ELECTROENCEPHALOGRAM BISPECTRAL ANALYSIS DURING TIVA ANAESTHESIA. Summary

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1 Nowiny Lekarskie 2001, 70, 7, Z. ŻABA 1, S. SCHUBERT 2, K. HARBAUER 3, A. DOENICKE 3 ELECTROENCEPHALOGRAM BISPECTRAL ANALYSIS DURING TIVA ANAESTHESIA 3 Institute for Anesthesiology, Ludwig-Maximilians University, Munich; 2 Martin Luther University, Halle, Germany; 1 Institute for Anesthesiology, Karol Marcinkowski University of Medical Sciences in Poznań, Poland Summary KEY WORDS: Intravenous anesthetics: propofol and etomidate-lipuro, Depth of anaesthesia: Biapectral Index, Ambulatory anaesthesia The Bispectral Index (BIS) is a processed EEG parameter that has been validated as a measure of the sedative-hypnotic effects of anaesthetic drugs. Previous studies have suggested that bispectral index (BIS) monitoring can reduce anaesthetic usage. This study was undertaken to establish if its use could reduce anaesthetic costs. Forty-four patients were randomly assigned to receive TIVA with remifentanil and either propofol (Group I) or etomidate-lipuro (Group II). Each group was divieded in two subgroups: subgroup BIS-Monitored and subgroup Pre-BIS. During surgery, in BIS subgroups (BIS-Monitored), drugs were titrated to keep BIS level between 40 and 60, while in the standard groups (Pre-BIS ) drugs were titrated according to clinical parameters. BIS monitoring decreases both etomidate and propofol consumption, when compared to anaesthesia without BIS. BISPEKTRALNA ANALIZA ENCEFALOGRAFICZNA W CZASIE ZNIECZULENIA CAŁKOWICIE DOŻYLNEGO Streszczenie SŁOWA KLUCZOWE: anestetyki dożylne: propofol i etomidat-lipuro; głębokość znieczu- lenia: wskaźnik Bispectral Index, anestezja ambulatoryjna Monitorowanie poziomu znieczulenia za pomocą wskaźnika BIS (Bispectral Index) wykazało znaczną redukcję podawanych anestetyków podczas znieczulenia. Celem pracy było porównanie zużycia leków podczas znieczuleń całkowicie dożylnych (TIVA propofolowa v. TIVA etomidatowa) wykonywanych w trybie ambulatoryjnym przy sterowaniu głębokością znieczulenia za pomocą wskaźnika BIS. Badania przeprowadzono w randomizowanej grupie u 44 chorych obojga płci, przeznaczonych do krótkotrwałych ambulatoryjnych zabiegów chirurgicznych trwających nie dłużej niż jedną godzinę. Badania przeprowadzono w dwóch grupach: grupa I 22 chorych znieczulanych propofolem, grupa II 22 chorych znieczulanych etomidatem-lipuro. Ponadto każda z grup została podzielona na dwie podgrupy: podgrupa pierwsza Pre-BIS bez sterowania

2 778 Z. Żaba et al. poziomem znieczulenia za pomocą BIS-u oraz podgrupa druga Pre-BIS-Monitored w której głębokość znieczulenia kontrolowana była przy udziale BIS-u. Indukcję znieczulenia przeprowadzono podając: remifentanyl w dawce 1 µg/kg oraz albo etomidat w dawce 0,3 mg/kg lub propofol w dawce 2 mg/kg. Następnie chorych intubowano maską krtaniową. Dawki leków do podtrzymania znieczulenia dobierano na podstawie oceny tradycyjnej poziomu znieczulenia (w podgrupach Pre-BIS) oraz przy pomocy monitorowania wartości BIS-u (w podgrupach BIS-Monitored) i wynosiły one: dla etomidatu od 1 do 0,2 mg/kg/h, dla propofolu od 8 do 3 mg/kg/h oraz dla remifentanylu od 0,25 do 0,1 µg/kg/min. Dawki leków obniżano w podgrupach BIS-monitored do zalecanego zakresu wartości BIS stosowanego podczas znieczulenia, tj. pomiędzy 60 a 40. Monitorowanie głębokości znieczulenia za pomocą wskaźnika BIS umożliwia znaczne zmniejszenie dawek anestetyków (etomidatu o 30% i propofolu o 22%). Zastosowanie BIS-u spowodowało znaczne skrócenie czasu budzenia się pacjenta oraz czasu ekstubacji w grupie etomidatowej, BIS okazał się pożytecznym parametrem do zapewnienia większego bezpieczeństwa pacjentowi podczas znieczulenia. Indtroduction In clinical practice, indirect and non-specific signs are used for monitoring anaesthetic adequacy. These include haemodynamic, respiratory, muscular and autonomic signs. These measures do not indicate adequacy of anaesthesia in reliable manner. Direct monitoring of anaesthetic effect should be possible by EEG measurement. EEG information can be reduced, condensed and simplified, leading to single numbers. The bispectral index, derived from bispectral analysis of the EEG measures the hypnotic component of anesthesia, and is a very promising tool for measuring adequacy of anaesthesia [6, 8, 11, 15]. One of the more difficulty in clinical practice is to correlate depth of anesthesia and drugs administration. BIS monitoring has been demonstrated to reduce anesthetics usage [2, 3, 9, 16, 20]. The current study investigated the effect of using BIS monitoring on propofol and etomidate consumption. Methods After IRB (Ethical Committee) approval and written informed consent, 44 patients scheduled for day-case surgery expected to last less than 1 hour were enrolled in a double-blind, four-arm randomized study. One patient from propofol group was excluded from the study, because had shivering by induction and must be intubated. Patients were divided in two groups: Group I Propofol (n = 21) patients received propofol; Group II Etomidate-Lipuro (n = 22) patients received etomidatelipuro.

3 Electroencephalogram bispectral analysis during Tiva anaesthesia 779 Each group was divided in two subgroups: 1. Subgroup Pre-BIS drugs were titrated according to clinical parameters. 2. Subgroup BIS-Monitored drugs were titrated to keep BIS level between 40 and 60. For each groups demographics did not differ, only duration of surgery in propofol BIS- Monitored subgroup was 12 min. longer, as compared to Pre-BIS subgroup. Table I. Data of patients Group I - Propofol Group II - Etomidate Pre-BIS BIS-Monit. Pre-BIS BIS-Monit. Number Females Males Age (yrs) Height (cm) Body weight (kg) Anaesthesia duration (min) ,3 ± 14,2 170,2 ± 8,2 72,4 ± 7,8 47 ± 7, ,1 ± 18,4 171 ± 7,5 68,1 ± 6,7 59,8 ± 11, ,8 ± 9,2 174,1 ± 11,8 73,8 ± 8,9 49,3 ± 6, ,5 ± 16,4 172 ± 5,3 70 ± 10,2 53,6 ± 7,1 After premedication with midazolam 1 mg i.v. anesthesia was induced with remifentanil (1 µg/kg) and either etomidate (0,3 mg/kg) or propofol (2 mg/kg). Anaesthesia was maintained with remifentanil (0,25 µg/kg/min) and either etomidate (1 mg/kg/h) or propofol (8 mg/kg/h) in subgroup 1. Doses of etomidate and propofol were reduced in subgroup 2 according to the EEG criterion 40 60% Bispectral Index. Noninvasive blood pressure monitoring, heart rate, oxygen saturation, end-tidal concentration of carbon dioxide (ETCO20), and EEG were recorded. Recovery outcomes (eye opening, name telling) were determined, that means time to eye opening and time to name telling. The BIS value was displayed and recorded using Aspect Medical System monitor. We used electrodes Zipprep which were applied to the forehead. Data were analyzed using Student t- and Wilcoxon tests, as appropriate P values < 0,05 were considered statistically significant. Dada are presented as mean ± SD. Results After anaesthetic induction occurred BIS decrease to 40 in etomidate group, and 50 in propofol group, after intubation the bispectral index had recovered to 60, maintenance of anaesthesia between BIS level 40 and

4 780 Z. Żaba et al. 60, after stopping infusions of the drugs at the end of surgery BIS had returned to baselines values. We observed lower BIS values in etomidate group compared to propofol group about 10%. Results are presented in tables II V. Table II. Mean ± SD propofol and remifentanil doses in group I Group I - Propofol Pre-BIS BIS-Monit. Test Pretreatm.+ Bolus dose Induction dose (mg) 159 ± 36,2 150 ± 31,7 NS Maintenance rate of propofol (mg/kg/min.) 0,12 ± 0,035 0,09 ± 0,02 IS Maintenance rate of propofol (mg/kg/h) 6,9 ± 2,82 5,4 ± 2,5 IS Dose of propofol during anaesthesia (mg) 387 ± 32,6 361 ± 21,4 NS Total dose of propofol (mg) 546 ± 48,5 511 ± 36,7 NS Maintenance rate of remifentanil (mg/kg/min) 0,28 ± 0,04 0,23 ± 0,05 IS Total dose of remifentanil (mg) 1005 ± ± 326 NS IS significant differences (p < 0,05); NS no significant differences Table III. Mean ± SD etomidate and remifentanil doses in group II Pretreatm.+ Bolus dose Induction dose (mg) Maintenance rate of etomidate (mg/kg/min) Maintenance rate of etomidate (mg/kg/h) Dose of etomidate during anaesthesia (mg) Group II - Etomidate Pre-BIS BIS-Monit. Test 26 ± 5,7 24,5 ± 6,2 NS 0,014 ± 0,003 0,010 ± 0,001 IS 0,85 ± 0,21 0,61 ± 0,15 IS 49,5 ± 11,8 37,3 ± 5,3 IS Total dose of etomidate (mg) 75,5 ± 8,9 61,8 ± 10,2 IS Maintenance rate of remifentanil 0,22 ± 0,06 0,21 ± 0,05 NS (µg/kg/min) Total dose of remifentanil (µg) 867 ± ± 213 NS

5 Electroencephalogram bispectral analysis during Tiva anaesthesia 781 Table IV. Mean ± SD values of times and BIS in group I Group I - Propofol Pre-BIS BIS-Monit. BIS value at surgery end (propofol infusion end ) 53,4 ± 9,03 Rec. time - eye opening (min-sec) 6,09 ± 1,24 8,54 ± 3,12 BIS value during eye opening 76,1 ± 8,84 Rec. time - name telling (min-sec) 7,02 ± 2,52 9,31 ± 3,42 Extubation time (min-sec) 6,69 ± 3,92 8,72 ± 2,93 BIS value during extubation 76,8 ± 9,5 Table V. Mean ± SD values of times and BIS in group II Group II - Etomidate Pre-BIS BIS-Monit. BIS value at surgery end (etomidate infusion end ) 47,4 ± 9,60 Rec. time - eye opening (min-sec) 9,47 ± 3,49 5,13 ± 2,78 BIS value during eye opening 65,4 ± 18,61 Rec. time - name telling (min-sec) 12,08 ± 6,35 9,87 ± 3,41 Extubation time (min-sec) 11,25 ± 5,18 6,61 ± 3,85 BIS value during extubation 72,4 ± 19,5 Discussion In group I the consumption of propofol decreased by 22%, as compared to standard group (Tab. II). In group II consumption of etomidate decreased by 30%, as compared to standard group (Tab. III). In BIS-monitored group the time elapsed from cessation of anaesthetics to orientation decreased significantly. Recovery to eye opening was shorter in the etomidate Pre-BIS subgroup by 4,5 minutes (Tab. V). Our findings are consistent with the below studies with respect to anaesthetics consumption. Gan et al. [4] reported a randomized, controlled, blinded, multicenter trial using a standard propofol-alfentanil-nitrous oxide anaesthetic technique. Patients were randomized either to a blinded, standard practice group or to standard practice with BIS titration. Propofol infusions were adjusted by clinical observation in the standard practice group and by titration to BIS values of during maintenance in the unblinded group. The propofol infusion rate required for maintenance of anaesthe-

6 782 Z. Żaba et al. sia was decreased in the BIS group compared with the standard practice group. Time to extubation was 11,22 min in the control group and decreased to 7,27 min with BIS titration. This study demonstrated that hypnotic titration during anaesthetic maintenance can speed emergence and recovery from anaesthesia while reducing propofol use. Song et al. [17] studied female outpatients undergoing laparoscopic tubal ligation. Patients were randomly assigned to receive either desflurane or sevoflurane anaesthesia, or the anaesthesiologist was either unaware of BIS value (blinded) or used BIS (to value near 60) to titrate volatile anesthetic dose. Volatile anaesthetic usage decreased significantly by 30-38% compared with blinded controls. Time to extubation decreased from 6,5 min to 3,6 min for desflurane and from 7,7 min to 5,5 min for sevoflurane. Paventi et al. [12] studied 100 patients undergoing abdominal surgery randomly allocated to one of two groups of 50 each with or without BIS monitoring. In BIS group the consumption of sevoflurane decreased by 40% while the consumption of remifentanil decreased by 10%, as compared to group without BIS monitoring. Continues real-time measurement of anaesthetic effect using BIS should allow optimization of drug delivery to each patient, preventing both potential underdosing and overdosing of hypnotic medications. The upper limit of hypnotic titration is defined by the absence of awareness and memory. It should also be associated with the minimum dose of hypnotic agent. Awareness (a state of being aware, i.e., conscious) is one of the major causes of patient s complaints. The reported incidence of intraoperative recall varies from 0,2 to 2% [5, 7, 10, 18, 19]. Prevention of relative hypnotic overmedication should speed emergence and recovery [1, 13, 14]. Conclusions Monitoring of depth of anaesthesia by BIS allows significant reduction of the infusion rate of the hypnotic (etomidate: 30%, propofol: 22%). BIS is, therefore, a useful parameter for safe, low-dose maintenance of anaesthesia. References 1. Badrinath S., Avramov M. N., Papaioannou B.S. and Ivankovich A.D.: The impact of EEG-Bispectral Index monitoring on drug usage and recovery during ambulatory anaesthesia. Anaesth Analg, 88, S1-424, Doenicke A., Roizen M. F., Hoernecke R., Harbauer K., Schubert S., and Żaba Z.: TIVA with etomidate or propofol in day case surgery: is the bispectral index a useful parameter for to lower the maintenance dose? Anaesth Analg,

7 Electroencephalogram bispectral analysis during Tiva anaesthesia , S 53, Friedberg B.L., Sigl J.C.: Bispectral Index ( BIS ) monitoring decreases propofol usage in propofol ketamine office based anaesthesia. Anesth Analg, 88, S 54, Gan T.J., Glass P.S.A., Windsor A., Payne F., et all.: Bispectral index monitoring allows faster emergence and improved recovery from propofol, alfentanil, and nitrous oxide anesthesia. Anaesthesiology, 87, , Ghoneim M. M.: Awareness during anesthesia. Anaesthesiology, 92, , Johansen J. W., Sebel P. S.: Development and clinical application of electroencephalographic bispectrum monitoring. Anesthesiology, 93, , Kearse L. A., Rosov C., Zaslavsky A., Connors P., et all: Bispectral Analysis of the Elektroencephalogram predicts conscious processing of information during propofol sedation and hypnosis. 8. Kissin Igor: Depth of anaesthesia and bispectral index monitoring. Anaesth Analg, 90, , Leslie K., Sessler D., Smith W., Larson M. et all: Prediction of movement during Propofol/Nitrous Ox`ide anaesthesia. Anaesthesiology, 84, 52-63, Liu J., Singh H., White P.: Electroencephalographic bispectral index correlates with intraoperative recall and depth of propofol induced sedation. Anaesth Analg, 84, , Liu J., Wu G., Singh H., Gaines G.Y. et all.: Use of EEG bispectral analysis for assessing depth of sedation.. Anaesthesiology, V 79, No 3A, A455, Sept., Paventi S., Santevecchi A., Sacco V. et all: Sevoflurane and remifentanil anaesthesia titrated on bispectral index monitoring analysis of drug managements, European Journal of Anaesthesiology, Volume 18, Supplement 21, A-69, Pavlin D. J., Freund P., Koerschgen M. E., Bower J., and Bowdle T. A.: Monitoring Bispectral Index decreases recovery time in outpatient surgery. Anaesth Analg, 88, S55, Sebel P., Rampil I., Cork R. I in.: Bispectral Analysis for monitoring anesthesia a multicenter study. Anaesthesiology, V 79, No 3A, A178, Sept., Schneider G., Sebel P.: Monitoring depth of anaesthesia. European Journal of Anaesthesiology, 14, 21 28, Singh H.: Bispectral index (BIS) monitoring during propofol induced sedation and anaesthesia, European Journal of Anaesthesiology, 16, 31-36, Song D., Girish P.J., White P.F.: Titration of volatile anaesthetics using bispectral index facilitates recovery after ambulatory anaesthesia. Anaesthesiology, 87, 842-8, Takkallapalli R., Mehta M., DeLima L., Patel A., May W. and Eichhorn J.: Bispectral Index: can it predict arousal from noxious stimuli during GA? Anaesth Analg, 88, S 58, Takahashi S., Sakai T. and Matsuki A.: Relationship between Bispectral Index and sleep stages in man. Anaesth Analg, 88, S57, Vernon J. M., Lang E., Sebel P. S., Manberg P.: Prediction of movement using bispectral electroencephalographic analysis during propofol/alfentanil or isoflurane / alfentanil anesthesia. Anaesth Analg, 80, 780-5, 1995.

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