Anesth Pain Med 2011; 6: 191～194 ￭Research Article￭

Effect of intravenous induction agents on emergence delirium after in pre-school aged children undergoing adenotonsillectomy

Department of Anesthesia and Pain Medicine, Seoul Eulji Hospital, College of Medicine, Eulji University, Seoul, Korea

Ju Youn Choi, Hye Jin Park, Hyo Seok Kang, So Jin Park, Jae Woo Lee, and Seung Kwon Baek

Background: In pre-school aged children, the occurrence of Recent meta-analysis has evaluated potential prophylactic emergence delirium (ED) is increased after sevoflurane anesthesia. treatments using propofol, α2-adrenergic receptor agonist, mida- The purpose of this study was to evaluate if intravenous inducting zolam and to reduce ED, but their efficacy remains agents such as propofol, ketamine or thiopental sodium affected the development of ED. controversial [4]. Therefore, we performed this study to com- Methods: A total of 62 children between 3 and 6 years of age pare the severity and incidence of ED when propopol, keta- scheduled for elective tonsillectomy and adenoidectomy were mine or thiopental was used as induction agents during sevo- divided into 3 groups in a double-blinded manner. Anesthesia was induced using one of the three drugs intravenously: 5 mg/kg of flurane anesthesia in pre-school aged children undergoing adeno- , 1 mg/kg of ketamine or 2 mg/kg of propofol. tonsillectomy. Anesthesia was then maintained with sevoflurane. The develop- ment of ED was assessed in the post-anesthetic care unit. Results: The propofol and ketamine group showed a significantly MATERIALS AND METHODS lower pediatric anesthesia emergence agitation (PAEA) score and a lower incidence of ED compared with the thiopental group. After receiving institutional review board approval and Conclusions: Propofol and ketamine decreased the development obtaining written informed parental consent, 62 children, 3−6 of emergence delirium when used as an induction agent. (Anesth years of age with American Society of Anesthesiologists Pain Med 2011; 6: 191∼194) (ASA) physical status I or II, scheduled for elective tonsillec- Key Words: Children, Emergence delirium, Ketamine, Propofol, tomy and adenoidectomy were included into the study. The Sevoflurane, Thiopental. children were randomly divided into 3 treatment groups. Child- ren with a history of allergies, previous adverse anesthesia INTRODUCTION experiences, developmental delay, or psychological disorders were excluded from study. All patients were required to fast Sevoflurane is widely used in pediatric surgery because of for at least 6 h and no premedication prior to surgery was the rapidity of induction and emergence from anesthesia, mini- provided. Ringer’s lactate solution was provided at an mal respiratory irritability and reduced cardio-depressive effect appropriated rate for body weight and NPO duration. When the [1]. However, emergence delirium (ED) is found more com- patients arrived at the operating room, ECG, noninvasive blood monly after sevoflurane anesthesia compared with other means pressure and SpO2 were started. Anesthesia was of inhalation anesthesia [2,3]. Previous studies reported that induced using either 5 mg/kg of thiopental, 1 mg/kg of ketamine younger children are prone to develop ED [2]. or 2 mg/kg of propofol intravenously in a double blind manner. 0.02 mg/kg of atropine was administrated to prevent brady- Received: December 23, 2010. cardia before infusing the induction agent. 0.6 mg/kg of Revised: 1st, January 10, 2011; 2nd, January 20, 2011. Accepted: February 22, 2011. rocuronium was also given intravenously for muscle relaxation Corresponding author: Hye Jin Park, M.D., Ph.D., Department of after loss of consciousness. Anesthesia was maintained with Anesthesia and Pain Medicine, Seoul Eulji Hospital, College of Medicine, 3% sevoflurane and 50% N O in oxygen. At 15 min prior to Eulji University, Hagye-dong, Nowon-gu, Seoul 139-230, Korea. Tel: 2 82-2-970-8084, Fax: 82-2-970-8084, E-mail: [email protected] ending the surgery, all patients were administrated ketorolac

191 192 Anesth Pain Med Vol. 6, No. 2, 2011 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

0.5 mg/kg intravenously for pain control. Table 1. Demographic Data and Children’s and Infants’ Postoperative After arriving at the postanesthetic care unit (PACU), ED Pain Scale (CHIPPS) was assessed at 0 min, 10 min, 20 min and 30 min on a 4 Propofol Ketamine Thiopental point scale as follows: 1, calm; 2, not calm, but could easily Age (yr) 5.0 ± 0.8 5.4 ± 1.0 5.1 ± 0.8 be calmed; 3, not easily calmed, moderately agitated or rest- Gender (M/F) 11/9 14/6 13/9 less; and 4, combative, excited or disoriented. If grade 3 or 4 Height (cm) 117.1 ± 9.1 119.0 ± 10.3 115.7 ± 8.2 was present more than one time during the PACU observation Weight (kg) 23.7 ± 6.1 23.6 ± 4.8 22.7 ± 6.9 period, to the activity was classified to represent ED [5]. We ASA (I/II) 17/3 16/4 18/4 Operation time (min) 64.1 ± 11.3 68.2 ± 17.6 70.0 ± 14.1 also used the Pediatric Anesthesia Emergence Agitation (PAEA) PACU stay time (min) 52.6 ± 3.0 51.1 ± 3.1 50.5 ± 1.8 scale to incorporate cognitive related assessment items [6]. To CHIPPS in PACU assess postoperative pain, we used the Children and Infants 0 min 6.0 ± 2.4 6.6 ± 2.7 8.6 ± 1.8* Postoperative Pain Scale (CHIPPS) [7]. 30 min 2.5 ± 0.6 2.8 ± 1.3 3.5 ± 1.0 Three anesthesiologists were involved in the study. Clinical Values are number of patients or mean ± SD. *P ＜ 0.05 com- management of the patient was performed by the first anesthe- pared with other groups. siologist. All above induction agents were prepared and hidden behind drapes and administrated by the second anesthesiologist Table 2. The Pediatric Anesthesia Emergence Agitation Scale (PAEA) according to the group to which the patients was randomized. in PACU The recording of all variables in the PACU were performed Time in PACU Propofol Ketamine Thiopental by the third anesthesiologist who was blinded to the group to which the patient was assigned. 0 min 14.4 ± 0.4* 14.7 ± 0.4* 18.2 ± 2.0 Statistical analysis was performed using SPSS 11.5 (SPSS 10 min 15.0 ± 4.1* 15.3 ± 3.9* 18.5 ± 2.2 20 min 9.6 ± 3.7 9.6 ± 3.8 11.8 ± 2.0 Inc., Chicago, IL, USA). Values are presented as means ± SD 30 min 4.5 ± 2.0* 5.5 ± 3.1 6.8 ± 2.0 or number (%). A sample size of 20 in each group was calcu- lated to 80% power to detect the PAEA mean difference, 3.5 Values are mean ± SD. *P ＜ 0.05 compared with thiopental groups. and the expected standard deviation, 3.5 with a significant α value, 0.05. We used one-way Analysis of Variance (ANOVA), Pearson’s chi-square test and Fisher’s exact test for statistical 0.008) and ketamine group (P = 0.02) had a lower incidence analysis. A value of P ＜ 0.05 was considered significant. of ED compared with the thiopental group. There were no significant differences in CHIPPS, PAEA and RESULTS ED incidence between the propofol and the ketamine group.

There were no significant differences in demographic data, DISCUSSION duration of exposure to sevoflurane and PACU stay time among the three groups (Table 1). However, immediately after ED has been defined by Sikich and Lerman [6] as a arriving to the PACU, the thiopental group displayed higher disturbance in a child’s awareness of and attention to his or CHIPPS scores than the propofol (P = 0.002) and ketamine her environment with disorientation and perceptual alterations groups (P = 0.02). including hypersensitivity to stimuli and hyperactive motor The propofol group showed a significantly lower PAEA at 0 behavior in the immediate postanesthesia period. Despite its min (P = 0.002), 10 min (P = 0.004) and 30 min (P = 0.008) general disappearance within 15 min, ED is considered a after arriving in the PACU compared with the thiopental potentially serious complication because it can increase the risk group. The ketamine group showed a lower PAEA at 0 min for injury and require extra nursing care. ED may also require (P = 0.004) and 10 min (P = 0.01) compared with the thio- supplemental sedative and analgesic medications which may pental group (Table 2). delay discharge from PACU. The incidence of ED in the PACU was 45.0% (9/20) in the The etiology of ED is currently unknown. Recent hypotheses propofol group, 50.0% (10/20) in the ketamine group and emphasize rapid emergence. It causes patients to be in a dis- 86.3% (19/22) in the thiopental group. The propofol (P = sociate state, that is, children are awaken with altered cognitive Ju Youn Choi, et al：Emergence delirium and induction agents 193 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏 perception. Other factors such as postoperative pain and pre- compared to Tsai’s reports. The different dose of propofol operative anxiety have been proposed as contributing to or might partially explain in the different results found in a exacerbating this problem [8,9]. Our study showed that keta- relatively brief surgery. Viitanen et al. [19] reported that 3.0 mine and propofol used as an induction agent decreased the mg/kg propofol used as an induction agent decreased emer- development of emergence delirium in pre-school aged gence agitation in early children. children. Although Chen et al. [10] reported that the children All sedatives do not have a prophylactic effect for ED. in the ketamine group were more agitated compared with the and thiopental have been reported not to reduce propofol or midazolam group undergoing cataract surgery, ED [20-23]. Why these drugs cannot reduce ED is unclear. many studies reported that ketamine had preventive effect for Breschan et al. [20] suggested amnesia and sleep disturbance ED. Low dose oral ketamine decreased the incidence of ED in induced by midazolam as possible causes. Our study displayed pre-school aged children undergoing dental repair [11]. Dalens a high incidence of ED in the thiopental group (86.3%) with et al. [12] reported that a small dose (0.25 mg/kg) of other studies reporting similar results (70−100%) [21-23]. A ketamine could prevent emergence agitation after sevoflurane possible explanation for our finding is that thiopental has anesthesia for MRI imaging. A recent meta-analysis showed no anti-analgesic effects [24]. Postoperative pain is considered a correlation of the efficacy of ketamine, α2 agonist or fentanyl contributing factor in developing ED. Accordingly, increased in postoperative pain control and ED decreasing [4]. These pain perception could be related to ED. Another possible results suggest that the properties to induce emergence sedation explanation is that thiopental in low concentrations could are more important in preventing ED than the analgesic induce excitation and a median frequency increase in EEG properties of the drugs. In animal study, ketamine potentiates [25]. Excitement induced by thiopental might be related to the the release of melatonin [13], which can attenuate emergence development of ED. agitation following sevoflurane [14]. Our study showed the There are some limitations in our study. First limitation is ketamine group and propofol group had significantly a lower that all children showed a relatively high incidence of ED. We CHIPPS scores compared with the thiopental group. Given that did not administrate additive drugs for children developing ED CHIPPS is based, or part on behavior manifestations, it is not in the PACU. Single administration of propofol or ketamine possible to completely separate the pain sensation and agitated was insufficient to decrease ED effectively. Jung et al [26] behavior in pre-school aged children. Considering propofol has reported co-administration of ketamine and fentanyl reduced the no analgesic properties, CHIPPS is thought to reflect more of risk of ED in 1/68 compared with thiopental. Additional admi- an agitation state than pain sensation. nistration of other medication such as fentanyl to manage Propofol has been reported to decrease the incidence of ED children in the PACU may be required. Second, we did not [5,15,16]. Propofol’s effect in decreasing ED could be evaluate for any preoperative anxiety. Children were not pre- accounted for by the residual sedative effect and induction of medicated and anesthesia was induced without attending their a positive mood [5]. Despite similar recovery times with sevo- parents. It is easy to assume that these children experienced a flurane, the incidence of ED was lower in children after relatively high level of anxiety preoperatively. Considering that propofol anesthesia than after sevoflurane anesthesia [5,15]. preoperative anxiety is related to develop ED [8], preoperative Also, a small dose of propofol at the end of surgery decreased anxiety evaluation may have been useful. the incidence of ED without delaying discharge from PACU In conclusion, ketamine and propofol used as an induction [16]. But the effect of propofol used as an induction agent is agent significantly decreased the severity and frequency of ED controversial. Since propofol is rapidly distributed and meta- when compared with thiopental in pre-school aged children bolized (first exponential phase half life 2−3 min, second undergoing adenotonsillectomy. exponential phase half life 34−56 min) [17], blood concen- trations of propofol can be too low to effectively decrease ED in PACU. 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