Comparision of Different Dose of Neostigmine at Advanced Decurarization

Study Overview
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Brief Summary
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Neuromuscular blockers (NMB) are currently used in anesthesia. Residual paralysis (RP) due to NMB is responsible for respiratory disorders after extubation. Neuromuscular blockade is monitored by train-of-four (TOF) stimulation at the adductor pollicis. To exclude a RP a mechanomyographic TOF ratio of 0.9 is mandatory. But mecanomyography is not available in clinical routine. Acceleromyography is the most currently monitoring available in daily practice but it has been proved that an acceloromyographic (AMG) TOF ratio of 1.0 is necessary to exclude a RP. The incidence of RP in recovery room is underestimated. So to perform a safe extubation, reversal of the neuromuscular blockade is necessary when an AMG TOF ratio has not reached 1.0. Reversal of neuromuscular blockade is achieved with neostigmine. The recommended dose is 0.04 mg/kg. The administration of neostigmine causes parasympathomimetic effects which has to be reversed with atropine. When neuromuscular blockade is light (AMG TOF ratio of 0.4 which corresponds to the absence of fade at the visual evaluation of the TOF), a low dose of neostigmine might be sufficient with less side effects expected. The goal of the study is to compare the delay between a light neuromuscular block and an AMG TOF ratio of 1.0 for three neostigmine regimens of neostigmine 0.04, 0.02, 0.01 mg/kg with atropine respectively 0.02, 0.01, 0.005 mg/kg and a placebo.

Official Title
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Randomized, Controlled, Double-blind, Prospective Study, Comparing Different Doses of Neostigmine at Advanced Decurarization .

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: neostigmine
* Drug: neostigmine
* Drug: neostigmine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient > 18 years informed consent signed Patient undergoing any type of scheduled surgery under general anesthesia for which curarization with eventually a maintenance is indicated ASA score between I to III Exclusion Criteria: patient > 75 years and < 18 years body mass index > 32 mg/m² neurology disease, neuromuscular or muscular disease peripheral neuropathy coronary heart disease asthma familial history of malign hyperthermia difficulty of intubation and ventilation full stomach known or suspected allergy to one of the study drug mecanique obstruction of digestive or urinary tract open-angle glaucoma patient with risk of urinary retention linked to urethra-prostatic disorder concomittant medication with a influence known on neuromuscular (aminosid, anti-convulsif and corticosteroid child bearing women or nursing mother no affiliation at a social security

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>neostigmine 0.04 mg.kg associated with atropine 0.02 mg/kg | Drug: neostigmine<br>* 0.04 mg/kg IV bolus, injection when the of train of four is > or = to 40 %<br>|
| Active Comparator: 2<br>neostigmine 0.02 mg.kg associated with atropine 0.01 mg/kg | Drug: neostigmine<br>* 0.02 mg/kg IV bolus, injection when the of train of four is > or = to 40 %<br>|
| Active Comparator: 3<br>neostigmine 0.1 mg.kg associated with atropine 0.05 mg/kg | Drug: neostigmine<br>* 0.01 mg/kg IV bolus, injection when the of train of four is > or = to 40 %<br>|
| No Intervention: 4<br>no injection of neostigmine | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mesure of the Train-of-four (TOF) | train-of-four monitoring (also known as neuromuscular monitoring), is a technique used during recovery from the application of general anesthesia to objectively determine how well a patient's muscles are able to function, by recording muscle response after nerves electrical stimulation. | from neostigmine injection to TOF ratio = 0.9 and 1.0, evaluated every minute up to 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neostigmine, neuromuscular blocking agent, train of four, anesthesia