Comparison of Esketamine and Sevoflurane on Emergence Agitation

• ClinicalTrials.gov Identifier: NCT05321160
• Recruitment Status: Recruiting
• First Posted: April 11, 2022
• Last Update Posted: April 25, 2022
• Sponsor: Eye & ENT Hospital of Fudan University
• Information provided by (Responsible Party): Eye & ENT Hospital of Fudan University

Tracking Information

• First Submitted Date: March 25, 2022
• First Posted Date: April 11, 2022
• Last Update Posted Date: April 25, 2022
• Actual Study Start Date: March 10, 2021
• Estimated Primary Completion Date: April 14, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 2, 2022)

the incidence of emergence agitation [ Time Frame: duration from the time patients arrived the post-anesthesia care unit to the time of leaving to the ward, average 20 minutes ]

the incidence of emergence agitation

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 18, 2022)

• length of stay in the post-anesthesia care unit [ Time Frame: duration from the time patients arrived the post-anesthesia care unit to the time of leaving to the ward, average 20 minutes ]
  the time of patients staying in post-anesthesia care unit
• CPS score [ Time Frame: scores at the time point of 1 minutes after extubation ]
  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.
• the incidence of respiratory depression [ Time Frame: during the surgery ]
  decreased tidal volume or weak chest undulation
• the incidence of desaturation [ Time Frame: during the surgery ]
  the incidence of oxygen saturation below 95% caused by anesthetic agents
• intraocular pressure [ Time Frame: the time after intubation and topical anesthesia within 1 minute ]
  intraocular pressure after induction
• respiration rate [ Time Frame: 1minutes before induction;1minutes after induction;1minutes before intubation;1minutes after intubation,3 minutes after intubation ]
  respiration rate
• mean blood pressure [ Time Frame: 1minutes before induction;1minutes after induction;1minutes before intubation;1minutes after intubation,3 minutes after intubation ]
  mean blood pressure
• heart rate [ Time Frame: 1minutes before induction;1minutes after induction;1minutes before intubation;1minutes after intubation,3 minutes after intubation ]
  heart rate
• extubation time [ Time Frame: duration from the time that patients arrived in post-anesthesia care unit to the time of extubation, average 10 minutes ]
  extubation time

Original Secondary Outcome Measures (submitted: April 2, 2022)

• length of stay in the post-anesthesia care unit [ Time Frame: duration from the time patients arrived the post-anesthesia care unit to the time of leaving to the ward, average 20 minutes ]
  the time of patients staying in post-anesthesia care unit
• CPS score [ Time Frame: scores at the time point of 1 minutes after extubation ]
  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.
• the incidence of respiratory depression [ Time Frame: during the surgery ]
  decreased tidal volume or weak chest undulation
• the incidence of desaturation [ Time Frame: during the surgery ]
  the incidence of oxygen saturation below 95% caused by anesthetic agents
• intraocular pressure [ Time Frame: the time after intubation and topical anesthesia within 1 minute ]
  intraocular pressure after induction
• requirements for additional propofol [ Time Frame: during the surgery ]
  If the target level of sedation was not achieved, an additional 0.1mg/kg propofol was injected and repeated if necessary
• mean blood pressure [ Time Frame: 1minutes before induction;1minutes after induction;1minutes before intubation;1minutes after intubation,3 minutes after intubation ]
  mean blood pressure
• heart rate [ Time Frame: 1minutes before induction;1minutes after induction;1minutes before intubation;1minutes after intubation,3 minutes after intubation ]
  heart rate
• extubation time [ Time Frame: duration from the time that patients arrived in post-anesthesia care unit to the time of extubation, average 10 minutes ]
  extubation time

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison of Esketamine and Sevoflurane on Emergence Agitation
• Official Title: Comparison of Esketamine and Sevoflurane on Emergence Agitation for Pediatric Ophthalmological Procedure

Brief Summary

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

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Emergence Agitation

Intervention

• Drug: Esketamine
  0.5 mg/kg esketamine for induction and 0.25 mg/kg esketamine at the beginning of surgery
  Other Name: s(+)ketamine
• Drug: Sevoflurane
  5% sevoflurane for induction and 3-4% sevoflurane for maintain
  Other Name: Sevoflurane Inhalation Solution

Study Arms

• Experimental: Group E
  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.
  Intervention: Drug: Esketamine
• Active Comparator: Group S
  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.
  Intervention: Drug: Sevoflurane

Publications *

• Liao R, Li JY, Liu GY. Comparison of sevoflurane volatile induction/maintenance anaesthesia and propofol-remifentanil total intravenous anaesthesia for rigid bronchoscopy under spontaneous breathing for tracheal/bronchial foreign body removal in children. Eur J Anaesthesiol. 2010 Nov;27(11):930-4. doi: 10.1097/EJA.0b013e32833d69ad.
• 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(4):419-24.
• 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 Nov;83(5):917-20.
• White PF, Schüttler J, Shafer A, Stanski DR, Horai Y, Trevor AJ. Comparative pharmacology of the ketamine isomers. Studies in volunteers. Br J Anaesth. 1985 Feb;57(2):197-203.
• Patrizi A, Picard N, Simon AJ, Gunner G, Centofante E, Andrews NA, Fagiolini M. Chronic Administration of the N-Methyl-D-Aspartate Receptor Antagonist Ketamine Improves Rett Syndrome Phenotype. Biol Psychiatry. 2016 May 1;79(9):755-764. doi: 10.1016/j.biopsych.2015.08.018. Epub 2015 Aug 24.
• Eich C, Verhagen-Henning S, Roessler M, Cremer F, Cremer S, Strack M, Russo SG. Low-dose S-ketamine added to propofol anesthesia for magnetic resonance imaging in children is safe and ensures faster recovery--a prospective evaluation. Paediatr Anaesth. 2011 Feb;21(2):176-8. doi: 10.1111/j.1460-9592.2010.03489.x.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 2, 2022): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 17, 2022
• Estimated Primary Completion Date: April 14, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Months to 72 Months (Child)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Fang Tan, Phd; 8613611716000; tanfang@eentanesthesia.com

Contact: Wenjing Yi; 8613636547402; ywjeline@hotmail.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05321160
• Other Study ID Numbers: EA and esketamine
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Eye & ENT Hospital of Fudan University
• Original Responsible Party: Same as current
• Current Study Sponsor: Eye & ENT Hospital of Fudan University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fang Tan; Anesthesiology Department of Affiliated Eye and ENT Hospital, Fudan University

• PRS Account: Eye & ENT Hospital of Fudan University
• Verification Date: April 2022