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Electroencephalogram bispectral index predicts hemodynamic and arousal reactions during induction of anesthesia in patients undergoing cardiac surgery
Electroencephalogram Bispectral Index Predicts Hemodynamic and Arousal Reactions During Induction of Anesthesia in Patients Undergoing Cardiac Surgery Martin Heck, MD, Bernhard Kumle, MD, Joachim Boldt, MD, Johannes Lang, MD, Andreas Lehmann, MD, and Werner Saggau, MD tearing after intubation, whereas no patient of the other groups showed signs of arousal. Mean arterial blood pressure remained stable in the BIS 60 and 50 groups, whereas in the BIS 40 group it decreased significantly to lower values before and after intubation. Patients in the BIS 40 group needed significantly more fluid replacement and injections of norepinephrine compared with the other groups. No significant changes in heart rate were detected. Conclusions: Electroencephalogram BIS predicts hemodynamic and arousal reaction resulting from induction of anesthesia and endotracheal intubation. BIS value should be kept at 50 before intubation to ensure safe hemodynamic conditions during induction of anesthesia in cardiac surgical patients. Copyright © 2000 by W.B. Saunders Company
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when a BIS value of 60 was reached after induction of anesthesia, group II patients were intubated at a BIS value of 50, and group III patients were intubated at a BIS value of 40. All patients were premedicated with 20 to 40 mg of clorazepate in the evening and 1 to 2 mg of flunitrazepam 1 hour before the operation. After arrival in the operating room, electrocardiogram (ECG) electrodes were placed for a 5-lead ECG, and pulse oximetry was obtained from an index finger. A 14G peripheral venous catheter was inserted, and an infusion of 500 mL of saline solution was started. An arterial catheter for invasive blood pressure measurement was placed in the left or right radial artery. BIS monitoring was performed with an Aspect1000 EEG monitor (Aspect Medical Systems, Inc, Natick, MA). EEG electrodes were placed in a bifrontal montage after skin preparation with disinfectant alcohol and slight rubbing. When electrode impedance exceeded 10 k⍀, skin preparation was repeated, and the electrode was replaced. After preoxygenation of at least 2 minutes, anesthesia was induced with 0.1 mg/kg of midazolam and a continuous infusion of sufentanil at a rate of 1.5 g/h. After loss of the eyelash reflex, a bolus of pancuronium, 0.1 mg/kg, was given for muscle relaxation. Every 30 seconds, sufentanil in increments of 25 g was administered to titrate the BIS down to the predetermined values of 60, 50, or 40. When the determined BIS level was stable for at least 30 seconds and after an interval of at least 2 minutes after the muscle relaxant was given, patients were intubated orally by an experienced anesthesiologist who was not involved in data collection. When mean arterial pressure decreased to ⬍70 mmHg, fluid replacement with a colloidal solution
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Objective: To evaluate hemodynamic and clinical responses to induction of anesthesia and intubation at 3 different values of the electroencephalogram bispectral index (BIS). Design: Prospective randomized trial. Setting: University-affiliated hospital. Participants: Forty-five patients undergoing elective coronary artery bypass graft surgery. Interventions: Patients were assigned to 3 groups (n ⴝ 15 for each group). Anesthesia was induced with midazolam, sufentanil, and pancuronium. In each group, sufentanil was titrated to a BIS value of 60, 50, or 40 before intubation. Mean arterial blood pressure, heart rate, incidence of coughing, tearing, and need for fluid replacement or injections of norepinephrine were recorded before intubation as well as immediately and 1 and 2 minutes after intubation. Measurements and Main Results: Thirteen patients intubated at a BIS value of 60 coughed and 14 experienced
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ESIDES SKIN INCISION and other surgical stimuli, induction of anesthesia and endotracheal intubation are major stress factors in patients undergoing general anesthesia for surgery. Especially in cardiac surgical patients, life-threatening hemodynamic events may occur at these times. The correct time for intubation is generally thought to be when the eyelash reflex has disappeared and when the onset time of the muscle relaxant has passed.1 Arousal phenomena, such as coughing and tearing, with subsequent hemodynamic reactions, including hypertension and tachycardia, after laryngoscopy and intubation occur often as well as decreases in heart rate and arterial blood pressure with the injection of anesthetic agents. Several electrophysiologic parameters, including the electroencephalogram (EEG), have been introduced to estimate anesthetic depth. Some computerized EEG data are reported to be correlated with the degree of anesthesia or sedation.2 One of these parameters is the bispectral index (BIS), which is reported to be one of the most reliable parameters of depth of anesthesia.3 In a prospective randomized trial, the authors evaluated hemodynamic and clinical responses to induction of anesthesia and endotracheal intubation at different levels on the BIS monitor.
KEY WORDS: electroencephalogram, bispectral index, hemodynamics, intubation, depth of anesthesia
MATERIALS AND METHODS
Forty-five patients with good left ventricular ejection fraction and an age less than 75 years undergoing elective coronary artery bypass graft (CABG) surgery were included in the study. All patients suffered from 3-vessel coronary artery disease, arterial hypertension, and hyperlipoproteinemia. Medications in all patients included isosorbide mononitrate and -blockers. Patients with reduced left ventricular function (left ventricular ejection fraction ⬍50%), atrial or ventricular pacemakers, history of cerebral illness, trauma, or ischemia and with significant carotid stenosis were excluded from the study. Patients with infusions of catecholamines or vasodilators before anesthesia were also excluded. Approval by the local ethics committee was obtained, and all patients gave their informed consent. The patients were randomly assigned to 3 study groups (n ⫽ 15 for each group). Group I patients were intubated
From the Department of Anesthesiology and Operative Intensive Care, and the Clinic of Cardiac Surgery, Klinikum der Stadt Ludwigshafen am Rhein gGmbh, Ludwigshafen am Rhein, Germany. Address reprint requests to Joachim Boldt, MD, Klinikum der Stadt Ludwigshafen am Rhein gGmbh, Klinik fu¨r Anaesthesiologie und Operative Intensivmedizin, Bremserstrasse 79, D-67063 Ludwigshafen am Rhein, Germany. Copyright © 2000 by W.B. Saunders Company 1053-0770/00/1406-0013$10.00/0 doi:10.1053/jcan.2000.18447
Journal of Cardiothoracic and Vascular Anesthesia, Vol 14, No 6 (December), 2000: pp 693-697
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Table 1. Demographic Data Variable
BIS 60
BIS 50
BIS 40
Age (yrs) Height (cm) Weight (kg) LVEF (%)
62.9 ⫾ 7.5 171.6 ⫾ 5.6 84.6 ⫾ 11.4 59.9 ⫾ 7.7
62.5 ⫾ 7.0 170.5 ⫾ 4.5 77.1 ⫾ 12.4 58.5 ⫾ 8.1
65.9 ⫾ 7.1 166.9 ⫾ 10.2 75.4 ⫾ 14.6 62.7 ⫾ 8.9
NOTE. Values are expressed as mean ⫾ SD. Abbreviations: BIS, bispectral index; LVEF, left ventricular ejection fraction.
T0—before induction of anesthesia T1—immediately before laryngoscopy and endotracheal intubation T2—immediately after inflating the cuff of the endotracheal tube T3—1 minute after endotracheal intubation T4—2 minutes after endotracheal intubation
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(gelatin) was started. If blood pressure did not respond to the fluid challenge, norepinephrine was given in increments of 5 g. At 5 times, mean arterial blood pressure (MAP), heart rate, and BIS value were recorded:
differences were seen in baseline values of the BIS (group I, 93.3 ⫾ 2.2; group II, 89.5 ⫾ 6.8; group III, 89.4 ⫾ 4.6). In group I, the BIS value dropped to 59.5 ⫾ 1.2 before intubation versus 49.5 ⫾ 1.6 in group II and 39.8 ⫾ 1.7 in group III. Immediately after intubation, BIS values remained stable in all groups (57.7 ⫾ 8.7 in group I, 48.7 ⫾ 7.1 in group II, and 40.5 ⫾ 2.6 in group III) but dropped to lower values 1 minute (51.4 ⫾ 9.0 in group I, 44.3 ⫾ 7.7 in group II, and 37.9 ⫾ 6.5 in group III) and 2 minutes (50.8 ⫾ 7.8 in group I, 44.7 ⫾ 6.8 in group II, and 37.1 ⫾ 3.6 in group III) after endotracheal intubation (Fig 1). BIS values before and immediately after intubation were significantly different among the groups but were not significantly different 1 and 2 minutes after intubation. BIS values after intubation were not significantly different from BIS values before intubation in all groups. The dose of sufentanil needed to reach the defined level of BIS did not differ significantly among the 3 study groups. In group I, 1.6 ⫾ 0.4 g/kg (130 ⫾ 36.9 g) of sufentanil was needed versus 1.6 ⫾ 0.5 g/kg (120 ⫾ 23.8 g) in group II and 1.7 ⫾ 0.3 g/kg (126.7 ⫾ 22.1 g) in group III (Fig 2). Baseline values of MAP did not show significant differences among the groups (group I, 94.3 ⫾ 6.9 mmHg; group II, 93.3 ⫾ 6.8 mmHg; group III, 95.7 ⫾ 10.8 mmHg). After induction of anesthesia, MAP decreased significantly from the baseline before intubation (p ⬍ 0.05) in all groups. No differences were seen between groups I and II (78.9 ⫾ 9.8 mmHg v 78.5 ⫾ 10.6 mmHg), but in group III, MAP decreased significantly (p ⬍ 0.05) to 64.5 ⫾ 9.7 mmHg. After endotracheal intubation, MAP remained stable in groups I and II (88.1 ⫾ 14.2 mmHg v 86.4 ⫾ 12.9 mmHg immediately after intubation, 85.6 ⫾ 16.4 mmHg v 85.9 ⫾ 12.9 mmHg after 1 minute, and 86.2 ⫾ 8.3 mmHg v 86.2 ⫾ 11.8 mmHg after 2 minutes); whereas in group III, MAP remained significantly lower immediately after intubation (70.1 ⫾ 9.1 mmHg), after 1 minute (69.6 ⫾ 9.4 mmHg), and after 2 minutes (72.9 ⫾ 8.8 mmHg) (Fig 3).
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The incidence of coughing and tearing during the 2 minutes after laryngoscopy and intubation was noted. The need for fluid replacement, the need for norepinephrine, and the doses of all drugs and infusions given were noted. Patients were considered as dropouts when intubation conditions were difficult (time for laryngoscopy and intubation ⬎1 min or ⬎1 attempt for intubation). Mean values and SD were calculated for all parameters. For statistical interpretation, 1- and 2-factorial analyses of variance (including multivariate analysis of variance followed by Scheffe’s test) and paired t-test were carried out. Chi-square analyses with Fisher’s exact tests were used for categoric data if appropriate; p values ⬍ 0.05 were considered significant. RESULTS
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No significant differences were seen in age, weight, height, gender, and left ventricular ejection fraction (Table 1). None of the patients had to be excluded from the trial because of difficult intubation conditions as defined earlier. No significant
Fig 1. Bispectral (BIS) index before and after intubation. Values are expressed as mean ⴞ SD. T0, baseline values; T1, values before intubation; T2, immediately after intubation; T3, 1 minute after intubation; T4, 2 minutes after intubation. * Significant between the groups (p < 0.05). 䊐, BIS 60 group; E, BIS 50 group; Œ, BIS 40 group.
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INDUCTION OF ANESTHESIA AND BIS MONITORING
Fig 2. Doses of sufentanil needed for intubation. Values are expressed as mean ⴞ SD. BIS, bispectral index.
anesthesia and episodes of tachycardia, hypertension, and arrhythmias after intubation are frequently detected.4 These hemodynamic responses do not present a problem for healthy patients but may be a risk for increased morbidity and mortality in patients with cardiovascular disease.5 Using echocardiographic imaging techniques, significant alterations of ventricular contractility, afterload, ejection fraction, and left end-diastolic volume can be detected in these patients.6 In daily practice, clinical parameters, such as sweating, tearing, and pupil size, are used to estimate anesthetic depth. Many of these parameters are not reliable, however, because they are altered by opioids and muscle relaxants. After a fixed weight-dependent dose of an induction drug, patients are usually intubated when the onset time of the muscle relaxant is over, the patient does not respond to verbal commands, and tactile responses such as the eyelash reflex
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No significant differences could be found in heart rates among the groups during the study period (Table 2). In group I, 13 patients coughed, and 14 patients showed tearing after laryngoscopy and insertion of an endotracheal tube, whereas none of the patients of groups II and III coughed or experienced tearing (p ⬍ 0.05). Volume replacement was not needed in group I but was necessary in 2 patients in group II and in 14 patients in group III (p ⬍ 0.05). Norepinephrine was not required in groups I and II but had to be used in 4 patients of group III (p ⬍ 0.05) (Table 3).
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DISCUSSION
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Besides surgical stimuli, induction of anesthesia and endotracheal intubation have the greatest impact on hemodynamics and vegetative functions of patients undergoing general anesthesia. Periods of profound hypotension after induction of
Fig 3. Mean arterial pressure (MAP) before and after intubation. Values are expressed as mean ⴞ SD. T0, baseline values; T1, values before intubation; T2, immediately after intubation; T3, 1 minute after intubation; T4, 2 minutes after intubation. * Significant from baseline values (p < 0.05); ⴙ Significant from groups I and II (p < 0.05). 䊐, I, BIS 60 group; E, II, BIS 50 group; Œ, III, BIS 40 group.
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T0 T1 T2 T3 T4
BIS 60
BIS 50
BIS 40
62.7 ⫾ 14.1 59.0 ⫾ 12.9 63.1 ⫾ 11.6 60.2 ⫾ 11.4 58.4 ⫾ 11.1
63.7 ⫾ 13.1 58.7 ⫾ 13.7 60.8 ⫾ 14.7 61.5 ⫾ 14.9 61.9 ⫾ 14.2
67.1 ⫾ 10.8 60.9 ⫾ 10.31 64.0 ⫾ 12.4 60.9 ⫾ 8.9 60.5 ⫾ 8.0
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NOTE. Values are expressed as mean ⫾ SD. Abbreviations: BIS, bispectral index; T0, baseline values; T1, values before intubation; T2, immediately after intubation; T3, 1 minute after intubation; T4, 2 minutes after intubation.
higher incidence of coughing and tearing in the BIS 60 group of the present study indicated an inadequate level of anesthesia. This indication is in agreement with the above-mentioned anesthetic range of BIS 40 to 5519 and suggests that intubation should be performed at a BIS level ⬍60 to avoid deleterious arousal reactions. Several studies investigating the influence of the BIS during induction of anesthesia have been published with controversial results. Mi et al20 found different hemodynamic reactions after intubation at the same BIS level after induction of anesthesia with propofol or propofol and fentanyl. The study of Hoffmann et al21 showed that the BIS provides an indication of blood pressure increases as a result of intubation in patients anesthetized with propofol and propofol and midazolam. In the present study, no significant increase in blood pressure after intubation was recorded in any group. This situation may be due to not only the use of different anesthetics and muscle relaxants but also to the fact that sufentanil was titrated before intubation. Masuda et al22 showed that propofol titrated to a BIS level of 40 did not lead to an increased blood pressure after intubation. In the present study, patients of the BIS 40 group showed a significantly lower MAP value than other patients, indicating too deep an anesthetic level. This finding and the lack of arousal signs in the BIS 50 group suggest that intubation in cardiac surgical patients should be performed at a BIS level of 50 to avoid arousal reactions and hemodynamic depression during induction of anesthesia. In cardiac anesthesia, opioids and benzodiazepines are commonly used because they have fewer hemodynamic side effects compared with volatile anesthetics. They have dose-dependent negative hemodynamic effects, however. Distinct interindividual and intraindividual differences in hypnotic, hemodynamic, and vegetative effects can be seen.23 The results of the present study reflect the interindividual response to opioids. Almost the same dose of sufentanil was required in all groups, but the difference of the clinical reactions among the groups was much greater, ranging from arousal reactions in group I to significant hemodynamic depression in group III. This finding suggests that anesthetics should be titrated to the desired level of anesthesia instead of giving a fixed weight-dependent dose. By monitoring the BIS, the dose of an induction drug can be adapted to the individual need of the patient. The higher incidence of coughing in group I may give the impression that intubation was performed earlier in this group and was related more to an inadequate onset time of pancuronium rather than insufficient anesthesia. The time interval between administration of pancuronium and intubation was not
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can no longer be obtained.1 Notwithstanding these clinical signs of adequate anesthesia depth, hemodynamic depression and arousal phenomena with deleterious effects are often seen. Electrophysiologic parameters have been repeatedly suggested for monitoring depth of anesthesia. Among the great number of different electrophysiologic parameters, 2 techniques have become popular: midlatency auditory evoked potentials and the computerized EEG.2 Many variations of the latter, such as median frequency, spectral edge frequency, and different band power ratios, have been correlated with anesthetic depth, response to endotracheal intubation, and intraoperative awareness.7-9 All of these parameters show great interindividual variations or varying effects when different anesthetic agents are used.10 A novel EEG-derived parameter is the BIS, which is based partly on the bispectral analysis of the EEG. In contrast to spectral analysis, BIS retains information on the interdependence of frequencies.11 The BIS is based on a combination of time domain, frequency domain, and second-order spectral subparameters and is optimized using a patient database. The output of the BIS monitor is computed to be a dimensionless number ranging from 0 to 100.2 In several studies, the BIS has been shown to predict movement in response to surgery,12,13 to detect consciousness with a variety of anesthetic drugs,14 to reflect different natural sleep stages in humans,15 to be a valuable monitor of the level of sedation,16 to correlate with plasma levels of anesthetics,3 and to decrease the recovery time in outpatient surgery.17 Compared with other EEG monitoring parameters, such as spectral edge frequency, median frequency, or auditory evoked potentials, the BIS appears to have the best predictive power during induction and recovery from general anesthesia.18 A multicenter study by Sebel et al13 showed satisfactory correlations of the BIS with movement because of skin incision under opioid-free anesthesia, whereas the administration of opioids led to poorer results. These findings are contradictory to the results of the present study but may be explained by different anesthetic regimens or by the hypothesis that arousal reactions because of intubation and skin incision are mediated by different neuronal pathways that are variously influenced by opioids. In awake patients, the BIS value was ⬎92, whereas during general anesthesia, the BIS values typically ranged from 40 to 55.19 In contrast, baseline values of the BIS in the present study were lower in all groups before induction of anesthesia because of the extensive premedication with benzodiazepines. The
Table 3. Incidence of Arousal Signs and Hemodynamic Interventions Variable
BIS 60
BIS 50
BIS 40
Coughing Tearing Volume Norepinephrine
13 14 0 0
0 0 2 0
0 0 13 4
NOTE. Values are expressed as absolute numbers of patients. Abbreviation: BIS, bispectral index.
INDUCTION OF ANESTHESIA AND BIS MONITORING
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recorded and neuromuscular blockade monitoring was not part of the study protocol. Because all groups received a mean dose of at least 120 g of sufentanil with a 20-g dose given every 30 seconds, however, it can be calculated that the time interval between the first bolus and the last was at least 2 to 3 minutes in all groups. The pancuronium onset time must have been enough to provide adequate neuromuscular blockade. In conclusion, the BIS is a monitoring tool that is easy to use
and interpret. The results of this study show that under the specific conditions of the anesthetic technique, monitoring of the BIS helped to find the ideal dose for induction of anesthesia in patients with increased cardiac risk. Its use can avoid deleterious reactions during induction of anesthesia and endotracheal intubation. Further studies need to be performed to show whether these data can be transferred to other anesthetic techniques.
REFERENCES 13. Sebel PS, Lang E, Rampil IJ: A multicenter study of bispectral electroencephalogram analysis for monitoring anesthetic effect. Anesth Analg 84:891-899, 1997 14. Glass PS, Bloom M, Kearse L, et al: Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane and alfentanil in healthy volunteers. Anesthesiology 86:836-847, 1997 15. Sleigh JW, Andrzejowski J, Steyn-Ross A, Steyn-Ross M: The bispectral index: A measure of depth of sleep? Anesth Analg 88:659661, 1999 16. Liu J, Singh H, White PF: Electroencephalographic bispectral index correlates with intraoperative recall and depth of propofol-induced sedation. Anesth Analg 84:185-189, 1997 17. Pavlin DJ, Freund P, Koerschgen ME, et al: Monitoring bispectral index decreases recovery time in outpatient surgery. Anesth Analg 88:S55, 1999 18. Sleigh JW, Donovan J: Comparison of bispectral index, 95% spectral edge frequency and approximate entropy of the EEG, with changes in heart rate variability during induction of general anesthesia. Br J Anaesth 82:666-671, 1999 19. Vernon JM, Long E, Sebel PS, Manberg P: Prediction of movement using bispectral electroencephalographic analysis during propofol/alfentanil or isoflurane/alfentanil anesthesia. Anesth Analg 80:780785, 1995 20. Mi WD, Sakai T, Takahashi S, Matsuhi A: Hemodynamic and electroencephalographic responses to intubation during induction of anesthesia with propofol or propofol/fentanyl. Can J Anaesth 45:19-22, 1998 21. Hoffmann E, Zsigmond E, Albrecht RF: The bispectral index during induction of anesthesia with midazolam and propofol. J Neurosurg Anesthesiol 8:15-20, 1996 22. Masuda T, Jinnouchi Y, Kitahata H, et al: Changes of arterial blood pressure and heart rate during induction of anesthesia with propofol— efficacy of propofol titrating using BIS as an indicator. Masui 48:621-626, 1999 23. Freye E: Opioide in der Medizin (ed 3). New York, NY, Springer, 1995, pp 155-157
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1. Heier T, Stehen PA: Assessment of anaesthesia depth. Acta Anaesthesiol Scand 40:1087-1100, 1996 2. Rampil IJ: A primer for EEG signal processing in anesthesia. Anesthesiology 89:980-1002, 1998 3. Doi M, Gajraj RJ, Mantzaridis H, Kenny GN: Relationship between calculated blood concentration of propofol and electrophysiological variables during emergence from anesthesia: comparison of bispectral index, spectral edge frequency, median frequency and auditory evoked potential index. Br J Anaesth 78:180-184, 1997 4. Prys-Roberts C, Greene LT, Meloche R, Foe¨x P: Studies of anaesthesia in relation to hypertension: II. Haemodynamic consequences of induction and endotracheal intubation. Br J Anaesth 43: 122-137, 1971 5. Kovac AL: Controlling the hemodynamic response to laryngoscopy and endotracheal intubation. J Clin Anesth 8:63-79, 1996 6. Kobayashi T, Horinouchi T, Matsukawa S, et al: Assessment of left ventricular contractility during intravenous induction of anesthesia by echocardiographic automated border detection. Masui 45:13351341, 1996 7. Drummond JC, Braun C, Perkins DE, Wolfe DE: A comparison of spectral edge frequency, a band power ratio, total power and dominance shift in the determination of depth of anesthesia. Acta Anaesthesiol Scand 35:693-699, 1991 8. Rampil IJ, Matteo RS: Changes in EEG spectral edge frequency correlate with the hemodynamic response to laryngoscopy and intubation. Anesthesiology 67:139-142, 1987 9. Schwilden H, Stoeckel H: Quantitative EEG-analysis during anesthesia with isoflurane in nitrous oxide at 1.3 and 1.5 MAC. Br J Anaesth 59:738-745, 1987 10. Dwyer RC, Rampil IJ, Eger EI, Bennett HL: The electroencephalogram does not predict depth of isoflurane anesthesia. Anesthesiology 81:403-409, 1994 11. Sigl JC, Chamoun NC: An introduction to bispectral analysis for the electroencephalogram. J Clin Monit 10:392-404, 1994 12. Kearse LA, Manberg P, Chamoun N, et al: Bispectral analysis of the electroencephalogram correlates with patient movement to skin incision during propofol/nitrous oxide anesthesia. Anesthesiology 81: 1365-1370, 1994
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when a BIS value of 60 was reached after induction of anesthesia, group II patients were intubated at a BIS value of 50, and group III patients were intubated at a BIS value of 40. All patients were premedicated with 20 to 40 mg of clorazepate in the evening and 1 to 2 mg of flunitrazepam 1 hour before the operation. After arrival in the operating room, electrocardiogram (ECG) electrodes were placed for a 5-lead ECG, and pulse oximetry was obtained from an index finger. A 14G peripheral venous catheter was inserted, and an infusion of 500 mL of saline solution was started. An arterial catheter for invasive blood pressure measurement was placed in the left or right radial artery. BIS monitoring was performed with an Aspect1000 EEG monitor (Aspect Medical Systems, Inc, Natick, MA). EEG electrodes were placed in a bifrontal montage after skin preparation with disinfectant alcohol and slight rubbing. When electrode impedance exceeded 10 k⍀, skin preparation was repeated, and the electrode was replaced. After preoxygenation of at least 2 minutes, anesthesia was induced with 0.1 mg/kg of midazolam and a continuous infusion of sufentanil at a rate of 1.5 g/h. After loss of the eyelash reflex, a bolus of pancuronium, 0.1 mg/kg, was given for muscle relaxation. Every 30 seconds, sufentanil in increments of 25 g was administered to titrate the BIS down to the predetermined values of 60, 50, or 40. When the determined BIS level was stable for at least 30 seconds and after an interval of at least 2 minutes after the muscle relaxant was given, patients were intubated orally by an experienced anesthesiologist who was not involved in data collection. When mean arterial pressure decreased to ⬍70 mmHg, fluid replacement with a colloidal solution
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Objective: To evaluate hemodynamic and clinical responses to induction of anesthesia and intubation at 3 different values of the electroencephalogram bispectral index (BIS). Design: Prospective randomized trial. Setting: University-affiliated hospital. Participants: Forty-five patients undergoing elective coronary artery bypass graft surgery. Interventions: Patients were assigned to 3 groups (n ⴝ 15 for each group). Anesthesia was induced with midazolam, sufentanil, and pancuronium. In each group, sufentanil was titrated to a BIS value of 60, 50, or 40 before intubation. Mean arterial blood pressure, heart rate, incidence of coughing, tearing, and need for fluid replacement or injections of norepinephrine were recorded before intubation as well as immediately and 1 and 2 minutes after intubation. Measurements and Main Results: Thirteen patients intubated at a BIS value of 60 coughed and 14 experienced
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ESIDES SKIN INCISION and other surgical stimuli, induction of anesthesia and endotracheal intubation are major stress factors in patients undergoing general anesthesia for surgery. Especially in cardiac surgical patients, life-threatening hemodynamic events may occur at these times. The correct time for intubation is generally thought to be when the eyelash reflex has disappeared and when the onset time of the muscle relaxant has passed.1 Arousal phenomena, such as coughing and tearing, with subsequent hemodynamic reactions, including hypertension and tachycardia, after laryngoscopy and intubation occur often as well as decreases in heart rate and arterial blood pressure with the injection of anesthetic agents. Several electrophysiologic parameters, including the electroencephalogram (EEG), have been introduced to estimate anesthetic depth. Some computerized EEG data are reported to be correlated with the degree of anesthesia or sedation.2 One of these parameters is the bispectral index (BIS), which is reported to be one of the most reliable parameters of depth of anesthesia.3 In a prospective randomized trial, the authors evaluated hemodynamic and clinical responses to induction of anesthesia and endotracheal intubation at different levels on the BIS monitor.
KEY WORDS: electroencephalogram, bispectral index, hemodynamics, intubation, depth of anesthesia
MATERIALS AND METHODS
Forty-five patients with good left ventricular ejection fraction and an age less than 75 years undergoing elective coronary artery bypass graft (CABG) surgery were included in the study. All patients suffered from 3-vessel coronary artery disease, arterial hypertension, and hyperlipoproteinemia. Medications in all patients included isosorbide mononitrate and -blockers. Patients with reduced left ventricular function (left ventricular ejection fraction ⬍50%), atrial or ventricular pacemakers, history of cerebral illness, trauma, or ischemia and with significant carotid stenosis were excluded from the study. Patients with infusions of catecholamines or vasodilators before anesthesia were also excluded. Approval by the local ethics committee was obtained, and all patients gave their informed consent. The patients were randomly assigned to 3 study groups (n ⫽ 15 for each group). Group I patients were intubated
From the Department of Anesthesiology and Operative Intensive Care, and the Clinic of Cardiac Surgery, Klinikum der Stadt Ludwigshafen am Rhein gGmbh, Ludwigshafen am Rhein, Germany. Address reprint requests to Joachim Boldt, MD, Klinikum der Stadt Ludwigshafen am Rhein gGmbh, Klinik fu¨r Anaesthesiologie und Operative Intensivmedizin, Bremserstrasse 79, D-67063 Ludwigshafen am Rhein, Germany. Copyright © 2000 by W.B. Saunders Company 1053-0770/00/1406-0013$10.00/0 doi:10.1053/jcan.2000.18447
Journal of Cardiothoracic and Vascular Anesthesia, Vol 14, No 6 (December), 2000: pp 693-697
693
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HECK ET AL
Table 1. Demographic Data Variable
BIS 60
BIS 50
BIS 40
Age (yrs) Height (cm) Weight (kg) LVEF (%)
62.9 ⫾ 7.5 171.6 ⫾ 5.6 84.6 ⫾ 11.4 59.9 ⫾ 7.7
62.5 ⫾ 7.0 170.5 ⫾ 4.5 77.1 ⫾ 12.4 58.5 ⫾ 8.1
65.9 ⫾ 7.1 166.9 ⫾ 10.2 75.4 ⫾ 14.6 62.7 ⫾ 8.9
NOTE. Values are expressed as mean ⫾ SD. Abbreviations: BIS, bispectral index; LVEF, left ventricular ejection fraction.
T0—before induction of anesthesia T1—immediately before laryngoscopy and endotracheal intubation T2—immediately after inflating the cuff of the endotracheal tube T3—1 minute after endotracheal intubation T4—2 minutes after endotracheal intubation
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(gelatin) was started. If blood pressure did not respond to the fluid challenge, norepinephrine was given in increments of 5 g. At 5 times, mean arterial blood pressure (MAP), heart rate, and BIS value were recorded:
differences were seen in baseline values of the BIS (group I, 93.3 ⫾ 2.2; group II, 89.5 ⫾ 6.8; group III, 89.4 ⫾ 4.6). In group I, the BIS value dropped to 59.5 ⫾ 1.2 before intubation versus 49.5 ⫾ 1.6 in group II and 39.8 ⫾ 1.7 in group III. Immediately after intubation, BIS values remained stable in all groups (57.7 ⫾ 8.7 in group I, 48.7 ⫾ 7.1 in group II, and 40.5 ⫾ 2.6 in group III) but dropped to lower values 1 minute (51.4 ⫾ 9.0 in group I, 44.3 ⫾ 7.7 in group II, and 37.9 ⫾ 6.5 in group III) and 2 minutes (50.8 ⫾ 7.8 in group I, 44.7 ⫾ 6.8 in group II, and 37.1 ⫾ 3.6 in group III) after endotracheal intubation (Fig 1). BIS values before and immediately after intubation were significantly different among the groups but were not significantly different 1 and 2 minutes after intubation. BIS values after intubation were not significantly different from BIS values before intubation in all groups. The dose of sufentanil needed to reach the defined level of BIS did not differ significantly among the 3 study groups. In group I, 1.6 ⫾ 0.4 g/kg (130 ⫾ 36.9 g) of sufentanil was needed versus 1.6 ⫾ 0.5 g/kg (120 ⫾ 23.8 g) in group II and 1.7 ⫾ 0.3 g/kg (126.7 ⫾ 22.1 g) in group III (Fig 2). Baseline values of MAP did not show significant differences among the groups (group I, 94.3 ⫾ 6.9 mmHg; group II, 93.3 ⫾ 6.8 mmHg; group III, 95.7 ⫾ 10.8 mmHg). After induction of anesthesia, MAP decreased significantly from the baseline before intubation (p ⬍ 0.05) in all groups. No differences were seen between groups I and II (78.9 ⫾ 9.8 mmHg v 78.5 ⫾ 10.6 mmHg), but in group III, MAP decreased significantly (p ⬍ 0.05) to 64.5 ⫾ 9.7 mmHg. After endotracheal intubation, MAP remained stable in groups I and II (88.1 ⫾ 14.2 mmHg v 86.4 ⫾ 12.9 mmHg immediately after intubation, 85.6 ⫾ 16.4 mmHg v 85.9 ⫾ 12.9 mmHg after 1 minute, and 86.2 ⫾ 8.3 mmHg v 86.2 ⫾ 11.8 mmHg after 2 minutes); whereas in group III, MAP remained significantly lower immediately after intubation (70.1 ⫾ 9.1 mmHg), after 1 minute (69.6 ⫾ 9.4 mmHg), and after 2 minutes (72.9 ⫾ 8.8 mmHg) (Fig 3).
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The incidence of coughing and tearing during the 2 minutes after laryngoscopy and intubation was noted. The need for fluid replacement, the need for norepinephrine, and the doses of all drugs and infusions given were noted. Patients were considered as dropouts when intubation conditions were difficult (time for laryngoscopy and intubation ⬎1 min or ⬎1 attempt for intubation). Mean values and SD were calculated for all parameters. For statistical interpretation, 1- and 2-factorial analyses of variance (including multivariate analysis of variance followed by Scheffe’s test) and paired t-test were carried out. Chi-square analyses with Fisher’s exact tests were used for categoric data if appropriate; p values ⬍ 0.05 were considered significant. RESULTS
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No significant differences were seen in age, weight, height, gender, and left ventricular ejection fraction (Table 1). None of the patients had to be excluded from the trial because of difficult intubation conditions as defined earlier. No significant
Fig 1. Bispectral (BIS) index before and after intubation. Values are expressed as mean ⴞ SD. T0, baseline values; T1, values before intubation; T2, immediately after intubation; T3, 1 minute after intubation; T4, 2 minutes after intubation. * Significant between the groups (p < 0.05). 䊐, BIS 60 group; E, BIS 50 group; Œ, BIS 40 group.
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Fig 2. Doses of sufentanil needed for intubation. Values are expressed as mean ⴞ SD. BIS, bispectral index.
anesthesia and episodes of tachycardia, hypertension, and arrhythmias after intubation are frequently detected.4 These hemodynamic responses do not present a problem for healthy patients but may be a risk for increased morbidity and mortality in patients with cardiovascular disease.5 Using echocardiographic imaging techniques, significant alterations of ventricular contractility, afterload, ejection fraction, and left end-diastolic volume can be detected in these patients.6 In daily practice, clinical parameters, such as sweating, tearing, and pupil size, are used to estimate anesthetic depth. Many of these parameters are not reliable, however, because they are altered by opioids and muscle relaxants. After a fixed weight-dependent dose of an induction drug, patients are usually intubated when the onset time of the muscle relaxant is over, the patient does not respond to verbal commands, and tactile responses such as the eyelash reflex
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No significant differences could be found in heart rates among the groups during the study period (Table 2). In group I, 13 patients coughed, and 14 patients showed tearing after laryngoscopy and insertion of an endotracheal tube, whereas none of the patients of groups II and III coughed or experienced tearing (p ⬍ 0.05). Volume replacement was not needed in group I but was necessary in 2 patients in group II and in 14 patients in group III (p ⬍ 0.05). Norepinephrine was not required in groups I and II but had to be used in 4 patients of group III (p ⬍ 0.05) (Table 3).
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DISCUSSION
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Besides surgical stimuli, induction of anesthesia and endotracheal intubation have the greatest impact on hemodynamics and vegetative functions of patients undergoing general anesthesia. Periods of profound hypotension after induction of
Fig 3. Mean arterial pressure (MAP) before and after intubation. Values are expressed as mean ⴞ SD. T0, baseline values; T1, values before intubation; T2, immediately after intubation; T3, 1 minute after intubation; T4, 2 minutes after intubation. * Significant from baseline values (p < 0.05); ⴙ Significant from groups I and II (p < 0.05). 䊐, I, BIS 60 group; E, II, BIS 50 group; Œ, III, BIS 40 group.
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HECK ET AL Table 2. Heart Rate (minⴚ1) Variable
T0 T1 T2 T3 T4
BIS 60
BIS 50
BIS 40
62.7 ⫾ 14.1 59.0 ⫾ 12.9 63.1 ⫾ 11.6 60.2 ⫾ 11.4 58.4 ⫾ 11.1
63.7 ⫾ 13.1 58.7 ⫾ 13.7 60.8 ⫾ 14.7 61.5 ⫾ 14.9 61.9 ⫾ 14.2
67.1 ⫾ 10.8 60.9 ⫾ 10.31 64.0 ⫾ 12.4 60.9 ⫾ 8.9 60.5 ⫾ 8.0
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NOTE. Values are expressed as mean ⫾ SD. Abbreviations: BIS, bispectral index; T0, baseline values; T1, values before intubation; T2, immediately after intubation; T3, 1 minute after intubation; T4, 2 minutes after intubation.
higher incidence of coughing and tearing in the BIS 60 group of the present study indicated an inadequate level of anesthesia. This indication is in agreement with the above-mentioned anesthetic range of BIS 40 to 5519 and suggests that intubation should be performed at a BIS level ⬍60 to avoid deleterious arousal reactions. Several studies investigating the influence of the BIS during induction of anesthesia have been published with controversial results. Mi et al20 found different hemodynamic reactions after intubation at the same BIS level after induction of anesthesia with propofol or propofol and fentanyl. The study of Hoffmann et al21 showed that the BIS provides an indication of blood pressure increases as a result of intubation in patients anesthetized with propofol and propofol and midazolam. In the present study, no significant increase in blood pressure after intubation was recorded in any group. This situation may be due to not only the use of different anesthetics and muscle relaxants but also to the fact that sufentanil was titrated before intubation. Masuda et al22 showed that propofol titrated to a BIS level of 40 did not lead to an increased blood pressure after intubation. In the present study, patients of the BIS 40 group showed a significantly lower MAP value than other patients, indicating too deep an anesthetic level. This finding and the lack of arousal signs in the BIS 50 group suggest that intubation in cardiac surgical patients should be performed at a BIS level of 50 to avoid arousal reactions and hemodynamic depression during induction of anesthesia. In cardiac anesthesia, opioids and benzodiazepines are commonly used because they have fewer hemodynamic side effects compared with volatile anesthetics. They have dose-dependent negative hemodynamic effects, however. Distinct interindividual and intraindividual differences in hypnotic, hemodynamic, and vegetative effects can be seen.23 The results of the present study reflect the interindividual response to opioids. Almost the same dose of sufentanil was required in all groups, but the difference of the clinical reactions among the groups was much greater, ranging from arousal reactions in group I to significant hemodynamic depression in group III. This finding suggests that anesthetics should be titrated to the desired level of anesthesia instead of giving a fixed weight-dependent dose. By monitoring the BIS, the dose of an induction drug can be adapted to the individual need of the patient. The higher incidence of coughing in group I may give the impression that intubation was performed earlier in this group and was related more to an inadequate onset time of pancuronium rather than insufficient anesthesia. The time interval between administration of pancuronium and intubation was not
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can no longer be obtained.1 Notwithstanding these clinical signs of adequate anesthesia depth, hemodynamic depression and arousal phenomena with deleterious effects are often seen. Electrophysiologic parameters have been repeatedly suggested for monitoring depth of anesthesia. Among the great number of different electrophysiologic parameters, 2 techniques have become popular: midlatency auditory evoked potentials and the computerized EEG.2 Many variations of the latter, such as median frequency, spectral edge frequency, and different band power ratios, have been correlated with anesthetic depth, response to endotracheal intubation, and intraoperative awareness.7-9 All of these parameters show great interindividual variations or varying effects when different anesthetic agents are used.10 A novel EEG-derived parameter is the BIS, which is based partly on the bispectral analysis of the EEG. In contrast to spectral analysis, BIS retains information on the interdependence of frequencies.11 The BIS is based on a combination of time domain, frequency domain, and second-order spectral subparameters and is optimized using a patient database. The output of the BIS monitor is computed to be a dimensionless number ranging from 0 to 100.2 In several studies, the BIS has been shown to predict movement in response to surgery,12,13 to detect consciousness with a variety of anesthetic drugs,14 to reflect different natural sleep stages in humans,15 to be a valuable monitor of the level of sedation,16 to correlate with plasma levels of anesthetics,3 and to decrease the recovery time in outpatient surgery.17 Compared with other EEG monitoring parameters, such as spectral edge frequency, median frequency, or auditory evoked potentials, the BIS appears to have the best predictive power during induction and recovery from general anesthesia.18 A multicenter study by Sebel et al13 showed satisfactory correlations of the BIS with movement because of skin incision under opioid-free anesthesia, whereas the administration of opioids led to poorer results. These findings are contradictory to the results of the present study but may be explained by different anesthetic regimens or by the hypothesis that arousal reactions because of intubation and skin incision are mediated by different neuronal pathways that are variously influenced by opioids. In awake patients, the BIS value was ⬎92, whereas during general anesthesia, the BIS values typically ranged from 40 to 55.19 In contrast, baseline values of the BIS in the present study were lower in all groups before induction of anesthesia because of the extensive premedication with benzodiazepines. The
Table 3. Incidence of Arousal Signs and Hemodynamic Interventions Variable
BIS 60
BIS 50
BIS 40
Coughing Tearing Volume Norepinephrine
13 14 0 0
0 0 2 0
0 0 13 4
NOTE. Values are expressed as absolute numbers of patients. Abbreviation: BIS, bispectral index.
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recorded and neuromuscular blockade monitoring was not part of the study protocol. Because all groups received a mean dose of at least 120 g of sufentanil with a 20-g dose given every 30 seconds, however, it can be calculated that the time interval between the first bolus and the last was at least 2 to 3 minutes in all groups. The pancuronium onset time must have been enough to provide adequate neuromuscular blockade. In conclusion, the BIS is a monitoring tool that is easy to use
and interpret. The results of this study show that under the specific conditions of the anesthetic technique, monitoring of the BIS helped to find the ideal dose for induction of anesthesia in patients with increased cardiac risk. Its use can avoid deleterious reactions during induction of anesthesia and endotracheal intubation. Further studies need to be performed to show whether these data can be transferred to other anesthetic techniques.
REFERENCES 13. Sebel PS, Lang E, Rampil IJ: A multicenter study of bispectral electroencephalogram analysis for monitoring anesthetic effect. Anesth Analg 84:891-899, 1997 14. Glass PS, Bloom M, Kearse L, et al: Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane and alfentanil in healthy volunteers. Anesthesiology 86:836-847, 1997 15. Sleigh JW, Andrzejowski J, Steyn-Ross A, Steyn-Ross M: The bispectral index: A measure of depth of sleep? Anesth Analg 88:659661, 1999 16. Liu J, Singh H, White PF: Electroencephalographic bispectral index correlates with intraoperative recall and depth of propofol-induced sedation. Anesth Analg 84:185-189, 1997 17. Pavlin DJ, Freund P, Koerschgen ME, et al: Monitoring bispectral index decreases recovery time in outpatient surgery. Anesth Analg 88:S55, 1999 18. Sleigh JW, Donovan J: Comparison of bispectral index, 95% spectral edge frequency and approximate entropy of the EEG, with changes in heart rate variability during induction of general anesthesia. Br J Anaesth 82:666-671, 1999 19. Vernon JM, Long E, Sebel PS, Manberg P: Prediction of movement using bispectral electroencephalographic analysis during propofol/alfentanil or isoflurane/alfentanil anesthesia. Anesth Analg 80:780785, 1995 20. Mi WD, Sakai T, Takahashi S, Matsuhi A: Hemodynamic and electroencephalographic responses to intubation during induction of anesthesia with propofol or propofol/fentanyl. Can J Anaesth 45:19-22, 1998 21. Hoffmann E, Zsigmond E, Albrecht RF: The bispectral index during induction of anesthesia with midazolam and propofol. J Neurosurg Anesthesiol 8:15-20, 1996 22. Masuda T, Jinnouchi Y, Kitahata H, et al: Changes of arterial blood pressure and heart rate during induction of anesthesia with propofol— efficacy of propofol titrating using BIS as an indicator. Masui 48:621-626, 1999 23. Freye E: Opioide in der Medizin (ed 3). New York, NY, Springer, 1995, pp 155-157
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1. Heier T, Stehen PA: Assessment of anaesthesia depth. Acta Anaesthesiol Scand 40:1087-1100, 1996 2. Rampil IJ: A primer for EEG signal processing in anesthesia. Anesthesiology 89:980-1002, 1998 3. Doi M, Gajraj RJ, Mantzaridis H, Kenny GN: Relationship between calculated blood concentration of propofol and electrophysiological variables during emergence from anesthesia: comparison of bispectral index, spectral edge frequency, median frequency and auditory evoked potential index. Br J Anaesth 78:180-184, 1997 4. Prys-Roberts C, Greene LT, Meloche R, Foe¨x P: Studies of anaesthesia in relation to hypertension: II. Haemodynamic consequences of induction and endotracheal intubation. Br J Anaesth 43: 122-137, 1971 5. Kovac AL: Controlling the hemodynamic response to laryngoscopy and endotracheal intubation. J Clin Anesth 8:63-79, 1996 6. Kobayashi T, Horinouchi T, Matsukawa S, et al: Assessment of left ventricular contractility during intravenous induction of anesthesia by echocardiographic automated border detection. Masui 45:13351341, 1996 7. Drummond JC, Braun C, Perkins DE, Wolfe DE: A comparison of spectral edge frequency, a band power ratio, total power and dominance shift in the determination of depth of anesthesia. Acta Anaesthesiol Scand 35:693-699, 1991 8. Rampil IJ, Matteo RS: Changes in EEG spectral edge frequency correlate with the hemodynamic response to laryngoscopy and intubation. Anesthesiology 67:139-142, 1987 9. Schwilden H, Stoeckel H: Quantitative EEG-analysis during anesthesia with isoflurane in nitrous oxide at 1.3 and 1.5 MAC. Br J Anaesth 59:738-745, 1987 10. Dwyer RC, Rampil IJ, Eger EI, Bennett HL: The electroencephalogram does not predict depth of isoflurane anesthesia. Anesthesiology 81:403-409, 1994 11. Sigl JC, Chamoun NC: An introduction to bispectral analysis for the electroencephalogram. J Clin Monit 10:392-404, 1994 12. Kearse LA, Manberg P, Chamoun N, et al: Bispectral analysis of the electroencephalogram correlates with patient movement to skin incision during propofol/nitrous oxide anesthesia. Anesthesiology 81: 1365-1370, 1994