Effect of Sugammadex vs. Neostigmine/Glycopyrrolate on Pediatric Emergence Delirium in Sevoflurane-rocuronium Anesthesia

A Prospective, Double-blind, Randomized Study to Investigate the Effect of Sugammadex vs. Neostigmine/Glycopyrrolate on Emergence Delirium During Sevoflurane-rocuronium Anesthesia in Pediatric Patients

The aim of this study is to investigate the effect of sugammadex vs. a conventional acetylcholinesterase inhibitor, neostigmine on emergence delirium (ED) during sevoflurane-rocuronium anesthesia in pediatric patients Additionally, the efficacy features of sugammadex compared to neostigmine will be examined by measuring the time from start of administration of reversal agents to recovery of train-of-four (TOF) ratio to 0.7, 0.8, and 0.9.

Although the etiology of ED remains unclear, a sense of suffocation or breathing difficulty during emergence from anesthesia has been suggested as a possible cause. Thus, reversal of neuromuscular blockade with sugammadex in pediatric patients maintained with sevoflurane-rocuronium anesthesia may decrease ED due to its faster reversal of neuromuscular blockade and decreased possibility of residual blockade.

Study Overview

• Status: Completed
• Conditions: Emergence Delirium
• Intervention / Treatment: Drug: Sugammadex Injection [Bridion]; Drug: Neostigmine+Glycopyrronium

Detailed Description

Emergence delirium (ED) is a postanesthetic phenomenon that develops in the early phase of general anesthesia recovery, (usually within the first 30 minutes,) and is defined as "a disturbance in a child's awareness of and attention to his/her environment with disorientation and perceptual alterations including hypersensitivity to stimuli and hyperactive motor behavior" . Children are often irritable, uncompromising, uncooperative, incoherent, and inconsolably crying, moaning, kicking, or thrashing. The incidence of ED varies from 2 to 80%, occurring more frequently in preschool boys. Risk factors also include the following: sevoflurane or desflurane anesthesia; ear, nose and throat surgery; preoperative anxiety. ED is known to increase physical, psychological, and financial burdens in the postanesthesia care unit, which emphasizes the importance of its prevention.

The aim of this study is to investigate the effect of sugammadex vs. a conventional acetylcholinesterase inhibitor, neostigmine on emergence delirium (ED) during sevoflurane-rocuronium anesthesia in pediatric patients Additionally, the efficacy features of sugammadex compared to neostigmine will be examined by measuring the time from start of administration of reversal agents to recovery of TOF ratio to 0.7, 0.8, and 0.9.

Although the etiology of ED remains unclear, a sense of suffocation or breathing difficulty during emergence from anesthesia has been suggested as a possible cause. Thus, reversal of neuromuscular blockade with sugammadex in pediatric patients maintained with sevoflurane-rocuronium anesthesia may decrease ED due to its faster reversal of neuromuscular blockade and decreased possibility of residual blockade.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, Korea, Republic of, 50612
      • Pusan National University Yangsan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologist (ASA) physical status I or II, preschool children scheduled for an elective tonsillectomy with or without adenoidectomy will be included in the study.

Exclusion Criteria:

• Patients will be excluded in cases of emergency surgery, developmental, psychological, cognitive or communication disorders, known or suspected neuromuscular disorders that may impair neuromuscular blockade, significant renal or hepatic dysfunction, coagulation disorders, family history of malignant hyperthermia, allergy to any of the drugs included in the study protocol, or usage of medication known to interact with rocuronium or sugammadex.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sugammadex Injection [Bridion]; reversal of neuromuscular blockade with sugammadex	Drug: Sugammadex Injection [Bridion]; Return to T2 point (two contractions) on TOF device is replied by iv 2 mg/kg sugammadex administration, contained in a blinded syringe.; Other Names: Sugammadex
Active Comparator: Neostigmine+Glycopyrronium; reversal of neuromuscular blockade with neostigmine & glycopyrrolate	Drug: Neostigmine+Glycopyrronium; Return to T2 point (two contractions) on TOF device is replied by iv 0.06 mg/kg neostigmine and 0.005 mg/kg glycopyrrolate administration, contained in a blinded syringe.; Other Names: Neostigmine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pediatric Anesthesia Emergence Delirium Score	Maximum Pediatric Anesthesia Emergence Delirium (PAED) score after arrival in the PACU.Higher values represent more emergence delirium (worse) PAED Score is represented with total PAED score summed up of subscales. The total score is reported and it ranges from 0 to 20. Higher score means worse state.	within 30 minutes after arrival at post-anesthesia care unit (PACU)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Recovery of TOF Ratio to 0.7	Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.7	Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.7, assessed up to 60 minutes
Time to Regular Breathing	time from administration of reversal agent to time of deep, regular breathing	time from administration of reversal agent to time of deep, regular breathing, assessed up to 60 minutes
Time to Awakening	time from administration of reversal agent to time of eye opening or child showing purposeful movement	time from administration of reversal agent to time of eye opening or child showing purposeful movements, assessed up to 60 minutes
Time to Extubation	time from administration of reversal agent to time of tracheal extubation	time from administration of reversal agent to time of tracheal extubation, assessed up to 60 minutes
Time Recovery of TOF Ratio to 0.8	Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.8	Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.8, assessed up to 60 minutes
Time Recovery of TOF Ratio to 0.9	Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.9	Time from the start of administration of reversal agents to recovery of the TOF ratio to 0.9, assessed up to 60 minutes

Collaborators and Investigators

• Sponsor: Pusan National University Yangsan Hospital
• Investigators: Principal Investigator: Tae-Kyun Kim, MD, PhD, Pusan National University Yangsan Hospital

Publications and helpful links

General Publications

• Locatelli BG, Ingelmo PM, Emre S, Meroni V, Minardi C, Frawley G, Benigni A, Di Marco S, Spotti A, Busi I, Sonzogni V. Emergence delirium in children: a comparison of sevoflurane and desflurane anesthesia using the Paediatric Anesthesia Emergence Delirium scale. Paediatr Anaesth. 2013 Apr;23(4):301-8. doi: 10.1111/pan.12038. Epub 2012 Oct 9.
• Pieters BJ, Penn E, Nicklaus P, Bruegger D, Mehta B, Weatherly R. Emergence delirium and postoperative pain in children undergoing adenotonsillectomy: a comparison of propofol vs sevoflurane anesthesia. Paediatr Anaesth. 2010 Oct;20(10):944-50. doi: 10.1111/j.1460-9592.2010.03394.x. Epub 2010 Aug 24.
• Plaud B, Meretoja O, Hofmockel R, Raft J, Stoddart PA, van Kuijk JH, Hermens Y, Mirakhur RK. Reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric and adult surgical patients. Anesthesiology. 2009 Feb;110(2):284-94. doi: 10.1097/ALN.0b013e318194caaa.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): July 30, 2019
• Study Completion (Actual): December 30, 2019

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: July 23, 2017
• First Posted (Actual): July 25, 2017

Study Record Updates

• Last Update Posted (Actual): March 17, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: tonsillectomy; emergence delirium
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Emergence Delirium; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Adjuvants, Anesthesia; Cholinesterase Inhibitors; Parasympathomimetics; Glycopyrrolate; Neostigmine
• Other Study ID Numbers: PusanNUYH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes