Different Reversal Agents in Pediatric Day-case Cancer Surgery

Sugammadex Versus Neostigmine in Pediatric Day-case Cancer Surgery

The aim of this study was to compare the efficacy of sugammadex and neostigmine on

reversing neuromuscular blockers in pediatric patients undergoing outpatient surgical

procedures.

Study Overview

• Status: Unknown
• Conditions: Post-operative Residual Curarization
• Intervention / Treatment: Drug: Sugammadex Injection [Bridion]; Drug: Neostigmine

Detailed Description

Postoperative residual curarization (PORC)" a residual duration of action of muscle relaxants beyond the end of the operation" in postoperative patients is a succession of the presence of blocked nicotinic receptors. Even in observationally asymptomatic patients, 60-70% of these receptors can be still blocked. PORC can cause delayed recovery, hypoxia, metabolic derangement and rarely death. Cholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade (NMB). Among these agents neostigmine is the most potent and selective one. Cholinesterase inhibitors have multisystemic side effects. Since these agents are not selective to nicotinic receptors and also stimulate the muscarinic system, there can be quite a few serious adverse effects as follows: Bradycardia, QT lengthening, bronchoconstriction, hypersalivation and increased motility. To avoid these effects, concomitant anticholinergic agents, such as atropine or glycopyrolate, are administered to the patient. The incidence of PORC is still high with the prevalence of a train-of-four (TOF) ratio of less than 0.9 found in the postoperative recovery unit. Recent studies have been able to link even low levels of residual paralysis (TOF ratio <0.9) with significant impairment of pharyngeal muscle function, hypoxic ventilatory drive and decreased respiratory function in the immediate postoperative period.

Despite the knowledge of such side effects, and despite the introduction of various new neuromuscular blocking agents (NMBA) such as rocuronium or mivacurium over the last 15 years, no significant reduction in the incidence of residual neuromuscular blockade has so far been observable.

Today, sugammadex is an alternative to the decurarization procedure, which was traditionally executed with cholinesterase inhibitors. Sugammadex a γ-cyclodextrin with a high affinity to rocuronium and other aminosteroidal NMBA that allows the rapid and complete reversal of especially rocuronium-induced neuromuscular blockade, has raised hopes to overcome the problem of residual neuromuscular blockade. Sugammadex is proved to be a safe and superior agent in NMB reversal compared to neostigmine in adults.

PORC and the muscarinic side effects are not anticipated when using sugammadex,.

Also, due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, have the potential to displace succinylcholine as the "gold standard" muscle relaxant for rapid sequence induction.

The rudimentary neuromuscular junction, the variability of fibrin fibers, the differences in drug distribution and body volume in children change their neuromuscular conduction. These factors can cause prolonged recovery and increased risk of PORC. However, there is few studies in the literature concerning sugammadex administration in pediatric patients.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 14 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥2 years and < 18 years.
• American society of anesthesiologists (ASA) status 1-3.
• patients undergoing outpatient procedures

Exclusion Criteria:

• Known drug hypersensitivity.-
• History of renal or hepatic failure.
• Diseases of the neuromuscular junction.
• history of malignant hyperthermia.

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: Group S; Sugammadex for reversal of steroidal neuromuscular blockers, intravenous injection ,2mg/kg	Drug: Sugammadex Injection [Bridion]; Reversal of neuromuscular blockers
Active Comparator: Group N; Reversal of neuromuscular blockers, iv injection, 0.05 mg/kg	Drug: Neostigmine; Reversal of neuromuscular blockers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery time	time from neostigmine or sugammadex administration until recovery of the TOF ratio to 0.9%	time from reversal administration until TOF ratio reaches0.9%, ranging from 1 to 2.5 minutes, measured withThe train-of-four (TOF) equipment working with the nerve-muscle acceleromyometry principle (TOF Draeger Medical Systems, Inc.16 Electronic Avenue,

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
extubation time	time from neuromuscular blocker administration to extubation	time from muscle relaxant administration until extubation,extubation will be performed based on clinical criteria extubation timeis estimated to range from 50 to 55 minutes

Collaborators and Investigators

• Sponsor: National Cancer Institute, Egypt
• Investigators: Study Director: Mohamed MO Hegazy, MD, Cairo University; Study Director: Mohamed Ad Elramly, MD, Cairo University

Publications and helpful links

General Publications

• Ammar AS, Mahmoud KM, Kasemy ZA. A comparison of sugammadex and neostigmine for reversal of rocuronium-induced neuromuscular blockade in children. Acta Anaesthesiol Scand. 2017 Apr;61(4):374-380. doi: 10.1111/aas.12868. Epub 2017 Feb 10.
• Meretoja OA. Neuromuscular block and current treatment strategies for its reversal in children. Paediatr Anaesth. 2010 Jul;20(7):591-604. doi: 10.1111/j.1460-9592.2010.03335.x.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2019
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): October 1, 2019

Study Registration Dates

• First Submitted: June 18, 2019
• First Submitted That Met QC Criteria: June 21, 2019
• First Posted (Actual): June 25, 2019

Study Record Updates

• Last Update Posted (Actual): June 25, 2019
• Last Update Submitted That Met QC Criteria: June 21, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Delayed Emergence from Anesthesia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Parasympathomimetics; Neostigmine
• Other Study ID Numbers: Reversal agents in pediatrics

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