Adenotonsillectomy, Analgesia, Surgery
Conditions
Keywords
Pediatric Otolaryngology, Steroid, Placebo, Post-operative pain
Brief summary
The goal of this study is determine if an oral systemic course of steroids is a safe and effective option in lowering pain and complications following adenotonsillectomy in various pediatric age groups. A double blind, placebo-controlled randomized clinical trial of steroids (dexamethasone) versus placebo postoperatively will be performed. Investigators will determine if there is a difference in post-operative pain and complications between groups.
Detailed description
Purpose: To determine if post-operative dexamethasone is a safe and effective option in the reduction of post-operative pain and morbidity following adenotonsillectomy in various pediatric age groups. Methods: The subject population will be patients between the ages of 3 and 17 who will undergo adenotonsillectomy. The study will consist of two double-blinded arms - patients receiving a course of oral dexamethasone (doses on post-operative days 2, 4, and 6; 0.5 mg/kg; max dose: 20 mg) in addition to standard pain control regimen and patients receiving an oral placebo course in addition to standard pain control regimen. In the diary they will receive, patients or caregivers will record when specific pain medications were taken each day, a symptoms survey, and pain ratings measured by the Wong-Baker FACES Pain Rating Scale. Patients are able to return their diary at a post-operative appointment at CHP Main, through email by scanning the diary or taking pictures with their phone, or through mailing in the survey in a pre-stamped envelope. Demographic information such as age, race, gender, and household income will be extracted from the diary and the electronic medical record. Information such as surgical technique, concurrent operations, post-operative pain prescription (types, weight based dosage, and total days prescribed) will be extracted from the electronic medical record and recorded as well. Outcomes measured will include pain scale rating and rates of complications between the two groups. Significance: If it can be demonstrated that dexamethasone after adenotonsillectomy can reduce pain, complications, or need for opioid analgesics without appreciable side effects, a strong argument can be made for the addition of this inexpensive medication to routine post-operative adenotonsillectomy care. This would help with limiting the burden of clinical course of tonsillectomy. The primary and secondary outcome measures were refined prior to analysis. Originally, the primary outcome measure was average pain burden defined as average pain over 14 post-operative days before and after medications. However, study medication was not administered until day 2, and the power analysis was based on a study by Palme et al (2000) that compared mean pain ratings on postoperative days 2-8. Therefore, the primary outcome was revised to average pain over 2-8 post-operative days before medications. Average pain over 2-8 post-operative after medications was added as a secondary outcome. The original primary outcome combined analysis of pain before and after medication into one measure. However, pain scores were more commonly reported prior to medication than after. Due to missing post-medication scores, it was determined that the analysis would be more appropriately conducted separately for pain scores before and after medication.
Interventions
DRUGDexamethasone
IV Dexamethasone Sodium Phosphate will be prescribed orally at a dose of 0.5mg/kg with a max dose of 20mg to be taken the morning of days 2, 4, and 6 post-operatively. The Dexamethasone will be mixed by the parents with 5mL of pre-packaged cherry syrup
DRUGIbuprofen
Ibuprofen will be prescribed at 10 mg/kg to be taken every 6 hours for the first three post-operative days. After the first three days, the subject should take the ibuprofen every 6 hours as needed for pain control. The daily dose of ibuprofen is not to exceed 1200mg or more than 4 individual doses. It will be prescribed in liquid suspension form for ease of use in pediatric populations. Subjects or parents will purchase this medication and dosage will be given to subjects in easy-to-understand language.
DRUGAcetaminophen
Acetaminophen will be prescribed at 15mg/kg to be taken every 4 hours for the first three days, except when sleeping. After the first three days, the subject should take the acetaminophen every 4 hours as needed for pain control. The daily dose of acetaminophen is not to exceed 5 doses in 24 hours. It will be prescribed in liquid suspension form for ease of use in pediatric populations. Subjects or parents will purchase this medication and dosage will be given to subjects in easy-to-understand language.
DRUGPlacebo
An equal volume of water will be prescribed to patients (0.5mg/kg) with a max dose of 20mg to be taken the morning of days 2, 4, and 6 post-operatively. The placebo (water) will be mixed by the parents with 5mL of pre-packaged cherry syrup.
Sponsors
David Chi, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double blind placebo controlled randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patients age 3 - 17 undergoing adenotonsillectomy meet inclusion criteria
Exclusion criteria
* Patients with Down syndrome * Patients with a history of coagulopathy * Patients with craniofacial abnormalities other than plagiocephaly or submucous cleft palate (SMCP) * Caregivers who cannot speak, read, or write in English proficiently * Patients who take systemic corticosteroids during the enrollment period * Patients who take opioids during the enrollment period * Patients who take chronic opioids * Patients who are pregnant * Patients with allergy to or contraindication for taking any of the study medications * Patients who have the inability to communicate * Patients who have the inability to localize pain * Patients who have type 1 diabetes * Patients who have type 2 diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Pain Over 2-8 Post-operative Days Before Medications | 2-8 days post-operatively | Average pain over 2-8 post-operative days before medications. This is quantified using the validated Wong-Baker FACES pain metric. The scale is from 0 to 10 with 10 being worse outcome. Patients receive a take-home pain diary and for 14 days report their maximum pain both before and after taking each pain medication. The mean of the pain ratings prior to taking pain medications from post-operative days 2-8 will be the primary outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ED (Emergency Department) or Urgent Care Visits | 30 days post-operatively | Number of emergency department or urgent care visits in 30 post-operative days - assessed via the electronic medical record and the take-home pain diary. |
| Average Pain Burden Post-medication | 2-8 days post-operatively | Average pain over 2-8 post-operative days after medications. This is quantified using the validated Wong-Baker FACES pain metric. The scale is from 0 to 10 with 10 being worse outcome. Patients receive a take-home pain diary and for 14 days report their maximum pain both before and after taking each pain medication. The mean of the pain ratings one hour after talking pain medications from post-operative days 2-8 will be a secondary outcome measure. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pain Relief Satisfaction | 14 days post-operatively | Score assigned by the patient at the end of 14 post-operative days in the take-home pain diary using a 5-point Likert scale of 0 (strongly disagree) to 4 (strongly agree). Patients will respond to the following statement I am happy with the pain relief I received in the last 14 days with responses ranging from strongly agree to strongly disagree. The responses will be assigned a numerical value and the average value for all subjects in the group will be reported as the overall pain relief satisfaction. Higher scores indicate a better outcome. |
| Frequency of Request for Opioid Medication | 14 days post-operatively | Number of requests for opioid medication in 14 post-operative days - assessed via the electronic medical record and the take-home pain diary. |
| Frequency of Post-operative Oropharyngeal Bleed | 30 days post-operatively | Number of post-operative oropharyngeal bleeds in 30 post-operative days - assessed via the electronic medical record. |
| Need for Follow-up Appointment | Two months post-operatively | Does the parent/guardian believe his/her child would require a follow-up appointment - assessed using the individual pain diary. |
| Household Income | 14 days post-operatively | Total household income ranges will be assessed in the take-home pain diary and reported. |
| Number of Readmissions | 30 days post-operatively | Number of hospitalizations after discharge in 30 days - assessed using the electronic medical record and the take-home pain diary. |
| Side Effects of Medications | 14 days post-operatively | Number of side effects assessed daily including bleeding from mouth or throat, anxiety, difficulty breathing, nausea or vomiting, stomach pain/discomfort, fever (100.4F and higher) |
| Night-time Awakenings | 14 days post-operatively | Number of night-time awakenings reported in 14 days - assessed via the take-home pain diary. |
| Post-operative Nursing Phone Calls | 30 days post-operatively | Number of post-operative phone calls to nursing staff, obtained using the electronic medical record up to 30 days post-operatively. |
| Duration of Hospital Admission | 30 days post-operatively | Number of days in the hospital after surgery in 30 post-operative days - assessed via the electronic medical record |
| Education Level | 14 days post-operatively | Using the take-home pain diary, parents/guardians of the patients will identify the highest level of education achieved by anyone in the household. |
| Frequency of Each Analgesic Used | 14 days post-operatively | In the take-home pain diary, patients will place an 'x' on each time block every day that medication was given for each of the three medications. The frequencies will be summed for a total number and averaged within each group to determine the average number of times of each analgesic used. |
| Duration of Each Analgesic Used | 14 days post-operatively | Using the results of the take-home pain diary, the average number of days of use of each analgesic for each group will be calculated. The last day after which there is no subsequent use of analgesic will define the end-point of the duration of use. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexamethasone IV Dexamethasone Sodium Phosphate will be prescribed orally at a dose of 0.5mg/kg with a max dose of 20mg to be taken the morning of days 2, 4, and 6 post-operatively. The Dexamethasone will be mixed by the parents with 5mL of pre-packaged cherry syrup.
Patients will also receive acetaminophen and ibuprofen. Acetaminophen will be prescribed at 15mg/kg to be taken every 4 hours for the first three days, except when sleeping. Ibuprofen will be prescribed at 10 mg/kg to be taken every 6 hours for the first three post-operative days.
Patients and parents/caregivers will be asked to complete a pain diary which will be used to determine the level of pain control achieved with this regimen. Families will also be asked daily to check symptoms that were experienced by the child and their child's current comfortable diet. The diary will be completed by post-operative day 14. The diary will be returned via email, mail, or a post-operative appointment at the main hospital. | 105 |
| Placebo An equal volume of water will be prescribed to patients (0.5mg/kg) with a max dose of 20mg to be taken the morning of days 2, 4, and 6 post-operatively. The placebo (water) will be mixed by the parents with 5mL of pre-packaged cherry syrup.
Patients will also receive acetaminophen and ibuprofen. Acetaminophen will be prescribed at 15mg/kg to be taken every 4 hours for the first three days, except when sleeping. Ibuprofen will be prescribed at 10 mg/kg to be taken every 6 hours for the first three post-operative days.
Patients and parents/caregivers will be asked to complete a pain diary which will be used to determine the level of pain control achieved with this regimen. Families will also be asked daily to check symptoms that were experienced by the child and their child's current comfortable diet. The diary will be completed by post-operative day 14. The diary will be returned via email, mail, or a post-operative appointment at the main hospital. | 108 |
| Total | 213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 43 | 35 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Protocol Violation | 2 | 3 |
Baseline characteristics
| Characteristic | Total | Dexamethasone | Placebo |
|---|---|---|---|
| Age, Continuous | 7.1 years | 7.1 years | 6.9 years |
| Age, Customized 13-17 years old | 31 Participants | 14 Participants | 17 Participants |
| Age, Customized 3-7 years old | 120 Participants | 60 Participants | 60 Participants |
| Age, Customized 8-12 years old | 62 Participants | 31 Participants | 31 Participants |
| BMI Percentile at Baseline | 83.24 percentile | 81.04 percentile | 83.77 percentile |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 199 Participants | 97 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 7 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) White | 185 Participants | 91 Participants | 94 Participants |
| Region of Enrollment United States | 213 participants | 105 participants | 108 participants |
| Sex: Female, Male Female | 102 Participants | 48 Participants | 54 Participants |
| Sex: Female, Male Male | 111 Participants | 57 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 108 |
| other Total, other adverse events | 5 / 105 | 10 / 108 |
| serious Total, serious adverse events | 3 / 105 | 8 / 108 |
Outcome results
Primary
Average Pain Over 2-8 Post-operative Days Before Medications
Average pain over 2-8 post-operative days before medications. This is quantified using the validated Wong-Baker FACES pain metric. The scale is from 0 to 10 with 10 being worse outcome. Patients receive a take-home pain diary and for 14 days report their maximum pain both before and after taking each pain medication. The mean of the pain ratings prior to taking pain medications from post-operative days 2-8 will be the primary outcome measure.
Time frame: 2-8 days post-operatively
Population: Includes only patients who returned their pain diary (completed the study).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dexamethasone | Average Pain Over 2-8 Post-operative Days Before Medications | 4.2 score on a scale |
| Placebo | Average Pain Over 2-8 Post-operative Days Before Medications | 4.9 score on a scale |
Comparison: Null hypothesis: Average pain scores before medication will not be lower in the dexamethasone group compared with the placebo group.p-value: 0.03t-test, 1 sided
Secondary
Average Pain Burden Post-medication
Average pain over 2-8 post-operative days after medications. This is quantified using the validated Wong-Baker FACES pain metric. The scale is from 0 to 10 with 10 being worse outcome. Patients receive a take-home pain diary and for 14 days report their maximum pain both before and after taking each pain medication. The mean of the pain ratings one hour after talking pain medications from post-operative days 2-8 will be a secondary outcome measure.
Time frame: 2-8 days post-operatively
Population: Includes only patients who returned their pain diary (completed the study). One patient in the placebo group reported no post-medication pain scores.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexamethasone | Average Pain Burden Post-medication | 2.3 score on a scale |
| Placebo | Average Pain Burden Post-medication | 2.2 score on a scale |
Comparison: Null hypothesis: Average pain scores after medication will not be lower in the dexamethasone group compared with the placebo group.p-value: 0.98Wilcoxon (Mann-Whitney)
Secondary
ED (Emergency Department) or Urgent Care Visits
Number of emergency department or urgent care visits in 30 post-operative days - assessed via the electronic medical record and the take-home pain diary.
Time frame: 30 days post-operatively
Population: Excludes patients withdrawn due to protocol violations or physician decision.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dexamethasone | ED (Emergency Department) or Urgent Care Visits | 0 ED or Urgent Care Visits | 97 Participants |
| Dexamethasone | ED (Emergency Department) or Urgent Care Visits | 1 ED or Urgent Care Visit | 5 Participants |
| Dexamethasone | ED (Emergency Department) or Urgent Care Visits | 2 ED or Urgent Care Visits | 3 Participants |
| Dexamethasone | ED (Emergency Department) or Urgent Care Visits | 3 ED or Urgent Care Visits | 0 Participants |
| Placebo | ED (Emergency Department) or Urgent Care Visits | 3 ED or Urgent Care Visits | 1 Participants |
| Placebo | ED (Emergency Department) or Urgent Care Visits | 0 ED or Urgent Care Visits | 91 Participants |
| Placebo | ED (Emergency Department) or Urgent Care Visits | 2 ED or Urgent Care Visits | 2 Participants |
| Placebo | ED (Emergency Department) or Urgent Care Visits | 1 ED or Urgent Care Visit | 14 Participants |
Comparison: Null hypothesis: There will be no difference in the proportion of patients visiting the emergency department or urgent care (at least 1 time) post-operatively between dexamethasone and placebo groups.p-value: 0.07Fisher Exact
Other Pre-specified
Duration of Each Analgesic Used
Using the results of the take-home pain diary, the average number of days of use of each analgesic for each group will be calculated. The last day after which there is no subsequent use of analgesic will define the end-point of the duration of use.
Time frame: 14 days post-operatively
Other Pre-specified
Duration of Hospital Admission
Number of days in the hospital after surgery in 30 post-operative days - assessed via the electronic medical record
Time frame: 30 days post-operatively
Other Pre-specified
Education Level
Using the take-home pain diary, parents/guardians of the patients will identify the highest level of education achieved by anyone in the household.
Time frame: 14 days post-operatively
Other Pre-specified
Frequency of Each Analgesic Used
In the take-home pain diary, patients will place an 'x' on each time block every day that medication was given for each of the three medications. The frequencies will be summed for a total number and averaged within each group to determine the average number of times of each analgesic used.
Time frame: 14 days post-operatively
Other Pre-specified
Frequency of Post-operative Oropharyngeal Bleed
Number of post-operative oropharyngeal bleeds in 30 post-operative days - assessed via the electronic medical record.
Time frame: 30 days post-operatively
Other Pre-specified
Frequency of Request for Opioid Medication
Number of requests for opioid medication in 14 post-operative days - assessed via the electronic medical record and the take-home pain diary.
Time frame: 14 days post-operatively
Other Pre-specified
Household Income
Total household income ranges will be assessed in the take-home pain diary and reported.
Time frame: 14 days post-operatively
Other Pre-specified
Need for Follow-up Appointment
Does the parent/guardian believe his/her child would require a follow-up appointment - assessed using the individual pain diary.
Time frame: Two months post-operatively
Other Pre-specified
Night-time Awakenings
Number of night-time awakenings reported in 14 days - assessed via the take-home pain diary.
Time frame: 14 days post-operatively
Other Pre-specified
Number of Readmissions
Number of hospitalizations after discharge in 30 days - assessed using the electronic medical record and the take-home pain diary.
Time frame: 30 days post-operatively
Other Pre-specified
Pain Relief Satisfaction
Score assigned by the patient at the end of 14 post-operative days in the take-home pain diary using a 5-point Likert scale of 0 (strongly disagree) to 4 (strongly agree). Patients will respond to the following statement I am happy with the pain relief I received in the last 14 days with responses ranging from strongly agree to strongly disagree. The responses will be assigned a numerical value and the average value for all subjects in the group will be reported as the overall pain relief satisfaction. Higher scores indicate a better outcome.
Time frame: 14 days post-operatively
Other Pre-specified
Post-operative Nursing Phone Calls
Number of post-operative phone calls to nursing staff, obtained using the electronic medical record up to 30 days post-operatively.
Time frame: 30 days post-operatively
Other Pre-specified
Side Effects of Medications
Number of side effects assessed daily including bleeding from mouth or throat, anxiety, difficulty breathing, nausea or vomiting, stomach pain/discomfort, fever (100.4F and higher)
Time frame: 14 days post-operatively