use the terms consciousness, awareness, and wakefulness interchangeably.Distinctions between different types of learning and memory remain the subject of considerable debate. One such distinction, of particular interest to anesthesia, is between explicit and implicit learning. The essential difference is whether learning is manifested with or without concurrent awareness of remembering. 4,5The most recent study in which a structured interview was used in a large series of patients indicated that the incidence in nonobstetric and noncardiac surgical cases is 0.2%. 6 The incidence is similar after total intravenous anesthesia. 7 It is higher, however, when light anesthesia is used. The incidence in cardiac surgery ranges from 1.14–1.5%, 8,9 with a balanced anesthetic technique consisting of benzodiazepines, low-dose fentanyl, and a volatile agent. A higher incidence has been reported for obstetric cases 10(0.4%) and major trauma cases 11(11–43%), and this incidence varies according to the dose of anesthetic administered. Jones 12 estimates that only about 0.01% of patients report suffering from pain while being aware.Recently Cobcroft and Forsdick 13 and Moerman et al. 14 studied the consequences of recall of intraoperative events during anesthesia. Cobcroft and Forsdick described patients who responded to an article published by Forsdick about her own experience of awareness during anesthesia in a lay magazine widely distributed in Australia and New Zealand. Moerman et al. studied patients who were referred to them by anesthesiologists. Despite the different strategies of patient selection of the two groups, there was close agreement between the results. The two most frequent complaints were ability to hear events during surgery and sensations of weakness or paralysis, in addition to the recall of pain, if it was present. It seems that patients particularly recall conversations or remarks that are of a negative nature concerning themselves or their medical conditions. The most frequently reported postoperative effects were sleep disturbances, dreams and nightmares, flashbacks, and daytime anxiety.For many patients, the experience of awareness may not leave prolonged after effects; however, some develop post-traumatic stress disorder, marked by repetitive nightmares (usually poorly disguised replays of an operative situation), anxiety and irritability, a preoccupation with death, and a concern with sanity, that make the patients reluctant to discuss their symptoms. 15 It is not readily apparent why some patients develop a post-traumatic stress disorder and others do not.The medicolegal consequences of awareness remain of interest. Domino* recently analyzed claims from the American Society of Anesthesiologists Closed Claims Project. Claims for awareness during anesthesia were 2% of all claims. This incidence was similar to rates of claims for such familiar complications after anesthesia such as aspiration pneumonia and myocardial infarction. Female gender tripled the likelihood of an awareness claim, compared with other general anesthesia malpractice claims. Domino speculated that women may be more likely than men to sue for emotional injury.The precise concentration of anesthetic agent required to guarantee lack of recall is unknown. Minimal values of 0.8–1.0 minimum alveolar concentration of inhalation anesthetics currently appear acceptable. The effects of adding intravenous agents, such as benzodiazepines, propofol, and opioids, to inhalation anesthetics, as is sometimes done in clinical practice, remain to be studied. Inspection of the anesthetic records of awareness cases for relevant parameters such as heart rate, blood pressure, and anesthetic technique has not been helpful in retrospectively explaining why awareness or recall occurred. 8,14 Moerman et al. 14 also found that 65% of patients who experienced awareness and recall during general anesthesia did not inform their anesthesiologists about what happened. Asking the patient four simple questions-What was the last thing you remember before you went to sleep? What was the first thing you remember when you woke up? Can you remember anything in between these two periods? and Did you dream during your operation?-should be part of the anesthesiologists' postoperative interview and should allow the anesthesiologist to deal with this traumatic experience at an appropriate early time. Prompt referral to a qualified therapist and acknowledgment of what has happened yields the best chance for recovery.** Cobcroft and Forsdick 13 concluded that, in most cases of awareness, understanding of the phenomenon and its management by medical personnel were poor or entirely lacking.Conscious recall of intraoperative events is relatively rare and development of post-traumatic stress disorder is even more uncommon. However, when we consider that approximately 20 million general anesthetics are administered each year in the United States, a 0.2% incidence corresponds to 40,000 cases of awareness annually. It is probable that the incidence of this complication of anesthesia has reached a plateau and that further significant decreases depend on avoidance of “overly” light anesthetic techniques; gaining more knowledge about anesthetic requirements of patients; development of methods to detect consciousness during anesthesia 1; and disseminating information to anesthesiologists and their acceptance 9 of the virtues of vigilance and rational use of muscle relaxants (i.e., avoiding muscle paralysis unless it is needed for intubation or surgery and even then avoiding total paralysis if possible).Future insights into the epidemiologic characteristics and prevention of post-traumatic stress disorder associated with awareness, which may cause long-lasting devastating damage to patients' lives, are needed. Because of the low incidence, a multiple-center study is necessary, if such data are to be obtained.The concept of an awareness monitor that would track patients' arousal levels and warn of impending wakefulness is popular. Monitoring the mid-latency auditory-evoked responses 12 or the bispectral index of the electroencephalograph 16 seems promising as an indicator of loss of consciousness and its unintended return during surgery. However, it remains for future work to identify some parameter that unambiguously defines when consciousness is lost. Although this may be feasible and a monitor could possibly be developed and adapted for clinical practice, two questions remain to be answered: Do we need such a monitor?, and Can we afford it? The answers are likely to be far from certain or unanimous. Proponents for the development of such a monitor will probably refer to anesthesiologists' inability to determine reliably whether a given anesthetized and paralyzed patient is conscious during surgery. They will point to medical malpractice claims resulting from consciousness and recall during general anesthesia, the high incidence of wakefulness without recall that has been reported in some studies, 17–20 and the possible psychic trauma that may result from the unconscious storage of a traumatic event. 15,21 They may indicate that we currently have monitors for the actions of anesthetic drugs on the cardiovascular and respiratory systems and the neuromuscular junction but none for their actions on the brain, their primary target. Such a monitor also may help to ensure protection of the brain from injury under certain circumstances. Finally, such a monitor would be valuable in determining the role of consciousness in what is presumed to be implicit learning and memory (explained in the next section). This would have important clinical and theoretical implications. Could not the costs of a new monitor be justified by better outcome for the patients and shorter lengths of stay in the recovery room by improved intraoperative anesthetic management?Opponents of developing such a monitor would argue that consciousness and explicit recall of events during surgery are relatively rare. Because most cases occur from error by the anesthesiologist, 1 the most effective method of reducing their incidence is likely to relate to improved standards of care by anesthesiologists rather than dependence on a monitor. 22 A shorter stay in the operating room and in the recovery room through improved anesthetic management might not decrease costs. 23,24 The costs incurred for research and development of the monitor, which eventually will be passed on to the consumer, may exceed its benefits, and its purchase will have a low priority compared with other necessary current and future health care expenditures.Explicit memory refers to intentional or conscious recollection of prior experiences as assessed by tests of recall or recognition. Implicit memory, by contrast, refers to changes in performance or behavior that are produced by prior experiences on tests that do not require any intentional or conscious recollection of those experiences. 25 The basic distinction between explicit or direct tests and implicit or indirect tests involves the nature of the instructions given to the person being tested. In a direct test, participants are asked to recall or recognize events that may have occurred during anesthesia. In an indirect test, the instructions make no reference to events during the operation. There is now evidence that performance on both direct and indirect tests may reflect both conscious and unconscious memory processes. 26,27 In particular, indirect tests are prone to influence by explicit memory if participants become aware of the relationship between study and test items and exploit this knowledge. 28There are various types of indirect or implicit memory tests. Some types may be more sensitive for detecting evidence of retention of events occurring during anesthesia. Table 1lists the studies that used indirect tests of memory and identifies the anesthetic drugs used for maintenance of anesthesia, whether memory for information that was presented during anesthesia was found, and some brief comments. The task of recognition is usually construed as a measure of explicit memory, a view based on studies with patients with amnesia, whose performance on the task is usually impaired. 5 An alternative view, based on studies of healthy persons, is that recognition depends on both explicit and implicit memories. 27,56 According to Mandler, 56 two simultaneous processes are involved when a person must decide whether he or she recognizes an item. First, the “familiarity” of the item is retrieved; second, a search process determines whether the item was presented previously. The first process may fall within the domain of implicit memory. The success of some researchers with forced-choice recognition tasks in anesthetized patients (Table 1) may support this contention, assuming that patients are guessing and are guided by feelings of familiarity. Therefore we included this task in the table.An unforced recognition task, which allows participants not to respond if they are unsure, may be less sensitive to implicit memory than a recognition task in which participants are forced to respond to every test item, even if they believe they are only guessing, because guesses may reflect implicit memory. 75 Several groups of investigators found evidence for memory during anesthesia using forced-choice recognition tasks. 3,46,48,49,55Other tasks have been used with mixed results. An exception is the word-completion task, for which the results have been positive. However, this task, has been used only by two groups of investigators. 31,55Other variables in the studies that may influence their outcome include the anesthetic technique, the salience of the experimental stimuli, the number of stimulus presentations, the time interval between presentation and the test, and sample size.We could argue that any learning during general anesthesia is implicit, because the patient is rendered unconscious by the general anesthetic drugs. Skeptics may, however, counter that there is no reliable way to determine adequacy of anesthesia, particularly in the paralyzed patient. The interaction between the administered anesthetic doses and varying levels of surgical stimulation may lead to episodes of awareness. In addition, as we discuss later, explicit recall is abolished before loss of responsiveness, so it is possible for a patient to be responsive and conscious during surgery and yet not remember this after recovery. Therefore appropriate performance on indirect tests of memory after anesthesia may not necessarily imply the presence of unconscious learning and implicit memory during anesthesia. 26,58 Conceivably, an implicit test might show memory while an explicit test does not show memory because the former test is more sensitive than the latter, rather than because it engages a memory system different than the explicit one.Therefore it would be of interest to use procedures that may provide uncontaminated estimates of conscious and unconscious processes. Caseley-Rondi et al. 49 recommend two such approaches, “relatively sensitivity” and “qualitative differences,” that they assert might provide more rigorous evidence of unconscious learning during anesthesia.The “relative sensitivity” approach uses explicit and implicit tests that are as comparable as possible in all respects except whether they overtly request recollection of previously presented information. Under these circumstances, if participants show more memory on the implicit test than the explicit test, unconscious learning can be inferred. If the explicit and implicit tests differ in other respects, according to Caseley-Rondi et al., 49 these other differences might be responsible for any differences in performance and would complicate an interpretation in terms of unconscious learning. Unconscious learning during anesthesia has not yet been definitively demonstrated in a manner satisfying Caseley-Rondi et al.'s requirement, because the two studies using the most similar explicit and implicit tests-forced-choice recognition and preference judgments, respectively-did not demonstrate differential performance on these tests. 31,49The “qualitative differences” approach 49 uses a test in which conscious and unconscious learning should produce qualitatively different (i.e., opposite) effects on performance. For example, using a procedure developed by Jacoby et al., 59 participants might be presented with nonfamous names such as John Schultz during anesthesia. After operation, they would be presented with these names, mixed together with other nonfamous names and famous names, and asked to indicate whether each name is famous or not. They would be told before the test that all the names presented during anesthesia were not famous. Conscious retention of presentation of the name John Schultz during anesthesia should, therefore, lead to classifying it as nonfamous, whereas unconscious retention might lead to classifying it as famous.Application of the relative sensitivity and qualitative differences approaches may lead to more definitive demonstrations of unconscious learning during anesthesia. However, such methods may not appeal to all investigators. Tests that do not fit within these approaches may have other virtues; for example, they may prove more sensitive to learning during anesthesia or be more realistic or meaningful. It remains appropriate for investigators to use other types of tests to study learning during anesthesia, and, perhaps, to assume tentatively that learning detected by these tests is unconscious, provided that this assumption is consistent with patients' self-reports and anesthesia seems to be adequate; that is, patients cannot recollect hearing anything during anesthesia and they have no concept that a relationship exists between material that was presented during anesthesia and their performance on an incidental, seemingly “nonmemory” test. If patients have no concept of such a relationship, they cannot be aware that the presented material influences their performance on the test.Influence of Anesthetic Regimens on Outcomes of Studies. Because some benzodiazepines impair implicit memory, 60–62 it is prudent to avoid their use in studies of implicit memory during anesthesia. Block et al. 31 found that the anesthetic technique-nitrous oxide with opioids or with isoflurane-did not affect performance on the implicit memory tests that were used. However, an influence of anesthesia method could have been missed because of the small sample size. Kihlstrom et al. 41 found evidence for implicit memory during anesthesia with isoflurane but no implicit memory in a second study 42 in which they used nitrous oxide and sufentanil. Schwender et al. 44 found that in patients with implicit memory after operation, the midlatency auditory-evoked potentials during anesthesia continued to show a pattern similar to the awake state, but in contrast, in the patients without implicit memory, the waveforms were severely attenuated or abolished. Most of the patients in the first group were anesthetized with flunitrazepam and fentanyl and most of the patients in the second group were anesthetized with isoflurane and fentanyl or propofol and fentanyl. This may suggest that implicit memory is possible mainly under light anesthesia. The results of Jelicic et al., 37 in which they failed to replicate their earlier demonstration of learning 36 when they used nitrous oxide and enflurane instead of nitrous oxide and opioids, are consistent with this suggestion. The contradictory results of Kihlstrom et al. 41,42 may of of an earlier study rather than a difference by the two anesthetic and in an to the effects of different anesthetic on implicit learning during anesthesia (Table that can be in postoperative implicit memory during both nitrous oxide anesthesia and anesthesia with volatile However, learning of more information may be only possible in patients during nitrous oxide anesthesia, or with the it seems that, in the of a monitor for the of anesthesia, investigators should the anesthetic methods used as as possible with to drugs and their of and implicit memory tasks can be as or memory tests can be by the The of study on test performance has been because the in these tests the of the studied stimulus In contrast, an implicit test may provide information that is related to the studied information but with no apparent between the study and test of such tasks include general knowledge questions or The likelihood that participants or the if it was presented at study has been An of tasks according to whether they depend on or remains for example, presented evidence that both and processes may to in word-completion tests. It has been that anesthetized patients may better on rather than but there is evidence to this distinction to implicit memory and information that exists in memory a in memory of a that is part of a a new in memory learning a new and in memory some of that that There are two important differences between implicit memory for and new First, the of new in memory may require the to in some that are not necessary for and implicit memory for new information is to in severely Kihlstrom and therefore, that implicit memory for events during anesthesia might be to the of knowledge. However, the study of Block et al. 31 using and Jelicic et al. 36 using nonfamous names suggest that new or may be in memory during of The issue of of the material used in the memory tests is also of interest. is the or (i.e., the with which a stimulus a For example, if participants are asked to name of the some with high or are given frequently as whereas other with low or are given as Jelicic et al. and et al. patients with a task using familiar and familiar They evidence for learning during anesthesia. However, et al. from the research group found no such evidence when they used less familiar et al. found that, using the word-completion task, patients more evidence of for with high or compared with with from studies with with and without show that less familiar result in This may not be the in anesthetized et al. that with the information to which patients are during anesthesia is important for of In conscious persons, and of to the stimulus to but not et al. found that memory during anesthesia was apparent after but not after of a An that has been for these results is that patients may the presented material with an during surgery. et al. found that performance on indirect memory tests was for that were presented during anesthesia than for that were not presented at The investigators that memory may be by the experience of surgery. However, this in to studies that memory effects after et al.'s of their results were also Because the was only in the primary were not The were also based on the results of two entirely types of of Postoperative effects (i.e., hearing the on the ability to identify with the when they respond to the were found in anesthetized patients when they were early after after or as as after surgery. 44 The time of after could be by should be when they have from the effects of anesthetics on that could impair their but before effects have of the effects may according to the task used. that should be in the to changes in context between stimulus presentation and the memory test, it remains to be demonstrated that context effects influence performance on indirect tests of memory. may also with the administered during anesthesia, if the is and recently a of studies memory for events during anesthesia. as the interval between the of surgery and the administration of the memory test and there to be no memory when was more than after surgery.In contrast, of implicit memory, during depends on 75 pattern after surgery is severely with early of and sleep and with of sleep on the second and Conceivably, this might on the postoperative In studies evidence of learning during anesthesia, the effects usually have been This is consistent with the that only a of can during anesthesia, to a relatively light of anesthesia. more likely to be in studies with of patients, which provide to detect relatively small Studies with small such as patients, may lead to conflicting et al. this method in groups of investigators reported of of of the presence of light a of anesthesia during presentation of the and in the reports were negative both in anesthetized patients and in healthy with of inhalation addition to evidence of learning during anesthesia, the of the postoperative of patients by presentation during anesthesia of therapeutic suggestions a and postoperative recovery is an clinical Table the studies that have been done in this and reported that patients who therapeutic suggestions during anesthesia for shorter postoperative than did a In contrast, et al. could not a of the results of and and et al. concluded that and results may have been by chance in of patients to the group as a result of a relatively small sample Jelicic et al. patients to both will be and will have no or suggestions or some They contradictory and who both and suggestions less time in the than did patients in the other The the that the outcome might have been to
Ghoneim et al. (Fri,) conducted a review in Awareness and memory during general anesthesia. General anesthesia was evaluated. Explicit recall of intraoperative events during general anesthesia occurs in approximately 0.2% of nonobstetric and noncardiac cases, while evidence for unconscious implicit memory remains conflicting.