Effect of Dexmedetomidine in Sub-Tenon's Block on Emergence Agitation in Pediatric Strabismus Surgery under Sevoflurane Anesthesia.

Background: Numerous unfavorable complications may occur with strabismus surgery as emergency agitation (EA), oculocardiac reflex (OCR), postoperative pain, and postoperative nausea and vomiting (PONV). Aims: This study was designed to evaluate the dexmedetomidine effect in sub-Tenon's block on EA in strabismus surgery in the pediatric population under sevoflurane anesthesia. Design: This was a prospective randomized double-blind clinical trial. Patients and
Methods: Eighty American Society of Anesthesiologists (ASA) Physical Status Class I and II pediatric patients, in an age group ranging from 2 to 8 years of either sex, had strabismus surgery under sevoflurane anesthesia using laryngeal mask airway. Patients were divided randomly into two groups (each = 40). Sub-Tenon's block is performed in the operated eye with 0.5% bupivacaine (0.08 mL.kg-1) alone in Group B (bupivacaine group), and with 0.5% bupivacaine (0.08 mL.kg-1) and dexmedetomidine (0.5 μg.kg-1) in Group D (dexmedetomidine group). Hemodynamics were monitored, and OCR was recorded. Furthermore, postoperative EA (Pediatric Anesthesia Emergence Delirium and Cravero Scales), pain (Face, Legs, Activity, Cry, and Consolability), and incidence of PONV were recorded as well. Statistical Analysis: A prospective analysis of the collected data was performed using the SPSS program for Windows (version 26).
Results: The dexmedetomidine group exhibited a lower EA incidence, pain, and PONV as compared to the bupivacaine group. No statistically significant differences regarding hemodynamics, OCR, or emergence time were found between both the groups.
Conclusion: The addition of dexmedetomidine to bupivacaine in sub-Tenon's block can alleviate postoperative EA and nausea and vomiting with better pain management and hemodynamic stability in pediatric strabismus surgery under sevoflurane anesthesia. Copyright:

INTRODUCTION

Emergency agitation (EA) is a clinical condition where excitement occurs after awakening postoperatively. Mental disturbances in the form of delusions, confusion, and hallucinations were expressed as restless physical actions occurring involuntarily. This may cause adverse effects including bleeding from the site of surgery, inadvertent removal of intravenous (i.v.) catheters, self-harm, psychological trauma, and delayed discharge from the postanesthesia care unit (PACU).[1]

EA has reportedly a higher incidence of 10%–80% in children between 2 and 6 years of age than in adults. Such incidence has been particularly recorded in pediatric ophthalmology units. Several factors contributed to this as pain, mental status, age, duration of surgery, type of anesthesia, and the inability to see.[2]

Strabismus surgery is a common pediatric surgery. However, it can be associated with undesirable effects in the perioperative period, including oculocardiac reflex (OCR), postoperative nausea and vomiting (PONV), postoperative pain, in addition to the EA.[3]

Sevoflurane is a commonly used inhalational agent, especially in pediatric anesthesia as it has rapid induction and recovery due to its low blood–gas partition coefficient.[4] However, EA is commonly reported during the early stage of emergence from sevoflurane anesthesia, most frequently in preschool children.[5] This may be referred to intrinsic effects of sevoflurane as well as its fluoride ions and compound A degradation products.[6]

Sub-Tenon's block is a technique used safely in children for ocular conduction anesthesia for postoperative pain relief and hence reduces the need for analgesics.[7] Most importantly, it can decrease EA after surgery for strabismus eliciting satisfaction of both the patients and their families.[8]

Dexmedetomidine is a new selective α2 receptor agonist having analgesic and sedative effects without respiratory suppression. It was found that dexmedetomidine decreases EA in various procedures under sevoflurane. It can reduce the incidence of postoperative pain, PONV, and OCR during strabismus surgery.[9] It can also reduce the incidence of postoperative pain, PONV, and OCR.[9] In addition, it has been used for regional anesthesia in different clinical backgrounds as a local anesthetic adjuvant, sub-Tenon's block included.[10]

This study aimed to assess the effectiveness of the addition of dexmedetomidine to bupivacaine in sub-Tenon's block to minimize postsevoflurane EA in children having strabismus surgery, regarding the incidence of EA, pain scores, PONV, OCR, and hemodynamic stability.

PATIENTS AND METHODS

This study is a prospective randomized double-blind clinical trial that included 80 patients of pediatric age group (2–8 years) with the American Society of Anesthesiologists Physical Status Classes I and II of either sex. They were planned for strabismus surgery electively using sevoflurane anesthesia in Mansoura Ophthalmology Center between 2019 and 2021. After approval by the Institutional Board Review (R/19.03.460) and clinical trial registry (NCT04485273), all parents of participating children signed written informed consent after ensuring confidentiality in compliance with the ethical guidelines of the Declaration of Helsinki (2013). The excluded patients were as follows: developmentally delayed children, mental or neurological disorders, hyperactive airway diseases, contraindication to use of laryngeal mask airway (LMA), bleeding or coagulation diathesis, drug hypersensitivity, other eye disorders, and if parents refused to consent.

Preoperative evaluation was performed (history taking, clinical assessment, and laboratory investigations). One day before the operation, the procedure and study design were explained to the included children's parents, with fasting instructions (8 h for solid food and 2 h for clear fluids). No premedication drug was given.

The eligible 80 were assigned randomly into two groups (each n = 40): bupivacaine group (Group B) and dexmedetomidine group (Group D) using a computer-generated randomization schedule to be kept in opaque-sealed envelopes opened only after the consent.

Upon patient arrival to the operating theater, pulse oximetry was applied, face mask was used to induce anesthesia by inhalation of 8% sevoflurane in 100% O2, in presence of parents. Then, peripheral i.v. cannula was established and electrocardiogram and noninvasive blood pressure (Datex-Ohmeda Cardiocap, Finland) were attached as well. Appropriate size of LMA (Ambu, Glen Burnie, USA) connected to a capnography was selected to keep the airway after adequate jaw relaxation. Afterward, sevoflurane concentration was lowered to 2%–3% in 40% O2 to maintain anesthesia throughout the procedure, while spontaneous ventilation was made to achieve end-tidal CO2 levels of 35–40 mmHg. All children received intraoperative analgesia in the form of i.v. acetaminophen (15 mg.kg−1). Maintenance fluid therapy of Ringer's solution was introduced.

Thereafter, sub-Tenon's block was performed in the operated eye with bupivacaine 0.5% (0.08 mL.kg−1) alone in Group B (bupivacaine group) but with bupivacaine 0.5% (0.08 mL.kg−1) and dexmedetomidine (0.5 μg.kg−1) in Group D (dexmedetomidine group).

Sub-Tenon's injection was made under vision using the microscope. Both anesthesiologist and surgeon were blinded to the content of the solution injected. A Lieberman lid speculum was applied after conjunctival sterilization with povidone-iodine 4%. An inferonasal conjunctival and Tenon incision was made with Westcott scissors, bare sclera was exposed, and then a posterior pocket was fashioned with curved Stevens scissors. After reaching the posterior sub-Tenon space, a 19G curved blunted tip sub-Tenon's cannula (25 mm) was used to deliver the solution into the sub-Tenon's space, the local anesthetic solution was injected slowly into the space, and the surgery was performed 10 min later.

By the end of the operation, the sevoflurane was turned off, LMA was removed in a deep plane of anesthesia, and 100% O2 was administered via a face mask, while airway is closely observed for any obstruction, laryngospasm, or breath holding. Later, as the patients could spontaneously breathe without assistance, they were transferred to PACU.

Collected data

Heart rate (HR) and mean arterial blood pressure (MAP) were recorded at 10-min intervals throughout the procedure and then every 30 min for 2 h in the PACU. During surgery, OCR (rapid decrease in HR by ≥25% from the baseline) was treated by asking the surgeon to stop stimulation, or i.v. atropine (0.01 mg.kg−1) if this was insufficient or HR <60 beats.min−1. Incidence of OCR and number of patients who required atropine were recorded as well.

The Pediatric Anesthesia Emergence Delirium (PAED) scale with scores ranging from 0 to 20 [Table 1][11] and 5-step Cravero Scale [Table 2][12] were recorded at 10-min intervals after awakening for 30 min. A total PAED score ≥12 or Cravero Scale ≥4 was considered EA; parental presence was allowed, and if failed, i.v. propofol (1 mg.kg−1) was given. Emergence time (from anesthetic discontinuation to the first response on verbal command) was also recorded.

Table 1

Pediatric Anesthesia Emergence Delirium Scale[11]

Behavior

1-The child makes eye contact with the caregiver

2-The child’s actions are purposeful

3-The child is aware of surroundings

4-The child is restless

5-The child is inconsolable

Scores of 1, 2, 3 are reverse, 4=Not at all, 3=Just a little, 2=Quite a bit, 1=Very much, 0=Extremely, while scores 4 and 5: 0=Not at all, 1=Just a little, 2=Quite a bit, 3=Very much, 4=Extremely

Table 2

Cravero Scale[12]

Behavior	Score
Obtunded with no response to stimulation	1
Asleep but responsive to movement or stimulation	2
Awake and responsive	3
Crying (for 3 min)	4
Thrashing behavior requiring restraint	5

The intensity of pain based on the Face, Legs, Activity, Cry, and Consolability (FLACC) scale between 0 and 10 (0 representing no pain and 10 representing the worst imaginable pain) was assessed at 0, 1, 2, 4, 6, 12, and 24 h after surgery [Table 3].[13] Acetaminophen i.v. in a dose (10 mg.kg−1) was administered if the score is >4 or upon request of the patient. The time to first analgesic request and total paracetamol requirements of the first 24 postoperative hours were recorded as well.

Table 3

Face, Legs, Activity, Cry, and Consolability Scale[13]

FLACC score
Category	0 points	1 point	2 points
Face	Disinterested	Occasional grimace, withdrawn	Frequent frown, or clenched jaw
Legs	No position or relaxed	Uneasy, restless, tense	Kicking or legs drawn up
Activity	Normal position	Squirming tense	Arched, rigid, or jerking
Cry	No crying	Moans or whimpers	Constant crying, screams, or sobs
Consolability	Content, relaxed	Distractible	Inconsolable

Scores add up in range from 0 to 10. FLACC=Face, Legs, Activity, Cry, and Consolability

Incidence of PONV was reported throughout the first 24 postoperative hours. It was managed by i.v. ondansetron (0.1 mg.kg−1); total antiemetic requirements were also recorded.

Statistical methods

For calculation of the study sample size, we used a priori G*power analysis (Faul, Erdfelder, Lang, Buchner, 2007, version 3, University of Dusseldorf, Germany) based on α (type I error) = 0.05 and β (type II error) = 0.2 (power = 80%). Thirty-eight patients per group were sufficient to find a difference of 25% in the incidence of EA between them. There was a predicted 5% dropout of cases, so 40 subjects were required in each group to detect such difference.

Analysis of the collected data was performed using the SPSS program for Windows (version 26, IBM Corp, Armonk, New York, USA). At first, data normality was checked using the Kolmogorov–Smirnov test. Qualitative or categorical variables were presented as numbers and percentages to be compared using the Chi-square test or Fisher's exact test. Continuous variables were expressed as mean ± standard deviation if normally distributed, and median (range) for nonnormal data. Both the groups were compared parametrically using Student's t-test, and nonparametrically with MannWhitney U-test. All data were considered statistically significant if P ≤ 0.05, where more significant results were obtained with smaller P values.

RESULTS

In the present study, 89 patients were recruited and assessed for eligibility, while only 80 patients were enrolled and analyzed, as seen in the CONSORT flowchart [Figure 1]. There was an insignificant difference between patients of both the groups regarding age, gender, weight, duration of surgery, and anesthesia (P > 0.05) [Table 4].

Figure 1

CONSORT flowchart

Table 4

Patient demographic data

Demographic data	Group B (n=40)	Group D (n=40)	P
Age (years)	4.56±2.46	5.04±2.31	0.47
Gender, n (%)
Male	18 (45.0)	15 (37.5)	0.49
Female	22 (55.0)	25 (62.5)
Weight (kg)	15.78±4.85	15.86±5.95	0.96
Duration of surgery (min)	69.90±16.25	68.11±17.63	0.38
Duration of anesthesia (min)	76.23±15.47	74.27±14.59	0.29

Data are expressed as mean±SD, or n (%). SD=Standard deviation

According to hemodynamics, both the groups were comparable in HR and MAP throughout the surgery and during their stay in PACU (P > 0.05) [Figures 2 and 3]. Furthermore, no statistically significant differences were detected between both the groups in relation to incidence of OCR and number of patients who required atropine (P > 0.05) [Table 5].

Figure 2

Intraoperative HR mean values (beat/min). HR = Heart rate, PACU = Postanesthesia care unit

Figure 3

Intraoperative MAP mean values (mmHg). MAP = Mean arterial blood pressure, PACU = Postanesthesia care unit

Table 5

Incidence of oculocardiac reflex, number of patients who required atropine, incidence of postoperative nausea and vomiting, and total antiemetic requirements (mg)

	Group B (n=40), n (%)	Group D (n=40), n (%)	P
Incidence of OCR	11 (27.5)	14 (35.0)	0.47
Number of patients who required atropine	5 (12.5)	7 (17.5)	0.53
Incidence of PONV	20 (50.0)	10 (25.0)	0.02*
Total antiemetic requirements (mg)	1.38±0.27	1.12±0.14	0.03*

*P≤0.05 was considered statistically significant. Data are expressed as mean±SD, or n (%). OCR=Oculocardiac reflex, PONV=Postoperative nausea and vomiting, SD=Standard deviation

In the PACU, PAED scores were significantly lower in Group D as compared to Group B at all measurements (P ≤ 0.001). In addition, Group D showed a statistically significant decrease in the number of patients with high Cravero scores (4 and 5) relative to Group B (P < 0.05). However, difference in emergence times was statistically nonsignificant between the two groups (P > 0.05) [Table 6].

Table 6

Pediatric Anesthesia Emergence Delirium, Cravero scores, and emergence time (min)

	Group B (n=40)	Group D (n=40)	P
PAED awakening	13.92±1.73	11.81±1.75	≤0.001*
PAED 10	13.87±1.19	11.59±1.98	≤0.001*
PAED 20	13.80±1.74	11.07±1.36	≤0.001*
PAED 30	12.10±2.21	10.55±0.98	≤0.001*
Incidence of Cravero score, n (%)	15 (37.5)	7 (17.5)	0.04*
Incidence of Cravero score, n (%)	10 (25.0)	3 (7.5)	0.03*
Emergence time (min)	12.8±1.65	12.04±0.88	0.12

*P≤0.05 was considered statistically significant. Data are expressed as mean±SD, or n (%). PAED=Pediatric Anesthesia Emergence Delirium, SD=Standard deviation

Considering FLACC pain scores, statistically significant low values were detected in Group D relative to Group B in the first 6 postoperative hours (P ≤ 0.01). In comparison to Group B, Group D was associated with significantly longer time to the first analgesic request and less total paracetamol requirements (P ≤ 0.01) [Table 7]. As regards PONV, patients in Group D had a statistically significant less incidence of PONV and total antiemetic requirements as compared to Group B (P < 0.05) [Table 5].

Table 7

Face, Legs, Activity, Cry, and Consolability, time to first analgesic request (min), and total paracetamol requirements (mg)

	Group B (n=40)	Group D (n=40)	P
FLACC after surgery	1 (0-2)	1 (0-1)	≤0.01*
FLACC 1 h	2 (1-3)	1–(0-2)	≤0.01*
FLACC 2 h	5 (4-5)	4 (3-5)	≤0.01*
FLACC 4 h	4 (3-5)	3 (1-5)	≤0.01*
FLACC 6 h	3 (2-4)	2 (0-3)	≤0.01*
FLACC 12 h	2 (1-3)	1 (1-3)	0.12
FLACC 24 h	1 (0-1)	1 (0-1)	0.19
Time to first analgesic request (min)	72.26±21.63	89.71±27.46	≤0.01*
Total paracetamol requirements (mg)	246.2±49.8	221.2±33.7	≤0.01*

*P≤0.05 was considered statistically significant. Data are expressed as mean±SD, or median (range). FLACC=Face, Legs, Activity, Cry, and Consolability, SD=Standard deviation

DISCUSSION

Emergence agitation as a definition is not clearly characterized and has been confused with emergence delirium. It can be defined as a disorder in child's attention and awareness to surroundings along with disorientation and perceptual alterations that involves hypersensitivity and motor behavioral hyperactivity in the postoperative period. Such cognitive disturbance coincides with various factors as preoperative anxiety, pain, PONV and any restlessness of child in the recovery period.[14] Incidence of EA after ocular surgery is specifically high due to visual consequences.[2]

In the current study, we attempted avoiding these contributing factors. To reduce agitation and separation anxiety, parental attendance was allowed during mask induction. The results of our study suggest that the addition of dexmedetomidine to bupivacaine in preemptive sub-Tenon's block can effectively reduce postsevoflurane EA, pain, and PONV while maintaining hemodynamic stability in pediatric patients undergoing strabismus surgery.

This reduction was reflected as significantly lower PAED, Cravero, and FLACC scores in Group D as compared to Group B, a finding that can be attributed to the ability of dexmedetomidine to extend the duration of bupivacaine analgesia through its α2 adrenergic receptor agonism via vasoconstriction of nearby blood vessels, cholinergic stimulation, Aδ and C fiber blockade, in addition to its central sedative and analgesic effects by systemic absorption or diffusion into the cerebrospinal fluid through optic nerve sheath.[15] This analgesic promoting effect together with its systemic absorption makes the adjunct use of dexmedetomidine in the sub-Tenon's block capable of decreasing EA after sevoflurane-based anesthesia through facilitation of a smoother emergence.

Indeed, there was a significant positive correlation between the PAED and FLACC Scales in our data. This is consistent with previous studies which demonstrated that PAED and FLACC Scales have overlapping behavioral elements making it difficult to precisely distinguish real pain from EA in young children.[16]

To the best of our knowledge, there are limited data about dexmedetomidine use in sub-Tenon's block for children undergoing strabismus surgery, so it can be valuable to assess its effects in minimizing EA. Apart from i.v. administration, reports about its use for regional anesthesia in the pediatric literature are scanty and even more rare for pediatric ocular blocks. For these reasons, we relied in our discussion on the few available trials in the pediatric population and tried to explore its use in adults, with some extrapolation and comparison to published pediatric literature.

Dexmedetomidine has been used widely in pediatric population via i.v. route to decrease EA after sevoflurane/desflurane anesthesia in various ophthalmological and nonophthalmological surgeries. Zhu et al. conducted a meta-analysis to compare the impact of dexmedetomidine relative to fentanyl, midazolam, and placebo. They found that dexmedetomidine decreased the incidence of EA, PONV, and number of patients requiring rescue analgesics, without clinically significant hemodynamic effects.[17] Likewise, Rao et al. in 2020 including >50 trials showed similar results; dexmedetomidine had reduced the incidence of EA in pediatric patients significantly.[18]

Regarding pediatric strabismus surgery, perioperative dexmedetomidine can alleviate EA, postoperative pain, and PONV and may reduce the incidence of OCR, but not influence PACU stay duration.[9] The current results are compatible with several studies which showed that low dose of i.v. dexmedetomidine use helped to reduce the EA severity, postoperative pain, and rescue analgesia in pediatric cataract and strabismus surgeries under sevoflurane or desflurane anesthesia.[1920]

Besides the i.v. route, a recent meta-analysis comparing intranasal dexmedetomidine with other premedications has revealed that its administration provided satisfactory child sedation with parent separation. It reduced EA, use of rescue analgesics, and PONV as well.[21] Similarly, it seems to decrease postoperative pain and EA in strabismus surgery under sevoflurane-based anesthesia.[22]

In terms of pediatric regional anesthesia in nonophthalmological cases, several studies evaluating dexmedetomidine as an adjunct to caudal, epidural, or nerve blocks exhibited a lower incidence of EA and reported longer postoperative requirements.[2324]

In the adult population, multiple studies stated that dexmedetomidine use in ocular blocks has shortened onset, prolonged sensory and motor blockade, reduced intraocular pressure, and improved postoperative pain and patient and surgeon satisfaction.[252627]

In agreement with the present study, Ye et al. in 2015 found that 0.5–1 μg.kg−1 dexmedetomidine addition to ropivacaine in the retrobulbar block had increased its potency and prolonged its duration, with lower VAS scores and analgesic requirements for vitreoretinal surgery in children. However, they also documented a significant prolongation in median wake-up time in the dexmedetomidine group, a finding that does not cope with our current study in which emergence times were comparable between both the groups.[28] This discrepancy can be attributed to the fact that we defined emergence time from anesthetic discontinuation to the first response on verbal command, meanwhile, they used achievement of Aldrete score of 8 as an endpoint.

Consistently with our study results, in another trial, Ye et al. in 2019 assessed the adjunctive use of 1 μg.kg−1 dexmedetomidine with retrobulbar ropivacaine in children undergoing vitreoretinal surgery. This regimen had provided hemodynamic stability, stress response suppression, in addition to the significant fewer number of children who experienced pain and EA. Contrary to our results, they also recorded no episodes of PONV in any group even in the GA group without block.[29] This conflict may be related to the higher incidence of PONV in our strabismus surgery rather than in vitreoretinal surgeries.

Parallel to this study, Jin et al. reported in their meta-analysis that dexmedetomidine had a significant prophylactic antiemetic effect in both pediatric and adult populations under general anesthesia; however, only one of these included trials investigated children scheduled for strabismus surgery.[30]

In accordance with the current results, Moolagani et al. compared the effect of the addition of 10-, 15-, 20-μg dexmedetomidine to ropivacaine peribulbar block in cataract surgery. Stable hemodynamic parameters such as HR and MAP in the perioperative periods were comparable in all the groups.[31] On the other hand, adding dexmedetomidine to ropivacaine, bupivacaine, or lidocaine mixtures in peri- or retrobulbar blocks for cataract surgery has been reported to have statistically significant lower HR and MAP at some time points. However, these effects are far from being clinically considerable and no intervention is required.[3233]

In our series, dexmedetomidine did not increase the incidence of OCR, a finding described by Song et al. as well.[34] Although dexmedetomidine decreases HR by its sympatholytic effect coinciding with reductions in the plasma catecholamines, surprisingly some previous reports found a decreased incidence of OCR with its administration.[3536]

Our study has some limitations. First, bispectral index monitoring was not used to measure the depth of anesthesia which probably would have interfered with emergence time and EA scores. Second, we relied on analgesia from sub-Tenon's block and i.v. paracetamol, and did not administer narcotics which would have affected the PAED score with their sedative effect. Future studies may be conducted on a larger number of pediatric patients for optimization of dexmedetomidine dose in the sub-Tenon block in such population.

CONCLUSION

The use of dexmedetomidine as an adjuvant to bupivacaine in the sub-Tenon's block is safe and effective in decreasing incidence of postoperative EA and nausea and vomiting, in addition to providing better pain management and hemodynamic stability in pediatric strabismus surgery under sevoflurane anesthesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.