|Year : 2015 | Volume
| Issue : 4 | Page : 529-534
Comparative study between the effect of propofol and fentanyl on the incidence and severity of emergence agitation after sevoflurane anesthesia in pediatrics
Hany M Yassin, Maged L Boules MD
Department of Anaesthesiology, Faculty of Medicine, Al Fayoum University, Egypt
|Date of Submission||17-Jan-2014|
|Date of Acceptance||19-Feb-2014|
|Date of Web Publication||29-Dec-2015|
Maged L Boules
35 Ibrahim El Baessy Street, Ahmed Oraby St Agouza, Giza 12411, Fayoum
Source of Support: None, Conflict of Interest: None
The occurrence of emergence agitation (EA) in pediatric patients who received sevoflurane anesthesia is a common postoperative problem.
This study aimed to compare the efficacy of propofol versus fentanyl to decrease the incidence of EA using an emergence behavior scale - pediatric agitation emergence delirium (PAED).
Patients and methods
This study was performed on three patient groups undergoing the same surgical procedure, under sevoflurane anesthesia: the first received saline as a control, the second received propofol, and the third received fentanyl. Thereafter, we compared the efficacy on incidence and severity of EA using an emergence behavior scale - PAED.
Regarding the frequency of agitation, the highest frequency was observed in the control group followed by the propofol group and then the fentanyl group (46.9, 18.8, and 12.5%, respectively). The onset of agitation was delayed in the propofol and fentanyl groups when compared with the control group (P < 0.01 and 0.02, respectively). There was no statistically significant difference between the three groups regarding the duration of agitation. The PAED scoring revealed no significant difference between the propofol and fentanyl groups (P = 0.239), but a highly significant difference between both of them and the control group was found (P < 0.001).
Both propofol and fentanyl decrease the incidence and the severity of EA, but there is no reliable significance when comparing both drugs. We recommend further studies to declare other drugs that have potency to decrease the incidence and to treat the EA.
Keywords: emergence agitation, fentanyl, pediatric anesthesia, propofol, sevoflurane anesthesia
|How to cite this article:|
Yassin HM, Boules ML. Comparative study between the effect of propofol and fentanyl on the incidence and severity of emergence agitation after sevoflurane anesthesia in pediatrics. Ain-Shams J Anaesthesiol 2015;8:529-34
|How to cite this URL:|
Yassin HM, Boules ML. Comparative study between the effect of propofol and fentanyl on the incidence and severity of emergence agitation after sevoflurane anesthesia in pediatrics. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2019 Jun 25];8:529-34. Available from: http://www.asja.eg.net/text.asp?2015/8/4/529/172728
| Introduction|| |
Emergence agitation (EA) was first described in the literature in the early 1960s, where children anesthetized with ether, cyclopropane, or ketamine undergoing tonsillectomy, thyroidectomy, and circumcision experienced crying, thrashing, and disorientation during emergence from anesthesia  .
EA in children, associated with general anesthesia with the new highly insoluble volatile agents, sevoflurane and desflurane, has been well described  . The use of sevoflurane even for anesthesia of short duration continues to be complicated by this phenomenon  . This has been attributed, in part, to rapid emergence not allowing for acclimation to a strange environment  . General anesthesia with propofol, which also allows a fast recovery, is usually associated with a calm, sometimes euphoric recuperative state  .
Today, approximately four million children undergo anesthesia each year, and EA has been identified as a significant problem in children recovering from anesthesia with a reported incidence ranging between 10 and 80%  . EA is characterized by a variety of presentations including crying, excitation, agitation, and delirium occurring during the early stage of emergence from anesthesia in children  . It can also lead to loss of intravenous catheters and disconnected cables and monitoring instruments  . Since 1960s, this topic has been studied and investigated with multiple comparative studies on inhalational and intravenous anesthesia and effects of adjuvant drugs to general anesthesia, and different assessment tools have been described.
This study aimed to investigate the incidence of EA in three patient groups undergoing the same surgical procedure, under sevoflurane anesthesia: the first received saline as a control, the second received propofol, and the third received fentanyl. Thereafter, we compared the efficacy of propofol versus fentanyl to decrease the incidence of EA using an emergence behavior scale - pediatric agitation emergence delirium (PAED), a four-point scale.
| Patients and methods|| |
After the approval of the institutional review board and written informed consent was obtained from parents, 96 children aged 2-8 years, with American Society of Anesthesiologists' physical status I or II, scheduled to undergo inguinal hernia repair were prospectively enrolled in the study and randomly assigned, by means of random numbers generated by a computer, to either the propofol group, the fentanyl group, or the control group.
Exclusion criteria included mental, neurologic, and psychological diseases, developmental disorder, sleep apnea, treatment with sedatives, full stomach, or indication for rapid sequence induction. Children were fasting for 6 h. An ECG, pulse oximeter, and noninvasive arterial blood pressure monitor were attached.
Induction and maintenance
Inhalational induction was performed with sevoflurane (5-8%); after loss of consciousness (absence of lash reflex), sevoflurane concentration was reduced to 3% and assisted ventilation was initiated with a face mask. Thereafter, assisted ventilation was switched gradually to controlled ventilation with sevoflurane 2% after intravenous atracurium (0.5 mg/kg) administration, and tracheal intubation was performed with the guidance of the peripheral nerve stimulator.
Anesthesia was maintained with 2% sevoflurane and increments of atracurium when necessary. In all groups, general anesthesia was conducted with intermittent positive pressure ventilation delivering a minute volume of 70-80 ml/kg to maintain normocapnea.
A total flow rate of 3-4 l/min was administered to the patients. After tracheal intubation, the lungs were ventilated mechanically with 100% oxygen.
After induction of anesthesia, all patients received 0.5 mg/kg intravenous ketorolac tromethamine (Ketolac) for the control of postoperative pain and 1 mg/kg intravenous dexamethasone (maximum 16 mg) for the control of postoperative pain  , nausea, and vomiting.
Emergence and extubation
Sevoflurane was discontinued. Patients in the propofol group (n = 32) received 1 mg/kg propofol at the end of surgery and patients in the fentanyl group (n = 32) received 1 mg/kg fentanyl diluted in 10 ml NaCl 0.9%, whereas patients in the control group (n = 32) received 10 ml NaCl 0.9%.
With the guidance of the peripheral nerve stimulator, residual curarization was reversed with prostigmine (0.05 mg/kg)/atropine (0.02 mg/kg) followed by suction and extubation. Children were transferred to the postanesthesia care unit (PACU). On arrival to the PACU, patients were received by one of their parents, who stayed with them until discharge.
The anesthesiologist collecting the data was blinded to the group to which the patient was assigned. The PAED scale devised by Sikich et al.  was used to assess EA [Table 1].
Values of the PAED scale were obtained by a different investigator in all children; agitation was assessed immediately after removal of the endotracheal tube, and continuously thereafter until all children are calm. The highest scores were recorded. In the PACU, the nurse and the anesthesiologist who recorded measurements and observations were unaware of the group to which the child was assigned. In addition, parents and patients were blinded to the treatment allocation.
The following time intervals were recorded: duration of surgery (from skin opening until skin closure), duration of sevoflurane administration (from the initiation of induction until discontinuation of sevoflurane), and duration of anesthesia (from the initiation of induction until removal of endotracheal tube). In addition, the following time intervals were recorded from the time of discontinuation of sevoflurane: the time to removal of the endotracheal tube; the time to the first response to a simple verbal command, which is defined as time of emergence; and the onset and duration of agitation whenever it occurred.
Children were discharged from the PACU when hemodynamically stable, fully awake, and free of pain, vomiting, or agitation. Immediately before discharge, parents were asked to assess the quality of the PACU stay of their children based on the following satisfaction scale: 1 = excellent, 2 = good, 3 = poor, and 4 = bad.
Incidence of EA in the control groups in previous studies was around 50%  . Aiming to decrease the incidence of EA down to 15% and a and b error of 0.05 and 0.2, respectively, a sample size of 32 in each group was calculated. Continuous data were reported as mean (SD) and were analyzed using analysis of variance test for multiple comparisons with least significant difference test for post-hoc analysis. Categorical data were reported as percentages and were analyzed using one-way multivariate analysis of variance test. Ordinal data such as pain score and PAED score were reported as median and interquartile range (IQR) and were analyzed using the Kruskal-Wallis one-way analysis of variance test. A P value less than 0.05 was considered statistically significant.
All statistical calculations were performed using Microsoft Excel version 7 (Microsoft Corporation, Redmond, Washington, USA) and SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, Illinois, USA) programs.
| Results|| |
The demographic data such as age, weight, and sex showed no significant difference between different groups as shown in [Table 2] and [Table 3].
The emergence time showed significant difference between the three groups (P < 0.001) [Table 4] and [Figure 1].
Regarding the frequency of agitation, the highest frequency was observed in the control group followed by the propofol group and then the fentanyl group (46.9, 18.8, and 12.5%, respectively).
The onset of agitation was delayed in the propofol and fentanyl groups when compared with the control group as shown in [Figure 2] (P < 0.01 and 0.02, respectively).
There was no statistically significant difference between the three groups regarding the duration of agitation as shown in [Table 5].
The PAED score is the gold standard for assessment of the degree of EA; [Table 6] shows no significant difference between the propofol versus fentanyl groups, but a highly significant difference between both of them and the control group was found (P < 0.001).
[Figure 3] illustrates the parents satisfaction as excellent in each group; the highest percentage was reported in the fentanyl group, followed by the propofol group and then the control group.
| Discussion|| |
The etiology of EA in children is not yet fully understood; however, possible risk factors are anesthetic properties, rapid emergence from anesthesia, postoperative pain, preschool age, preoperative anxiety, and child temperament. Many clinical studies have shown that EA in children is a common phenomenon after sevoflurane-based or desflurane-based anesthetics, with an incidence that is significantly higher compared with halothane-based or propofol-based anesthetics  .
In our study, we investigated the incidence of EA in three groups (control, propofol, and fentanyl) that underwent sevoflurane anesthesia. We compared the efficacy of propofol versus fentanyl to decrease the incidence of EA in the same age group and surgical procedure. The PAED emergence behavior scale was used to evaluate the degree of EA.
After discontinuation of sevoflurane, the emergence time (time to the first response) was 14.19 ± 2.375 min for control, 18.78 ± 1.755 min for propofol, and 16.78 ± 1.913 min for fentanyl (P < 0.001). It is noted that propofol delays the emergence time more than fentanyl (P < 0.001) and both delays are more than the control group (P < 0.001); this is comparable with the study by Aouad et al.  who found a significant delay in the emergence time in the propofol group compared with the control group (23.4 ± 5.7 min propofol vs. 19.7 ± 5 min control; P = 0.004).
Regarding the incidence of EA, we found that the incidence in the control group was 46.9%, in the propofol group was 18.8%, and in the fentanyl group was 12.5%. In addition, Welborn et al.  and Kulka et al.  described EA as a common phenomenon with an incidence ranging between 10 and 80%.
Propofol has been used by many authors to decrease EA occurring after sevoflurane. In an attempt to minimize EA after desflurane, Cohen et al.  supplemented the inhalational anesthetic with 2 mg/kg propofol at the beginning of surgery. However, the authors did not demonstrate any reduction in the incidence of EA. This result is expected because propofol has a short duration of action that may not outlast the duration of the surgery.
Aouad et al.  described a decrease in EA following propofol administration (1 mg/kg) at the end of surgery, as plasma concentration of propofol can be effective.
Fentanyl is a potent opioid, which can decrease EA following sevoflurane anesthesia by its high efficacy on perioperative analgesia as well as its sedative effect  . Cravero et al.  have shown that fentanyl 1 mg/kg intravenously given 10 min before the discontinuation of the anesthetic in patients undergoing nonpainful procedures decreased the incidence of EA from 56 to 12%.
In the present study, the onset of agitation was recorded after discontinuation of sevoflurane, and there was a statistically significant difference between the three groups (P = 0.002), with more delay in the onset of agitation in the propofol group.
No statistically significant difference between the propofol group and the fentanyl group was found, but both of them delayed the onset of agitation compared with the control group. In contrast, Aouad et al.  did not find a significant difference between the propofol and control groups regarding the onset of agitation.
The duration of EA in this study showed no statistically significant difference between the three groups (P = 0.6); this is in agreement with the studies by Aouad et al.  and Cravero et al.  who recorded no difference in duration of EA.
To assess the severity of EA, we used the PAED score introduced by Sikich and Lerman  , which is a reliable and valid tool that may minimize measurement error in the clinical evaluation of EA, with a threshold value of 10, above which treatment of EA is required.
The average PAED scale score was as follows: control had median of 8.5 and IQR of 7-13; propofol had median of 6.5 and IQR of 5-8; and fentanyl had median of 5 and IQR of 5-7 (P < 0.001). There was a significant difference between control versus propofol (P < 0.001) and between control versus fentanyl (P < 0.001). These results showed that the EA was more severe in the control group when compared with the propofol and fentanyl groups. However, there was no significant difference between the propofol versus fentanyl groups (P = 0.239). In agreement with our results, Kim et al.  described the mean PAED score as 4.3 in the propofol group, 4.9 in the fentanyl group (P = 0.682), and lower than 9.0 in the control group (P<0.001). In a previous study performed on children undergoing strabismus surgery, it was found that the PAED score was 8.6 ± 3.9 in the propofol group versus 11.5 ± 4.5 in the control group (P = 0.004).
A limitation to the use of the PAED score in the assessment of EA after strabismus surgery is the presence of the item regarding eye contact (the child makes eye contact with the caregiver). In addition, Przybylo et al.  found that 44% of children have altered behavior on emergence from anesthesia after strabismus surgery. Hence, in this study we chose the inguinal hernia repair as the type of surgery to avoid such a weak point.
The parent satisfaction was statistically comparable; it was the best with the fentanyl group, less with the propofol group, and the worst with the control group, with a percentage of 43.8% excellent for the control group, 75% excellent for the propofol group, and 81.2% excellent for the fentanyl group. This is comparable with the study by Aouad et al.  who found that parent satisfaction was 41.7% excellent for control and 75.9% excellent for the propofol group (P = 0.002), but the parent satisfaction is subjective data and cannot be so reliable.
Our study involved a relatively small number of patients. This is attributed to the strict inclusion criteria.
Similar to all investigations of EA, our study is limited by the lack of a widely used and validated tool for measuring agitation.
All scores were recorded by one blinded observer to eliminate issues of inter-rater variability. Other limitations to this study include short time of study and subjective indicators.
| Conclusion|| |
There was a significant difference when using propofol or fentanyl, as both decrease the incidence and the severity of EA, but there is no reliable significance when comparing both drugs.
We recommend further studies to declare other drugs that have potency to decrease the incidence and to treat the EA.
| Acknowledgements|| |
Conflicts of interest
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]