Anesthesia, Opioid Use, Sleep Disorder, Surgery, Tonsillitis
Conditions
Keywords
Tonsillectomy, Opioid-Free, Ketorolac, Dexmedetomidine, Acute postoperative pain relief, Opioid, Morphine, Fentanyl
Brief summary
Prospective randomized controlled trial to determine if opioid-free anesthetic for tonsillectomy is non-inferior to standard opioid-containing anesthetic
Detailed description
Objectives: Primary: To determine if an opioid-free anesthetic provides equivalent acute postoperative pain relief in tonsillectomy. Secondary: To determine if post-operative pain at home is not significantly different with an opioid-free regimen compared to an opioid containing regimen for tonsillectomy. Study Design: Prospective, randomized, multi-center trial study Study Interventions and Measures: Subject will be randomized to 1:1 intra-operative opioid-free (OFG) vs traditional care anesthetic with opioids (TCG) group The primary endpoint is the median pain score (calculated by a blinded validated observer in the recovery room at two time intervals) between the two cohorts.
Interventions
DRUGKetorolac
Ketorolac (0.5mg/kg; maximum 15mg intravenously) will be given at end of procedure after evaluation for hemostasis.
DRUGDexmedetomidine
Dexmedetomidine (1ug/kg with maximum 50ug intravenously) will be given at beginning of procedure.
DRUGMorphine
Morphine (0.05-0.1 mg/kg intravenously) will be given intra-operatively per institutional standard clinical care.
DRUGFentanyl
Fentanyl (0.5-2 ug/kg intravenously) will be given intra-operatively per institutional standard clinical care.
Sponsors
University of Pennsylvania
University of Tennessee
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The unblinded members are the treating anesthesiologist for the case, staff who randomize, and collect and enter intra-op medications into electronic data capture (EDC). Blinded members include the subject/family members, the surgeon, staff who perform post-op assessment, physician investigator who perform any adverse event/serious adverse event (AE/SAE) assessments, statistician and data safety monitoring board (DSMB).
Intervention model description
Subject will be randomized to 1:1 intra-operative opioid-free (OFG) vs traditional care anesthetic with opioids (TCG) group.
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
1. Males or females age 2 to 18 years. 2. American Society of Anesthesiologists {ASA) ≤ 3 physical classification system 3. Girls after menarche must have a negative pregnancy test. 4. Scheduled tonsillectomy or tonsillectomy combined with adenoidectomy and/or ear tube placement at the Children's Hospital of Philadelphia (CHOP) main or ambulatory surgical centers. 5. Parental/guardian permission (informed consent) and if appropriate, child assent
Exclusion criteria
1. Current (Within the last 30 days) opioid use for pain control 2. High risk for surgical site hemorrhage, determined by bleeding disorder diagnosis or evidence or poor hemostasis 3. Multiple scheduled surgeries at the same time other than adenoidectomy and/or ear tube placement 4. History of drug abuse, chronic pain, bleeding disorder 5. Chronic disease such as sickle cell disease for which treatment with opioids may be clinically indicated 6. Significant congenital disorders, medication allergies or comorbidities, specifically a pre-disposition to bradycardia or conduction abnormalities, cyanotic cardiac disease and use of medications that would increase risk of bleeding or bradycardia. 7. History of hepatic dysfunction, renal dysfunction, thrombocytopenia, or anemia (including pre-surgery laboratory abnormalities) 8. History of hypersensitivity to NSAIDs 9. Patients with asthma, including patients who have experienced aspirin- or NSAID-sensitive asthma or a history of exacerbation when aspirin or NSAIDs are administered (e.g. bronchospasm, urticaria, etc.) 10. Subjects receiving medications that could impact metabolism of either study drug should also be excluded 11. Trisomy 21 diagnosis 12. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures. 13. Patients on a Ketogenic diet 14. Parents or subjects who do not speak English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean FLACC (Face, Legs, Activity, Cry, Consolability) Pain Score | up to 1 hour | Mean FLACC pain assessment scores are calculated 15 and 30 minutes after awakening, Scores are calculated by a blinded study team observer. Minimum Score: 0 and Maximum Score: 10. Higher scores indicate worse outcomes. One Nursing Maximum FLACC pain score is obtained by an unblinded patient Registered Nurse (RN) during the patient's Post-Anesthesia Care Unit (PACU) stay within one hour of awakening. The pain score is collected from the nursing documentation in the electronic medical record. FLACC Minimum Score: 0 and Maximum Score: 10 Higher scores indicate worse outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Sought Unplanned Medical Attention | up to post-op day 30 | Number of participants who were readmitted to the hospital and sought unplanned medical attention (phone calls, office visits, emergency department visits) by chart review and questionnaires for readmission and medical reattendance, including calls to physician |
| Number of Participants Who Were Readmitted to the the Hospital | Up to post-op day 30 | Number of participants who were readmitted to the hospital by chart review and questionnaires for readmission and medical reattendance, including calls to physician. |
| Number of Participants With Non-artefactual Percentage of Oxygen Saturation (SpO2)<90% (>30 Seconds) | up to post-op day 30 | Number of participants with non-artefactual percentage of oxygen saturation (SpO2) less than 90% for greater than 30 seconds). Collected in the recovery room and chart review |
| Number of Participants With Nausea, Vomiting, Pruritis | up to post-op day 30 | Collected in recovery room and asked in questionnaires, collected from parents on post-operative days 1, 5, and 30. |
| Family Satisfaction With Patient Recovery Based on Five-point Likert Score | assessed at post-op days 1, 5, and 30 | Follow-up questionnaire to family on post-op days 1, 5, and 30. Parents will be asked to rank how satisfied they are with their child's recovery by using these two prompts: I am satisfied with my child's recovery, and I am satisfied with my child's pain control at home. They will choose from the following options: Strongly agree = 1, Agree = 2, Undecided = 3, Disagree = 4, Strongly Disagree =5. Minimum score is 1, Max is 5. Higher scores indicate worse outcomes. Data assessed at post-op days 1, 5, and 30 were averaged. |
| Number of Participants That Experienced Any Post-operative Bleeding Throughout the Study | up to post-op day 30 | Follow-up questionnaires administered on post-operative day 1, 5, ad 30 and chart review. Question: Has your child had any bright red blood in their mouth? Answer options: Yes/No |
| Number of Patients Receiving Rescue Opioids | up to post-op day 30 | How many subjects received rescue opioids after surgery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Traditional Care Group (TCG) Traditional anesthetic with opioids group will receive institutional standard clinical care for tonsillectomy, including a standardized opioid dose at the beginning of the case and again at the end if needed. Dexmedetomidine and Ketorolac will not be used intra-operatively in this cohort to prevent confounding.
Morphine: Morphine (0.05-0.1 mg/kg intravenously) will be given intra-operatively per institutional standard clinical care.
Fentanyl: Fentanyl (0.5-2 ug/kg intravenously) will be given intra-operatively per institutional standard clinical care. | 18 |
| Opioid-Free Group (OFG) Opioid-Free group will receive institutional standard clinical care for tonsillectomy, without opioids, but including Dexmedetomidine and Ketorolac.
Ketorolac: Ketorolac (0.5mg/kg; maximum 15mg intravenously) will be given at end of procedure after evaluation for hemostasis.
Dexmedetomidine: Dexmedetomidine (1ug/kg with maximum 50ug intravenously) will be given at beginning of procedure. | 17 |
| Total | 35 |
Baseline characteristics
| Characteristic | Opioid-Free Group (OFG) | Total | Traditional Care Group (TCG) |
|---|---|---|---|
| Age, Customized | 6.47 years | 4.97 years | 3.56 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 10 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 25 Participants | 15 Participants |
| Sex: Female, Male Female | 12 Participants | 22 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 13 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 17 |
| other Total, other adverse events | 4 / 18 | 6 / 17 |
| serious Total, serious adverse events | 2 / 18 | 0 / 17 |
Outcome results
Primary
Mean FLACC (Face, Legs, Activity, Cry, Consolability) Pain Score
Mean FLACC pain assessment scores are calculated 15 and 30 minutes after awakening, Scores are calculated by a blinded study team observer. Minimum Score: 0 and Maximum Score: 10. Higher scores indicate worse outcomes. One Nursing Maximum FLACC pain score is obtained by an unblinded patient Registered Nurse (RN) during the patient's Post-Anesthesia Care Unit (PACU) stay within one hour of awakening. The pain score is collected from the nursing documentation in the electronic medical record. FLACC Minimum Score: 0 and Maximum Score: 10 Higher scores indicate worse outcomes.
Time frame: up to 1 hour
Population: Nurse maximum pain score not documented for 2 subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Traditional Care Group (TCG) | Mean FLACC (Face, Legs, Activity, Cry, Consolability) Pain Score | 15 minutes | 3.56 score on a scale | Standard Deviation 3.45 |
| Traditional Care Group (TCG) | Mean FLACC (Face, Legs, Activity, Cry, Consolability) Pain Score | 30 minutes | 2.28 score on a scale | Standard Deviation 2.7 |
| Traditional Care Group (TCG) | Mean FLACC (Face, Legs, Activity, Cry, Consolability) Pain Score | Nurse Max Score up to 1 hour | 5.29 score on a scale | Standard Deviation 4.3 |
| Opioid-Free Group (OFG) | Mean FLACC (Face, Legs, Activity, Cry, Consolability) Pain Score | 15 minutes | 2.47 score on a scale | Standard Deviation 3.04 |
| Opioid-Free Group (OFG) | Mean FLACC (Face, Legs, Activity, Cry, Consolability) Pain Score | 30 minutes | 1.88 score on a scale | Standard Deviation 2.67 |
| Opioid-Free Group (OFG) | Mean FLACC (Face, Legs, Activity, Cry, Consolability) Pain Score | Nurse Max Score up to 1 hour | 5.69 score on a scale | Standard Deviation 4.27 |
Secondary
Family Satisfaction With Patient Recovery Based on Five-point Likert Score
Follow-up questionnaire to family on post-op days 1, 5, and 30. Parents will be asked to rank how satisfied they are with their child's recovery by using these two prompts: I am satisfied with my child's recovery, and I am satisfied with my child's pain control at home. They will choose from the following options: Strongly agree = 1, Agree = 2, Undecided = 3, Disagree = 4, Strongly Disagree =5. Minimum score is 1, Max is 5. Higher scores indicate worse outcomes. Data assessed at post-op days 1, 5, and 30 were averaged.
Time frame: assessed at post-op days 1, 5, and 30
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Traditional Care Group (TCG) | Family Satisfaction With Patient Recovery Based on Five-point Likert Score | Recovery Satisfaction | 1.4 score on a scale |
| Traditional Care Group (TCG) | Family Satisfaction With Patient Recovery Based on Five-point Likert Score | Pain Control Satisfaction | 1.6 score on a scale |
| Opioid-Free Group (OFG) | Family Satisfaction With Patient Recovery Based on Five-point Likert Score | Recovery Satisfaction | 1.3 score on a scale |
| Opioid-Free Group (OFG) | Family Satisfaction With Patient Recovery Based on Five-point Likert Score | Pain Control Satisfaction | 1.5 score on a scale |
Secondary
Number of Participants That Experienced Any Post-operative Bleeding Throughout the Study
Follow-up questionnaires administered on post-operative day 1, 5, ad 30 and chart review. Question: Has your child had any bright red blood in their mouth? Answer options: Yes/No
Time frame: up to post-op day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Traditional Care Group (TCG) | Number of Participants That Experienced Any Post-operative Bleeding Throughout the Study | 0 Participants |
| Opioid-Free Group (OFG) | Number of Participants That Experienced Any Post-operative Bleeding Throughout the Study | 0 Participants |
Secondary
Number of Participants Who Sought Unplanned Medical Attention
Number of participants who were readmitted to the hospital and sought unplanned medical attention (phone calls, office visits, emergency department visits) by chart review and questionnaires for readmission and medical reattendance, including calls to physician
Time frame: up to post-op day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Traditional Care Group (TCG) | Number of Participants Who Sought Unplanned Medical Attention | 1 Participants |
| Opioid-Free Group (OFG) | Number of Participants Who Sought Unplanned Medical Attention | 3 Participants |
Secondary
Number of Participants Who Were Readmitted to the the Hospital
Number of participants who were readmitted to the hospital by chart review and questionnaires for readmission and medical reattendance, including calls to physician.
Time frame: Up to post-op day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Traditional Care Group (TCG) | Number of Participants Who Were Readmitted to the the Hospital | 1 Participants |
| Opioid-Free Group (OFG) | Number of Participants Who Were Readmitted to the the Hospital | 0 Participants |
Secondary
Number of Participants With Nausea, Vomiting, Pruritis
Collected in recovery room and asked in questionnaires, collected from parents on post-operative days 1, 5, and 30.
Time frame: up to post-op day 30
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Traditional Care Group (TCG) | Number of Participants With Nausea, Vomiting, Pruritis | Nausea | 2 participants |
| Traditional Care Group (TCG) | Number of Participants With Nausea, Vomiting, Pruritis | Vomiting | 2 participants |
| Traditional Care Group (TCG) | Number of Participants With Nausea, Vomiting, Pruritis | pruritis | 0 participants |
| Opioid-Free Group (OFG) | Number of Participants With Nausea, Vomiting, Pruritis | Vomiting | 0 participants |
| Opioid-Free Group (OFG) | Number of Participants With Nausea, Vomiting, Pruritis | Nausea | 1 participants |
| Opioid-Free Group (OFG) | Number of Participants With Nausea, Vomiting, Pruritis | pruritis | 0 participants |
Secondary
Number of Participants With Non-artefactual Percentage of Oxygen Saturation (SpO2)<90% (>30 Seconds)
Number of participants with non-artefactual percentage of oxygen saturation (SpO2) less than 90% for greater than 30 seconds). Collected in the recovery room and chart review
Time frame: up to post-op day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Traditional Care Group (TCG) | Number of Participants With Non-artefactual Percentage of Oxygen Saturation (SpO2)<90% (>30 Seconds) | 1 Participants |
| Opioid-Free Group (OFG) | Number of Participants With Non-artefactual Percentage of Oxygen Saturation (SpO2)<90% (>30 Seconds) | 1 Participants |
Secondary
Number of Patients Receiving Rescue Opioids
How many subjects received rescue opioids after surgery
Time frame: up to post-op day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Traditional Care Group (TCG) | Number of Patients Receiving Rescue Opioids | 9 Participants |
| Opioid-Free Group (OFG) | Number of Patients Receiving Rescue Opioids | 11 Participants |