Anesthesia, General, Neuromuscular Blockade
Conditions
Keywords
sugammadex, pharmacokinetics, pharmacodynamics, pediatric anesthesia
Brief summary
This study administers sugammadex sodium to pediatric patients under general anesthesia with rocuronium. Pharmacokinetic and pharmacodynamic analysis are performed based on plasma concentration of sugammadex sodium and monitoring of neuromuscular blockade.
Detailed description
This study enrolls pediatric patients undergoing surgery under general anesthesia with need for early reversal of neuromuscular blockade, aged between 2 and 18 years old. After routine anesthetic induction with 1% propofol and 0.6mg/kg of rocuronium, maintenance of anesthesia with total intravenous anesthesia is commenced. 15 minutes after rocuronium administration, 2 or 4 or 8mg/kg of sugammadex sodium or conventional neuromuscular reversal agent is administered according to randomization table. For neuromuscular monitoring, train-of-four (TOF) count and T4/T1 ratio are monitored, with recording of the time to recovery of the T4/T1 ratio to 0.7, 0.8 and 0.9. For pharmacokinetic analysis, patient blood sample is obtained before / 2 min after rocuronium administration, before / 2min / 5min / 15min / 60min / 120min / 240min / 480min after sugammadex administration. Plasma concentration of rocuronium and sugammadex sodium are analyzed via high-performance liquid chromatography with mass spectrometric detection.
Interventions
Intravenous injection of 2mg/kg of sugammadex sodium 15 minutes after rocuronium administration
Intravenous injection of 4mg/kg of sugammadex sodium 15 minutes after rocuronium administration
Intravenous injection of 8mg/kg of sugammadex sodium 15 minutes after rocuronium administration
Intravenous injection of 0.02mg/kg of atropine and 0.03mg/kg of neostigmine
Sponsors
Ministry of Food and Drug Safety, Korea
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
All of below * Pediatric patients undergoing surgery under general anesthesia with requirement of early reversal of neuromuscular blockade * Aged between 2 and 17 * American Society of Anesthesiologists Physical Status Classification 1 and 2
Exclusion criteria
Any of below * One or more legal guardian declines to enroll in the study * History of hypersensitivity to any anesthetic agents including rocuronium * Presence of underlying cardiovascular or genitourinary disease * Under usage of neuromuscular blocking agents before surgery * Under usage of drugs influencing the effect of neuromuscular blocking agents * History of malignant hyperthermia * Anticipation of massive hemorrhage during surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neuromuscular Recovery | up to 30 minutes to 1 hour | Time to recovery of train-of-four T4/T1 ratio to 90% after sugammadex sodium or neuromuscular reversal agent administration up to 30 minutes to 1 hour. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentrations | From anesthetic induction to 480 minutes after sugammadex administration | Plasma concentrations of rocuronium and sugammadex sodium |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex 2mg Administer 2mg/kg of sugammadex 15 minutes after rocuronium administration
Sugammadex Injection 2mg/kg: Intravenous injection of 2mg/kg of sugammadex sodium 15 minutes after rocuronium administration | 10 |
| Sugammadex 4mg Administer 4mg/kg of sugammadex 15 minutes after rocuronium administration
Sugammadex Injection 4mg/kg: Intravenous injection of 4mg/kg of sugammadex sodium 15 minutes after rocuronium administration | 10 |
| Sugammadex 8mg Administer 8mg/kg of sugammadex 15 minutes after rocuronium administration
Sugammadex Injection 8mg/kg: Intravenous injection of 8mg/kg of sugammadex sodium 15 minutes after rocuronium administration | 10 |
| Conventional Reversal Administer conventional neuromuscular reversal agent (0.02mg/kg of atropine and 0.03mg/kg of neostigmine) 15 minutes after rocuronium administration
Neuromuscular reversal agent injection: Intravenous injection of 0.02mg/kg of atropine and 0.03mg/kg of neostigmine | 10 |
| Total | 40 |
Baseline characteristics
| Characteristic | Sugammadex 2mg | Sugammadex 4mg | Sugammadex 8mg | Conventional Reversal | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 40 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 6.5 years | 10 years | 6 years | 8.5 years | 7 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 40 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment South Korea | 10 participants | 10 participants | 10 participants | 10 participants | 40 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 4 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 6 Participants | 5 Participants | 21 Participants |
| Type of surgery Brain | 6 Participants | 4 Participants | 7 Participants | 10 Participants | 27 Participants |
| Type of surgery Spine | 4 Participants | 6 Participants | 3 Participants | 0 Participants | 13 Participants |
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 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Neuromuscular Recovery
Time to recovery of train-of-four T4/T1 ratio to 90% after sugammadex sodium or neuromuscular reversal agent administration up to 30 minutes to 1 hour.
Time frame: up to 30 minutes to 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex 2mg | Neuromuscular Recovery | 5.7 Minutes | Standard Deviation 4.7 |
| Sugammadex 4mg | Neuromuscular Recovery | 3.1 Minutes | Standard Deviation 1 |
| Sugammadex 8mg | Neuromuscular Recovery | 1.1 Minutes | Standard Deviation 1 |
| Conventional Reversal | Neuromuscular Recovery | 43.7 Minutes | Standard Deviation 28.2 |
Secondary
Plasma Concentrations
Plasma concentrations of rocuronium and sugammadex sodium
Time frame: From anesthetic induction to 480 minutes after sugammadex administration
Population: Cmax of sugammadex and rocuronium
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugammadex 2mg | Plasma Concentrations | Rocuronium | 5.3 mcg/mL | Standard Deviation 1.9 |
| Sugammadex 2mg | Plasma Concentrations | Sugammadex | 28.5 mcg/mL | Standard Deviation 9.6 |
| Sugammadex 4mg | Plasma Concentrations | Rocuronium | 8.0 mcg/mL | Standard Deviation 2.1 |
| Sugammadex 4mg | Plasma Concentrations | Sugammadex | 58.2 mcg/mL | Standard Deviation 12.5 |
| Sugammadex 8mg | Plasma Concentrations | Rocuronium | 5.4 mcg/mL | Standard Deviation 3 |
| Sugammadex 8mg | Plasma Concentrations | Sugammadex | 118.9 mcg/mL | Standard Deviation 13 |
| Conventional Reversal | Plasma Concentrations | Rocuronium | 6.8 mcg/mL | Standard Deviation 3.1 |