Anesthesia
Conditions
Keywords
neostigmine, neuromuscular blocking agent, train of four, anesthesia
Brief summary
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.
Interventions
DRUGneostigmine
0.04 mg/kg IV bolus, injection when the of train of four is \> or = to 40 %
Sponsors
Centre Hospitalier Departemental Vendee
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mesure of the Train-of-four (TOF) | from neostigmine injection to TOF ratio = 0.9 and 1.0, evaluated every minute up to 1 hour | 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. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neostigmine 40 µg/kg neostigmine 0.04 mg.kg associated with atropine 0.02 mg/kg
neostigmine: 0.04 mg/kg IV bolus, injection when the of train of four is \> or = to 40 % | 16 |
| Neostigmine 20 µg/kg neostigmine 0.02 mg.kg associated with atropine 0.01 mg/kg
neostigmine: 0.02 mg/kg IV bolus, injection when the of train of four is \> or = to 40 % | 14 |
| Neostigmine 10 µg/kg neostigmine 0.1 mg.kg associated with atropine 0.05 mg/kg
neostigmine: 0.01 mg/kg IV bolus, injection when the of train of four is \> or = to 40 % | 15 |
| Placebo no injection of neostigmine | 15 |
| Total | 60 |
Baseline characteristics
| Characteristic | Neostigmine 40 µg/kg | Neostigmine 20 µg/kg | Neostigmine 10 µg/kg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 50.7 years STANDARD_DEVIATION 17.6 | 51.9 years STANDARD_DEVIATION 18.1 | 60.2 years STANDARD_DEVIATION 11.4 | 50.6 years STANDARD_DEVIATION 14.8 | 53.3 years STANDARD_DEVIATION 16 |
| ASA Physical Status Classification System ASA I | 8 Participants | 6 Participants | 2 Participants | 2 Participants | 18 Participants |
| ASA Physical Status Classification System ASA II | 8 Participants | 7 Participants | 11 Participants | 13 Participants | 39 Participants |
| ASA Physical Status Classification System ASA III | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| BMI | 23.9 kg/m² STANDARD_DEVIATION 3.6 | 25.4 kg/m² STANDARD_DEVIATION 3.7 | 26.9 kg/m² STANDARD_DEVIATION 4 | 26.9 kg/m² STANDARD_DEVIATION 3.3 | 25.7 kg/m² STANDARD_DEVIATION 3.8 |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 4 Participants | 6 Participants | 22 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 11 Participants | 9 Participants | 38 Participants |
| surgery time | 80.2 minute STANDARD_DEVIATION 40.4 | 75.8 minute STANDARD_DEVIATION 32.4 | 84.1 minute STANDARD_DEVIATION 54.9 | 78.1 minute STANDARD_DEVIATION 44.3 | 79.6 minute STANDARD_DEVIATION 43.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 14 | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 | 0 / 15 | 0 / 15 |
Outcome results
Primary
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.
Time frame: from neostigmine injection to TOF ratio = 0.9 and 1.0, evaluated every minute up to 1 hour
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Neostigmine 40 µg/kg | Mesure of the Train-of-four (TOF) | recovery time to TOF ratio of 0.9 | 3.8 minute |
| Neostigmine 40 µg/kg | Mesure of the Train-of-four (TOF) | recovery time to TOF ratio of 1.0 | 5.5 minute |
| Neostigmine 20 µg/kg | Mesure of the Train-of-four (TOF) | recovery time to TOF ratio of 1.0 | 7.8 minute |
| Neostigmine 20 µg/kg | Mesure of the Train-of-four (TOF) | recovery time to TOF ratio of 0.9 | 4.5 minute |
| Neostigmine 10 µg/kg | Mesure of the Train-of-four (TOF) | recovery time to TOF ratio of 0.9 | 11.5 minute |
| Neostigmine 10 µg/kg | Mesure of the Train-of-four (TOF) | recovery time to TOF ratio of 1.0 | 17 minute |
| Placebo | Mesure of the Train-of-four (TOF) | recovery time to TOF ratio of 0.9 | 19 minute |
| Placebo | Mesure of the Train-of-four (TOF) | recovery time to TOF ratio of 1.0 | 26 minute |