A Prospective, Multi-center, Randomized Controlled Study of Muscle Relaxation Effect and Safety of Mivacurium Chloride in Pediatric Surgery Patients

Study Overview
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Brief Summary
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To evaluate the effect and safety of mivacurium chloride in pediatric patients.

Official Title
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A Prospective, Multi-center, Randomized Controlled Study of Neuromuscular Blocking Effect and Safety of Mivacurium Chloride in Pediatric Patients

Conditions
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Efficacy and Safety of Mivacurium Chloride for Pediatric Patients

Intervention / Treatment
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* Drug: mivacurium chloride
* Drug: midazolam
* Drug: ketamine
* Drug: propofol
* Drug: Remifentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The parent/guardian must sign a parental permission consent document American Society of Anesthesiologists (ASA) physical status class 1-3 Elective surgery patients with tracheal intubation, and the operation duration is expected to be longer than 30 min but no longer than 120 min(cleft lip and palate, orthopedic, bilateral hernia, bilateral cryptorchidism, hypospadias crack, and other ear, nose and throat surgery, etc) Age between 2 months to 14 Years Exclusion Criteria: BMI<18kg/m2 or BMI>31kg/m2 Patients with serious respiratory, cardiovascular disease, and liver and kidney dysfunction[AST（glutamic oxalacetic transaminase）,ALT(glutamic-pyruvic transaminase)>1.5 Normal;BUN(blood urea nitrogen)>Normal)] Patients with asthma or airway hyperresponsiveness, neuromuscular patients disease or cachexia Preoperative hemoglobin less than 10g/L Hypoproteinemia TP（total protein) <45g/L Diabetic patients Patients with difficulty airway Patients with Known or suspected atypical plasma cholinesterase gene homozygous Burn patients Patients with serious acid-base imbalances, or severe electrolyte imbalance Patients with neuromuscular relaxants in a week Patients prohibited with muscle relaxants, or allergy to any component of mivacurium Patients participated in any drug clinical trial with 30 days before the start of the study Other situations not suitable for inclusion Blood loss more than 10 ml/kg in surgery

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 14 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1<br>age: 2 to 12 months induction dosage of mivacurium chloride: 0.15 mg/kg administration: intravenous injection for 20 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 2<br>age: 2 to 12 months induction dosage of mivacurium chloride: 0.15 mg/kg administration: intravenous injection for 40 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 3<br>age: 2 to 12 months induction dosage of mivacurium chloride: 0.20 mg/kg administration: intravenous injection for 20 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 4<br>age: 2 to 12 months induction dosage of mivacurium chloride: 0.20 mg/kg administration: intravenous injection for 40 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 5<br>age: 13 to 35 months induction dosage of mivacurium chloride: 0.20 mg/kg administration: intravenous injection for 20 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 6<br>age: 13 to 35 months induction dosage of mivacurium chloride: 0.20 mg/kg administration: intravenous injection for 40 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 7<br>age: 13 to 35 months induction dosage of mivacurium chloride: 0.25 mg/kg administration: intravenous injection for 20 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 8<br>age: 13 to 35 months induction dosage of mivacurium chloride: 0.25 mg/kg administration: intravenous injection for 40 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 9<br>age: 3 to 6 years induction dosage of mivacurium chloride: 0.20 mg/kg administration: intravenous injection for 20 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 10<br>age: 3 to 6 years induction dosage of mivacurium chloride: 0.20 mg/kg administration: intravenous injection for 40 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 11<br>age: 3 to 6 years induction dosage of mivacurium chloride: 0.25 mg/kg administration: intravenous injection for 20 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 12<br>age: 3 to 6 years induction dosage of mivacurium chloride: 0.25 mg/kg administration: intravenous injection for 40 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 13<br>age: 7 to 14 years induction dosage of mivacurium chloride: 0.20 mg/kg administration: intravenous injection for 20 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 14<br>age: 7 to 14 years induction dosage of mivacurium chloride: 0.20 mg/kg administration: intravenous injection for 40 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 15<br>age: 7 to 14 years induction dosage of mivacurium chloride: 0.25 mg/kg administration: intravenous injection for 20 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|
| Experimental: group 16<br>age: 7 to 14 years induction dosage of mivacurium chloride: 0.25 mg/kg administration: intravenous injection for 40 s | Drug: mivacurium chloride<br>* intravenously injected during induction with the dose according to allocated group, and intravenously injected with the dose of 0.1 mg/kg when T1 recovers to 25% during period of maintenance.<br>* Other names: mivacron;Drug: midazolam<br>* Before induction: after moving into operating room, oral administration with dose of 0.5 mg/kg or mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: ketamine<br>* mixed with ketamine (midazolam 10 mg+ ketamine 100 mg) with dose of 0.1 ml/kg by intramuscular route for uncooperative children Induction: for children who didn't receive mixture of midazolam and ketamine before induction, it will be given with the dose of 0.05 ml/kg<br>Drug: propofol<br>* Induction: 2 to 3 mg/kg Maintenance: 50 to 100 mcg/kg/min<br>Drug: Remifentanil<br>* Induction: 2 mcg/kg Maintenance: 0.1 to 0.3 mcg/kg/min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intubation score | Krieg Tracheal Intubation Score Score ： 1 2 3 4 Laryngoscopy ： Easy Fair Difficult Impossible Vocal cords： Open Moving Closing Closed Coughing： None Diaphragm Mild Severe A total score of 3-4 = excellent, 5-7 = good, 8-10 = poor, 11-12 = bad. | 1 minute within intubation | 
| muscle relaxation effect | Recording T1 and TOFR（Train of four ratio) before/after the induction of anesthesia -Onset time of Mivacurium：time from end of injection until occurrence of maxi- mum block Duration of clinical relaxation：time to recovery of Tl(the first response in the TOF) to 25% Recovery index：Time interval during with T1 recovered from 25% | from baseline to no more than 120 minutes after intubation |