Being conscious while presumed to be under general anaesthesia is called awareness . Explicit awareness, especially with pain, is of great concern to both patients and anaesthesiologists [2,3]. Long-term outcomes as well as precipitating factors have been studied [4,5]. Traditional high opioid-based techniques were reported to cause high incidences of awareness, but balanced anaesthesia techniques were found to be safer [6-8]. The role of sevoflurane has not been studied in relation to awareness. The aim of the present study was to observe the effects of using sevoflurane during cardiopulmonary bypass (CPB) on the incidence of awareness. We have therefore used auditory stimuli applied with earphones and standard tapes during different periods of the operation.
The Regional Ethics Committee approved the study and informed patient consent was obtained. Fifty-nine patients >17 yr of age undergoing open-heart surgery (i.e. coronary artery bypass grafting (CABG), mitral valve replacement (MVR), aortic valve replacement (AVR), reoperation for Tetralogy of Fallot) in Hacettepe University Hospital during April-September 1999 were entered into the study. All patients were questioned about past anaesthesia and awareness experiences and were informed that they would be asked questions about intraoperative experiences and dreams in the postoperative period. Patients who had cognitive or orientation dysfunction or who did not assent to be entered into the study were excluded, as were patients who still were not extubated at the 24th hour after operation.
Diazepam 5 mg was administered intravenously (i.v.) as premedication 30 min before the induction of anesthesia. All patients were monitored via intra-arterial cannulae for invasive arterial pressure measurement, central venous cannulae and pulse oximetry. Urine output and clinical signs of awakening, e.g. movement, pupil size or lacrimation, were also recorded. Anaesthesia was induced with etomidate 0.3 mg kg−1, dehydrobenzperidol 5 mg, fentanyl 5 μg kg−1, and maintained with sevoflurane 2%, fentanyl 5 μg kg−1 and 50% N2O in O2. Muscle relaxation for tracheal intubation was achieved with vecuronium 0.1 mg kg−1; additional vecuronium was given during surgery. During cardiopulmonary bypass, the patients were randomly assigned to two groups. Random allocation was done by assigning the first 10 patients to Group 1, the next 10 patients to Group 2, and so on. Group 1 received dehydrobenzperidol 5 mg i.v. with an additional 5 mg if cardiopulmonary bypass lasted >90 min, and fentanyl 10 μg kg−1 during cardiopulmonary bypass. Group 2 received an inspired concentration of sevoflurane 2% (applied via a standard vaporizer) and fentanyl 10 μg kg−1. In the post-bypass period, anaesthesia was maintained in all patients as in the prebypass period.
Persistent systemic hypertension (i.e. a systolic arterial pressure >140 mmHg) was treated with an infusion of nitroglycerin. Hypotensive periods (i.e. systolic blood pressure ≤80 mmHg or >20% change from baseline values) were also documented and treated with ephedrine i.v. Bradycardia (i.e. heart rate <60 beats min−1) was treated with atropine i.v. Haematocrit concentrations were maintained between 25 and 35%, and core temperatures were between 28 and 32°C during bypass. The cardiopulmonary bypass flow was maintained between 2.0 and 2.5 L min−1 m2 and the mean perfusion pressure at 50-70 mmHg; hypotensive periods (i.e. mean pressure <50 mmHg) were treated with i.v. and patients were assessed for tracheal extubation 6-12 h after operation.
After anaesthesia had been induced, earphones were placed over patients' ears and kept there until transport to the intensive care unit (ICU) at the end of the operation. Three different audiotapes were played during the operation: one containing radio static and assorted noises such as ringing telephones during the prebypass period, a tape of a famous Turkish folk music singer during the actual period of bypass, followed by classical music during the post-bypass period. All patients were interviewed after 8 (if extubated) and 24 h after operation for evidence of explicit awareness. The same member of staff completed the interviews before the patient left the ICU. Each patient was asked the following standard set of questions at both interviews [6,9]:
- What was the last thing you remembered before surgery?
- What was the very next thing you remembered?
- Can you remember anything in between these two experiences?
- Did you hear or feel anything during the operation?
- Did you have any dreams during the operation? If yes, what was the dream like?
- Did you hear any sound or music during your anaesthesia period?
Patients who had explicit awareness were given explanations by the senior author and attending anaesthesiologist.
Results involving nominal data were analysed via contingency tables and t-tests were used for rational data.
Fifty-nine patients were entered into the study. Thirty patients were in Group 1 (five cases of awareness) and 29 patients in Group 2 (no cases of awareness). The demographic data, as well as operation and duration of bypass and body mass index (BMI), are presented in Table 1. No significant differences between the groups were found.
Twenty-six patients had histories of previous operation, and only two of the females reported previous experiences of awareness. One of these patients was in Group 1, the other was in Group 2, and neither reported awareness in this study.
The number of patients undergoing CABG, MVR, AVR, mitral plus aortic valve replacement and reoperation for Tetralogy of Fallot were 41, eight, five, four and one respectively. Owing to the predominance of CABG operations, 39 of 59 patients were males. Of these, 2/39 experienced awareness, and of the women, 3/20, the difference being not statistically significant. There were two cases of awareness at <60 yr of age (2/36) and three >60 yr (3/23). The difference was not statistically significant. Only six patients were obese (BMI > 30 kg m−2), with one case of awareness.
During the postoperative interviews, five patients gave histories of explicit awareness, although no clinical signs such as sweating, tears, etc. were observed during their operation. Since our hospital had not yet acquired a bispectral index (BSI) measuring device at the time of the study, BSI could not measured during the study. Data about these patients are presented in Table 2. All patients stated that they heard folk music performed by a male singer. Patients 3 and 4 correctly named the singer, and Patient 5 gave the name of another folk singer with a similar tone of voice, and Patient 4 also mentioned hearing some buzzing sounds and a telephone ringing (Table 2). None of these patients reported any dreams, and there was no experience of any pain. None of the patients demonstrated any clinical signs of awakening such as movement or lacrimation during the operation. All patients with awareness were visited by the senior and attending anaesthesiologist on the second postoperative day and were given explanations and reassurances.
There were no significant differences between groups with respect to episodes of bradycardia, hypotension or hypertension before, during or after the bypass period (P > 0.05).
The increasing concern about the incidence and outcome of awareness has led to numerous studies in the last two decades. There have been reports of awareness as high as 23% associated with cardiac surgery . Recent studies employing balanced anaesthesia techniques report very low incidences such as 0.4% [6,9]. Moerman and colleagues reported awareness in two of 33 patients who underwent anaesthesia for implantation of a defibrillator . We have found 5/59 (8.4%) cases of awareness, all of which were in the group receiving a standard regimen (Group 1). Five of 30 patients in the dehydrobenzperidol plus fentanyl group - which is Group 1 - gave histories of awareness. This high incidence (16.6%) proves the need to employ some form of continuous technique, e.g. propofol infusion or volatile agent during cardiopulmonary bypass. Inadequate general anaesthesia has been implicated as the major source of awareness during all kinds of surgery [5,9].
There were 3/20 females and 2/39 males with awareness in this study. Although the difference between genders is not statistically significant, it is in accordance with previous studies [4,5]. Obesity was implicated as a factor in the series of Guerra  and of Gilron and colleagues . We had only six patients with a BMI > 30 kg m−2: not enough to conduct statistical analysis. It should be noted, however, that the only patient with a BMI > 30 kg m−2 who experienced awareness gave a history of hearing the tapes played during bypass as well as before bypass. All other patients with awareness in Group 1 stated they heard the tape only during bypass.
We used standard tapes and a structured interview to identify awareness during certain periods of surgery. Concentration of the volatile anaesthesia was kept constant by the anaesthesiologist and was not reduced before termination of the bypass. Such a reduction just before cessation was listed as a possible cause of awareness by Dowd and colleagues . We hoped to identify this period by obtaining a history of awareness about both music tapes. There were no reports of awareness in the sevoflurane group, which may be due to continuous high sevoflurane concentrations.
There have been ample reports about monitoring techniques of depth for anaesthesia [8,13]. We could not monitor auditory-evoked potentials (AEPs), but studies with AEPs showed that perception and processing of auditory information is suppressed only with deep levels of anaesthesia . Schwender and colleagues  reported that all of 45 patients they interviewed because of histories of awareness mentioned auditory perception. It has been shown that even patients who do not have explicit recall after operation respond to verbal commands during anaesthesia . Williams and Sleigh recently reported that there was an ability to have conscious awareness of auditory input without necessarily being able to demonstrate this by responding to verbal command . Numerous studies have used AEPs to assess the depth of anaesthesia obtained with different doses of several anaesthetics [16-18]. Some studies used verbal commands and the auditory input on tapes instead of AEPs. Audiotapes played via earphones have been used for studies of depth of anaesthesia and learning under anaesthesia . We used this technique to block out other forms of noise and conversation during the operation and to assess the period of awareness.
There has been some controversy about the optimal timing of interviews . We attempted to interview the patients 8 h after the operation, but only 32/59 patients were extubated at this time. The patients were also tired and unwilling to talk at this time. They were more co-operative at 24 h and we did not find any inconsistencies between the 8 and 24 h histories. By conducting the interviews at 24 h, we could still converse with all patients before they left the ICU. We did not think it necessary to conduct follow-up interviews later since previous studies found a decline in positive history of awareness with time .
Previous studies stated that patients who reported awareness or dreams were significantly younger than those who did not [5,20]. We could not demonstrate such a difference, which may be due to the fact that most (42/59) of our patients were >50 yr of age.
Using a volatile anaesthetic during cardiopulmonary bypass may be of some concern because of possible myocardial depressant effects. Several animal and clinical studies have been carried out to identify this issue. It has been concluded that sevoflurane decreases arterial pressure, myocardial contractility and baroreflex function in a manner similar to other volatile anaesthetics, and it appears to offer a more stable heart rate profile than either isoflurane or desflurane . Likewise, we did not find any statistically significant differences between the two groups with respect to haemodynamic properties and we could treat any hypotensive incidences with standard drugs.
This study supports the hypothesis that sevoflurane combined with opioid reduces the incidence of awareness during cardiopulmonary bypass while exhibiting haemodynamic effects comparable with our conventional technique. We cannot claim any superiority for sevoflurane over other volatile agents or infusion techniques. New studies with higher patient numbers are required to clarify this issue. Using the chosen anaesthetic agent with continuous dosing would be helpful in decreasing the incidence of awareness, which is still an important problem.
1. Jones JG. Perception and memory during general anaesthesia. Br J Anaesth
2. Heier T, Steen PA. Awareness in anaesthesia: incidence, consequences, and prevention. Acta Anaesthesiol Scand
3. Blacher RS. Awareness during surgery. Anesthesiology
4. Moerman N, Van Dam FS, Oosting J. Recollections of general anaesthesia: a survey of anaesthesiological practice. Acta Anaesthesiol Scand
5. Ranta SO, Laurila R, Saairo J, Ali-Melkkila T, Hynynen M. Awareness with recall during general anaesthesia: incidence and risk factors. Anesth Anal
6. Dowd NP, Cheng DCH, Karski JM, Wong DT, Munroe JA, Sadler AN. Intraoperative awareness in fast-track cardiac anaesthesia. Anesthesiology
7. Goldman L, Shah MV, Hebden MW. Memory of cardiac anaesthesia - psychological sequelae in cardiac patients of intraoperative suggestion and operating room conversation. Anaesthesia
8. Bailey AR, Jones JG. Patients' memories of events during general anaesthesia. Anaesthesia
9. Russell IF, Wang M. Absence of memory for intraoperative information during surgery under adequate general anaesthesia. Br J Anaesth
10. Moerman A, Herregods L, Foubert L, et al.
Awareness during anaesthesia for implantable cardioverter defibrillator implantation. Recall of defibrillation shocks. Anaesthesia
11. Guerra F. Awareness and recall. Int Anaesthesiol Clin
12. Gilron I, Solomon P, Plourde G. Unintentional intraoperative awareness during sufentanil anaesthesia for cardiac surgery. Can J Anaesth
13. Munglani R, Andrade J, Sapsford DJ, Baddeley A, Jones JG. A measure of consciousness and memory during isoflurane administration: the coherent frequency. Br J Anaesth
14. Schwender D, Kunze-Kronawitter H, Dietrich P, Klasing S, Forst H, Madler C. Conscious awareness during general anaesthesia: patient perceptions, emotions, cognition, and reactions. Br J Anaesth
15. Newton DEF, Thornton C, Konieczko K, et al.
Levels of consciousness in volunteers breathing sub-MAC concentrations of isoflurane. Br J Anaesth
16. Williams ML, Sleigh JW. Auditory recall and response to command during recovery from propofol anaesthesia. Anaesth Intensive Care
17. Reinsel RA, Veselis RA, Heino R, Miodownik S, Alagesan R, Bedford RE. Effect of midazolam on the auditory event related potential: measures of selective attention. Anesth Analg
18. Schwender D, Klasing S, Madler C, Pöppel E, Peter K. Effects of benzodiazepines on mid-latency auditory evoked potentials. Can J Anaesth
19. Oxorn D, Orser B, Ferris LE, Harrington E. Propofol and thiopental anaesthesia: a comparison of the incidence of dreams and perioperative mood alterations. Anesth Analg
20. Ranta S, Jussila J, Hynynen M. Recall of awareness during cardiac anaesthesia: influence of feedback information to the anaesthesiologist. Acta Anaesthesiol Scand
21. Ebert TJ, Harkin CP, Muzi M. Cardiovascular responses to sevoflurane: a review. Anesth Analg