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The Efficacy of Intraoperative EEG to Predict the Occurrence of Emergence Agitation in the Postanesthetic Room After Sevoflurane Anesthesia in Children
ORIGINAL ARTICLE
The Efficacy of Intraoperative EEG to Predict the Occurrence of Emergence Agitation in the Postanesthetic Room After Sevoflurane Anesthesia in Children Young-Eun Jang, MD, Sung-Ae Jeong, MD, Sun-Young Kim, RN, In-Kyung Song, MD, Ji-Hyun Lee, MD, Jin-Tae Kim, MD, Hee-Soo Kim, MD, PhD Purpose: Emergence agitation (EA) is common after sevoflurane anesthesia, but there are no definite predictors. This study investigated whether intraoperative electroencephalography (EEG) can indicate the occurrence of EA in children. Design: A prospective predictive study design was used. Methods: EEG-derived parameters (spectral edge frequency 95, beta, alpha, theta, and delta power) were measured at 1.0 minimum alveolar concentration (MAC) and 0.3 MAC of end-tidal sevoflurane (EtSEVO) in 29 patients. EA was evaluated using an EA score (EAS) in the postanesthetic care unit on arrival (EAS 0) and at 15 and 30 minutes after arrival (EAS 15 and EAS 30). The correlation between EEG-derived parameters and EAS was analyzed using Spearman correlation, and receiver-operating characteristic curve analysis was used to measure the predictability. Findings: EA occurred in 11 patients. The alpha power at 1.0 MAC of EtSEVO was correlated with EAS 15 and EAS 30. The theta/alpha ratio at 0.3 MAC of EtSEVO was correlated with EAS 30. The area under the receiver-operating characteristic curve of percentage of alpha bands at 0.3 MAC of EtSEVO and the occurrence of EA was 0.672. Conclusions: Children showing high-alpha powers and low theta powers (5 low theta/alpha ratio) during emergence from sevoflurane anesthesia are at high risk of EA in the postanesthetic care unit.
Keywords: pediatrics, emergence agitation, EEG, general anesthesia. Ó 2016 by American Society of PeriAnesthesia Nurses
Young-Eun Jang, MD, Sung-Ae Jeong, MD, Sun-Young Kim, RN, In-Kyung Song, MD, Ji-Hyun Lee, MD, Jin-Tae Kim, MD, and Hee-Soo Kim, MD, Department of Anesthesiology and Pain medicine, Seoul National University Hospital, Seoul, South Korea. Conflict of interest: None to report. Address correspondence to Hee-Soo Kim, Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea; e-mail address: [email protected]. Ó 2016 by American Society of PeriAnesthesia Nurses 1089-9472/$36.00 http://dx.doi.org/10.1016/j.jopan.2015.10.001
Journal of PeriAnesthesia Nursing, Vol -, No - (-), 2016: pp 1-8
SEVOFLURANE IS ONE OF the most commonly used anesthetic agents. Its low blood/gas coefficient, nonpungency, and nonairway irritating properties make it the anesthetic agent of choice for rapid induction and emergence in infants and children. However, emergence agitation (EA) or emergence delirium, defined as an ‘‘acute and transient confusional state,’’ is one of the most common side effects in children after sevoflurane anesthesia with 1,2 or without surgery3,4 EA or emergence delirium was used synonymously in the literature. The reports of incidence of EA are varied from 10% to 50%, to as high as 80%.1-4
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EA itself is self-limited and does not show severe sequelae; but it might cause difficulties in managing patients during the postanesthesia care unit (PACU) stay, as well as startle the parents. There are many studies on the prevention of EA.2,4-8 In addition, several risk factors of EA such as preschool age, preoperative temperament and anxiety degree,8 sevoflurane,9,10 or surgical procedures1,11,12 are suggested. However, there is no definitive intraoperative predictive factor for EA. Several studies report the abnormal findings of electroencephalography (EEG) in children during delirious status.13-15 These findings suggested that the patients with EA show different EEG patterns during general anesthesia. There was also one study that reported postoperative EA was associated with an increase in the portion of slow EEG rhythm at the lowest BIS value during the induction of anesthesia in children.16 Therefore, EEG findings might have a correlation to the occurrence of EA in children. We investigated whether intraoperative EEG changes during sevoflurane anesthesia are related to the occurrence or degree of EA in children.
Methods Study Purpose The purpose of this study was to evaluate the efficacy of changes of intraoperative EEG to predict the occurrence of EA in PACU after sevoflurane anesthesia in children aged from 1 to 6 years (n 5 29). Study Design and Procedures This prospective predictive study was approved by the Institutional Review Board of Seoul National University Hospital (H-1202-094-399; Apr 12, 2012, Seoul, Korea) and registered at cris.nih.go. kr (KCT0000652). After obtaining informed consent from parents or guardians whose children were scheduled for strabismus surgery, we recruited 31 patients aged from 1 to 6 years. They were classified as American Society of Anesthesiologists physical status I or II. Patients with an abnormal airway, reactive airway disease such as asthma, or a history of upper respiratory tract infection in the preceding 4 weeks,
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mental retardation, attention-deficit hyperactivity disorder, previous abnormalities in EEG, or cerebral palsy were excluded. Study Variables and Data Collection The patients did not receive premedication. On arrival to the operating room, the patients were monitored with electrocardiography, pulse oximetry (SpO2), noninvasive arterial blood pressure, end-tidal CO2, end-tidal sevoflurane concentration (EtSEVO), and single-channel EEG-derived parameters monitor (not raw EEG; Solar 8000, GE, Milwaukee, WI) by pediatric anesthesiologists. All data from the patient monitor were recorded and stored in a personal computer. Anesthesia was induced with 6 mg/kg of sodium thiopental and 0.02 mg/kg of atropine. After loss of consciousness, the patients were ventilated with inspired 8.0 vol% of sevoflurane in 6 L/min of oxygen via a pediatric circle system. The patients were fully relaxed with 0.6 mg/kg of rocuronium and appropriate size of laryngeal mask airway was inserted after confirming the muscle relaxation with neuromuscular blockade monitoring. The anesthesia was maintained around 1.0 MAC (one minimum alveolar concentration; 2.0 to 2.5 vol% of sevoflurane according to patients’ age17) in approximately 50% oxygen in air with a total inflow of 2.5 L/min. The patients were ventilated with appropriate respiratory rate and tidal volume to keep 35 to 40 mm Hg of endtidal CO2. The concentration of sevoflurane was maintained at 1.0 MAC during surgery and adjusted by patient’s blood pressure or heart rate. At the end of surgery, the concentration of sevoflurane was reduced and maintained 0.3 MAC (MAC awake; 0.5 to 0.7 vol% of sevoflurane) for 5 minutes before turning the vaporizer off. If the patient could respond to verbal comment, laryngeal mask airway was removed after reversal of neuromuscular blockade confirmed by sustained head lift (.5 seconds). After the patient was transferred to the PACU, he/she was fully awakened. In the PACU, electrocardiography, NIBP, SpO2, and the respiratory rate were monitored. EA was evaluated, using the EA score (EAS; Table 1),18 when the patient first arrived in the PACU (EAS 0), 15 minutes (EAS 15), and 30 minutes after arrival (EAS 30) because EA usually lasts around 30 minutes.1 EA was identified when the
INTRAOPERATIVE EEG AND EMERGENCE AGITATION
Table 1. Emergence Agitation Score Score 1 2 3 4 5
Behavior Sleeping Awake, calm Irritable, crying Inconsolable crying Severe restlessness, disorientation
children showed an EAS of 4 or 5 at least once, and 0.1 mg/kg of nalbuphine was administered intravenously as treatment.4 Children with agitated responses to pain (eg, complaining or localizing of pain) were not considered to have EA. If the EA was managed by administration of nalbuphine, no more medication was received, and the patients were closely monitored by the caregivers. EEG was recorded continuously from the induction of anesthesia until the end of anesthesia. The electrode was placed on the forehead to record single monopolar channel at FP2 (right frontal polar site) referenced by A2 (right earlobe site) by international 10 to 20 system (Figure 1). The electrode impedance was checked automatically and maintained at , 5 kG. The EEG was analyzed in the frequency domain automatically. Spectral edge frequency 95 (SEF95 5 the frequency below which 95% of the EEG power is located), spectral bands of beta (13 to 30 Hz), alpha (8 to
Figure 1. The international 10 to 20 system of electroencephalographic montage.Adapted from http://commons.wikimedia.org/wiki/File:21_electro des_of_International_10-20_system_for_EEG.svg.
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13 Hz), theta (4 to 8 Hz), and delta (0 to 4 Hz) were analyzed, calculated, and expressed as a percentage of total spectral power. These parameters were analyzed and shown in the patient’s monitor by embedding manufacturer’s software. The monitor presented the analyzed data every 10 seconds. These EEG-derived parameters at 1.0 MAC (20 minutes during the maintenance of anesthesia) and 0.3 MAC (5 minutes during emergence) of sevoflurane anesthesia were averaged and analyzed. For quality control of EEG data, the artifacts of EEG by electric cautery or patients’ movements were removed. Data Analysis Patients’ characteristics were compared between patients with EA and patients without EA using Mann–Whitney U test. The correlation of EEGderived parameters and EAS was analyzed using Spearman correlation. If there was meaningful correlation, simple regression analysis was performed. Receiver-operating characteristic (ROC) curve of EEG parameters and overall EA (EAS $ 4) were analyzed to evaluate their predictability. Statistical analysis was performed using SPSS 19.0 (IBM, Somers, NY). P value , .05 was considered significant.
Results Thirty-one patients were enrolled in the study and completed the EEG recording. However, data from two patients was discarded because of the data artifacts of EEG. Patients’ characteristics, surgery, anesthetic, and PACU stay time, and depth of anesthesia by SEF95 are shown in Table 2. The incidence of EA was 11 of 29 patients (37.9%). Six patients experienced EA on the arrival at PACU. Four who developed EA at 15 minutes after arrival had an EAS of 2 or 3 at arrival. After these 10 patients had been given 0.1 mg/kg of nalbuphine, only three still exhibited EA at 30 minutes after PACU arrival. One patient suffered EA through the entire PACU stay (39 minutes). Patients who showed EA after administration of nalbuphine were transferred to Phase 2 recovery with continuous SpO2 monitoring, and there were no adverse effects. The use of nalbuphine was effective in 63.4% (7/11). However, subgroup analysis showed no difference between responders and nonresponders to nalbuphine. There was no significant adverse effect in PACU in any child.
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Table 2. Patients’ Characteristics Characteristics
All; n 5 29
EA(1); n 5 11
EA(2); n 5 18
P Value
Age (y) Sex (M/F) Height (cm) Weight (kg) Surgery time (min) Anesthetic time (min) PACU stay (min) SEF95 at 1 MAC (Hz) SEF95 at 0.3 MAC (Hz)
3.7 6 1.5 14/15 102.1 6 12.3 16.3 6 4.3 26.2 6 12.2 47.2 6 13.8 36.0 6 9.1 12.1 6 2.7 18.7 6 3.8
3.7 6 1.3 6/5 104.2 6 11.1 16.7 6 3.9 29.8 6 15.6 50.9 6 16.4 35.1 6 8.6 11.6 6 2.4 18.2 6 3.3
3.7 6 1.6 8/10 100.9 6 13.2 16.1 6 4.6 24.1 6 9.4 45.0 6 11.9 36.5 6 9.7 12.4 6 3.0 19.0 6 4.1
.95 N/A .64 .55 .34 .41 .71 .44 .78
EA, emergence agitation; EA(1), patients with emergence agitation; EA(2), patients without emergence agitation; PACU, postanesthetic care unit. Values are presented as mean 6 standard deviation.
Spearman correlation of EEG-derived parameters during sevoflurane anesthesia (1.0 MAC and 0.3 MAC of EtSEVO) and EAS are shown in Table 3. The alpha power at 0.3 MAC of EtSEVO was positively correlated with EAS 15 and EAS 30 (Spearman correlation coefficient 5 0.392 and 0.566, P 5 .035 and .001, respectively). The theta/alpha ratio at 0.3 MAC of EtSEVO was negatively correlated with EAS 30 (Spearman correlation coefficient 5 20.478, P 5 .009). There were no significant differences in SEF95 at 1.0 MAC and 0.3 MAC of EtSEVO between patients with EA and patients without EA (Table 2). An
example of the different courses of theta and alpha powers during sevoflurane anesthesia in patients with and without EA is shown in Figure 2. The area under the ROC curve of EEG-derived parameters for EA is shown in Table 4. The area under the ROC curve of the percentage of alpha bands at 0.3 MAC of EtSEVO and the occurrence of EA was 0.672 (Figure 3), and 29.3% of alpha bands at 0.3 MAC of EtSEVO showed a 72.7% sensitivity and 55.6% specificity. The positive predictive value and negative predictive value were 0.58 and 0.43, respectively.
Table 3. Correlation Analysis of EEG-Derived Parameters and EA Score (n 5 29) Spearman correlation coefficient (P value) EtSEVO 1 MAC
0.3 MAC
EEG (Mean ± SD) SEF95 (Hz) Beta (%) Alpha (%) Theta (%) Delta (%) Theta/alpha SEF95 (Hz) Beta (%) Alpha (%) Theta (%) Delta (%) Theta/alpha
12.1 6 2.7 19.5 6 4.8 22.2 6 4.7 25.7 6 4.8 32.3 6 7.1 1.2 6 0.3 18.7 6 3.8 32.6 6 8.3 31.3 6 7.0 16.8 6 4.7 19.1 6 6.3 0.6 6 0.2
EAS 0
EAS 15
EAS 30
20.213 (.267) 20.241 (.208) 20.117 (.547) 0.173 (.369) 0.049 (.800) 0.200 (.297) 0.075 (.697) 0.033 (.863) 0.144 (.456) 0.006 (.977) 20.022 (.090) 20.134 (.489)
20.012 (.951) 20.136 (.481) 0.216 (.261) 20.269 (.158) 0.066 (.732) 20.243 (.204) 0.018 (.927) 20.005 (.979) 0.392 (.035)* 20.164 (.395) 20.306 (.107) 20.282 (.139)
20.195 (.311) 20.185 (.338) 0.046 (.813) 20.243 (.203) 0.235 (.220) 20.181 (.346) 20.160 (.408) 20.169 (.381) 0.566 (.001)* 20.248 (.194) 20.146 (.449) 20.478 (.009)*
EEG, electroencephalography; EA, emergence agitation; EtSEVO, end-tidal sevoflurane concentration; SD, standard deviation; EAS 0, EA score at the arrival on postanesthetic care unit; EAS 15, EA score 15 minutes after arrival; EAS 30, EA score 30 minutes after arrival; MAC, minimum alveolar concentration; SEF95, spectral edge frequency 95. Statistically significant, *P , .05.
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Figure 2. An example of time courses of percentages of theta and alpha bands of electroencephalography during sevoflurane anesthesia. Three-year-old child with emergency agitation (EA; left) showed high-alpha power and low-theta power during the maintenance of anesthesia (theta 5 22.7, alpha 5 23.5, theta/alpha ratio 5 0.96, and Spectral edge frequency 95 [SEF95] 5 16.6) and emergency (theta 5 12.8, alpha 5 46.2, theta/alpha ratio 5 0.28, and SEF95 5 11.1), whereas 3-year-old child without EA (right) showed low-alpha power and high-theta power during the maintenance of anesthesia (theta 5 34.0, alpha 5 19.8, theta/alpha ratio 5 1.71, and SEF95 5 11.3) and emergency (theta 5 17.1, alpha 5 36.1, theta/alpha ratio 5 0.47, and SEF95 5 17.2). EAS score (EAS) of these children at 0, 15, and 30 minutes after postanesthetic care unit arrival were ‘‘3/5/4’’ (left), and ‘‘2/1/2’’ (right), respectively. End-tidal sevoflurane concentrations are shown with bars. MAC, minimum alveolar concentration.
Discussion Our data showed a significant relationship between the percentage of EEG bands (high-alpha powers) during emergence from sevoflurane anesthesia and the EAS in the PACU.
(8 to 13 Hz) are usually seen in relaxed, awake patients with their eyes closed, and thought be related to the decrease of inhibitory activity of reticular nucleus on thalamic pacemaker cells. During alpha wave-predominant meditation or light sedation,
The rhythmic activity in EEG is divided into several specific frequency bands; in the present study, the relative portion of beta, alpha, theta, and delta waves was monitored. Beta waves (13 to 30 Hz) are thought to be the result of sensory stimuliactivating reticular-activating system which desynchronizes the thalamic pacemaker cells. Alpha waves Table 4. AUC of ROC Curve of EEG-Derived Parameters for EA EEG parameters
EtSEVO
AUC of ROC curve
Alpha Theta/alpha ratio
0.3 MAC 0.3 MAC
0.672 0.374
AUC, area under curve; ROC, receiver-operating characteristic; EA, emergence agitation; EEG, electroencephalography; EtSEVO, end-tidal sevoflurane; MAC, minimum alveolar concentration.
Figure 3. Receiver-operating characteristic (ROC) analysis of alpha power at 0.3 minimum alveolar concentration (MAC) of end-tidal sevoflurane (EtSEVO) and the occurrence of emergency agitation (EA). The area under ROC curve is 0.672.
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thalamic pacemaker cells regulate and synchronize the thalamocortical activity. Theta waves (4 to 8 Hz) are normally seen during sleep and thought to be related to the inhibition of thalamic pacemaker cells by gamma-aminobutyric acidergic action of reticular nucleus. During deep sleep, delta (0 to 3 Hz) waves are prominent and reflect extreme depression of thalamus.19 According to the thalamic theory, halogenated inhalation anesthetics cause unconsciousness by decreasing the neuronal activity of thalamocortical neurons (thalamic shunt).20 Previous studies revealed this influence of inhalation anesthetics on EEG-derived parameters (SEF95 and the four frequency bands)21,22; incremental concentration of inhalation anesthetics changes the EEG from fast (beta and alpha) waves during spontaneous arousal to slow (theta and delta) waves during anesthesia. SEF95 has been used to estimate the depth of anesthesia, and previous studies suggested SEF95 values for adequate anesthesia (10 to 14 Hz) and awaken state (15 to 20 Hz).21,22 The values of SEF95 data in the present study during the maintenance of anesthesia (1.0 MAC of EtSEVO) and emergence (0.3 MAC of EtSEVO) were within these ranges, respectively (Table 2). SEF95 value does not reflect the relative percentage of each spectral band (beta, alpha, theta, and delta waves); it only reflects the sum of them. Therefore, it might be possible that there was a difference in alpha and theta bands without the difference in SEF95 values between patients with EA and without EA (Table 2). Bispectral index and entropy (monitoring depth of anesthesia by EEG-based algorithms) are one of the most commonly used methods to measure the depth of anesthesia. Although some evidence supports their use in children, it is not as confirmative as adults and has large individual and situational differences. We did not use them in the present study, the depth of anesthesia was adequate and uniform in all the patients by adjusting the MAC values, and the intraoperative vital signs were stable in all patients. We obtained the single-channel EEG-derived parameters from the forehead because of feasibility for future use.
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A previous study showed that children who demonstrated agitation during induction showed slower EEG frequency during the second minute of induction compared with those who did not demonstrate agitation regardless, of the type of premedication.16 In the present study, induction of anesthesia was performed with high concentration of sevoflurane (8.0 vol%) with high fresh gas flow rate (6 L/min). Therefore, changes of EEGderived parameters during induction were too rapid to observe. Instead, we obtained EEGderived parameters at 0.3 MAC of EtSEVO (MAC awake) for 5 minutes during emergence. Other articles reported that high concentration of sevoflurane (8.0 vol%) induced the epileptiform EEG during induction.23 However, recent studies showed the use of lower concentration of sevoflurane did not avoid the risk of EEG abnormalities.24 We used high concentration of sevoflurane during induction because it took a long-time induction with lower concentration of inhalation agent comparing with short surgery time. Although there might be an epileptiform EEG during induction, we could not get the raw EEG data from the patient monitor, and we did not realize the change of EEG. In addition, there were no epileptic movements from the children after anesthesia. Higher alpha power and lower theta/alpha ratio during emergence from sevoflurane anesthesia were positively correlated to EAS in PACU. This trend means less gamma-aminobutyric acidergic inhibition of thalamic pacemaker cells and more thalamocortical activity during emergence from sevoflurane anesthesia.25 Taken together, rapid recovery from EEG suppression of sevoflurane anesthesia was correlated with high EAS in PACU. There are two possible explanations for this phenomenon; patients with EA have high baseline EEG activity and/or are more resistant to EEG suppression of sevoflurane. However, the positive predictive value and negative predictive value of alpha power at 0.3 MAC of EtSEVO were low and failed to show good predictability of the occurrence of EA. These findings were after the EEG analysis; therefore, we could not apply the findings during the anesthesia to detect the EA. However, if we were to develop an algorithm that calculates the powers of EEG in real time, we could apply these findings clinically.
INTRAOPERATIVE EEG AND EMERGENCE AGITATION
Smit et al26 showed that individual differences in EEG spectral power reflect their genetic variance in brain development. Factors such as neuronal myelination, synaptic density, and dendritic outgrowth affect the volumes of gray and white matter and eventually result in different baseline theta and alpha spectral powers. Pediatric patients have large individual differences in the development of their central nervous system,27 and these differences can affect not only their baseline EEG activity and their EEG response to sevoflurane anesthesia, but also postoperative EA. However, no evidence exists regarding these issues. We could not monitor postoperative EEG during emergence (less than MAC awake) and PACU stay due to motion artifacts. There is no previous study about EEG monitoring in PACU. Previous studies conducted in the intensive care unit or ward indicated that the delirious patients showed significant lower alpha power and higher theta power, resulting in high theta/alpha ratio.28,29 However, febrile delirium in pediatric patients with influenza,28 or early postoperative delirium in elderly patients after open-heart surgery29 are not the same situation as the present study. Pediatric EEG data during EA after sevoflurane anesthesia could be hardly obtained.
Limitations There are several limitations in the present study. First, it was a noncontrolled, observational study of small score and sample size. Second, as mentioned before, we could not get the raw EEG data at PACU because of the patients’ discomfort and involuntary movement. Monitoring EEG in
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PACU, especially during EA, would have given more information about EA. Third, sevoflurane that remains in the body may have played a role in sedation, pain control, and EA in PACU. Fourth, the present study was conducted under sevoflurane anesthesia for strabismus surgery. Although adequate muscle relaxation was achieved, and EMG was monitored simultaneously to exclude the effect of electric activity muscle, passive movement of extraocular muscle and eyelid would affect the EEG signal. In addition, along with otolaryngeal surgery, strabismus surgery showed a high incidence of EA (from 44% to 47%) than other pediatric surgery.1,11,12 Finally, we did not assess the preoperative anxiety or distress, which might be a predisposing factor to EA. However, the previous study demonstrated that anxious patients behave similarly to their less anxious counterparts on induction of anesthesia with propofol proven by BIS.30 Therefore, anxiety level might have less effect on EEG.
Conclusion A larger clinical trial with EEG monitoring in PACU and during EA is needed in the future for an accurate assessment. In addition, investigating the effect of alpha power lowering at the emergence from sevoflurane anesthesia to prevent EA may clarify the relationship between intraoperative EEG and EA. In conclusion, this preliminary study presented that the relative percentage of EEG bands during sevoflurane anesthesia showed significant relationship with postoperative EAS and the possibility of prediction of EA by EEG in PACU.
References 1. Voepel-Lewis T, Malviya S, Tait AR. A prospective cohort study of emergence agitation in the pediatric postanesthesia care unit. Anesth Analg. 2003;96:1625-1630. table of contents. 2. Chen JY, Jia JE, Liu TJ, Qin MJ, Li WX. Comparison of the effects of dexmedetomidine, ketamine, and placebo on emergence agitation after strabismus surgery in children. Can J Anaesth. 2013;60:385-392. 3. Isik B, Arslan M, Tunga AD, Kurtipek O. Dexmedetomidine decreases emergence agitation in pediatric patients after sevoflurane anesthesia without surgery. Paediatr Anaesth. 2006; 16:748-753.
4. Dalens BJ, Pinard AM, Letourneau DR, Albert NT, Truchon RJ. Prevention of emergence agitation after sevoflurane anesthesia for pediatric cerebral magnetic resonance imaging by small doses of ketamine or nalbuphine administered just before discontinuing anesthesia. Anesth Analg. 2006;102: 1056-1061. 5. Kararmaz A, Kaya S, Turhanoglu S, Ozyilmaz MA. Oral ketamine premedication can prevent emergence agitation in children after desflurane anaesthesia. Paediatr Anaesth. 2004;14: 477-482. 6. Shukry M, Clyde MC, Kalarickal PL, Ramadhyani U. Does dexmedetomidine prevent emergence delirium in children
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after sevoflurane-based general anesthesia? Paediatr Anaesth. 2005;15:1098-1104. 7. Dahmani S, Stany I, Brasher C, et al. Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies. Br J Anaesth. 2010;104:216-223. 8. Mizuno J, Nakata Y, Morita S, Arita H, Hanaoka K. Predisposing factors and prevention of emergence agitation. Masui. 2011;60:425-435. 9. Kuratani N, Oi Y. Greater incidence of emergence agitation in children after sevoflurane anesthesia as compared with halothane: A meta-analysis of randomized controlled trials. Anesthesiology. 2008;109:225-232. 10. Oh AY, Seo KS, Kim SD, Kim CS, Kim HS. Delayed emergence process does not result in a lower incidence of emergence agitation after sevoflurane anesthesia in children. Acta Anaesthesiol Scand. 2005;49:297-299. 11. Przybylo HJ, Martini DR, Mazurek AJ, Bracey E, Johnsen L, Cote CJ. Assessing behaviour in children emerging from anaesthesia: Can we apply psychiatric diagnostic techniques? Paediatr Anaesth. 2003;13:609-616. 12. Aouad MT, Yazbeck-Karam VG, Nasr VG, El-Khatib MF, Kanazi GE, Bleik JH. A single dose of propofol at the end of surgery for the prevention of emergence agitation in children undergoing strabismus surgery during sevoflurane anesthesia. Anesthesiology. 2007;107:733-738. 13. Jacobson S, Jerrier H. EEG in delirium. Semin Clin Neuropsychiatry. 2000;5:86-92. 14. Koponen H, Partanen J, Paakkonen A, Mattila E, Riekkinen PJ. EEG spectral analysis in delirium. J Neurol Neurosurg Psychiatry. 1989;52:980-985. 15. Prugh DG, Wagonfeld S, Metcalf D, Jordan K. A clinical study of delirium in children and adolescents. Psychosom Med. 1980;42:177-195. 16. Constant I, Leport Y, Richard P, Moutard ML, Murat I. Agitation and changes of Bispectral Index and electroencephalographic-derived variables during sevoflurane induction in children: Clonidine premedication reduces agitation compared with midazolam. Br J Anaesth. 2004;92:504-511. 17. Lerman J, Sikich N, Kleinman S, Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology. 1994;80:814-824. 18. Cole JW, Murray DJ, McAllister JD, Hirshberg GE. Emergence behaviour in children: Defining the incidence of excite-
JANG ET AL ment and agitation following anaesthesia. Paediatr Anaesth. 2002;12:442-447. 19. Jameson LC, Sloan TB. Using EEG to monitor anesthesia drug effects during surgery. J Clin Monit Comput. 2006;20: 445-472. 20. Peltier SJ, Kerssens C, Hamann SB, Sebel PS, ByasSmith M, Hu X. Functional connectivity changes with concentration of sevoflurane anesthesia. Neuroreport. 2005;16: 285-288. 21. Schwender D, Daunderer M, Klasing S, Finsterer U, Peter K. Power spectral analysis of the electroencephalogram during increasing end-expiratory concentrations of isoflurane, desflurane and sevoflurane. Anaesthesia. 1998;53:335-342. 22. Schwender D, Daunderer M, Mulzer S, Klasing S, Finsterer U, Peter K. Spectral edge frequency of the electroencephalogram to monitor ‘‘depth’’ of anaesthesia with isoflurane or propofol. Br J Anaesth. 1996;77:179-184. 23. Vakkuri A, Yli-Hankala A, Sarkela M, et al. Sevoflurane mask induction of anaesthesia is associated with epileptiform EEG in children. Acta Anaesthesiol Scand. 2001;45:805-811. 24. Julliac B, Cotillon P, Guehl D, Richez B, Sztark F. Targetcontrolled induction with 2.5% sevoflurane does not avoid the risk of electroencephalographic abnormalities. Ann Fr Anesth Reanim. 2013;32:e143-e148. 25. Ries CR, Puil E. Mechanism of anesthesia revealed by shunting actions of isoflurane on thalamocortical neurons. J Neurophysiol. 1999;81:1795-1801. 26. Smit DJ, Boomsma DI, Schnack HG, Hulshoff Pol HE, de Geus EJ. Individual differences in EEG spectral power reflect genetic variance in gray and white matter volumes. Twin Res Hum Genet. 2012;15:384-392. 27. Lenroot RK, Schmitt JE, Ordaz SJ, et al. Differences in genetic and environmental influences on the human cerebral cortex associated with development during childhood and adolescence. Hum Brain Mapp. 2009;30:163-174. 28. Okumura A, Nakano T, Fukumoto Y, et al. Delirious behavior in children with influenza: Its clinical features and EEG findings. Brain Dev. 2005;27:271-274. 29. Plaschke K, Fichtenkamm P, Schramm C, et al. Early postoperative delirium after open-heart cardiac surgery is associated with decreased bispectral EEG and increased cortisol and interleukin-6. Intensive Care Med. 2010;36:2081-2089. 30. Morley AP, Papageorgiou CH, Marinaki AM, Cooper DJ, Lewis CM. The effect of pre-operative anxiety on induction of anaesthesia with propofol. Anaesthesia. 2008;63:467-473.
The Efficacy of Intraoperative EEG to Predict the Occurrence of Emergence Agitation in the Postanesthetic Room After Sevoflurane Anesthesia in Children Young-Eun Jang, MD, Sung-Ae Jeong, MD, Sun-Young Kim, RN, In-Kyung Song, MD, Ji-Hyun Lee, MD, Jin-Tae Kim, MD, Hee-Soo Kim, MD, PhD Purpose: Emergence agitation (EA) is common after sevoflurane anesthesia, but there are no definite predictors. This study investigated whether intraoperative electroencephalography (EEG) can indicate the occurrence of EA in children. Design: A prospective predictive study design was used. Methods: EEG-derived parameters (spectral edge frequency 95, beta, alpha, theta, and delta power) were measured at 1.0 minimum alveolar concentration (MAC) and 0.3 MAC of end-tidal sevoflurane (EtSEVO) in 29 patients. EA was evaluated using an EA score (EAS) in the postanesthetic care unit on arrival (EAS 0) and at 15 and 30 minutes after arrival (EAS 15 and EAS 30). The correlation between EEG-derived parameters and EAS was analyzed using Spearman correlation, and receiver-operating characteristic curve analysis was used to measure the predictability. Findings: EA occurred in 11 patients. The alpha power at 1.0 MAC of EtSEVO was correlated with EAS 15 and EAS 30. The theta/alpha ratio at 0.3 MAC of EtSEVO was correlated with EAS 30. The area under the receiver-operating characteristic curve of percentage of alpha bands at 0.3 MAC of EtSEVO and the occurrence of EA was 0.672. Conclusions: Children showing high-alpha powers and low theta powers (5 low theta/alpha ratio) during emergence from sevoflurane anesthesia are at high risk of EA in the postanesthetic care unit.
Keywords: pediatrics, emergence agitation, EEG, general anesthesia. Ó 2016 by American Society of PeriAnesthesia Nurses
Young-Eun Jang, MD, Sung-Ae Jeong, MD, Sun-Young Kim, RN, In-Kyung Song, MD, Ji-Hyun Lee, MD, Jin-Tae Kim, MD, and Hee-Soo Kim, MD, Department of Anesthesiology and Pain medicine, Seoul National University Hospital, Seoul, South Korea. Conflict of interest: None to report. Address correspondence to Hee-Soo Kim, Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul 110-744, South Korea; e-mail address: [email protected]. Ó 2016 by American Society of PeriAnesthesia Nurses 1089-9472/$36.00 http://dx.doi.org/10.1016/j.jopan.2015.10.001
Journal of PeriAnesthesia Nursing, Vol -, No - (-), 2016: pp 1-8
SEVOFLURANE IS ONE OF the most commonly used anesthetic agents. Its low blood/gas coefficient, nonpungency, and nonairway irritating properties make it the anesthetic agent of choice for rapid induction and emergence in infants and children. However, emergence agitation (EA) or emergence delirium, defined as an ‘‘acute and transient confusional state,’’ is one of the most common side effects in children after sevoflurane anesthesia with 1,2 or without surgery3,4 EA or emergence delirium was used synonymously in the literature. The reports of incidence of EA are varied from 10% to 50%, to as high as 80%.1-4
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EA itself is self-limited and does not show severe sequelae; but it might cause difficulties in managing patients during the postanesthesia care unit (PACU) stay, as well as startle the parents. There are many studies on the prevention of EA.2,4-8 In addition, several risk factors of EA such as preschool age, preoperative temperament and anxiety degree,8 sevoflurane,9,10 or surgical procedures1,11,12 are suggested. However, there is no definitive intraoperative predictive factor for EA. Several studies report the abnormal findings of electroencephalography (EEG) in children during delirious status.13-15 These findings suggested that the patients with EA show different EEG patterns during general anesthesia. There was also one study that reported postoperative EA was associated with an increase in the portion of slow EEG rhythm at the lowest BIS value during the induction of anesthesia in children.16 Therefore, EEG findings might have a correlation to the occurrence of EA in children. We investigated whether intraoperative EEG changes during sevoflurane anesthesia are related to the occurrence or degree of EA in children.
Methods Study Purpose The purpose of this study was to evaluate the efficacy of changes of intraoperative EEG to predict the occurrence of EA in PACU after sevoflurane anesthesia in children aged from 1 to 6 years (n 5 29). Study Design and Procedures This prospective predictive study was approved by the Institutional Review Board of Seoul National University Hospital (H-1202-094-399; Apr 12, 2012, Seoul, Korea) and registered at cris.nih.go. kr (KCT0000652). After obtaining informed consent from parents or guardians whose children were scheduled for strabismus surgery, we recruited 31 patients aged from 1 to 6 years. They were classified as American Society of Anesthesiologists physical status I or II. Patients with an abnormal airway, reactive airway disease such as asthma, or a history of upper respiratory tract infection in the preceding 4 weeks,
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mental retardation, attention-deficit hyperactivity disorder, previous abnormalities in EEG, or cerebral palsy were excluded. Study Variables and Data Collection The patients did not receive premedication. On arrival to the operating room, the patients were monitored with electrocardiography, pulse oximetry (SpO2), noninvasive arterial blood pressure, end-tidal CO2, end-tidal sevoflurane concentration (EtSEVO), and single-channel EEG-derived parameters monitor (not raw EEG; Solar 8000, GE, Milwaukee, WI) by pediatric anesthesiologists. All data from the patient monitor were recorded and stored in a personal computer. Anesthesia was induced with 6 mg/kg of sodium thiopental and 0.02 mg/kg of atropine. After loss of consciousness, the patients were ventilated with inspired 8.0 vol% of sevoflurane in 6 L/min of oxygen via a pediatric circle system. The patients were fully relaxed with 0.6 mg/kg of rocuronium and appropriate size of laryngeal mask airway was inserted after confirming the muscle relaxation with neuromuscular blockade monitoring. The anesthesia was maintained around 1.0 MAC (one minimum alveolar concentration; 2.0 to 2.5 vol% of sevoflurane according to patients’ age17) in approximately 50% oxygen in air with a total inflow of 2.5 L/min. The patients were ventilated with appropriate respiratory rate and tidal volume to keep 35 to 40 mm Hg of endtidal CO2. The concentration of sevoflurane was maintained at 1.0 MAC during surgery and adjusted by patient’s blood pressure or heart rate. At the end of surgery, the concentration of sevoflurane was reduced and maintained 0.3 MAC (MAC awake; 0.5 to 0.7 vol% of sevoflurane) for 5 minutes before turning the vaporizer off. If the patient could respond to verbal comment, laryngeal mask airway was removed after reversal of neuromuscular blockade confirmed by sustained head lift (.5 seconds). After the patient was transferred to the PACU, he/she was fully awakened. In the PACU, electrocardiography, NIBP, SpO2, and the respiratory rate were monitored. EA was evaluated, using the EA score (EAS; Table 1),18 when the patient first arrived in the PACU (EAS 0), 15 minutes (EAS 15), and 30 minutes after arrival (EAS 30) because EA usually lasts around 30 minutes.1 EA was identified when the
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Table 1. Emergence Agitation Score Score 1 2 3 4 5
Behavior Sleeping Awake, calm Irritable, crying Inconsolable crying Severe restlessness, disorientation
children showed an EAS of 4 or 5 at least once, and 0.1 mg/kg of nalbuphine was administered intravenously as treatment.4 Children with agitated responses to pain (eg, complaining or localizing of pain) were not considered to have EA. If the EA was managed by administration of nalbuphine, no more medication was received, and the patients were closely monitored by the caregivers. EEG was recorded continuously from the induction of anesthesia until the end of anesthesia. The electrode was placed on the forehead to record single monopolar channel at FP2 (right frontal polar site) referenced by A2 (right earlobe site) by international 10 to 20 system (Figure 1). The electrode impedance was checked automatically and maintained at , 5 kG. The EEG was analyzed in the frequency domain automatically. Spectral edge frequency 95 (SEF95 5 the frequency below which 95% of the EEG power is located), spectral bands of beta (13 to 30 Hz), alpha (8 to
Figure 1. The international 10 to 20 system of electroencephalographic montage.Adapted from http://commons.wikimedia.org/wiki/File:21_electro des_of_International_10-20_system_for_EEG.svg.
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13 Hz), theta (4 to 8 Hz), and delta (0 to 4 Hz) were analyzed, calculated, and expressed as a percentage of total spectral power. These parameters were analyzed and shown in the patient’s monitor by embedding manufacturer’s software. The monitor presented the analyzed data every 10 seconds. These EEG-derived parameters at 1.0 MAC (20 minutes during the maintenance of anesthesia) and 0.3 MAC (5 minutes during emergence) of sevoflurane anesthesia were averaged and analyzed. For quality control of EEG data, the artifacts of EEG by electric cautery or patients’ movements were removed. Data Analysis Patients’ characteristics were compared between patients with EA and patients without EA using Mann–Whitney U test. The correlation of EEGderived parameters and EAS was analyzed using Spearman correlation. If there was meaningful correlation, simple regression analysis was performed. Receiver-operating characteristic (ROC) curve of EEG parameters and overall EA (EAS $ 4) were analyzed to evaluate their predictability. Statistical analysis was performed using SPSS 19.0 (IBM, Somers, NY). P value , .05 was considered significant.
Results Thirty-one patients were enrolled in the study and completed the EEG recording. However, data from two patients was discarded because of the data artifacts of EEG. Patients’ characteristics, surgery, anesthetic, and PACU stay time, and depth of anesthesia by SEF95 are shown in Table 2. The incidence of EA was 11 of 29 patients (37.9%). Six patients experienced EA on the arrival at PACU. Four who developed EA at 15 minutes after arrival had an EAS of 2 or 3 at arrival. After these 10 patients had been given 0.1 mg/kg of nalbuphine, only three still exhibited EA at 30 minutes after PACU arrival. One patient suffered EA through the entire PACU stay (39 minutes). Patients who showed EA after administration of nalbuphine were transferred to Phase 2 recovery with continuous SpO2 monitoring, and there were no adverse effects. The use of nalbuphine was effective in 63.4% (7/11). However, subgroup analysis showed no difference between responders and nonresponders to nalbuphine. There was no significant adverse effect in PACU in any child.
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Table 2. Patients’ Characteristics Characteristics
All; n 5 29
EA(1); n 5 11
EA(2); n 5 18
P Value
Age (y) Sex (M/F) Height (cm) Weight (kg) Surgery time (min) Anesthetic time (min) PACU stay (min) SEF95 at 1 MAC (Hz) SEF95 at 0.3 MAC (Hz)
3.7 6 1.5 14/15 102.1 6 12.3 16.3 6 4.3 26.2 6 12.2 47.2 6 13.8 36.0 6 9.1 12.1 6 2.7 18.7 6 3.8
3.7 6 1.3 6/5 104.2 6 11.1 16.7 6 3.9 29.8 6 15.6 50.9 6 16.4 35.1 6 8.6 11.6 6 2.4 18.2 6 3.3
3.7 6 1.6 8/10 100.9 6 13.2 16.1 6 4.6 24.1 6 9.4 45.0 6 11.9 36.5 6 9.7 12.4 6 3.0 19.0 6 4.1
.95 N/A .64 .55 .34 .41 .71 .44 .78
EA, emergence agitation; EA(1), patients with emergence agitation; EA(2), patients without emergence agitation; PACU, postanesthetic care unit. Values are presented as mean 6 standard deviation.
Spearman correlation of EEG-derived parameters during sevoflurane anesthesia (1.0 MAC and 0.3 MAC of EtSEVO) and EAS are shown in Table 3. The alpha power at 0.3 MAC of EtSEVO was positively correlated with EAS 15 and EAS 30 (Spearman correlation coefficient 5 0.392 and 0.566, P 5 .035 and .001, respectively). The theta/alpha ratio at 0.3 MAC of EtSEVO was negatively correlated with EAS 30 (Spearman correlation coefficient 5 20.478, P 5 .009). There were no significant differences in SEF95 at 1.0 MAC and 0.3 MAC of EtSEVO between patients with EA and patients without EA (Table 2). An
example of the different courses of theta and alpha powers during sevoflurane anesthesia in patients with and without EA is shown in Figure 2. The area under the ROC curve of EEG-derived parameters for EA is shown in Table 4. The area under the ROC curve of the percentage of alpha bands at 0.3 MAC of EtSEVO and the occurrence of EA was 0.672 (Figure 3), and 29.3% of alpha bands at 0.3 MAC of EtSEVO showed a 72.7% sensitivity and 55.6% specificity. The positive predictive value and negative predictive value were 0.58 and 0.43, respectively.
Table 3. Correlation Analysis of EEG-Derived Parameters and EA Score (n 5 29) Spearman correlation coefficient (P value) EtSEVO 1 MAC
0.3 MAC
EEG (Mean ± SD) SEF95 (Hz) Beta (%) Alpha (%) Theta (%) Delta (%) Theta/alpha SEF95 (Hz) Beta (%) Alpha (%) Theta (%) Delta (%) Theta/alpha
12.1 6 2.7 19.5 6 4.8 22.2 6 4.7 25.7 6 4.8 32.3 6 7.1 1.2 6 0.3 18.7 6 3.8 32.6 6 8.3 31.3 6 7.0 16.8 6 4.7 19.1 6 6.3 0.6 6 0.2
EAS 0
EAS 15
EAS 30
20.213 (.267) 20.241 (.208) 20.117 (.547) 0.173 (.369) 0.049 (.800) 0.200 (.297) 0.075 (.697) 0.033 (.863) 0.144 (.456) 0.006 (.977) 20.022 (.090) 20.134 (.489)
20.012 (.951) 20.136 (.481) 0.216 (.261) 20.269 (.158) 0.066 (.732) 20.243 (.204) 0.018 (.927) 20.005 (.979) 0.392 (.035)* 20.164 (.395) 20.306 (.107) 20.282 (.139)
20.195 (.311) 20.185 (.338) 0.046 (.813) 20.243 (.203) 0.235 (.220) 20.181 (.346) 20.160 (.408) 20.169 (.381) 0.566 (.001)* 20.248 (.194) 20.146 (.449) 20.478 (.009)*
EEG, electroencephalography; EA, emergence agitation; EtSEVO, end-tidal sevoflurane concentration; SD, standard deviation; EAS 0, EA score at the arrival on postanesthetic care unit; EAS 15, EA score 15 minutes after arrival; EAS 30, EA score 30 minutes after arrival; MAC, minimum alveolar concentration; SEF95, spectral edge frequency 95. Statistically significant, *P , .05.
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Figure 2. An example of time courses of percentages of theta and alpha bands of electroencephalography during sevoflurane anesthesia. Three-year-old child with emergency agitation (EA; left) showed high-alpha power and low-theta power during the maintenance of anesthesia (theta 5 22.7, alpha 5 23.5, theta/alpha ratio 5 0.96, and Spectral edge frequency 95 [SEF95] 5 16.6) and emergency (theta 5 12.8, alpha 5 46.2, theta/alpha ratio 5 0.28, and SEF95 5 11.1), whereas 3-year-old child without EA (right) showed low-alpha power and high-theta power during the maintenance of anesthesia (theta 5 34.0, alpha 5 19.8, theta/alpha ratio 5 1.71, and SEF95 5 11.3) and emergency (theta 5 17.1, alpha 5 36.1, theta/alpha ratio 5 0.47, and SEF95 5 17.2). EAS score (EAS) of these children at 0, 15, and 30 minutes after postanesthetic care unit arrival were ‘‘3/5/4’’ (left), and ‘‘2/1/2’’ (right), respectively. End-tidal sevoflurane concentrations are shown with bars. MAC, minimum alveolar concentration.
Discussion Our data showed a significant relationship between the percentage of EEG bands (high-alpha powers) during emergence from sevoflurane anesthesia and the EAS in the PACU.
(8 to 13 Hz) are usually seen in relaxed, awake patients with their eyes closed, and thought be related to the decrease of inhibitory activity of reticular nucleus on thalamic pacemaker cells. During alpha wave-predominant meditation or light sedation,
The rhythmic activity in EEG is divided into several specific frequency bands; in the present study, the relative portion of beta, alpha, theta, and delta waves was monitored. Beta waves (13 to 30 Hz) are thought to be the result of sensory stimuliactivating reticular-activating system which desynchronizes the thalamic pacemaker cells. Alpha waves Table 4. AUC of ROC Curve of EEG-Derived Parameters for EA EEG parameters
EtSEVO
AUC of ROC curve
Alpha Theta/alpha ratio
0.3 MAC 0.3 MAC
0.672 0.374
AUC, area under curve; ROC, receiver-operating characteristic; EA, emergence agitation; EEG, electroencephalography; EtSEVO, end-tidal sevoflurane; MAC, minimum alveolar concentration.
Figure 3. Receiver-operating characteristic (ROC) analysis of alpha power at 0.3 minimum alveolar concentration (MAC) of end-tidal sevoflurane (EtSEVO) and the occurrence of emergency agitation (EA). The area under ROC curve is 0.672.
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thalamic pacemaker cells regulate and synchronize the thalamocortical activity. Theta waves (4 to 8 Hz) are normally seen during sleep and thought to be related to the inhibition of thalamic pacemaker cells by gamma-aminobutyric acidergic action of reticular nucleus. During deep sleep, delta (0 to 3 Hz) waves are prominent and reflect extreme depression of thalamus.19 According to the thalamic theory, halogenated inhalation anesthetics cause unconsciousness by decreasing the neuronal activity of thalamocortical neurons (thalamic shunt).20 Previous studies revealed this influence of inhalation anesthetics on EEG-derived parameters (SEF95 and the four frequency bands)21,22; incremental concentration of inhalation anesthetics changes the EEG from fast (beta and alpha) waves during spontaneous arousal to slow (theta and delta) waves during anesthesia. SEF95 has been used to estimate the depth of anesthesia, and previous studies suggested SEF95 values for adequate anesthesia (10 to 14 Hz) and awaken state (15 to 20 Hz).21,22 The values of SEF95 data in the present study during the maintenance of anesthesia (1.0 MAC of EtSEVO) and emergence (0.3 MAC of EtSEVO) were within these ranges, respectively (Table 2). SEF95 value does not reflect the relative percentage of each spectral band (beta, alpha, theta, and delta waves); it only reflects the sum of them. Therefore, it might be possible that there was a difference in alpha and theta bands without the difference in SEF95 values between patients with EA and without EA (Table 2). Bispectral index and entropy (monitoring depth of anesthesia by EEG-based algorithms) are one of the most commonly used methods to measure the depth of anesthesia. Although some evidence supports their use in children, it is not as confirmative as adults and has large individual and situational differences. We did not use them in the present study, the depth of anesthesia was adequate and uniform in all the patients by adjusting the MAC values, and the intraoperative vital signs were stable in all patients. We obtained the single-channel EEG-derived parameters from the forehead because of feasibility for future use.
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A previous study showed that children who demonstrated agitation during induction showed slower EEG frequency during the second minute of induction compared with those who did not demonstrate agitation regardless, of the type of premedication.16 In the present study, induction of anesthesia was performed with high concentration of sevoflurane (8.0 vol%) with high fresh gas flow rate (6 L/min). Therefore, changes of EEGderived parameters during induction were too rapid to observe. Instead, we obtained EEGderived parameters at 0.3 MAC of EtSEVO (MAC awake) for 5 minutes during emergence. Other articles reported that high concentration of sevoflurane (8.0 vol%) induced the epileptiform EEG during induction.23 However, recent studies showed the use of lower concentration of sevoflurane did not avoid the risk of EEG abnormalities.24 We used high concentration of sevoflurane during induction because it took a long-time induction with lower concentration of inhalation agent comparing with short surgery time. Although there might be an epileptiform EEG during induction, we could not get the raw EEG data from the patient monitor, and we did not realize the change of EEG. In addition, there were no epileptic movements from the children after anesthesia. Higher alpha power and lower theta/alpha ratio during emergence from sevoflurane anesthesia were positively correlated to EAS in PACU. This trend means less gamma-aminobutyric acidergic inhibition of thalamic pacemaker cells and more thalamocortical activity during emergence from sevoflurane anesthesia.25 Taken together, rapid recovery from EEG suppression of sevoflurane anesthesia was correlated with high EAS in PACU. There are two possible explanations for this phenomenon; patients with EA have high baseline EEG activity and/or are more resistant to EEG suppression of sevoflurane. However, the positive predictive value and negative predictive value of alpha power at 0.3 MAC of EtSEVO were low and failed to show good predictability of the occurrence of EA. These findings were after the EEG analysis; therefore, we could not apply the findings during the anesthesia to detect the EA. However, if we were to develop an algorithm that calculates the powers of EEG in real time, we could apply these findings clinically.
INTRAOPERATIVE EEG AND EMERGENCE AGITATION
Smit et al26 showed that individual differences in EEG spectral power reflect their genetic variance in brain development. Factors such as neuronal myelination, synaptic density, and dendritic outgrowth affect the volumes of gray and white matter and eventually result in different baseline theta and alpha spectral powers. Pediatric patients have large individual differences in the development of their central nervous system,27 and these differences can affect not only their baseline EEG activity and their EEG response to sevoflurane anesthesia, but also postoperative EA. However, no evidence exists regarding these issues. We could not monitor postoperative EEG during emergence (less than MAC awake) and PACU stay due to motion artifacts. There is no previous study about EEG monitoring in PACU. Previous studies conducted in the intensive care unit or ward indicated that the delirious patients showed significant lower alpha power and higher theta power, resulting in high theta/alpha ratio.28,29 However, febrile delirium in pediatric patients with influenza,28 or early postoperative delirium in elderly patients after open-heart surgery29 are not the same situation as the present study. Pediatric EEG data during EA after sevoflurane anesthesia could be hardly obtained.
Limitations There are several limitations in the present study. First, it was a noncontrolled, observational study of small score and sample size. Second, as mentioned before, we could not get the raw EEG data at PACU because of the patients’ discomfort and involuntary movement. Monitoring EEG in
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PACU, especially during EA, would have given more information about EA. Third, sevoflurane that remains in the body may have played a role in sedation, pain control, and EA in PACU. Fourth, the present study was conducted under sevoflurane anesthesia for strabismus surgery. Although adequate muscle relaxation was achieved, and EMG was monitored simultaneously to exclude the effect of electric activity muscle, passive movement of extraocular muscle and eyelid would affect the EEG signal. In addition, along with otolaryngeal surgery, strabismus surgery showed a high incidence of EA (from 44% to 47%) than other pediatric surgery.1,11,12 Finally, we did not assess the preoperative anxiety or distress, which might be a predisposing factor to EA. However, the previous study demonstrated that anxious patients behave similarly to their less anxious counterparts on induction of anesthesia with propofol proven by BIS.30 Therefore, anxiety level might have less effect on EEG.
Conclusion A larger clinical trial with EEG monitoring in PACU and during EA is needed in the future for an accurate assessment. In addition, investigating the effect of alpha power lowering at the emergence from sevoflurane anesthesia to prevent EA may clarify the relationship between intraoperative EEG and EA. In conclusion, this preliminary study presented that the relative percentage of EEG bands during sevoflurane anesthesia showed significant relationship with postoperative EAS and the possibility of prediction of EA by EEG in PACU.
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after sevoflurane-based general anesthesia? Paediatr Anaesth. 2005;15:1098-1104. 7. Dahmani S, Stany I, Brasher C, et al. Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies. Br J Anaesth. 2010;104:216-223. 8. Mizuno J, Nakata Y, Morita S, Arita H, Hanaoka K. Predisposing factors and prevention of emergence agitation. Masui. 2011;60:425-435. 9. Kuratani N, Oi Y. Greater incidence of emergence agitation in children after sevoflurane anesthesia as compared with halothane: A meta-analysis of randomized controlled trials. Anesthesiology. 2008;109:225-232. 10. Oh AY, Seo KS, Kim SD, Kim CS, Kim HS. Delayed emergence process does not result in a lower incidence of emergence agitation after sevoflurane anesthesia in children. Acta Anaesthesiol Scand. 2005;49:297-299. 11. Przybylo HJ, Martini DR, Mazurek AJ, Bracey E, Johnsen L, Cote CJ. Assessing behaviour in children emerging from anaesthesia: Can we apply psychiatric diagnostic techniques? Paediatr Anaesth. 2003;13:609-616. 12. Aouad MT, Yazbeck-Karam VG, Nasr VG, El-Khatib MF, Kanazi GE, Bleik JH. A single dose of propofol at the end of surgery for the prevention of emergence agitation in children undergoing strabismus surgery during sevoflurane anesthesia. Anesthesiology. 2007;107:733-738. 13. Jacobson S, Jerrier H. EEG in delirium. Semin Clin Neuropsychiatry. 2000;5:86-92. 14. Koponen H, Partanen J, Paakkonen A, Mattila E, Riekkinen PJ. EEG spectral analysis in delirium. J Neurol Neurosurg Psychiatry. 1989;52:980-985. 15. Prugh DG, Wagonfeld S, Metcalf D, Jordan K. A clinical study of delirium in children and adolescents. Psychosom Med. 1980;42:177-195. 16. Constant I, Leport Y, Richard P, Moutard ML, Murat I. Agitation and changes of Bispectral Index and electroencephalographic-derived variables during sevoflurane induction in children: Clonidine premedication reduces agitation compared with midazolam. Br J Anaesth. 2004;92:504-511. 17. Lerman J, Sikich N, Kleinman S, Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology. 1994;80:814-824. 18. Cole JW, Murray DJ, McAllister JD, Hirshberg GE. Emergence behaviour in children: Defining the incidence of excite-
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