Tonsillectomy
Conditions
Keywords
Sleep Apnea, Obstructive, Child, Snoring, Sleep Apnea Syndromes
Brief summary
The goal of this clinical trial is to compare general anesthesia with muscle relaxation and reversal of the relaxation at the end of surgery or without muscle relaxation in high-risk children having adenotonsillectomy surgery. The main questions it aims to answer are: 1. What is the impact of general anesthesia with muscle relaxation on opioid pain medication requirements during and after adenotonsillectomy? 2. What is the impact of general anesthesia with muscle relaxation on postoperative breathing complications and the adequacy of postoperative lung air volumes during breathing? Participants will wear three additional, noninvasive monitors during surgery, and one additional monitor after surgery. The amount of opioid pain medication required will be tracked, and the patient will be observed postoperatively for breathing complications. Measurements will be collected from the monitor worn postoperatively. Researchers will compare general anesthesia with muscle relaxation and reversal of relaxation at the end of surgery with general anesthesia without muscle relaxation to test the hypothesis that the approach using muscle relaxation reduces the amount of opioid pain medication required during and after surgery.
Detailed description
This will be a randomized, patient- and assessor-blinded, parallel arm, controlled trial assessing the efficacy of neuromuscular blockade with reversal during the anesthetic management of pediatric adenotonsillectomy (AT) to reduce intra- and postoperative opioid consumption and postoperative respiratory events in high-risk patients. Enrolled participants will be randomized by computer-generated assignment using stratified blocked randomization with a 1:1 allocation into 2 arms: neuromuscular blockade with reversal at the end of surgery and no neuromuscular blockade. Randomization will occur on the following strata: severe versus non-severe obstructive sleep apnea (OSA)/sleep disordered breathing. Patients/families, treating teams (except for the anesthesia team), and research staff/investigators responsible for measuring and adjudicating outcomes will be blinded to allocation. Primary Efficacy Objective - Evaluate intraoperative and postoperative opioid consumption in high-risk children having AT without muscle relaxation or with neuromuscular blocks and reversal with sugammadex. Secondary Objectives - (1) Evaluate postoperative respiratory events in high-risk children having AT without muscle relaxation or with neuromuscular blocks and reversal with sugammadex. The outcome of postoperative respiratory events will be a composite measure consisting of 1) airway obstruction or hypoxemia, defined as SpO2 less than 90 percent, requiring any of the following interventions: supplemental oxygen by nasal cannula or simple face mask, noninvasive positive airway pressure, or reintubation; or 2) unanticipated intensive care unit (ICU) admission. (2) Evaluate postoperative low minute ventilation (MV) episodes, defined as MV less than 40 percent predicted for at least 2 minutes and measured by a respiratory volume monitor (RVM), in high-risk children having AT without muscle relaxation or with neuromuscular blocks and reversal with sugammadex.
Interventions
DRUGRocuronium
After induction of anesthesia and placement of an IV, rocuronium 0.6 mg/kg (maximum dose 50mg) will be administered. Additional doses of rocuronium 0.2 mg/kg (maximum dose 15 mg) will be administered when the neuromuscular transmission monitor indicates a train of four count of 2 or greater.
DRUGSugammadex
When the surgery is completed, sugammadex 2 mg/kg will be administered if the neuromuscular transmission monitor indicates the train of four count is 2 or greater. Sugammadex 4 mg/kg will be administered if 1) the train of four count is 1, or 2) if the train of four count is 0 and the post tetanic count is at least 1. There is no maximum dose of sugammadex.
OTHERAnesthesia without neuromuscular blockade
Anesthesia without rocuronium or sugammadex
Sponsors
Merck Sharp & Dohme LLC
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
Patients/families, treating teams (except for the anesthesia team), and research staff/investigators responsible for measuring and adjudicating outcomes will be blinded to allocation.
Intervention model description
randomized, patient- and assessor-blinded, parallel arm, controlled trial
Eligibility
Sex/Gender
ALL
Age
2 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Children 2-12 years of age having tonsillectomy with or without adenoidectomy at Children's main Dallas campus * Considered high-risk\* with pre-planned overnight admission after surgery for respiratory monitoring \*High-risk children have any one of the following characteristics: age \< 3 years, severe obstructive sleep apnea (apnea-hypopnea index \> 10 events per hour), or obesity (body mass index \> 98th percentile).
Exclusion criteria
* Planned placement on positive airway pressure or supplemental oxygen postoperatively * Secondary procedures under the same anesthetic, except for myringotomy tubes or auditory brainstem response testing * Children with neuromuscular disorders such as congenital myopathies, myotonias, or myasthenia gravis * Known rocuronium, vecuronium, or sugammadex allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Intra- and Postoperative Opioid Consumption | From surgery start to discharge home, up to 24 hours | Continuous outcome of intravenous morphine milligram equivalents (MME) per kg of body weight |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Postoperative Respiratory Events | From post-anesthesia care unit admission to discharge home, up to 24 hours | Composite binary outcome consisting of 1) airway obstruction or hypoxemia, defined as SpO2 \<90%, requiring any of the following interventions: supplemental oxygen by nasal cannula or simple face mask, noninvasive positive airway pressure, or reintubation; or 2) unanticipated ICU admission. |
| Number of Low Minute Ventilation (MV) Events in the Post-anesthesia Care Unit | From post-anesthesia care unit admission to transfer to the postoperative ward, up to 8 hours | Count outcome of distinct episodes of low MV. MV - the product of respiratory rate and tidal volume - was continuously measured by a noninvasive respiratory volume monitor. Low MV events were defined as episodes of MV less than 40 percent predicted - calculated by the monitor based on the patient's body surface area - for at least two minutes. This definition is routinely used by the monitoring system. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neuromuscular Blockade Rocuronium 0.6 mg/kg IV (max 50 mg) intraop with repeated doses of 0.2 mg/kg (max 15 mg) as indicated. Sugammadex 2-4 mg/kg IV at the end of surgery.
SOC drugs:
1. Midazolam 0.5 mg/kg (max 15 mg) and acetaminophen 15 mg/kg (max 800 mg) PO 20-30 minutes before surgery.
2. Sevoflurane induction and maintenance
3. Dexamethasone 0.5 mg/kg IV (max 8 mg) intraop
4. Dexmedetomidine 0.3 mcg/kg IV (max 12 mcg) intraop
5. Fentanyl at the discretion of anesthesiologist. In the post-anesthesia care unit (PACU), fentanyl 0.5 mcg/kg IV (max 25 mcg) for pain score 4 or greater (max 3 doses).
6. Ondansetron 0.1 mg/kg (max 4 mg) IV intraop
7. Ibuprofen 10 mg/kg (max 500 mg) PO alternating with acetaminophen 15 mg/kg (max 800 mg) every 6 hours after surgery.
Monitoring:
1. Bispectral index system
2. TetraGraph neuromuscular transmission monitor
3. ExSpiron respiratory volume monitor in PACU
Rocuronium: After induction of anesthesia and IV placement, administration of rocuronium 0.6 mg/kg (max 50 mg). Administration of additional doses of 0.2 mg/kg (max 15 mg) when TetraGraph indicates a train of four count of 2 or greater.
Sugammadex: Administration of sugammadex 2 mg/kg at the end of surgery if the TetraGraph indicates the train of four count is 2 or greater. Sugammadex 4 mg/kg will be administered if 1) the train of four count is 1, or 2) if the train of four count is 0 and the post tetanic count is at least 1. There is no maximum dose of sugammadex. | 86 |
| No Neuromuscular Blockade Anesthesia will be administered in a standard fashion. Rocuronium and sugammadex will not be administered.
SOC drugs:
1. Midazolam 0.5 mg/kg (max 15 mg) and acetaminophen 15 mg/kg (max 800 mg) PO 20-30 minutes before surgery.
2. Sevoflurane induction and maintenance of anesthesia
3. Dexamethasone 0.5 mg/kg IV (max 8 mg) intraop
4. Dexmedetomidine 0.3 mcg/kg IV (max 12 mcg) intraop
5. Fentanyl at the discretion of the anesthesiologist. In the post-anesthesia care unit (PACU), fentanyl 0.5 mcg/kg IV (max 25 mcg) for pain score 4 or greater (max 3 doses).
6. Ondansetron 0.1 mg/kg (max 4 mg) IV intraop
7. Ibuprofen 10 mg/kg (max 500 mg) PO every 6 hours beginning after surgery and alternating with acetaminophen 15 mg/kg (max 800 mg) every 6 hours.
Device monitoring:
1. Bispectral index system intraop
2. ExSpiron respiratory volume monitor intraop and in PACU
Anesthesia without neuromuscular blockade: Anesthesia without rocuronium or sugammadex | 86 |
| Total | 172 |
Baseline characteristics
| Characteristic | Neuromuscular Blockade | Total | No Neuromuscular Blockade |
|---|---|---|---|
| Age, Continuous | 5.9 years STANDARD_DEVIATION 2.9 | 6.5 years STANDARD_DEVIATION 3.1 | 7 years STANDARD_DEVIATION 3.2 |
| Extreme prematurity | 1 Participants | 2 Participants | 1 Participants |
| Intraoperative bispectral index | 52 index STANDARD_DEVIATION 7 | 50 index STANDARD_DEVIATION 8 | 48 index STANDARD_DEVIATION 8 |
| Obesity | 37 Participants | 91 Participants | 54 Participants |
| Obstructive sleep apnea severity Mild obstructive sleep apnea | 11 Participants | 16 Participants | 5 Participants |
| Obstructive sleep apnea severity Moderate obstructive sleep apnea | 6 Participants | 15 Participants | 9 Participants |
| Obstructive sleep apnea severity No preoperative polysomnogram | 26 Participants | 55 Participants | 29 Participants |
| Obstructive sleep apnea severity Severe obstructive sleep apnea | 43 Participants | 86 Participants | 43 Participants |
| Race/Ethnicity, Customized Black | 21 participants | 38 participants | 17 participants |
| Race/Ethnicity, Customized Hispanic | 50 participants | 119 participants | 69 participants |
| Race/Ethnicity, Customized Non-Hispanic | 36 participants | 53 participants | 17 participants |
| Race/Ethnicity, Customized Other | 9 participants | 24 participants | 15 participants |
| Race/Ethnicity, Customized White | 56 participants | 110 participants | 54 participants |
| Sex: Female, Male Female | 39 Participants | 81 Participants | 42 Participants |
| Sex: Female, Male Male | 47 Participants | 91 Participants | 44 Participants |
| Trisomy 21 | 2 Participants | 3 Participants | 1 Participants |
| Upper respiratory infection symptoms | 6 Participants | 10 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 86 | 0 / 86 |
| other Total, other adverse events | 1 / 86 | 1 / 86 |
| serious Total, serious adverse events | 0 / 86 | 0 / 86 |
Outcome results
Primary
Cumulative Intra- and Postoperative Opioid Consumption
Continuous outcome of intravenous morphine milligram equivalents (MME) per kg of body weight
Time frame: From surgery start to discharge home, up to 24 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Neuromuscular Blockade | Cumulative Intra- and Postoperative Opioid Consumption | 0.209 IV morphine milligram equivalent/kg | Standard Error 0.009 |
| No Neuromuscular Blockade | Cumulative Intra- and Postoperative Opioid Consumption | 0.188 IV morphine milligram equivalent/kg | Standard Error 0.009 |
p-value: 0.12395% CI: [-0.005, 0.047]ANOVA
Secondary
Number of Low Minute Ventilation (MV) Events in the Post-anesthesia Care Unit
Count outcome of distinct episodes of low MV. MV - the product of respiratory rate and tidal volume - was continuously measured by a noninvasive respiratory volume monitor. Low MV events were defined as episodes of MV less than 40 percent predicted - calculated by the monitor based on the patient's body surface area - for at least two minutes. This definition is routinely used by the monitoring system.
Time frame: From post-anesthesia care unit admission to transfer to the postoperative ward, up to 8 hours
Population: Two patients in the no neuromuscular blockade group were missing respiratory volume monitor data and therefore the measure of low MV events.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neuromuscular Blockade | Number of Low Minute Ventilation (MV) Events in the Post-anesthesia Care Unit | 0 low minute ventilation events |
| No Neuromuscular Blockade | Number of Low Minute Ventilation (MV) Events in the Post-anesthesia Care Unit | 0 low minute ventilation events |
p-value: 0.00895% CI: [1.25, 4.52]Negative Binomial Regression
Secondary
Number of Participants With Postoperative Respiratory Events
Composite binary outcome consisting of 1) airway obstruction or hypoxemia, defined as SpO2 \<90%, requiring any of the following interventions: supplemental oxygen by nasal cannula or simple face mask, noninvasive positive airway pressure, or reintubation; or 2) unanticipated ICU admission.
Time frame: From post-anesthesia care unit admission to discharge home, up to 24 hours
Population: Postoperative ward respiratory events measured by administration of questionnaires to nursing staff. Number analyzed represents number of participants with questionnaires returned. PACU respiratory events measured by bedside observation by study staff. No participants had outcome measurements missing from the PACU.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Neuromuscular Blockade | Number of Participants With Postoperative Respiratory Events | Respiratory event PACU or ward | 32 Participants |
| Neuromuscular Blockade | Number of Participants With Postoperative Respiratory Events | Respiratory event PACU | 31 Participants |
| Neuromuscular Blockade | Number of Participants With Postoperative Respiratory Events | Respiratory event ward | 4 Participants |
| No Neuromuscular Blockade | Number of Participants With Postoperative Respiratory Events | Respiratory event PACU or ward | 38 Participants |
| No Neuromuscular Blockade | Number of Participants With Postoperative Respiratory Events | Respiratory event PACU | 37 Participants |
| No Neuromuscular Blockade | Number of Participants With Postoperative Respiratory Events | Respiratory event ward | 10 Participants |
p-value: 0.10295% CI: [0.26, 1.12]Mixed Models Analysis