Comparison of the Effect of Esketamine and Sevoflurane for Pediatric Ophthalmological Procedure

Study Overview
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Brief Summary
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Emergence agitation is the most common reason for post-anesthesia care unit delay. Sevoflurane is used frequently inhalational anaesthetic agent to provide pediatric anaesthesia because of the nonirritant nature. It has been successfully used for keeping spontaneous breathing without tracheal intubation. However, sevoflurane may cause emergence agitation as the incidence varied from 10%-80%. Although there are many sedative agents to reduce its incidence, such as propofol, midazolam, a2 adrenergic receptor agonists and ketamine, the efficacy remains limited. Ketamine, a neuroleptic anesthetic agent, contains two optical isomers, s(+)-ketamine (esketamine) and R(-)-ketamine. Esketamine is a right-handed split of ketamine, which has enhanced analgesic potency and lower incidence of psychotropic side effects compared to ketamine. It stimulate breathing due to N-Methyl-D-Aspartate receptor blockade, and could even effectively countered remifentanil-induced respiratory depression. The investigators compared the effectiveness of esketamine and sevoflurane in reducing the incidence of emergence agitation after painless ophthalmological procedure in pediatric patients.

Detailed Description
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Ophthalmological procedure such as suture remove, intraocular pressure (IOP) measurement, slit-lamp and fundoscopy are most frequently performed in operation with minor surgical stimulus, and the the duration of surgery is very short. Several anesthestic agents are available,but it is hard to balance short effect and fast rotation in post-anesthesia care unit. Emergence agitation is the most common reason for post-anesthesia care unit delay. Sevoflurane is used frequently inhalational anaesthetic agent to provide pediatric anaesthesia because of the nonirritant nature. It has been successfully used for keeping spontaneous breathing without tracheal intubation. However, sevoflurane may cause emergence agitation as the incidence varied from 10%-80%. Although there are many sedative agents to reduce its incidence, such as propofol, midazolam, a2 adrenergic receptor agonists and ketamine, the efficacy remains limited. Ketamine, a neuroleptic anesthetic agent, contains two optical isomers, s(+)-ketamine (esketamine) and R(-)-ketamine. Esketamine is a right-handed split of ketamine, which has enhanced analgesic potency and lower incidence of psychotropic side effects compared to ketamine. It stimulate breathing due to N-Methyl-D-Aspartate receptor blockade, and could even effectively countered remifentanil-induced respiratory depression. Additionally, several studies have reported ketamine could reduced agitation, but there is no study about esketamine on emergence agitation. The investigators compared the effectiveness of esketamine and sevoflurane in reducing the incidence of emergence agitation after painless ophthalmological procedure in pediatric patients.

Official Title
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Efficacy and Safety of Esketamine or Sevoflurane Add to Dexmedetomidine-based Sedation for Ophthalmology Procedure in Children

Conditions
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Adverse Event

Intervention / Treatment
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* Drug: Esketamine
* Drug: Sevoflurane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists physical status 1-2 required to remove the stitches by microscope after corneal surgeries Exclusion Criteria: psychiatric disorders cardiovascular disorders glaucoma contraindications to nasal intubation

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 72 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group E<br>1ug· kg-1 dexmedetomidine and 0.01mg·kg-1 atropine was administered intravenously. 0.5mg·kg-1 esketamine was administered by vein in one minute, and 0.25mg·kg-1 esketamine was given at the beginning of the surgery. | Drug: Esketamine<br>* 0.5 mg/kg esketamine for induction and 0.25 mg/kg esketamine at the beginning of surgery<br>* Other names: s(+)ketamine;|
| Active Comparator: Group S<br>1ug· kg-1 dexmedetomidine and 0.01mg·kg-1 atropine was administered intravenously. 5% sevoflurane(FIO2=100%, 3L·min-1) was used to induce anaesthesia by mask inhalation and 3-4 % sevoflurane (adjusted according to the depth of the anaesthesia,FIO2=100%, 2L·min-1) was maintained. | Drug: Sevoflurane<br>* 5% sevoflurane for induction and 3-4% sevoflurane for maintain<br>* Other names: Sevoflurane Inhalation Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the incidence of respiratory depression | respiratory rate <12 times per min or weak chest undulation | duration from the time patient received induction to the time of leaving to the ward, average 1 hour | 
| the incidence of desaturation | the incidence of oxygen saturation below 95% caused by anesthetic agent. | duration from the time patient received induction to the time of leaving to the ward, average 1 hour | 
| the incidence of hypotension | the incidence of systolic blood pressure< 30% of basal systolic blood pressure and lasted >5 minutes. | duration from the time patient received induction to the end of the anesthesia, average 15 minutes. | 
| the incidence of hypertension | the incidence of systolic blood pressure > 30% of basal systolic blood pressure | duration from the time patient received induction to the end of the anesthesia, average 15 minutes. | 
| the incidence of tachycardia | the incidence of heart rate increase over 30% of pre-induction and>120 beats per minute. | duration from the time patient received induction to the end of the anesthesia, average 15 minutes. | 
| the incidence of bradycardia | the incidence of heart rate less than 60 beats per minute | duration from the time patient received induction to the end of the anesthesia, average 15 minutes. | 
| the incidence of emergence agitation | the incidence of emergence agitation | duration from the time patients arrived the post-anesthesia care unit to the time of leaving to the ward, average 20 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| length of stay in the post-anesthesia care unit | the time of patients staying in post-anesthesia care unit | duration from the time patients arrived the post-anesthesia care unit to the time of leaving to the ward, average 20 minutes | 
| CPS score | The Cole 5-point scale CPS) score included five behaviors: 1=sleeping; 1=awake,calm;3=irritable, crying;4=inconsolable crying; 5=severe restlessness, disorientation. | scores at the time point of 1 minutes after extubation | 
| intraocular pressure | intraocular pressure after induction | the time after intubation and topical anesthesia within 1 minute | 
| diastolic pressure | diastolic pressure | 1minutes before induction; 1minutes before intubation; 1minutes after intubation; 3 minutes after intubation | 
| systolic pressure | systolic pressure | 1minutes before induction; 1minutes before intubation; 1minutes after intubation; 3 minutes after intubation | 
| heart rate | heart rate | 1minutes before induction; 1minutes before intubation;1minutes after intubation,3 minutes after intubation | 
| extubation time | extubation time | duration from the time that patients arrived in post-anesthesia care unit to the time of extubation, average 10 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adverse event, sevoflurane, esketamine