European Journal of Anaesthesiology 200320: 451-456 '© 2003 Buropean Acacemy of Anaesthesiology ISSN 0269-0219 Original Article Bispectral index monitoring in patients undergoing cardiac surgery under cardiopulmonary bypass G.D. Puri, S. 8. Munchy Postgraduate Institute of Medical Education and Research, Department of Anaestbesilogy and Intensive Care, Chandigarh, India Summary. Background and objective: Monitoring the depth of anaesthesia by the bispectral index facilitates che titration of anaesthetic drugs during operation as well as assisting in early recovery. We planned ¢o use this index to control the administration of anaesthetic agents in order to stabilize haemodynamics and promote recovery ftom anaes- thesia in patients undergoing cardiac surgery with cardiopulmonary bypass. Methade: Thiery adult parienes undergoing valve replacement or coronary artery geafting under cardiopulmonary bypass were studied in a prospective, randomized, controlled study. Bispectral index monitoring was used in all patients, Patients received isoflurane anaesthesia and boluses of morphine: in the seudy group, anaesthetic depth ‘was controlled using the bispectral index and clinical variables. In che control group, the bispectral index monitor could nut be viewed by the anaesthesiolugist. Dispectial inex, mean arterial pressure and heart rate were noted every 5 min, and the incidence of hypotension, hypertension, tachycardia and bradycardia also noted. The time to recovery, when patients started obeying commands, was also recorded. Results: Pacienes in the seudy group had significantly less hypertension and tachycardia (P< 0.05) than those in the conerol group. The time to recovery of consciousness was less in the study group chan in the control group (ns., P > 0.05). The bispectral index rose significantly in the control group ar the time of institution and termination of cardiopulmonary bypass (P < 0.05). Conclusions: Anaesthesia controlled by bispectral index monitoring decreases the incidence of haemodynamic disturbances and facilitates titration of anaesthetic agents during cardiopulmonary bypass and thus may assise recovery from anaesthesia Keywords: CARDIAC SURGICAL PROCEDURES, myocardial eevaccularization, coronary attory bypass; DIAGNOSTIC TECHNIQUES, NEUROLOGICAL, electroencephalography; SURGICAL PROCEDURES, OPERATIVE, extracorporeal circulation, cardiopulmonary bypass. Maintenance of a suitable depth of anaesthesia throughout surgery is essential t0 achieve fast recovery. Recently, the bispectral index (BIS) ~ a variable derived from che electroencephalogram CConsipudence wo) Govehan Pai, Dept of Anseeiigy and Tourane Cae, Posgtnne Insite of Metis Edson aed Resa Cun India 160012 Email gépu07hoemalcom; Te *91 522 Sargent 33; Ee 491 172 74000) ne 2902 RJA SHO (EEG) — has been shown co measure the hypnotic component of the anaestheric seare (1-3). Intra- operative titration of anaesthetic drugs using the BIS facilitates early return co consciousness after surgery 45]. In cardiac surgery, a successful anaesthetic techniqne requires horh haemodynamic stability ancl prevention of awareness. Cardiac surgical patients are more vulnerable to the harmful effects of either 00 light or too deep anaesthesia in respect of their often limited cardiovascular reserve: too deep an452. G.D. Puri and. S. Murthy anaesthetic may produce cardiovascular depression, while one too light may induce undesirable neuto- humoral responses. We decided to see how useful the BIS monitor behaves in this regard. The present study was planned co evaluate the effecc of BIS-controlled anaesthetic titration on haemodynamic stability and recovery characteristics. Methods ‘The study was conducted at the Department of Anaesthesia and Intensive Care. Postgraduace Institute of Medical Education and Research, Chandigarh, India. Our insticutional Review Commitcee approved the study. Thirty patients (18-70 yr) undergoing either coronary artery grafting (CABG) or valve replacement under cardiopulmonary bypass (CPB) were randomized into either a study group (using BIS) or a control group (no BIS) using computer- generated numbers. Subjects with known neuro- logical disorders, poor ventricular function (ejection fraction <40%), New York Heart Association (NYHA) Grade IV, diabetes mellitus, and those with impaired renal or hepatic function were excluded. Patients were premedicated with diazepam O.1mgkg”! orally the night before and on the morning of surgery, and morphine 0.1 mgkg™' ineramuscularly was given 45min before surgery. Peripheral intravenous access and ocher invasive mon- itoring catheters (arterial cannula and pulmonary artery catheter) were placed after administration of midazolam 0.05mgkg~'. Baseline haemodynamic variables were recorded. Patients were monicored by continuous invasive blood pressure decermi- nation, HR, electrocardiograph, pulse oximetry and train-of-four responses to neuromuscular stimulation (Biometet®; Myotest, Biometer International, Denmark). Anaesthesia was induced with morphine 0.2mgkg”!, midazolam 0.05 mgkg”' and chiopen- tal citrated co loss of the eyelash reflex: endotracheal incubation was facilitared with vecuronium 0.08 mg kg Four silver chloride electrodes were applied to the skin of che forehead —one over each outer malar bone, the thied ac the centre ofthe forchead and the fourth (ground electrode) on one side of the centre elec- trode. Impedance was checked and kepe at <2000 2. ‘The EEG signal was acquired using this frontal—C. montage and the BIS was displayed on the Aspect A-1000® EEG monitor (Aspect Medical Systems, Inc., Natik, MA, USA) on real-cime basis (BIS v.3.1). In the study group, the anaesthesiologist was allowed to see and use che monitor and accord- ingly he adjusted che isoflurane concentration or per- formed any necessary haemodynamic interventions. ‘The anaesthesiologist for the patients in che control ‘group was blinded to the BIS scores as the EEG ‘monitor was outwith his viewpoint. Anaesthesia was maintained with isoflurane; N20 (66% in Oz before CPB) and morphine 0.025 mgkg~*h”'. The administration of isoflurane ‘was titrated to keep BIS between 45 and 55 through- out the procedure except for the last 30 min when it was titrated to 65-75 in the study group. In the control group, che inhaled isoflurane concentration was adjusted according to standard clinical signs of adequacy of anaesthesia (tachycardia, hypertension, sweating, lacrimation, etc.) and with the aim of achieving rapid recovery from its effects. The increase in che vapour concentration was permitted when episodes of inadequate anaesthesia were detected by the anaeschesiologist. Central venous pressure and pulmonary artery pressures were monitored during surgery to optimize preload status. Inotropes were used if the cardiac index was <21Lmin~'m”? after ascertaining the adequate volume load from measure- ‘ments of che central venous pressure and pulmonary artery wedge pressure. Hypotension and bradycardia were treated by adjusting the doses of anaesthetic drugs, intravenous fluids (preload) or other necessary drugs. In the study group, if the BIS was wichin the normal range and there was hypertension or tachycardia, morphine 0.05-0.1 mgkg was given slowly intravenously before using vasodilators or B-adrenoceptor blocking drugs. ‘The extracorporeal circuit included a bubble oxy- _genator primed with Ringer’ lactate. Afeer the aortic root had been cannulated, the necessary cannulae were placed and moderate hypothermic cardiopulmonary wwas initiaeed, Body temperature was maintained to between 28 and 30°C in all patients. The oxygenator pump flows were maintained at 2,1~2.3Lmin”'m? with a mean systemic arterial pressure in the range 40-80 mmHg. Myocardial protection was achieved with cold potassium-enriched blood cardioplegia solu- tion and topical application of cold saline and ice slush, Morphine 3mg, midazolam Img and vecuronium 0.5 mg were added to the priming solution before the start of CPB. ‘Neuromuscular junction monitoring was per formed to maintain train-of-four twitches to <2 throughout surgery and no vecuronium was admin- istered during the last 15 min of surgery. This mon- itoring was continued after operation until all four twitches reappeared. After sternal closure, the BIS was titrated to 65-75 in the study group, The isoflurane was discontinued once the skin suturing had been completed, Alter operation, the Jungs of all patients were mechanically ventilated and consciousness was assessed every 5 min until all systems were stable and. verbal commands were obeyed. Patients were weaned {© 2003 European Academy of Anaesthesiology, Eamon Jura! of Anaitbviology 20: 451-436from controlled ventilation of the lungs using syn- chronized intermittent mandatory ventilation in the pressure suppore mode as soon as they were conscious, hhaemodynamically stable and could sustain adequate respiratory efforts, They were extubated after ascer- taining standard extubation criteria, Heart rate and MAP were recorded every 5 min throughout surgery. The haemodynamic disturbances were defined as: hypertension ~ MAP > 20% of base- line or >80 mmHg during CPB; hypotension ~ MAP <20% of baseline or <40mmHg during CPB; tachycardia — HR > 20% of baseline before CPB and >30% above baseline after CPB; bradycardia (absolute) — HR < 40 beats min! ‘An episode of alteration of HR or MAP was defined as any of the above-mentioned disturbances of these variables for >5 min. Though monitoring was continuous, we compared sustained haemo- dynamic disturbances for =5 min in this study. All 3105s fluctuations in arterial pressure and HR were treated immediately by adjusting the amounts of volatile anaesthetic, analgesics, intravenous fluids, B-adrenoceptor-blocking drugs, vasodilators or ‘vasoconstrictors. Haemodynamic disturbances in the window period of 5 min post-tracheal intubation and 15 min whilst insticucing and terminating CPB were not considered. BIS, MAP and HR — at the following predecermined times ~ were compared berween and. within the two groups. Preinduction (Pred), 15, 30, 45 and 60min after induction (I+ 15, 1+ 30, 1+ 45 and 1 + 60, respectively); start of CPB (B); 5, 30, 60, 90 and '120min atter che stare of CPB (B+5, B+ 30, B+ 60, B+90 and B+ 120, respectively); the end of bypass; 5, 30 and 60min after CPB (EB + 5, EB + 30, EB + 60, respec- tively), and at che end of surgery. The time to recovery was defined as the time interval from switching off the anaesthetic vaporizer to when che patient opened his or her eyes and obeyed verbal commands. Any patient who required supplementation of sedation after surgery, but before reaching the primary recovery end-point due to unprecedented events, was excluded from the study. Every patient was interviewed to determine any recall on the first postoperative day after the trachea had been extubated. Statistical analysis Parametric data was analysed wich unpaired and paired t-tests. Non-parametric variables were analysed with Fischer's exact test and the U-test as appropriate. Data are the mean * SD or the median and range. P < 0.05 was considered as statistically significant, Bispectral index monitoring daring cardiac bypass 453 Resules Patient characteristics distribution in each group is shown in Table 1. There was no significant difference berween the ewo groups (P > 0.05). MAP and HR remained stable throughout the periods of surgery ‘and bypass and did not differ beeween treatment and control groups at the predetermined time intervals ‘There was a significant fall in MAP a the initiation of CPB (P <0.5) and a rise in MAP on termination of bypass (P < 0.05) in both groups. ‘The mean baseline (preinduction) BIS values were 92.17 + 1,95 and 92.43 + 4.35 in the study and control groups, respectively (Table 2). There was a significant rise in the BIS after initiation and termi- nation of bypass in the control group (P < 0.05, paired scest). Ae the end of surgery, the BIS wat lower in the control group (67.42 = 15.24) than in the study group (75 + 5.59) (n.3.) ‘There were no differences in the time to reach the defined recovery end-point or the time to eracheal extubation between the two groups (Table 3). Only one patient in the control group recovered within 10min of the isoflurane vaporizer being swieched off, whereas five patients in the study group did so. None of the patients in the study group had recall of intraoperative events when interviewed on the first postoperative day, while one patient in the control ‘group had awareness during the sternotomy. This “Table 1. Patin characteristics data (mean + SD). Seady group Control group GIS) n= 1) (w= 16) Agegn 38.25 + 1402 3208 + 13.84 Weighs (ka) S317 2792 5117 # 1135 Heighe (a) 165010 1640.10 Preoperative drugs Bradeenocepeot blocking 6 > drugs ACE inhibiors 6 5 Ce*-channelblocking 5 4 drugs Digoxin 8 10 Coronary artery bypass eft 6 5 Micra valve replacement 6 8 Sorgery “Aomtic valve replacement 1 1 ‘Moric and miteal valve 1 2 replacement Preoperative mean arterial 9601558 100.5 + 164 pressure (mms) Ejection fraction (%) 545455 526*65 Duraion of surgery (min) 29545285 + 40 Cardiopulmonary Bypass i0z355 Izzie tire (rio) [No significa difecence berween the cwo groupe, P > O05; est, 1 Fishers emer test. {© 2003 European Academy of Anaesthesiology, Earuon Jurnal of Anatbsology 20: 451-456454 GD, Pariand SS, Murthy ‘Table 2. bispectral index, mean arterial pressure and heart rate variables at vasious intervals duting the cudy (ean * SD). BIS control BIS seady HR contol HR study MAP control__MAP study Preinduction yazas yene La ras 26 wit at pepe 105 35256 53267 oses 935 +209 854 * 160 1430 s21 2110 54293 n2=9 948+ 236 882+ 160 144s S13 e538 50273 708 =9 926+ 222 875 = 170 1460 454+ 40 524= 68 3628 94622213 876 * 160 B 506 #72 506 =59) - Se 180 785 £171 Bts ose82 517105 - - 5772180 538 = 149 B+ 30 S1£G8 443287 = 588 = 150 se2= 143, B+60 527 #26 461 =32 - 5992130 93 B+90 564120 - = 39.7 = 100 122 B+ 120 638294 - 6 +140 6722155 Ena of bypass 5644250 497 +60 - - 625282 sos tus EB+5 28420 BAe 6s 980 76329 w2212s" 8342170 EB +30 99276 564273 89590 82 89.15 163 83.25 19.2 EB +60 duiata ors280 © 1348 2849 ala £176 539-2 181 End of surgery oA* 153 456 21s 93229 997 = 198 grea BIS: Bipeceal index HIR: heat ae; MAP: mean aera pressure; B: start of earopulmonary bypass: B+ 5, + 30, 8 + 60, B+ 90, 1B 120 5, 30, 60,90 nd 1 20min afer tar of bypass respectively; BB = 5, BB + 30, EB + 60 5, 30 and 6Omin ater end of cariopulmonary bypass spectively. "P< 0.05, pared with preceding Sage "Table 3. Time needed eo achieve the recovery end-p tracheal exubation (mean * SD). Study group Control group (ISG =I) = 16) Recovery end-poine (min) 18.5 = 11.5 Time to teacheal 72243 excubation (b) awarencee ° 1 ‘No significa difeence between the ewa group; P > 0.05, re, "Table 4. Haemodyoamic disturbances (median and range) Study group Control group BY@=1) — @=16) Hypotension ‘Number ofpatients 9 10 Episodes B 20 Median (range) 103) 20-3) Hypertension Number ofpatienss 4 10 nes 6 28 Median (rage) 00-2) 20-5) Talyeaais Number of patients 7 B Episodes B 30 Median (ange) 20-2) 30-109 Bradycardia ‘Number of poients 1 2 Episodes I 2 Nedian ange) 0) oe) P< 0005 (Ces patient had episodes of tachycardia during this period of stimulus and his BIS ac that time was 75 There was no significant difference in the number of patients. suffering haemodynamic disturbances (Table 4). The number of episodes of hypertension and tachycardia were significantly higher in the control group (P < 0.05, U-test). Discussion Anaesthesiologists ticrate doses of anaesthetic deugs based on the haemodynamic responses to noxious stimulation — which may not necessarily mean aware- ness ~ nor does a lack of any haemodynamic change ‘guarantee unconsciousness [6]. This approach is feasible in normal healthy individuals but does not guarantee safety in patients with compromised car- diopulmonary systems. Ideally, the safe approach would be co titrate drugs according to their pre- sumed effect-site concentrations or any measure that reflects this effect. In clinical practice, it would be easier to rely upon a monitor that reflects effect-sice changes produced by drugs rather than on complex: mathematical exponentials involved in calculating effect-site concentrations. Differences in drug sensi- tiviey between individuals can also occur despite iden- tical effect-site concentrations. This can be caused by different receptor sub-types. This is one of the rea- sons why a monitor of anaesthetic depth, e.g. the BIS. monitor, may improve anaesthesia. Thus, effect-site concentrations may not necessarily be a reliable mea- sure of drug effec. (© 2003 European Academy of Anaesthesiology, Eurpeen Journal of Anzestbaisogy 20: 451-456‘The BIS has been demonstrated co be safe and ffi- cient as a pharmacodynamic measure of the central effects of anaesthetics during shore surgical proce- dures (41. Ie is desirable eo ascertain how the index performs during long surgical procedures, where there will be changes in the pharmacokinetics of drugs and because both ‘too deep’ and ‘too light’ anaesthesia can be detrimental ro patients. The phar- macokinetics of drugs are altered in cardiac surgical patients because of altered haemodynamics, concur- rent cardiovascular medications and partly because of the effects of CPB. Furthermore, anaesthetic titra tion — based on HR and arterial pressure responses — may be hindered due to vasoactive medication, .g. B-adrenoceptor blocking drugs, calcium channel- blocking drugs and other cardioacrive drugs thae the patient may be receiving. A decreased incidence of tachycardia and hypertension in the BIS-controlled group may be due to improvements in the titration of drugs in the smady group. As the BIS provides additional information of the hypnotic state, the anaesthesiologist should be able to react before such. haemodynamic changes occur. Though monitoring ‘was continuous we compared haemodynamic distur- bances for periods of 5 min in this study. All gross fluctuations in arterial pressure and HR were treated immediately with a standard protocol of adjustment of the volatile anaesthetic concentration, and the administration of hypnotics, analgesics, ineravenous fluids, -adrenoceptor blocking drugs, and vasodila- tors. Five minutes is a reasonable time to adjust these conditions according to the patient requirement based on feedback. The endotracheal incubation period and the periods immediately associated with the institution or termination of CPB were excluded from consideration. Such periods of gross hacmody- namic change are associated with alterations in drug concentration, a change in body temperature, vaso- active drug administration and direct cardiac manip- ulation, which may be primarily responsible and thus unrelated to anesthetic depth exclusively. The arcerial pressure and HR at the time of termination. of CPB were comparable between the ewo groups, alchough the BIS was higher in the control group. This demonstrates that che anaesthesiologist was mainly reacting co the haemodynamic variables and trying to restore them to normal while unknowingly accepting a lightly anaesthetized patient The cracheal extubation timings were similar in both groups. This may be because the time to tracheal extubation depends on many other factors such as haemodynamic stability. chese drainage and physio- logical variables such as body temperature chat could have affected recovery. These are not dependent on anaesthetic management alone. Moreover, conscious- ness cannot be the sole predictor of successful tracheal Bispectral index monitoring during cardiac bypass 455 extubation. Three patients, two in the study group and one in the control group, were extubated after 10h. Two of these patients ~ one each in both groups — required moderate inotropic support in the immediate postoperative period, while one in the study group had chronic obstructive airway disease and was left intubated for 24 h. There are few studies evaluating the role of BIS monitoring in cardiac surgical patients. Barr and colleagues assessed che BIS as a monitor of the depth of anaesthesia during fentanyl and midazolam anaes- thesia in patients undergoing coronary artery bypass surgery [7 They found that during clinically adequate anaesthesia, the BIS varied considerably and they could not relate it to drug concentration, Similarly, Doi and colleagues found BIS values co be quite variable during cardiac anaesthesia during CPB [sI. In both seudies the drugs were not titrated to achieve an objective end-point but were given in fixed, predetermined doses. The variable BIS values achieved may indicate the variability in the phar- macokinetics and pharmacodynamics in different individuals undergoing cardiac surgery. In contrast, Schmidlia and colleagues found the BIS to be the only EEG measurement that paralleled the clinical course of anaesthesia in patients undergoing CABG ich propofol-fentanyl anaesthesia during hypother- mic CPB 91. ‘The rise in the BIS values during the institution of bypass may be due to alteration in che brain- blood concentration gradient for anaesthetic drugs because of haemodilution. The rise was not signifi- cant in the BIS-titrated group. The anaesthesiologist might have foreseen the impending ‘light’ anaesthe- sia from the values and rends of the BIS and increase the anaesthetic concentration accordingly. There was no significant difference in MAP between the two groups during this period. The rise in BIS, at the institution of CPB in the control group, may also be due to lowering of anaesthetic delivery by the anaes- thesiologist in order co maintain arterial pressure; while in the study group, the anaesthesiologist adjusted the vasoactive drugs to maintain pressure while keeping the BIS constant. ‘The observed jump in the BIS values at the time of termination of CPB may be due to the tempera- ture rise in the brain which raises the anaesthetic requirement. There is also a tendency on the part of the anaesthesiologise co concencrare more on haemo- dynamics than the depth of anaesthesia at this par- ticular moment. As there was no significant rise in BIS values whilst inscituting or terminating CPB in the study group, it may be concluded thae BIS monitoring ~ and titrating anaesthetic deugs accord- ingly ~ is likely to avoid the chance of inadequate depth of anaesthesia. Fortunately, only one patient in (© 2003 Buropean Academy of Anaesthesiology, Earpers Jornal of Anauteily 20: 451-456456. G.D. Pari and. 8. Murthy our control group reported awareness and that was at the time of sternotomy. This seudy failed co demonstrate any significant improvement in the time to secovery when the BIS ‘was used to titrate the anaesthetic administration co supplemene routine physiological monitoring. How- ever, before discrediting the concept of BIS monitor- ing for rhis purpose, we should consider factors that ‘might have overshadowed the possible advantages of such monitoring in this regard. Residual neuromus- cular blockade could have affected the assessment of recovery ‘The fanction of the neuromuscular junc- tion was only monitored until che recovery ofall four ‘witches following the train-of-four stimuli and all patients had recovered four cwitches in the first 10 min after cessation of anaesthesia. Ie was presumed that patients’ ability to respond co verbal commands ‘would be unaffected by this partial neuromuscular blockade, However, chere is still the possibility that some patients may not have been able to respond eat- lier chan 10 min because of the effect of the muscle relaxane when all four twitches had not recovered. In general technology assessment studies it is known thar rechnology influences those practitioners that use it for a small number of their patients thereby improving che outcome for all [10]. No measures were caken in this study to addresses the influence of learning so thar it is not biased against new technol- ogy. Moreover, the BIS by itself is shown to be an effective teaching tool [11]. Alehough in our study the patients were randomly assigned to the use of the BIS, or nor, statistical techniques were not applied to determine whether the outcome in fact differed, Moreover, only one anaesthesiologist supervised the anaesthetic procedure in all patients. Recruitment of fewer patients may also be the reason for the differ- ences being insignificant. In this scudy, the patients were followed up for 24h after tracheal extubation to determine the incidence of awareness. Following up patients for longer periods after operation is more desirable to devermine the teue incidence of recal (121 In conclusion, the BIS monitor in patients under- going cardiac surgery (CABG and valve repair/teplace- ment) under moderate hypothermic CPB decreases the incidence of haemodynamic disturbances and facilitates the titration of adequate amounts of volatile anaesthetic during whole-body perfusion wich che extracorporeal circulation. References A. Mouion JM, Lang E, Sebel PS, Manberg PL Prediction fof movement using bispectral electroencephalographic analysis dusing propofolalfenanil or isofluranealfenta anesthesia. Anat Analg 1995; 80: 780-785 Liw J, Singh H, White PF. Electro encephalogram bispec: tral analysis predicts che depth of midazolam-induced sedation, Anatbsvsligy 1996; 84: 64-69, Kearse Jr LA, Manberg P, Chamoun N, Debros Zaslavsky A. Bispoctral analysis of the electroencephalo- grim cotolates with patient movement to skin mason ‘ducing propofol/nicrous oxide anesthesia. Amashasilogy 1994; 81: 1365-1370. 4, Song D, Joshi GP, White PF Titration of volatile anes- thecice using biepectest index facilitates recovery after ambulatory anesthesia. Ansitbuialay 1997; 87; 842-848. 5. Gan TJ, Glass PS, Windsor A, ef . Bispectral index monitoring allows fstet emergence and improved recov- ery fom propofol, alfentanil and niccous oxide anesthesia, Ansbailogy 1997; 87: 808-815. 6. Hug CC. Does opioid “Aneschesa’ exist? Anurbeislogy 1990; 73: 1-4 11. Barr, Anderson RE, Samuelsson S, Owall A, Jakobsson JG. Fentanyl and midazolam anaesthesia for coronary Bypass surgery 4 clineal study of bispectral electroencephalogram snalysis, drug concentrations and reall BJ Anaesth 2000; 84; 749-752, 8. Dai M, Gajesj RJ, Manroaritie H, Kenny GNC. Finer af cardiopulmonary bypass and hypothermia on electroen- cephalographic variables Ansezbasia 1997; 52: 1048-1055. 9. Schmidlin D, Haer P, Schmid ER. Monitoring level of sedation sd bispectral EEG analysis berween hypochermic sod normothermic cardiopulmonary bypass. Br J Anaesth 2000; 86: 769-776. 10. Roizen ME, Toledano A. Technology assessment and the learning contamination bias. Anith Anclg 1994, 79: A10-A12, 11. Kumar A, De Deyne C, Strays M, Vondelinckee G, Heylen R. Use of bispectral EEG monitoring eo evaluate training in anesthesia. BrJ Anau 1999; 82 Suppl): AAT. 12, Sandin RH, Awareness during anaesthesia: a prospective case study. Lanst 2000; 355: 707-71 {© 2003 European Academy of Anseshesiology, Eursern Journal of Anasbsligy 20: 451-436