Reversal of Residual Neuromuscular Blockade at Train-of-four Ratio 0.3 With Sugammadex and Neostigmine

Study Overview
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Brief Summary
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The aim of this study is to estimate the optimal dose of sugammadex and neostigmine reversal of a vecuronium-induced residual neuromuscular block at train-of-four ratio 0.3.

Detailed Description
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Sugammadex is a modified γ-cyclodextrin compound that reverses the neuromuscular blockade produced by steroidal nondepolarizing muscle relaxants such as rocuronium,vecuronium and pipecuronium by encapsulating them, making them unavailable to interact with the nicotinic acetylcholine receptors at the neuromuscular junction.However, residual neuromuscular blocks between reappearance of T4 and train-of-four ratio (TOFR)=0.5 are more frequent in clinical practice compared with profound or deep blocks and have not been investigated for sugammadex previously. Unlike neostigmine, sugammadex is efficacious in reversing profound (no responses to either train-of-four (TOF) or posttetanic count stimulation) or deep (posttetanic count of 1 or 2) neuromuscular block (NMB) in doses of 16 and 4 mg/kg, respectively. However, shallow neuromuscular blocks are more frequent in clinical practice compared with profound or deep blocks and have not been investigated for sugammadex previously.

Official Title
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Dose Finding Study for Reversal of Vecuronium-induced Neuromuscular Blockade at Train-of-four Ratio 0.3 With Sugammadex and Neostigmine

Conditions
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Neuromuscular Blockade

Intervention / Treatment
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* Drug: Sugammadex
* Drug: Neostigmine
* Drug: Saline 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1 age of 18 to 65 yr, 2 body mass index 18.5 to 25.0 kg/m2, 3 American Society of Anesthesiologists physical status I to III 4 scheduled for elective surgery with an expected duration of at least 60min under general anesthesia with intubation of the trachea or laryngeal mask 5 patients having given informed consent to the study Exclusion Criteria: 1 patients who had participated in another clinical trial within 1 month 2 Patients with suspected difficult airway, bronchial asthma, chronic obstructive pulmonary disease 3 known neuromuscular disease 4 suspected malignant hyperthermia 5 hepatic or renal dysfunction 6 glaucoma 7 allergy to the medication that used in this trial 8 taking medicaments that might influence the effect of NMB agents 9 pregnant, or breastfeeding state 10 taking medication known to alter the effect of neuromuscular blocking agents( toremifene .etc)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| sugammadex 0.125<br>Sugammadex group: sugammadex 0.125 mg/kg IV once at the reappearance of TOF 0.3 | Drug: Sugammadex<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0)<br>* Other names: Org 25969;|
| Sugammadex 0.25<br>Sugammadex group: sugammadex 0.25 mg/kg IV once at the reappearance of TOF 0.3 | Drug: Sugammadex<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0)<br>* Other names: Org 25969;|
| Sugammadex 0.5<br>Sugammadex group: sugammadex 0.5 mg/kg IV once at the reappearance of TOF 0.3 | Drug: Sugammadex<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0)<br>* Other names: Org 25969;|
| Sugammadex 1.0<br>Sugammadex group: sugammadex 1.0 mg/kg IV once at the reappearance of TOF 0.3 | Drug: Sugammadex<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0)<br>* Other names: Org 25969;|
| Sugammadex 2.0<br>Sugammadex group: sugammadex 2.0 mg/kg IV once at the reappearance of TOF 0.3 | Drug: Sugammadex<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0)<br>* Other names: Org 25969;|
| Neostigmine 10<br>Neostigmine group: neostigmine 10 µg/kg IV once at the reappearance of TOF 0.3 | Drug: Neostigmine<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.<br>* Other names: Prostigmin;|
| Neostigmine 25<br>Neostigmine group: neostigmine 25 µg/kg IV once at the reappearance of TOF 0.3 | Drug: Neostigmine<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.<br>* Other names: Prostigmin;|
| Neostigmine 40<br>Neostigmine group: neostigmine 40 µg/kg IV once at the reappearance of TOF 0.3 | Drug: Neostigmine<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.<br>* Other names: Prostigmin;|
| Neostigmine 55<br>Neostigmine group: neostigmine 55 µg/kg IV once at the reappearance of TOF 0.3 | Drug: Neostigmine<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.<br>* Other names: Prostigmin;|
| Neostigmine 70<br>Neostigmine group: neostigmine 70 µg/kg IV once at the reappearance of TOF 0.3 | Drug: Neostigmine<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.<br>* Other names: Prostigmin;|
| Placebo<br>Placebo group: Saline 0.9% IV once at the reappearance of TOF 0.3 | Drug: Saline 0.9%<br>* At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of saline 0.9%.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to TOF 0.9 after the administration of reversal agent | The time to achieve TOF (Train of Four stimulation) ratio to 0.9 following the investigational drug or placebo administration. | the general anesthesia time 1 hour at least | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of reparalysis | Determining whether patients receiving reversal agent will have a train-to-four ratio <0.8 during total recovery time (from TOF reach 0.9 first time to post-anaesthesia care unit (PACU) departure) | approximately 1 hour | 
| incidence of adverse event | Documenting whether patients will have some adverse events(such as hypoxia bradycardia nausea and vomiting) from anesthesia commence to PACU departure. | the general anesthesia and recovery time 2 hours at least | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sugammadex neostigmine