Effect of remifentanil or esmolol on bispectral index and entropy to tracheal intubation during propofol anesthesia

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1 Anesth Pain Med 2010; 5: 304~309 Research Article Effect of remifentanil or esmolol on bispectral index and entropy to tracheal intubation during propofol anesthesia Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, Seoul, Korea Yoon Ji Choi, Hye Won Shin, Yun Hee Kim, Sung Uk Choi, Ji Yong Park, Seung Zhoo Yoon, and Seong-Ho Chang Background: The bispectral index (BIS) and entropy (response entropy, state entropy; RE, SE) have been used to monitor the anesthetic depth, and the difference between RE and SE (RE-SE difference) may represent the nociceptive stimuli during general anesthesia. This study was designed to determine whether BIS or entropy (RE, SE, and RE-SE difference) represent the response to tracheal intubation with iv bolus of remifentanil or esmolol for stable hemodynamic control during propofol anesthesia. Methods: Eighty-nine patients were randomly divided into three groups (the control, esmolol, and remifentanil groups). Patient received propofol by target controlled infusion with air 2 L/min and O 2 2 L/min. After the maintenance with target effect site concentration of propofol 5μg/ml for 5 min, patients received normal saline or esmolol 1.0 mg/kg or remifentanil 1.0μg/kg iv bolus according to group. And rocuronium 0.6 mg/kg iv bolus was administered and tracheal intubation was done. We measured mean arterial pressure (MAP), heart rate (HR), BIS, and entropy (RE, SE, RE-SE difference) during tracheal intubation. Results: Changes in MAP or HR after tracheal intubation were greater in the control and esmolol groups than those in the remifentanil group. Although BIS, RE, and SE did not increase after intubation in all groups, but RE-SE difference significantly increased at 1 min after tracheal intubation in the control and esmolol group, but was unchanged in the remifentanil group. Conclusions: Among BIS, RE, SE and RE-SE difference, RE-SE difference is the good indicator for estimate of nociception during tracheal intubation. (Anesth Pain Med 2010; 5: ) Key Words: Bispectral index, Entropy, Esmolol, Remifentanil, Propofol. Received: June 3, Revised: June 24, Accepted: July 13, Corresponding author: Hye Won Shin, M.D., Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, 126-1, Anam-dong, Sungbuk-gu, Seoul , Korea. Tel: , Fax: , hwshin99@yahoo.com INTRODUCTION Bispectral index (BIS) calculated from electroencephalograph (EEG) and entropy calculated from EEG irregularities have been used as a measure of the hypnotic component during anesthesia [1,2]. Entropy has two components [response entropy (RE) and state entropy (SE)]. RE is computed from the EEG and EMG activities of facial muscles and shows increased response to nociception, whereas SE is computed from EEG activity and represents degree of sedation [3]. In recent studies, it has been reported that the difference between RE and SE (RE-SE difference) indicate increased responses to nociceptive stimulation [4,5]. Nociceptive stimuli such as tracheal intubation, induce hypertension or tachycardia via sympathetic stimulation and is associated transient hemodynamic changes. For stable hemodynamic control, opioids, analgesics, sympatholytic drugs, and sedative-hypnotics are used during tracheal intubation. Opioid remifentanil is a useful analgesics for brief ambulatory surgical procedures because of its rapid onset, titrability, and short duration of action [6-8], whereas β-adrenergic antagonist esmolol is used for the prevention or treatment for unwanted perioperative hemodynamic responses and the reduction of the propofol concentration to prevent movement at skin incision [9-11]. In previous studies [8,9], iv bolus injection of remifentanil 1μg/kg or esmolol 1 mg/kg was found to be effective for prevent the hemodynamic changes induced by tracheal intubation. This study was designed to evaluate whether BIS or entropy (RE, SE, and RE-SE difference) represent the response to tracheal intubation with iv bolus of remifentanil 1μg/kg or esmolol 1 mg/kg during propofol anesthesia. 304

2 Yoon Ji Choi, et al:the change of BIS or entropy after tracheal intubation 305 MATERIALS AND METHODS This study was approved by the institutional review board of hospital and informed consent was obtained from all participating patients. Ninety-three ASA physical status I or II patients, 25 to 55 yr old, scheduled for elective surgery were recruited. Patients with a history of hypertension, diabetes mellitus, a cardiovascular or cerebrovascular disease, and those receiving medications that affect cardiovascular function or with an expected intubation difficulty were excluded. Patients were randomly allocated using a computer-generated randomization schedule to one of three groups (the control, esmolol, and remifentanil groups). All patient received glycopyrrolate 0.2 mg im premedication 30 to 45 min prior to the induction of anesthesia. Standard monitors [non-invasive blood pressure, heart rate, pulse oximetry (Datex-Ohmeda R, GE Healthcare, Finland)] were applied in a preoperative area. For the BIS and entropy monitoring, a BIS sensor (A-2000 System XP BIS monitor, Aspect Medical systems, USA) and an entropy sensor (M-Entropy TM, Datax- Ohmeda Division, Finland) were placed over the temporofrontal area of forehead after careful skin preparation. The locations of BIS or entropy sensors over left and right sides of foreheads were decided by flipping a coin. After sensor application, the impedance was checked automatically and BIS was updated every 15 sec. All study drugs were diluted to a volume 10 ml with normal saline. The anesthesiologist was unaware of study drug or group identification. After preoxygenation with O 2 mask 8 L/min, every patient received propofol (Fresofol R, Fresenius Kabi, France) by target controlled infusion (TCI: Orchestra TM, Fresenius Vial S.A., France) using Schnider model [12]. After the target effect site concentration of propofol 5μg/ml had been reached for 5 min, normal saline or esmolol (Brevibloc R, Bristol-Myers Squibb, USA) 1.0 mg/kg or remifentanil (Ultiva R, GlaxoSmithKline, USA) 1.0μg/kg was administered as iv bolus over 10 sec, and then rocuronium bromide (Esmeron R, Organon, Korea) 0.6 mg/kg iv bolus was administered over 10 sec. Anesthesia maintained at the target effect site concentration of propofol 5 μg/ml with air 2 L/min and O 2 2 L/min with controlled ventilation during study period. At 90 sec after the rocuronium injection, tracheal intubation was done by the same anesthesiologist. Anesthesia was maintained at a target effect-site concentration of propofol 3μg/ml with air 2 L/min and O 2 2 L/min. End-tidal CO 2 was maintained around 35 mmhg during study period. We measured mean arterial pressure (MAP), heart rate (HR) before induction (baseline), immediately before intubation (preintubation), and at 1, 2, and 3 minutes after intubation. BIS, entropy (RE, SE) were measured at baseline, pre-intubation, and at 30 sec, 1, 2 and 3 minute after intubation, and then we calculated RE-SE difference from RE, SE (we measured two times at each measuring points, and then used as data as mean of values for considering a time window of BIS and entropy). Data are expressed as means ± SD or numbers. Statistical analysis was performed using SPSS (Chicago, USA). Differences within groups were analyzed by repeated measures ANOVA, and post-hoc comparisons were performed using Dunnett s test. Differences between groups were analyzed by ANOVA. P values of < 0.05 were considered statistically significant. Table 1. Demographic Data Groups Control (n = 29) RESULTS Four patients were excluded due to hypertension before induction (1 patient) and detachment of BIS or entropy sensors during study periods (3 patients). Eighty-nine patients were included in this study. There were no significant differences among groups with respect to age, weight, height and the baseline value of MAP, HR, BIS, entropy (RE, SE, RE-SE difference) (P > 0.05) (Table 1, Fig. 1 3). Compared with baseline value, MAP in the control group decreased at pre-intubation and increased at 1 and 2 min after intubation, and MAP in the esmolol group decreased at pre-intubation and at 2 and 3 min after intubation, and MAP in the remifentanil group decreased at pre-intubation and at 1, 2, and 3 min after intubation (P < 0.05) (Fig. 1). Compared Esmolol (n = 30) Remifentanil (n = 30) Gender (M/F) 14/16 15/15 16/14 Age (yr) 44.1 ± ± ± 15.9 Height (cm) ± ± ± 8.9 Weight (kg) 66.9 ± ± ± 11.6 Values are means ± SD or number of patients. Control group: normal saline, Remifentanil group: remifentanil 1μg/kg, Esmolol group: esmolol 1 mg/kg, No significant differences were found among the groups.

3 306 Anesth Pain Med Vol. 5, No. 4, 2010 Fig. 1. Changes in mean arterial pressure (MAP) and heart rate (HR) during the induction of anesthesia. Control group: normal saline, Remifentanil group: remifentanil 1μg/kg, Esmolol group: esmolol 1 mg/kg, baseline: before anesthetic induction, pre-intubation: immediately before intubation, 1 min, 2 min, 3 min: 1, 2, 3 minute after tracheal intubation. *P < 0.05 versus baseline value, P < 0.05 compared with the control group, P < 0.05 compared with the esmolol group. and 3 min after intubation compared with baseline in all groups (P < 0.05) (Fig. 2, 3), but no significant differences were found among groups (P > 0.05) (Fig. 2, 3). RE-SE difference in all groups decreased at pre-intubation and at 1, 2, and 3 min after intubation compared with baseline (P < 0.05) (Fig. 3), but RE-SE difference in the control and esmolol groups were higher at 1 min after intubation than in the remifentanil group (P < 0.05) (Fig. 3). DISCUSSION Fig. 2. Changes of Bispectral index (BIS) during the induction of anesthesia. Control group: normal saline, Remifentanil group: remifentanil 1μg/kg, Esmolol group: esmolol 1 mg/kg, baseline: before anesthetic induction, pre-intubation: immediately before intubation, 1 min, 2 min, 3 min: 1, 2, 3 minute after tracheal intubation. *P < 0.05 versus baseline value. with the control group, MAP in the esmolol group was lower at 1, 2, and 3 min after intubation, and MAP in remifentanil group was lower at pre-intubation, and at 1, 2, and 3 min after intubation (P < 0.05) (Fig. 1). Compared with the esmolol group, MAP in the remifentanil was lower at 1, 2, and 3 min after intubation (P < 0.05) (Fig. 1). HR increased at 1, 2, and 3 min after intubation in all groups compared with baseline. HR in the esmolol and remifentanil groups were lower at 1, 2, and 3 min after intubation than in the control group (P < 0.05) (Fig. 1). BIS, RE and SE decreased at pre-intubation and at 1, 2, This study was undertaken to investigate whether BIS or entropy represents the response to tracheal intubation with iv bolus of remifentanil or esmolol for stable hemodynamic control during propofol anesthesia. BIS, RE and SE were not changed in all groups, but RE-SE difference was increased in the control and esmolol group in response to tracheal intubation. Depth of anesthesia consists of two components with sedation and analgesia. It has become common practice to measure depth of sedation using an EEG-based monitor, whereas depth of analgesia is more difficult to measure because of the variability of anesthetic drug requirements [13] and is usually assessed by patient movements, lacrimation, tachycardia, and hypertension. In clinical practice, BIS or entropy are used to monitor sedation, and prevent arousal during anesthesia. In recent study, the value of RE-SE difference represents the degrees of analgesia or nociception [4,5]. Entropy is computed from EEG and facial muscle activity, and is a measure of irregularity using entropy algorithm [14].

4 Yoon Ji Choi, et al:the change of BIS or entropy after tracheal intubation 307 Fig. 3. Changes of response entropy (RE), state entropy (SE), and RE-SE difference (RE-SE) during the induction of anesthesia. Control group: normal saline, Remifentanil group: remifentanil 1μg/kg, Esmolol group: esmolol 1 mg/kg, baseline: before anesthetic induction, pre-intubation: immediately before intubation, 1 min, 2 min, 3 min: 1, 2, 3 minute after tracheal intubation. *P < 0.05 versus baseline, P < 0.05 compared with the control group, P < 0.05 compared with the esmolol group, P < 0.05 compared with the pre-intubation value. Generally, RE (0 100) is calculated from Hz of EEG and EEG more than 32 Hz contain fast frontal electromyography (femg) that may be useful for the assessment of nociception during surgery. SE is calculated from Hz of EEG, which is associated with cortical activity [14]. During deep anesthesia, RE-SE difference is around zero, but RE increases during recovery from anesthesia or at inadequate analgesia by the contraction of facial muscles [15,16]. If a nociceptive stimulation is given, it may activate facial muscles and increase femg amplitude [17]. In general, upper facial muscles are relatively resistant to the effects of neuromuscular blocking (NMB) agents as compared with hand muscles, which are usually used for neuromuscular monitoring, and femg may be activated by painful stimuli in the 100% TOF blockade of thenar muscles [18,19]. Accordingly, the increase of RE-SE difference caused by femg activity, provide a measure of nociception [4,5]. The time windows of BIS, RE, and SE are 10, 2 15, and sec [4]. When anesthetic depth is monitored by these three parameters, they show different characteristics during arousal. RE increases first in parallel with muscle activation and this is followed some seconds later by SE [14]. Vakkuri et al. [20] reported that RE indicate emergence from anesthesia 11 sec before SE, and 12.4 sec before BIS. In our study, the values of RE-SE difference after tracheal intubation, was 6.26 in the control group, 5.6 in the esmolol group, and 1.8 in the remifentanil group. RE-SE difference in the control and esmolol group, significantly increased compared with the remifentanil group after tracheal intubation. In control and esmolol group, the increase of RE-SE difference represents the degree of nociception with hemodynamic changes even under the muscle relaxation state. Rocuronium dose-dependently suppresses the entropy response to tracheal intubation during propofol anesthesia [21] and small values of RE-SE difference within a range of 10 in our study may be due to the effect of NMB. During propofol infusion at light anesthetic depth (BIS 60 or propofol TCI 2μg/ml), remifentanil infusion induced significant decrease in BIS [7,22,23]. This was due to the increase of propofol plasma concentration by reduction of cardiac output

5 308 Anesth Pain Med Vol. 5, No. 4, 2010 with remifentanil infusion [24]. However, during propofol infusion at deep anesthetic depth (propofol TCI 4μg/ml), remifentanil infusion did not change the BIS [25]. In a study by Shin et al. [26], a plot of BIS against anesthetic depth was found to follow an S shaped curve from the awake to anesthetic state. BIS changes rapidly during light anesthesia (BIS 60 to 70), but only slightly during deep anesthesia (BIS 30 to 50). In our study, BIS was not changed during deep anesthetic condition with target effect site concentration of propofol 5μg/ml during tracheal intubation. There were many studies for the change of BIS by esmolol. Esmolol 1 mg/kg iv bolus reduced MAP and HR but did not affect BIS [27]. This lack of an effect of esmolol on BIS, was due to a delay of min between esmolol administration and the onset of maximal effect [28]. However, in other studies, esmolol 1 mg/kg iv bolus with infusion, attenuated the change of hemodynamics, BIS, entropy (RE, SE, RE-SE difference) by tracheal intubation [29,30]. Esmolol 1 mg/kg iv bolus in our study was insufficient to prevent hemodynamic change and nociception. In the other studies using esmolol 1 mg/kg iv bolus with 250μg/kg/min infusion [29], there was no change of hemodynamics or RE-SE difference during tracheal intubation. And Johansen et al. [11] reported that the use of esmolol 1 mg/kg with 250μg/kg/min infusion during anesthesia, significantly decreased the anesthetic requirement for skin incision. The use of esmolol as anesthetic adjuvant could be to reduce anesthetic and opioid requirement, to maintain hemodynamic stability [31]. The mechanisms about analgesic effect of esmolol may be the change of opioid pharmacokinetics and the implication with inhibitory G protein [31]. Coloma et al. [9] reported that iv esmolol and remifentanil are equally effective in maintaining stable hemodynamics during laparoscopic procedures, and Valjus et al. [15] reported the finding was not significantly different between esmolol 1 mg/kg and remifentanil 1.5μg/kg. Remifentanil blocked the change of MAP and HR to tracheal intubation completely, but esmolol was only effect at blocking the change of HR to tracheal intubation. These findings concur with the study results of Ornstein et al. [32], that is, the direct receptor mediated effect of esmolol on HR has a more rapid onset than its indirect effect on MAP, which is dependent on the inhibition of renin synthesis. Esmolol decreased HR rapidly with a half-time of 4.8 min, and decreased MAP with a half-time of 42 min. In conclusion, BIS, RE and SE did not represent the nociceptive response to tracheal intubation, but RE-SE difference indicating the degree of nociceptive stimulation, represent the degree of nociceptive response block with remifentanil or esmolol iv during propofol anesthesia. REFERENCES 1. Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997; 86: Gan TJ, Glass PS, Windsor A, Payne F, Rosow C, Sebel P, et al. Bispectral index monitoring allows faster emergence and improved recovery from propofol, alfentanil, and nitrous oxide anesthesia. BIS Utility Study Group. Anesthesiology 1997; 87: Hans P, Giwer J, Brichant JF, Dewandre PY, Bonhomme V. Effect of an intubation dose of rocuronium on spectral entropy and bispectral Index responses to laryngoscopy during propofol anaesthesia. Br J Anaesth 2006; 97: Wheeler P, Hoffman WE, Baughman VL, Koenig H. Response entropy increases during painful stimulation. J Neurosurg Anesthesiol 2005; 17: Takamatsu I, Ozaki M, Kazama T. Entropy indices vs the bispectral index for estimating nociception during sevoflurane anaesthesia. Br J Anaesth 2006; 96: Thompson JP, Hall AP, Russell J, Cagney B, Rowbotham DJ. Effect of remifentanil on the haemodynamic response to orotracheal intubation. Br J Anaesth 1998; 80: Koitabashi T, Johansen JW, Sebel PS. Remifentanil dose/electroencephalogram bispectral response during combined propofol/ regional anesthesia. Anesth Analg 2002; 94: O'Hare R, McAtamney D, Mirakhur RK, Hughes D, Carabine U. Bolus dose remifentanil for control of haemodynamic response to tracheal intubation during rapid sequence induction of anaesthesia. Br J Anaesth 1999; 82: Coloma M, Chiu JW, White PF, Armbruster SC. The use of esmolol as an alternative to remifentanil during desflurane anesthesia for fast-track outpatient gynecologic laparoscopic surgery. Anesth Analg 2001; 92: Gold MI, Sacks DJ, Grosnoff DB, Herrington C, Skillman CA. Use of esmolol during anesthesia to treat tachycardia and hypertension. Anesth Analg 1989; 68: Johansen JW, Flaishon R, Sebel PS. Esmolol reduces anesthetic requirement for skin incision during propofol/nitrous oxide/morphine anesthesia. Anesthesiology 1997; 86: Schnider TW, Minto CF, Gambus PL, Andersen C, Goodale DB, Shafer SL, et al. The influence of methods of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology 1998; 88: Bouillon TW, Bruhn J, Radulescu L, Andresen C, Shafer TJ, Cohane C, et al. Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis, tolerance of laryngoscopy,

6 Yoon Ji Choi, et al:the change of BIS or entropy after tracheal intubation 309 bispectral index, and electroencephalographic approximate entropy. Anesthesiology 2004; 100: Viertiö-Oja H, Maja V, Särkelä M, Talja P, Tenkanen N, Tolvanen-Laakso H, et al. Description of the Entropy algorithm as applied in the Datex-Ohmeda S/5 Entropy Module. Acta Anaesthesiol Scand 2004; 48: Valjus M, Ahonen J, Jokela R, Korttila K. Response Entropy is not more sensitive than State Entropy in distinguishing the use of esmolol instead of remifentanil in patients undergoing gynaecological laparoscopy. Acta Anaesthesiol Scand 2006; 50: Mathews DM, Cirullo PM, Struys MM, De Smet T, Malik RJ, Chang CL, et al. Feasibility study for the administration of remifentanil based on the difference between response entropy and state entropy. Br J Anaesth 2007; 98: van Gils M, Korhonen I, Yli-Hankala A. Methods for assessing adequacy of anesthesia. Crit Rev Biomed Eng 2002; 30: Pathak D, Sokoll MD, Barcellos W, Kumar V. A comparison of the response of hand and facial muscles to non-depolarising relaxants. Anaesthesia 1988; 43: Paloheimo M, Edmonds HL Jr, Wirtavuori K, Tammisto T. Assessment of anaesthetic adequacy with upper facial and abdominal wall EMG. Eur J Anaesthesiol 1989; 6: Vakkuri A, Yli-Hankala A, Talja P, Mustola S, Tolvanen-Laakso H, Sampson T, et al. Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia. Acta Anaesthesiol Scand 2004; 48: Kawaguchi M, Takamatsu I, Kazama T. Rocuronium dosedependently suppresses the spectral entropy response to tracheal intubation during propofol anaesthesia. Br J Anaesth 2009; 102: Strachan AN, Edwards ND. Randomized placebo-controlled trial to assess the effect of remifentanil and propofol on bispectral index and sedation. Br J Anaesth 2000; 84: Lysakowski C, Dumont L, Pellegrini M, Clergue F, Tassonyi E. Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia. Br J Anaesth 2001; 86: Upton RN, Ludbrook GL, Grant C, Martinez AM. Cardiac output is a determinant of the initial concentrations of propofol after short-infusion administration. Anesth Analg 1999; 89: Guignard B, Menigaux C, Dupont X, Fletcher D, Chauvin M. The effect of remifentanil on the bispectral index change and hemodynamic responses after orotracheal intubation. Anesth Analg 2000; 90: Shin HW, Ban YJ, Lee HW, Lim HJ, Yoon SM, Chang SH. Arousal with iv epinephrine depends on the depth of anesthesia. Can J Anaesth 2004; 51: Berkenstadt H, Loebstein R, Faibishenko I, Halkin H, Keidan I, Perel A. Effect of a single dose of esmolol on the bispectral index scale (BIS) during propofol /fentanyl anaesthesia. Br J Anaesth 2002; 89: Johansen JW. Esmolol promotes electroencephalographic burst suppression during propofol/alfentanil anesthesia. Anesth Analg 2001; 93: Kawaguchi M, Takamatsu I, Masui K, Kazama T. Effect of landiolol on bispectral index and spectral entropy responses to tracheal intubation during propofol anaesthesia. Br J Anaesth 2008; 101: Figueredo E, Garcia-Fiemtes G EM. Assessment of the efficacy of esmolol on the haemodynamic changes induced by laryngoscopy and tracheal intubation: A meta-analysis. Acta Anaesthesiol Scand 2001; 45: Masaki E. Antinociceptive effects of landiolol and esmolol. Masui 2006; 55: Orstein E, Young WL, Ostapkovich N, Matteo RS, Diaz J. Are all effects of esmolol equally rapid in onst? Anesth Analg 1995; 81: