Anesth Pain Med 2014; 9: 138-143 ￭Clinical Research￭

The effect of spectral entropy on propofol use and recovery in children

Department of and Pain Medicine, Dong-A University College of Medicine, *Myung Sung Pain Clinic, Busan, Korea

Ji-yeon Lee, So Ron Choi, Chan Jong Chung, Ji Hyeon Lee, Ji-hye Park, and Chang-Yeoul Baik*

Background: The evaluation of depth using electro- use. Now, however, depth can be measured using encephalography showed reduction in recovery time from anesthe- electroencephalography (EEG)-based devices, such as bispectral sia and decrease in the amount of anesthesia used. This research index (BIS), and spectral entropy; these monitors can indicate compared the dosage of propofol and the recovery characteristics when anesthesia was controlled using spectral entropy monitoring the level of consciousness during anesthesia [1-4]. One study and when it was controlled by hemodynamic changes. demonstrated that the control of anesthesia using BIS monitoring Methods: Seventy children of the American Society of Anesthes- decreased the anesthetic use and shortened recovery time [5]. iologists physical class I–II, ages 3–10, that were scheduled for general anesthesia were randomly distributed into two groups. The Entropy measurements reflect EEG signal irregularity. With children were sedated with (0.15 mg/kg), and anesthesia increasing anesthesia depth, EEG patterns change regularly while was induced with fentanyl (2.0 μg/kg), propofol (2.5 mg/kg), and entropy decreases. Because EEG-based monitoring systems cal- rocuronium (0.6 mg/kg). Anesthesia was maintained with propofol culate an index that reflects the hypnotic component of anest- continuous IV infusion under N2O in O2. For the Entropy Group, the state entropy (SE) was maintained at 40–60, and for the hesia, the EEG signal is closely related to entropy and hypn- Standard Group, anesthesia was maintained so that the heart rate osis levels during anesthesia [6]. and systolic were at 20% of the standard value. Entropy parameters are calculated using 2 different frequency Results: Last 10 minutes of the surgery, the SE and RE (Respo- ranges. State entropy (SE) is computed at 0.8 to 32 Hz, and nse entropy) were significantly higher for the Entropy Group when compared to the Standard Group (P ＜ 0.05). The maintenance primarily consists of EEG, and a small amount of facial elect- dose of propofol was significantly lower for the Entropy Group when romyography (FEMG). Response entropy (RE) includes addi- ＜ compared to the Standard Group (P 0.05). The times taken tional higher frequencies (up to 47 Hz), which reflects both for recovery were all significantly shorter for the Entropy Group than EEG and fast muscle activity from the frontal muscle. Entropy the Standard Group (P ＜ 0.05). Conclusions: Entropy guided anesthetic administration was parameters range from 0 (suppression state of EEG) to 91 associated with reduced propofol use and faster recovery in children (awake) for SE, and 0–100 for RE. The difference between SE compared to standard practice. (Anesth Pain Med 2014; 9: 138-143) and RE corresponds to the contribution of the FEMG-dom- Key Words: Child, Entropy, Intravenous anesthesia, Propofol. inated high-frequency band. Decreasing values indicate deepening levels of hypnosis [6]. Controlling anesthesia depth in adults with spectral entropy INTRODUCTION monitoring has been shown to reduce anesthetic dosage and In the past, the depth of anesthesia was assessed by measu- shorten recovery time [4,7-9]. Anesthesia depth monitoring is ring hemodynamic changes, to control the amount of anesthetic useful in children, as well. In several studies, the use of BIS and spectral entropy monitoring was suitable for providing Received: October 14, 2013. appropriate anesthesia and controlling the depth of sedation in Revised: 1st, December 12, 2013; 2nd, December 20, 2013. children [10-12]. Accepted: February 6, 2014. In one study, the use of BIS in children three years of age Corresponding author: So Ron Choi, M.D., Ph.D., Department of Anesthesiology and Pain Medicine, Dong-A University College of and older shortened recovery time and reduced the sevoflurane Medicine, 26, Daesingongwon-ro, Seo-gu, Busan 602-715, Korea. Tel: dose required to maintain an adequate level of anesthesia [13]. 82-51-240-5390, Fax: 82-51-247-7819, E-mail: [email protected] In another study, the use of entropy monitoring in children This article is a Master’s Thesis by Ji-yeon Lee.

138 Ji-yeon Lee, et al：Entropy monitoring in children 139 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏 similarly reduced the sevoflurane dose and recovery time [14]. thing effort or when HR increased 20% or more compared Most studies involving children have evaluated volatile anes- with the baseline value, rocuronium (0.25 mg/kg) or fentanyl thetic agents. On the other hand, there is almost no research (1 μg/kg) was injected, respectively. examining the use of intravenous agents. This study aims to At the end of the surgery, propofol was suspended without evaluate the effect of spectral entropy monitoring on propofol tapering, and glycopyrrolate (10 μg/kg) and pyridostigmine (0.1 anesthesia and recovery time in pediatric surgery. mg/kg) were administered. Extubation was performed after spontaneous breathing was confirmed. From the end of surgery, MATERIALS AND METHODS lengths of time to tracheal extubation, eye opening in response to verbal commands, being able to say patient’s own name, This study enrolled children aged 3–10 years with American and complete recovery were recorded. Complete recovery was Society of Anesthesiologists physical status classification I–II defined as a modified Aldrete score of 9 or higher [15]. who were scheduled for general anesthesia. The children were The SBP, diastolic blood pressure (DBP), HR, RE, and SE to undergo procedures such as inguinal hernia repair or soft were recorded as follows; baseline, immediately after intubation, tissue surgery. The purpose and method of the study were at 5 minute intervals during surgery, immediately after end of explained to the parents of all children, and informed consent surgery, immediately after extubation, and 5 minutes after extu- was obtained. Children with neurological problems or bation. The total and standardized dose of propofol were undergoing head and neck surgery were excluded from the measured. study. The patients were divided into two groups: the Standard Postoperative nausea and vomiting (PONV) and emergence group and the spectral entropy-guided (Entropy) group. agitation (EA) were observed in the postanesthesia care unit All patients were premedicated with intravenous midazolam (PACU). A different independent study assistant recorded all of (0.15 mg/kg) before induction. After the children were sedated, these data in the PACU. The day after surgery, all patients they were delivered to the operating room. Standard anesthetic were interviewed and asked about intraoperative awareness. monitoring was used (Datex-Ohmeda S/5TM anesthesia monitor; Applying a priori analysis, at least 33 patients had to be GE, Helsinki, Finland). Before application of the entropy sensor, enrolled in each group to detect a 20% difference in propofol the skin was wiped with an alcohol swab and then allowed to use with an α of 0.05 and a statistical power of 0.9. This dry. Spectral entropy electrode was placed to the forehead and study enrolled 35 patients per group. temple with a frontal-temporal montage. In the Standard group, Statistical analysis was performed using SPSS for Windows a study assistant recorded the entropy measurements so that 12.0. Nominal data were compared using the chi-square test, the anesthesiologist was unaware of these figures. In the and parametric data were compared with the Mann-Whitney U Entropy group, the anesthesiologist used the entropy index as test. The data are expressed as mean ± SD and numbers. the standard for controlling anesthesia. Statistical significance was defined as P ＜ 0.05. Anesthesia was induced with fentanyl (2 μg/kg) and propofol (2.5 mg/kg) with 100% O2. Endotracheal intubation was perfo- RESULTS rmed using rocuronium (0.6 mg/kg). Controlled ventilation was started with a tidal volume of 8 ml/kg, and the respiratory Seventy patients participated in this research, and no child rate was controlled to maintain end-tidal carbon dioxide at 35– 40 mmHg. Propofol infusion was started with 200 μg/kg/hr. Table 1. Demographic Data Anesthesia was maintained with propofol and 66% N2O in O2. Before start of the surgery, local infiltration anesthesia was Entropy (n = 35) Standard (n = 35) performed. Age (yr) 5.9 ± 2.5 5.3 ± 2.1 In the Standard group, propofol was adjusted to maintain Sex (M/F) 26/9 23/12 heart rate (HR) and systolic blood pressure (SBP) within 20% Height (cm) 118.1 ± 14.7 115.1 ± 14.7 of the baseline values that measured after the children were Weight (kg) 22.2 ± 6.2 21.6 ± 6.7 sedated with intravenous midazolam. In the Entropy group, Anesthesia time (min) 68.6 ± 26.3 85.7 ± 46.1 Operation time (min) 33.8 ± 23.8 42.3 ± 39.8 propofol was adjusted to maintain SE values in the range of 40–60. When detected patient’s spontaneous brea- All values are expressed as mean ± SD. 140 Anesth Pain Med Vol. 9, No. 2, 2014 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏 was excluded. There were no differences in demographic data, In the postoperative interview, no patients complained of operation time, or anesthesia time between the two groups intraoperative awareness. No patients in the Entropy group (Table 1). complained of PONV but one patient in the Standard group There also were no differences in SBP, DBP and HR complained of PONV. Nine patients in each group showed between the two groups during anesthesia (Fig. 1). In addition, EA. SE and RE values during maintenance of anesthesia were higher in the Entropy group than in the Standard group at 10 DISCUSSION and 5 min before end of surgery and end of surgery (P ＜ 0.05) (Fig. 2). The induction of general anesthesia is accompanied by an The times to tracheal extubation, to eye opening after verbal increase in high-frequency EEG activity that spreads from the commands, to being able to say their name and to complete frontal region to more posterior regions of the brain. Such a recovery were significantly shorter in Entropy group than in propagation of high-frequency EEG activity increases the Standard group (P ＜ 0.05) (Table 2). degree of sedation and eventually results in loss of consci- The required dose of propofol was significantly lower in the ousness [16]. Entropy group (180.2 ± 39.3 μg/kg/min) compared with the One study reported that BIS-guided anesthetic management Standard group (233.6 ± 63.8 μg/kg/min) (P ＜ 0.05). The decreased the use of an anesthetic use and induced fast incidence of fentanyl requirements was higher in the Standard recovery in children, although there were no important diff- group than in the Entropy group (13 vs. 3, P ＜ 0.05). The erences in the anesthesia amount and recovery time between incidence of rocuronium requirements showed no significant the Standard group and BIS group among those aged 3 years difference between the Standard and Entropy groups (8 vs. 12). and under. Similar to BIS monitoring, spectral entropy is an

Fig. 1. The changes of hemodynamic parameters. There were no differences in heart rates, systolic blood pressure and diastolic blood pressure between the two groups during anesthesia. Values are mean ± SD. T1: baseline, T2: Immediately after intubation, T3: 5 minutes after intubation, T4: 10 minutes after intubation, T5: 10 minutes before end of surgery, T6: 5 minutes before end of surgery, T7: Immediately after end of surgery, T8: Immediately after extubation, T9: 5 minutes after extubation. *P ＜ 0.05 compared with Standard group. (A) Systolic blood pressure, (B) Diastolic blood pressure, (C) Heart rates. Ji-yeon Lee, et al：Entropy monitoring in children 141 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Fig. 2. The changes of entropy parameters. For Last 10 minutes of the surgery, in Entropy group’s SE and RE values were higher than in the Standard group. Values are mean ± SD. T1: baseline, T2: Immediately after intubation, T3: 5 minutes after intubation, T4: 10 minutes after intubation, T5: 10 minutes before end of surgery, T6: 5 minutes before end of surgery, T7: Immediately after end of surgery, T8: Immediately after extubation, T9: 5 minutes after extubation. *P ＜ 0.05 compared with standard group. (A) State entropy, (B) Response entropy.

Table 2. Recovery Time Therefore, spectral entropy was used in this study. In this study, spectral entropy guidance for propofol control Entropy Standard during anesthesia in children aged 3–10 years decreased anest- (n = 35) (n = 35) hetic requirements and shortened recovery time. These results Time to extubation (min) 15.6 ± 8.7* 22.5 ± 8.4 are similar to those reported in research conducted with adults Time to eye opening (min) 25.0 ± 10.6* 37.1 ± 14.9 [9]. Time to say name (min) 32.7 ± 11.8* 42.5 ± 14.9 Time to complete recovery (min) 38.7 ± 12.3* 48.2 ± 13.8 There were no significant differences in the SE and RE values between the two groups until 10 minutes after induction. All values are expressed as mean ± SD. *P ＜ 0.05 compared There were differences in the SE and RE values during the with the Standard group. last 10 minutes of surgery, when the Entropy group had sign- ificantly higher values than the Standard group. effective tool for measuring the degree of unconsciousness Kang et al. [7] studied the use of sevoflurane in adults and [4,8]. A recent study revealed that spectral entropy is effective showed that anesthetic depth was deeper among patients in in measuring the level of hypnosis in children under anesth- whom anesthesia was controlled using hemodynamic parameters esia, with spectral entropy showing the same effectiveness as compared with an Entropy group. Therefore, the Entropy group BIS monitoring [10]. used less sevoflurane and experienced a shorter recovery time. A study for children over 3 year old, entropy-guided anes- Vakkuri et al. [9] conducted entropy study in adults, alfe- thetic management reduced volatile agent concentration [14]. ntanil was given to keep HR and BP within 20% of the Not only volatile but also intravenous anesthetic agents are baseline values with propofol- anesthesia. Alfentanil used widely in pediatric anesthesia. This study was conducted consumption during the last 15 minutes was higher in the with intravenous anesthesia. Propofol is commonly used in Entropy group. We used fentanyl instead of alfentanil. Alfe- children, and its use in pediatric anesthesia has been examined ntanil infusion was adjusted by RE-SE difference in the in other study [17]. BIS responds more slowly than entropy to entropy group, and by hemodynamics, with HR and BP in the the onset of burst suppression with increasing levels of standard group. However, in this study, we administered propofol-induced hypnosis [4]. Rigby-Jones and Syeyd [17] fentanyl when HR increased 20% of baseline. Fentanyl was suggested caution with regard to the use of BIS for the more required in the Standard group unlikely Vakkuri’s study. titration of propofol infusions in children and have In this study, spectral entropy-guided propofol during anest- demonstrated a lack of sensitivity for the discrimination of hesia for children aged 3–10 years reduced the anesthetic deep sedation levels in children using the BIS system. dosage and shortened the recovery time. Other studies with 142 Anesth Pain Med Vol. 9, No. 2, 2014 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏 adults have shown similar results. One multicenter study maint- ained anesthesia with propofol, nitrous oxide, and alfentanil. ACKNOWLEDGMENTS The Entropy group showed higher entropy values during the last 15 minutes of surgery, smaller propofol consumption, and This study was supported by research funds from Dong-A a faster recovery time [9]. University. 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