|Year : 2014 | Volume
| Issue : 3 | Page : 340-345
Premedication with dexmedetomidine decreases emergence agitation after sevoflurane anesthesia in children
Nermin S Boules, Hossam Z Hanna
Department of Anesthesiology and Pain Management, National Cancer Institute, Cairo University, Cairo, Egypt
|Date of Web Publication||27-Aug-2014|
Nermin S Boules
1 Kasr El Aini Street, Fom El Khalig, Cairo
Source of Support: None, Conflict of Interest: None
Diagnostic procedures such as bone marrow aspiration and biopsy have increased in recent years. The pain during such procedures is too much for most children to tolerate, and therefore general anesthesia with sevoflurane is the only choice. Emergence agitation (EA) is described as a mental disturbance during the recovery from general anesthesia. The aim of this study is to test the hypothesis that, because of its sedative effects, the use of dexmedetomidine decreases EA and improves parents and nurses' satisfaction after sevoflurane-based anesthesia in children.
Patients and methods
A total of 200 children aged 2-6 years, scheduled for bone marrow aspirations and biopsies, in a hospital procedure room, were enrolled. Patients were randomized into two groups: group D, receiving dexmedetomidine (2 μg/kg) in 10 ml saline over 2 min; and group S, receiving 10 ml saline over 2 min. Procedure duration, recovery time, and discharge time were recorded. Agitation score and parents and nurses' satisfaction scores were assessed.
There were no significant differences between groups in the duration of the procedure or the time of discharge. The recovery time was longer in group D. Both parents and nurses' satisfaction scores were significantly lower in group D. Both agitation score and percent of patients who had agitation were significantly lower in group D. The mean arterial blood pressure and heart rate were significantly lower in group D.
Dexmedetomidine is an effective drug to reduce EA in pediatric patients after sevoflurane anesthesia without prolongation in the time of discharge, and provide better parents and nurses' satisfaction scores, which may allow better performance of the nurses.
Keywords: dexmedetomidine, emergence agitation, satisfaction score, sevoflurane anesthesia
|How to cite this article:|
Boules NS, Hanna HZ. Premedication with dexmedetomidine decreases emergence agitation after sevoflurane anesthesia in children. Ain-Shams J Anaesthesiol 2014;7:340-5
|How to cite this URL:|
Boules NS, Hanna HZ. Premedication with dexmedetomidine decreases emergence agitation after sevoflurane anesthesia in children. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2022 Aug 19];7:340-5. Available from: http://www.asja.eg.net/text.asp?2014/7/3/340/139562
| Introduction|| |
The number of diagnostic procedures such as bone marrow aspirations (BMAs) and biopsies has increased markedly in recent years. Both the pain and the age make such procedures too difficult to be performed without anesthesia . Therefore, general anesthesia may be the only choice.
Sevoflurane (polyfluorinated methyl, isopropyl ether) is a popular inhalational anesthetic for children and outpatients, as it is less pungent with a relative lack of airway irritation, has a more rapid induction and emergence because of its lower solubility in blood and in tissues, and it has greater hemodynamic stability than the other potent inhalational agents . However, when it is used as a sole anesthetic agent, it is associated with a relatively high incidence of emergence agitation (EA) that may be harmful to the patient himself and to the caregiver [3,4]; EA occurs even in the absence of any surgical intervention .
EA is a term used to describe a mental disturbance during recovery from general anesthesia, consisting of hallucinations, delusions, and confusion manifested by moaning, crying, nonpurposeful restlessness, involuntary physical activity, and thrashing about in bed . The children often refuse to be comforted, even by their parents. It was one of the major causes of dissatisfaction of the parents and overload to the attending nurses.
The exact etiology of EA is unknown; however, many explanations have been postulated, including rapid removal of residual anesthetics , lack of adaptation of young children to the environment after awakening, anxiety from separation from their parents, sympathetic hyperactivation, and increased pain sensation . However, Cohen et al.  excluded that rapid removal of residual anesthetics may be the cause of EA, as propofol also permits rapid emergence from general anesthesia but is not associated with agitation. In addition, many patients' reports confirmed that pain was not significant, and the need to treat EA with analgesics and sedatives postoperatively may delay recovery and discharge from the postanesthesia care unit (PACU) .
Dexmedetomidine, a selective α2 adrenoceptor agonist (ratio of α2 /α1 activity 1620 : 1), may explain the potent effects of sedation without unwanted cardiovascular effects from α1 receptor activation .
The aim of this study is to test the hypothesis that because of its sedative effects, the prophylactic use of dexmedetomidine reduces EA, thus improving parents and nurses' satisfaction after sevoflurane-based anesthesia in children that allows better performance of the attending nurses.
| Patients and methods|| |
This study was carried out in Children Cancer Hospital of Egypt (CCHE). After approval of the hospital review board and the ethical committee, informed written parental consent was obtained in all patients. A total of 200 preschool children aged 2-6 years with ASA I-III, scheduled for BMA and bone marrow biopsy (BMB), in a hospital procedure room, were enrolled in the study. Exclusion criteria included patients with respiratory distress of any cause, patients with any neurological impairment, and patients with previous history of agitation after sevoflurane anesthesia.
All patients underwent thorough preoperative assessment, which included history, physical examinations, and laboratory investigations. The patients were fasted overnight, but were encouraged to take clear fluids until 2 h before the induction of anesthesia.
All patients were induced by 100% oxygen and 5-8% sevoflurane using multiple-step inhalational technique. No preoperative sedation was administered. All patients were monitored by ECG, noninvasive blood pressure, pulse oximeter, and capnography. The heart rate (HR), oxygen saturation (SO 2 ), and the end-tidal carbon dioxide (EtCO 2 ) were continually monitored and recorded every 10 min. The mean arterial blood pressure (MAP) and the respiratory rate were measured every 5 min and recorded every 10 min. After appropriate depths of anesthesia were obtained, a 22- or 24-G intravenous catheter was inserted into a peripheral vein. An appropriate-sized laryngeal mask (with regard to the age and weight of the child) was introduced, and then sevoflurane was maintained at 2-3% in 50% oxygen-air mixture. All patients were administered 10 mg/kg paracetamol infusion over 10 min and 1% lidocaine at the site of needle entry to reduce the pain. Patients were randomly allocated by computer-generated random numbers into two groups (100 patients each): dexmedetomidine group and saline group.
The dexmedetomidine group (group D) received dexmedetomidine (2 μg/kg) (Precedex; Abbott Laboratories Inc., Abbott Park, Illinois, USA) (supplied in 2 ml ampoules at a concentration of 100 μg/ml) in 10 ml saline over 2 min, and the saline group (group S) received 10 ml saline over 2 min. All syringes with dexmedetomidine or saline were prepared by the same investigator. Administration of anesthesia and the study drugs and data collection were carried out by other investigator blinded to the study drugs.
After the end of the procedure, sevoflurane was discontinued, and the laryngeal mask airway (LMA) was removed. The patient was transferred to the recovery room with the attending nurse and a responsible parent.
The following times were recorded:
(1) Procedure duration in minutes (the time from starting induction till discontinuation of the anesthetic gas).
(2) Recovery time in minutes (the time from discontinuation of the anesthetic gas till recovery evidenced by first cry or purposeful movement, whichever is earlier).
(3) Discharge time in minutes (the time from discontinuation of the anesthetic gas till the child met the discharge criteria) , which were:
(a) Oxygen saturation more than 95%.
(b) Stable and satisfactory airway patency.
(c) Hemodynamic stability.
(d) Intact airway protective reflexes.
(e) Ability to walk unaided or talk according to his age.
(4) Agitation score was recorded every 10 min in the recovery room (it is a four-point scale where calm = 1; crying but can be consoled = 2; crying but cannot be consoled = 3; and agitated = 4) . Children with score 3 or 4 were considered having EA attack, and if persisted more than 3 min a rescue dose of midazolam (0.05 mg/kg) was administered. The number of patients who had attacks, the number of attacks, and number of patients receiving treatment were recorded.
(5) Parent and nurse satisfaction was assessed using linear scale, where 0 = very satisfied and 10 = very dissatisfied. This score is used initially to assess patient satisfaction after the interventional pain therapy; however, we used it to assess the satisfaction of the child's recovery .
(6) Complication such as hypoxia (SO 2 < 90%), laryngospasm, apnea, nausea, and vomiting were recorded and managed accordingly.
Sample size calculation
0Sample size calculation was carried out using the comparison of parent satisfaction score between group S and group D, as it was the primary outcome of our study. As reported in a pilot study on 20 children, the mean ± SD of this score in group S was ˜4.45 ± 1.90, whereas in group D the mean ± SD was 2.65 ± 0.58. Accordingly, we calculated that the minimum proper sample size was 19 patients in each arm to be able to detect a real difference of 1.8, with 80% power, and 3.0 cases in each arm to achieve 95% power, at an α-value of 0.05 level using Student's t-test for independent samples. Sample size calculation was carried out using Stats Direct statistical software version 2.7.2 for MS Windows (Stats Direct Ltd, Cheshire, UK).
In addition, sample size calculation was carried out using the comparison of nurse satisfaction score between group S and group D, as it was the primary outcome of our study. As reported in a pilot study on 20 children, the mean ± SD of this score in group S was ˜4.8 ± 1.10, whereas in group D the mean ± SD was 2.55 ± 0.61. Accordingly, we calculated that the minimum proper sample size was five patients in each arm to be able to detect a real difference of 2.25, with 80% power at an α- value of 0.05 level using Student's t-test for independent samples. Sample size calculation was carried out using Stats Direct statistical software version 2.7.2 for MS Windows (Stats Direct Ltd).
Data were statistically described in terms of mean ± SD, median and range, or frequencies (number of cases) and percentages when appropriate. Student's t-test was used to compare normally distributed continuous variables between the two groups and Mann-Whitney U-test for independent samples. For comparing categorical data, χ2 -test was conducted. Exact test was used instead when the expected frequency is less than 5. P-values less than 0.05 were considered statistically significant. All statistical calculations were carried out using computer program SPSS version 15 (Statistical Package for the Social Science; SPSS Inc., Chicago, Illinois, USA) for Microsoft Windows.
| Results|| |
All the enrolled patients completed the study. Demographic data among the groups were statistically insignificant [Table 1].
There were no statistically significant differences between the two groups with regard to the type of interventional procedure or its duration [Table 1]. There was no statistically significant difference between the two groups with regard to the discharge time, but the recovery time was longer in the dexmedetomidine group (P = 0.002) compared with the saline group [Table 2].
Both parents and nurses' satisfaction scores were significantly higher in group D in comparison with group S (P = 0.012 and 0.007, respectively) ([Figure 1], [Table 3]).
Both agitation score and percent of patients who had agitation were significantly lower in the dexmedetomidine group (P ≤ 0.05) [Table 4].
The MAP, HR, and respiratory rate were significantly lower in the dexmedetomidine group compared with the saline group. There was no statistically significant difference in the oxygen saturation (SO 2 ) and the end-tidal carbon dioxide (EtCO 2 ) between both the groups [Table 5].
There was no statistically significant difference between the two groups in all reported postprocedure complications [Table 6].
| Discussion|| |
The results of the present study showed that there were no statistically significant differences between the two groups with regard to the duration of the procedure. We found that the dexmedetomidine group showed longer recovery time than that of the control group, which may be because of the anxiolytic and analgesic effects of dexmedetomidine. However, there is no statistically significant difference in discharge time as dexmedetomidine is a short-acting drug. Regarding the agitation score, the dexmedetomidine group has significantly lower agitation score and significantly lower incidence of occurrence of agitation. Moreover, there were better parents and nurses' satisfaction in the dexmedetomidine group than in the control group, and this may be because of the decrease in the incidence of EA. MAP and HR were significantly lower in the dexmedetomidine group just before anesthetic discontinuation; this may be because of its sympatholytic effect.
In children cancer hospital, almost all patients are exposed to BMA and/or BMB at least once during their treatment plan. Therefore, at least 50-60 patients were exposed to anesthesia daily in the procedure room for BMA and BMB. Good performance in this unit needs rapid and smooth recovery of the patients with good parents and nurses' satisfaction.
Many studies examined the EA occurred with sevoflurane anesthesia, especially in pediatric patients. Some studies assumed the presence of pain as a predisposing factor for postoperative agitation and studied the effectiveness of different analgesic drugs administered either as prophylaxis or for treatment of agitation [13-15]. In the present study, we tried to exclude the presence of pain as the cause of EA by administering the patients paracetamol infusion and by injecting lidocaine at the site of the needle entry to reduce the pain.
Others studied the effect of sedation as midazolam on EA [16,17], and reported the presence of anxiety and separation as a cause of EA. Many studies used clonidine for the prevention of EA [18-20]. However, dexmedetomidine is a potent α2 agonist with an affinity for α2 receptors that is eight times greater than that of clonidine. Dexmedetomidine has activity at different sites throughout the central nervous system. The sedative and anxiolytic effects of dexmedetomidine result mainly from its activity in the locus ceruleus in the brain stem. Stimulation of α2 adrenergic receptors at this site reduces central sympathetic output, resulting in increased firing of inhibitory neurons. The presence of dexmedetomidine at α2 adrenergic receptors in the dorsal horn of the spinal cord modulates the release of substance P and results in its analgesic effects .
In agreement with the present study, many studies used intraoperative dexmedetomidine in different doses for prevention of EA in different pediatric surgeries and even in diagnostic procedure as MRI. Isik et al.  concluded that administration of 1 μg/kg intravenous dexmedetomidine after anesthesia induction significantly decreases the occurrence of EA in children undergoing MRI under sevoflurane anesthesia (without surgical intervention).
Abdelhaleem et al.  found that the incidence of postoperative agitation in patients receiving sevoflurane was significantly decreased by either intravenous fentanyl (1 μg/kg) or dexmedetomidine (0.3 μg/kg) 10 min before the end of anesthesia.
In the study conducted by Patel et al. , in children undergoing tonsillectomy and adenoidectomy, an intraoperative initial loading dose of 2 μg/kg dexmedetomidine followed by an infusion at 0.7 μg/kg/h decreased intraoperative opiate and anesthetic requirements and decreased opiate requirements in the PACU, in comparison with intraoperative intravenous fentanyl. In addition, there was a significantly lower incidence and duration of severe EA in children who received dexmedetomidine.
Asaad et al.  compared the use of fentanyl (1 μg/kg) with dexmedetomidine (0.15 μg/kg) after the induction of anesthesia with sevoflurane in children between 5 and 10 years old, and showed a reduction in the incidence of EA (21.4 and 16.7%, respectively) when compared with placebo (40%).
Meng et al.  concluded that dexmedetomidine appeared to be safe and effective to reduce the incidence of early EA in children after tonsillectomy and that initial loading dose of 1 μg/kg followed by a maintenance infusion of 0.4 μg/kg/h was a better choice.
More recently, Chen et al.  compared the effects of intraoperative dexmedetomidine, ketamine, and placebo on postoperative EA in children undergoing strabismus surgery under sevoflurane anesthesia, and they found that time to LMA removal was similar in all groups. The peak PAED (pediatric anesthesia emergence delirium) scale scores for EA and the pain scores on the ward were lower in the dexmedetomidine and ketamine groups than in the placebo group. Incidence of vomiting was lower in the dexmedetomidine group (15%) than in the ketamine (44%) or placebo (45.8%) groups. Time for resumption of mental orientation and time to discharge from PACU were longer in the dexmedetomidine and ketamine groups than in the placebo group.
In addition, Gupta et al.  found that intraoperative use of dexmedetomidine in children undergoing spinal surgery results in a better recovery profile with reduced postoperative pain and EA, without adverse perioperative hemodynamic effects. They explained that dexmedetomidine may be beneficial in these children owing to its sedative, anxiolytic, and opioid-sparing properties, with minimal respiratory depression.
During the recovery of a child from anesthesia after BMA and/or BMB, parents and nurses play an important role as they deal directly with the child. During this period, EA may cause anxiety to parents that may be reflected on the performance of attending nurses and may affect work flow in the unit. The relation between the EA and the performance in the pediatric outpatient unit was not thoughtfully studied. In the present study, we focused on the parents and the nurses' satisfaction of the child recovery, as it is an indication of favorable recovery profile.
| Conclusion|| |
Dexmedetomidine is an effective drug to reduce EA in pediatric patients after sevoflurane anesthesia without prolongation in the discharge time, and it provides better parents and nurses' satisfaction scores that allow better performance of the attending nurses and facilitate the work flow.
| Acknowledgements|| |
| References|| |
|1.||Cravero J, Surgenor S, Whalen K. Emergence agitation in paediatric patients after sevoflurane anaesthesia and no surgery: a comparison with halothane. Paediatr Anaesth 2000; 10:419-424. |
|2.|| Goa KL, Noble S, Spencer CM. Sevoflurane in paediatric anaesthesia: a review. Paediatr Drugs 1999; 1:127-153. |
|3.|| Keaney A, Diviney D, Harte S, Lyons B. Postoperative behavioral changes following anesthesia with sevoflurane. Paediatr Anaesth 2004; 14:866-870. |
|4.|| Cohen IT, Finkel JC, Hannallah RS, Hummer, KA, Patel KM. Rapid emergence does not explain agitation following sevoflurane anaesthesia in infants and children: a comparison with propofol. Paediatr Anaesth 2003; 13:63-67. |
|5.|| Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology 2004; 100:1138-1145. |
|6.|| Welborn LG, Hannallah RS, Norden JM, Ruttimann, UE, Callan CM. Comparison of emergence and recovery characteristics of sevoflurane, desflurane, and halothane in pediatric ambulatory patients. Anesth Analg 1996; 83:917-920. |
|7.|| Lee YS, Kim WY, Choi JH, Son JH, Kim JH, Park YC. The effect of ketamine on the incidence of emergence agitation in children undergoing tonsillectomy and adenoidectomy under sevoflurane general anesthesia. Korean J Anesthesiol 2010; 58:440-445. |
|8.|| Demirbilek S, Togal T, Cicek M, Aslan U, Sizanli E, Ersoy MO. Effects of fentanyl on the incidence of emergence agitation in children receiving desflurane or sevoflurane anaesthesia. Eur J Anaesthesiol 2004; 21:538-542. |
|9.|| Ard J, Doyle W, Bekker A. Awake craniotomy with dexmedetomidine in pediatric patients. J Neurosurg Anesthesiol 2003; 15:263-266. |
|10.||Awad IT, Chung F. Factors affecting recovery and discharge following ambulatory surgery. Can J Anaesth 2006; 53:858-872. |
|11.||Aono J, Ueda W, Mamiya K, Takimoto E, Manabe M. Greater incidence of delirium during recovery from sevoflurane anesthesia in preschool boys. Anesthesiology 1997; 87:1298-1300. |
|12.||Kawamata M, Ishitani K, Ishikawa K, Sasaki H, Ota K, Omote K, Namiki A. Comparison between celiac plexus block and morphine treatment on quality of life in patients with pancreatic cancer pain. Pain 1996; 64:597-602. |
|13.||Galinkin JL, Fazi LM, Cuy RM, Chiavacci RM, Kurth CD, Shah UK, et al. Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia. Anesthesiology 2000; 93:1378-1383. |
|14.||Davis PJ, Greenberg JA, Gendelman M, Fertal K. Recovery characteristics of sevoflurane and halothane in preschool-aged children undergoing bilateral myringotomy and pressure equalization tube insertion. Anesth Analg 1999; 88:34-38. |
|15.||Jung HJ, Kim JB, Im KS, Oh SH, Lee JM. Effect of ketamine versus thiopental sodium anesthetic induction and a small dose of fentanyl on emergence agitation after sevoflurane anesthesia in children undergoing brief ophthalmic surgery. Korean J Anesthesiol 2010; 58:148-152. |
|16.||Lapin SL, Auden SM, Goldsmith LJ, Reynolds AM. Effects of sevoflurane anaesthesia on recovery in children: a comparison with halothane. Paediatr Anaesth 1999; 9:299-304. |
|17.||Viitanen H, Annila P, Viitanen M, Tarkkila P. Premedication with midazolam delays recovery after ambulatory sevoflurane anesthesia in children. Anesth Analg 1999; 89:75-79. |
|18.||Kulka PJ, Bressem M, Tryba M. Clonidine prevents sevoflurane-induced agitation in children. Anesth Analg 2001; 93:335-338. |
|19.||Bock M, Kunz P, Schreckenberger R, Graf BM, Martin E, Motsch J. Comparison of caudal and intravenous clonidine in the prevention of agitation after sevoflurane in children. Br J Anaesth 2002; 88:790-796. |
|20.||Tazeroualti N, De GF, De HS, De VA, Dierick A, Van der Linden P. Oral clonidine vs midazolam in the prevention of sevoflurane-induced agitation in children. A prospective, randomized, controlled trial. Br J Anaesth 2007; 98:667-671. |
|21.||Tobias JD. Dexmedetomidine: applications in pediatric critical care and pediatric anesthesiology. Pediatr Crit Care Med 2007; 8:115-131. |
|22.||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. |
|23.||Abdelhaleem A, Mohamed E, Manaa E. Fentanyl versus dexmedetomidine effect on agitation after sevoflurane anaesthesia. Saudi J Anaesth 2007; 1:57-61. |
|24.||Patel A, Davidson M, Tran MC, Quraishi H, Schoenberg C, Sant M, et al. Dexmedetomidine infusion for analgesia and prevention of emergence agitation in children with obstructive sleep apnea syndrome undergoing tonsillectomy and adenoidectomy. Anesth Analg 2010; 111:1004-1010. |
|25.||Asaad OM, Hafez M, Mohamed MY, El-mahgoup SS. Comparative study between prophylactic single dose of fentanyl and dexmedetomidine in the management of agitation after sevoflurane anesthesia in children. Egypt J Anaesth 2011; 27:31-37. |
|26.||Meng QT, Xia ZY, Luo T, Wu Y, Tang LH, Zhao B, et al. Dexmedetomidine reduces emergence agitation after tonsillectomy in children by sevoflurane anesthesia: a case-control study. Int J Pediatr Otorhinolaryngol 2012; 76:1036-1041. |
|27.||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. |
|28.||Gupta N, Rath GP, Prabhakar H, Dash HH. Effect of intraoperative dexmedetomidine on postoperative recovery profile of children undergoing surgery for spinal dysraphism. J Neurosurg Anesthesiol 2013; 25:271-278. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]