Risk Factors and Causes of Awareness
A history of awareness was present in 1.6% of cases and a difficult and prolonged laryngoscopy and intubation in 4.5%. The most frequent cause of awareness was overly light anesthesia (Table 8). Increased anesthetic requirement was assigned as the cause when the anesthetic was considered as adequate for the patient and the surgery and when malfunction or misuse of the anesthetic machine could be excluded.
The adoption of randomized controlled designs to answer important questions about awareness is prevented by its low incidence, ethical concerns about exposing patients to potential risk factors, e.g., very light anesthesia and inability to randomize clinical situations and practices, e.g., difficult and prolonged laryngoscopy and intubation (which is often unanticipated and has a low rate of occurrence)10 and complete muscle paralysis during maintenance of anesthesia (which is undesirable, but may be required by surgical conditions). Therefore, a major part of the literature concerning the causative and risk factors, autonomic and motor changes during the episodes, the nature of patients’ complaints in the postoperative period and the sequelae, is derived from anecdotal experiences and personal beliefs. We chose to analyze reported cases of awareness in the modern era from the first one in 1950 through August, 2005.
The sources of the awareness reports are of interest. While the major source came as expected from anesthesia journals, The Lancet, the prestigious British Medical Journal, published as many reports as Anesthesiology. Historically, the first report of awareness during anesthesia in the modern era came from the United Kingdom (and was published in a general medical journal8), and most of the studies of its incidence came from the United Kingdom and Scandinavia.
The incidence of awareness in general has decreased from 1.2% and 0.8% in the 1960s and 1970s to the current figure of 0.1% to 0.2%11 (with the exception of the reported incidence of 0.007% by Pollard et al.3). However, a different trend in the number of reports is apparent in the present study (Table 2). Winterbottom’s report in 19508 was followed by a hiatus of 9 yr, during which awareness was ignored as far as publications were concerned. Then, there followed a progressive increase that reached its peak from the 1990s onward. This increase may be partly explained by the trend toward publication of multiple reports in a single article, but equally important is the increased prominence of the subject. There is a heightened interest in the subject by anesthesia providers, as evidenced by studies of the effect of anesthetics and sedative-hypnotics on explicit and implicit memories, introduction of monitors that assess the depth of anesthesia, studies of the psychological and medico-legal consequences of awareness, review articles, book chapters, and a book. The public news media and entertainment industry also became interested in the subject and, through them, the patients.
Females were over-represented relative to males in the reported cases of awareness when compared to the control sample in Sebel et al.’s study. This is consistent with the results of other studies.11–14 Women recover more rapidly from anesthesia than men, which may suggest that they may be less sensitive to the effects of anesthetics on the brain.12,15,16 It has been suggested11,17 that there may be a higher incidence of awareness in obese patients for several reasons, including the often prolonged time for endotracheal intubation, the use of higher concentrations of oxygen in nitrous oxide-oxygen mixtures and the difficulty of giving appropriate doses of drugs without causing postoperative respiratory depression. Our survey does not corroborate this supposed risk. The preponderance of cardiac and obstetric procedures in the awareness reports compared to the nonawareness sample is to be expected, because of the tendency to use light anesthesia in these cases.11 Our findings regarding the time of reporting of awareness corroborate the current practice of interviewing patients more than once, including the recovery room.11
The anesthetic regimens that were reported in awareness cases used less premedicants, induction and maintenance anesthetics and less opioids as compared with the control sample. Patient movement during the operation was also noted in a relatively high number of awareness cases as was the development of hypertension and tachycardia. These signs, as well as the use of smaller amounts of anesthetic drugs and their adjuvants, are correlates of overly light anesthesia, which was the most common cause of awareness. An alternative explanation for the higher incidence of hypertension and tachycardia in the awareness sample is the attention, over approximately the last decade, to strict control of arterial blood pressure and heart rate during anesthesia, which could be displayed more in the control sample. There were no differences between the frequency of use of nitrous oxide and neuromuscular blockers in the awareness and nonawareness samples. There are no studies that rigorously assessed the risk of avoidance of nitrous oxide on the incidence of awareness. In a meta-analysis of the effect of omitting nitrous oxide in general anesthesia on postoperative emesis,18 an incidental finding was that omitting nitrous oxide increased the incidence of awareness. However, the representativeness of this finding is debatable, as only 29% of the trials that were analyzed included awareness as an outcome measure, the search strategy did not indicate that awareness was intended as an outcome, and the increased incidence of awareness when nitrous oxide was omitted was derived in large part from a single study19 in which the results were not significant. It was also clear that the total anesthetic dose, as defined by minimum alveolar anesthetic concentration multiples, was larger in the group given nitrous oxide.
Our finding of the absence of differences in the use of neuromuscular blockers between the experimental and control samples is not surprising. It does not contradict the reasoning that awareness is, to a large degree, an iatrogenic mishap caused by the use of muscle relaxants. The use of neuromuscular blockers has been ubiquitous since their introduction in 1942. Indeed, the first case report of awareness involved the use of curare.8 As opposed to the paralyzed but inadequately anesthetized patient who may regain consciousness while remaining motionless, a nonparalyzed patient will usually (but not invariably) communicate his or her wakefulness by movement, which alerts the anesthesia provider to deepen the anesthetic and thus lessens the incidence of recall. It is sound preventive advice to avoid muscle paralysis unless it is needed and even then to avoid total paralysis.
Many patients who become aware during surgery report a variety of complaints that are associated with considerable dissatisfaction with their anesthesia care.20 The most common complaint in this study was auditory perception (voices in 66% and noises in 17% of cases), followed by loss of motor function (inability to move in 34%, and sensation of weakness or paralysis in 17% of cases), pain (38%), and feelings of helplessness, anxiety, panic, impending death or catastrophe (34%). In a recent study by Samuelsson et al.,21 auditory and tactile perceptions were the most common (70% and 72% respectively), followed by feelings of helplessness, acute fear, and panic (56%, 58%, and 43% respectively). Pain was experienced by 46% of the patients.
Awareness may lead to postoperative sequelae that may persist for varying durations. Sleep problems were common (sleep disturbances in 19% and nightmares in 21% of patients). Fear of future anesthetics was reported in 20% of patients and daytime anxiety in 17%. Late psychological symptoms, which may lead to a severe and debilitating illness (posttraumatic stress disorder), were first described by Meyer and Blacher in 1961.22. We noted these symptoms in 22% of our patients. In the Samuelsson et al. study,21 there was a 33% incidence. In our review, inability to move and feelings such as helplessness, anxiety and panic were significantly related to the persistence of late psychological symptoms. Wang,23 based on his studies of victims of awareness in his practice, has suggested that frequently the inability to move during surgery raises the patient’s misconception that the state is irreversible, causing acute psychological trauma that may persist if it is not explained. Some authors have expressed their belief (without evidence) that pain would be a precipitating cause of prolonged psychological effects.1,24 Yet, pain and hearing voices or noises were not related to the late psychological symptoms in our review. These results are also corroborated by those of Samuelsson et al.21 and Guerra.25 It is interesting that Blacher26 has claimed earlier that patients who are wide awake, although they may suffer greatly during the procedure, may have fewer traumatic symptoms afterward than those who are in an obtunded state, perhaps because while awake what happens is not in doubt. Perhaps patients who complain initially of inability to move and experience feelings of helplessness, anxiety, panic, impending death or catastrophe should be paid particular attention and be referred early for psychiatric help. Guerra25 has suggested that the response to awareness may also depend on the patient’s personality and psychiatric history. Other factors, e.g., failure of the surgery to cure the patient, or the emergence of serious postoperative complications, may also play a part.27
This review suggested two risk factors for awareness during anesthesia. The first is the use of light anesthesia. The second is the presence of a history of awareness. The late Professor Utting28 warned anesthesiologists in 1975 that “a history of awareness should always be treated seriously and the anesthetic should be given with scrupulous care by a consultant anesthetist if medico-legal trouble is to be avoided.” It seems that this advice has not always been followed.
Difficult and prolonged laryngoscopy and intubation were associated with awareness in only 4.5% of the cases. Considering that the overall incidence of difficult intubation varies from 4.5% to 7.5%,10 it was not found to play a major role as a risk factor. Administration of supplemental doses of induction hypnotics should prevent the patients from regaining consciousness when this problem arises.
The major cause of awareness was overly light anesthesia at the time of the episode. Anesthetic machine malfunction or misuse and increased anesthetic requirement were much less frequent. The end-tidal anesthetic gas concentrations that prevent awareness are unknown. In a recent study by Avidan et al.,29 there were sustained periods during surgery when these concentrations were under 0.7 minimum alveolar concentration in 75% of 1937 patients who nevertheless did not experience awareness. In cases where light anesthesia is deemed necessary, the use of even small doses of amnesic drugs, e.g., scopolamine, midazolam, subanesthetic doses of ketamine, or inhaled anesthetics and/or regional anesthesia, should be considered.1 The use of a cerebral function monitor may reduce the incidence of awareness.3
Proper maintenance of anesthesia equipment, checkout protocols before administration of an anesthetic, gas analyzers sampling the inspired and end-tidal concentrations of the inhaled anesthetics, setting of alarms when vaporizers become empty and using total IV anesthesia only when the anesthesia providers have continuous access to the entire anesthetic delivery system can reduce the incidence of machine malfunction or misuse. Variability in response to anesthetics is common in everyday practice. It is possible that chronic use of alcohol, opioids and sedative hypnotics may increase the anesthetic dose needed to produce and maintain unconsciousness.1 Unfortunately, there was not enough information in our data about the use or abuse of these substances. Increased anesthetic requirement of some patients may be detected by the use of brain function monitoring.
The main strength of the present study is the large number of cases that were reviewed, increasing the confidence in our results and conclusions. However, issues relating to bias pose several challenges. Publication of case reports depends on voluntary efforts by the authors and acceptance by the editors of scientific journals. Another source of bias is the inability to precisely match the reported cases of awareness with control groups coming from the same time period. Although the majority of the cases were published in the period from 1990 to 2005, 22% of the cases came from an earlier period. Therefore, comparisons between data sets may have been influenced by changes over the years in certain characteristics, e.g., obesity of the general population or use of β-blockers in the perioperative period, which could affect the incidences of tachycardia and hypertension. Other differences in characteristics between the reported cases of awareness and the patients of Sebel at al.2 may have influenced the comparisons, and it was not feasible to control these, e.g., by analysis of covariance. A third source of bias relates to the lack of data in some reports concerning factors such as race, use of recreational drugs and others that may be relevant to the phenomenon of awareness. The high rates of missing data for some of the characteristics that we examined also limit confidence in the conclusions that can be reached concerning these characteristics. We do not know whether the individuals for whom information concerning a characteristic was not reported had the same distribution on that characteristic as the individuals for whom information was reported. Although we omitted any characteristic with more than 60% missing data from consideration, our conclusions may be regarded as tentative, pending independent confirmation.
In conclusion, we reviewed 271 cases of awareness and compared their data with those for patients who did not suffer from awareness. Despite the steady decline in the incidence of awareness since the 1960s and 1970s, an opposite trend in the number of reports was found. A preponderance of females was equivocal, and obesity did not seem to increase the incidence. About one-quarter of the aware patients received no volatile anesthetic or propofol during maintenance of anesthesia and there was less frequent use of premedicants and induction and maintenance drugs, except neuromuscular blockers, in this group. The use of nitrous oxide did not make a difference in the incidence of awareness. There was an over-representation of cardiac and obstetric procedures. Patients’ movements, tachycardia and hypertension were relatively common during surgery. Only 35% of patients reported the awareness episode during their stay in the recovery room. The most common complaints of patients were auditory perception and loss of motor power. Awareness may lead to both immediate and late psychological problems. Inability to move and feelings such as helplessness, anxiety and panic were significantly related to the persistence of late psychological symptoms. We suggest light anesthesia and a history of awareness, as risk factors; light anesthesia was the most common cause. We discussed our findings in light of the existing literature and suggest measures to decrease the incidence.
Professor and Chairman Michael Todd, MD, Department of Anesthesia, University of Iowa, planted the seed of this investigation by suggesting the study of patients who experienced awareness. Jeff Sigl, PhD, of Aspect Medical Systems graciously sent us the data of the patients who did not suffer from awareness. Miriam Zimmerman, PhD, Associate Professor, Department of Biostatistics, helped us with her expertise in statistical analysis.
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