Dexmedetomidine versus Ketamine for the Prevention of Emergence Agitation in Pediatric: A Prospective, Randomized, and Controlled Clinical Trial

Background: This study compares the effect of dexmedetomidine versus Ketamine for the prevention of emergence agitation in children undergoing general anaesthesia. Method: 75 Children are randomly allocated into three groups. Group C: Were assigned to receive normal saline. Group K: Were assigned to receive Ketamine 0.25 mg/kg. Group D: assigned to receive 0.25 ug /kg of dexmedetomidine, before the end of surgery. Results: There was no statistically significant difference in demographic data and intraoperative parameters between the three groups. But as regards to time to discharge, there was a significant difference between group C, group K and group D (group C = 39.96 ± 2.84, group K = 37.28 ± 3.80, group D = 35.08 ± 3.36 and P value = 0.0002). FLACC scale was low after extubation, before leaving the operating room and on arrival to PACU (small FLACC scale in group K, D than group C). PAED scoreless in Group K and Group D than Group C (postoperative, at 10 minutes, 20 min, 30 min). Conclusion: Ketamine and dexmedetomidine reduced the incidence and severity of emergence delirium effectively when compared to normal saline, and the effects of dexmedetomidine being much superior to Ketamine.

behavioural disturbances during early emergence from general anaesthesia and continues through the initial recovery period [1].
The true incidence of emergence agitation is unclear. Still, it can occur in as many as 30 to 50 percents of children who have general anaesthesia, and it is essential to diagnose emergence agitation, pain must control entirely [2].
Sevoflurane commonly used as an inhalational anaesthetic for pediatric patients. Sevoflurane induction can be achieved quickly and safely by inhalation using a mask, sevoflurane does not cause substantial hemodynamic changes, and return to the preoperative level of consciousness following anesthesia is rapid.
However, sevoflurane can result in emergence agitation. The incidence of emergence agitation after sevoflurane anaesthesia estimated at 80%. Emergence agitation occurs most frequently in preschool children during the early stage of emergence from anaesthesia [3] [4].
This emergence of agitation must manage by providing smooth emergence to pediatric patients. Under other circumstances, uncooperative, an irritable, inconsolable, and crying child with excessive motor activity may cause many complications for the parents, nursing and maybe children also harm themselves [5].
Although EA is commonly self-limited and happens within the first 30 min of stay in a postanesthesia care unit (PACU) and also can lead to disconnection of monitoring devices or intravenous catheters, physical damage, falling, increase in the risk of bleeding, and self-extubation [6] [7].
There are many factors to decrease the incidence of emergence agitation, such as Parental presence at emergence, physical restraints, or pharmacologic interventions [8]. But pharmacologic interventions remain to be the better method.
Different studies proved that medications such as ketamine propofol, fentanyl, ketofol, dexmedetomidine, clonidine, and midazolam had used to reduce the incidence of emergence agitation [9] [10].
This study compares the effect of dexmedetomidine versus Ketamine for the prevention of emergence agitation in children undergoing general anaesthesia.

Patients and Method
After approval of the institutional ethics committee and written informed consent by the parents of children, children aged ranged between 6 and 10 years belonging to ASA grade I and II scheduled for elective tonsillectomy, adenoidectomy or both. These patients randomly allocated for this prospective, randomized, controlled, study which conducted in Benha university hospitals from August 2019 to March 2020.
Exclusion criteria included children with developmental problems, inborn errors of metabolism, cerebral palsy, down syndrome, a history of epileptic fits, body weight less than 10 kg or greater than 30 kg (children below the age of 6 years with body weight more than 30 kg are obese with a risk of airway obstruction); patients with previous history of agitation after sevoflurane anesthesia and patients with respiratory distress of any cause; also, children with known allergy to any of the • Group C: Were assigned to receive normal saline (as a placebo) in a single syringe, the total volume made up to 10 ml. was given 10 min before the end of surgery. • Group K: Were assigned to receive Ketamine 0.25 mg/kg in a single syringe, the total volume made up to 10 ml. was given 10 min before the end of surgery.
• Group D: Were assigned to receive 0.25 ug /kg of dexmedetomidine, the total volume made up to 10 ml to ensure blinding, was given 10 min before the end of surgery.  (Table 1) [11].
The severity of emergence delirium evaluated using the pediatric anaesthesia emergence delirium scale (PAED) ( Table 2) with scores ranging from 0 to 20.
PAED scale was monitored immediately after emergence and at 10 min intervals after that until discharge from PACU (Table 2) [12] [13].
Patients transferred to the ward after being fully conscious with stable vital signs, calm, PAED score < 10. FLACC score < 5 and the absence of bleeding, pain, nausea or vomiting.

Statistical Analysis
Analysis of data is done by using SPSS Version 16. Quantitative data were presented as mean ± Standard deviation and analyzed by using the one way ANOVA test. Qualitative data were presented as numbers and percentages and analyzed by using the Chi-square test and Fisher exact test. We used repeated measure ANOVA test yo analyzed the Quantitative data of repeated measures in the same group, and the significant rules detected by post-hoc analysis. P-Value < 0.05 was considered statistically significant, and P-Value < 0.01 was considered statistically highly significant.
The sample size was determined to assume that the likelihood of sevoflurane  One-calm, two-not calm but could be easily consoled, three-moderately agitated or restless and not quickly quiet, four-combative, excited and thrashing around. PAED: Pediatric emergency delirium scale [12].

Result
The total number of patients registered during the study period was 75 in three groups 25 in each group. All the patients who enrolled in the study completed the study. The three groups were comparable for demographic characters as represented in Table 3, and as regards to the duration of surgery, duration of anaesthesia, emergence of time and time of discharge in Table 4. Heart rate between the three groups is shown in Table 5 and mean arterial pressure (Table 6).
Oxygen saturation between the three groups is presented in Table 7 and FLACC scale is presented in Table 8. PAED score was showed in Table 9.
There were no significant differences between the three groups as regard age, weight, sex (male or female), ASA grade (I or II) and type of surgery (Table 3).
There were no significant differences between the three groups as regards to       the duration of surgery, duration of anaesthesia and emergence of time (Table   4). But as regards to time to discharge significant between-group C and group K and group D. Time of discharge in group K and group D were significantly less than group C, and time of discharge was lower in group D than group K (Table   4).
Also there were no significant differences between the three groups as regards to Heart rate after extubation, postoperative at 10, 20, 30 minutes but before leaving OR (OPERATING ROOM) and on arrival to PACU, there is rise of heart rate in the group K (Table 5).
There were no significant differences between the three groups as regards to mean arterial pressure between the three groups ( Table 6). Also there were no significant differences between the three groups as regard to oxygen saturation between the three groups (Table 7).
There were significant differences between the three groups as regards to FLACC scale after extubation, before leaving the operating room (OR) and on arrival to PACU (low FLACC scale in group K, D than group C). But postoperative at 10, 20, 30 minutes, there were no significant differences between the three groups (Table 8). Also there were significant differences between the three groups as regards to PAED score, on arrival to PACU but postoperative, at 10 minutes, 20 min, 30 min, there are significant differences between, Group C with Group K and GROUP D. PAED score was small in Group K and GROUP D than Group C. Also PAED score in Group D smaller than Group K (Table 9).

Discussion
Emergence agitation defined as the number of children with disturbance of postoperative behaviour during emergence from sevoflurane anesthesia that measured by agitation scores mentioned in our study. Predisposing factors for emergence agitation include rapid emergence, pre-operative pain and anxiety, an intrinsic characteristic of the anaesthetic, preschool children, baseline mood of the child, and the type of surgery. Emergence agitation is the most common irritant complication during the time of extubation and in early recovery period [14].
Our study demonstrates that Ketamine and dexmedetomidine reduced the incidence and severity of emergence delirium effectively when compared to nor- tanyl. This study concluded that infusion of dexmedetomidine leading to significantly reduced for requirements of the postoperative opioid and also decrease of incidence of emergence agitation in children undergoing tonsillectomies and adenoidectomies [15].
Also in the study of Jain et al. have shown that dexmedetomidine reduced the rate of emergence agitation ranging between 4.8% and 17% with no hemodynamic effects after IV administration in doses between 0.3 and 1 ug/kg after induction of anesthesia [16]. It proved that α2 agonists decrease emergence agitation by their analgesic effect as well as by reducing the anaesthetic requirements [17].  Group N compared to the Group S. Emergence time was significantly longer in the Group N, but there was no difference in time to discharge from the PACU [19].
Another study had reported to decrease the rate of emergence agitation and decrease the frequency of postoperative analgesic requirement which is done by Prasad; et al. also found that Dexmedetomidine (0.3 ugs/kg) and ketofol (0.25 mg/kg and 1 mg/kg) caused a significant reduction in the incidence and severity of emergence agitation when compared to control group. Ketofol was as effective as dexmedetomidine in the prevention of emergence agitation when administered before the end of the surgery. Still, children delivered dexmedetomidine was calm and satisfied discharge criteria earlier than ketofol group [20].

Conclusion
Ketamine and dexmedetomidine reduced the incidence and severity of emergence delirium effectively when compared to normal saline, and the effects of dexmedetomidine being much superior to Ketamine.

Conflicts of Interest
The authors declare no conflicts of interest regarding the publication of this paper.