Pain, Tonsillitis
Conditions
Keywords
Tonsillectomy, Pain, Pediatric, Opioids, Tramadol, Codeine
Brief summary
Tonsillectomy is the most common pediatric surgical procedure performed in the US. The postoperative period can be particularly painful. Codeine (usually in mixed formulation with acetaminophen) is the most commonly prescribed opioid in the US. However, evolving data questions its ability to provide optimal pain relief, while avoiding side effects, especially in the postoperative setting. Tramadol may be a better option for children in the postoperative setting due to its well-documented analgesic properties, low potential for side effects, and excellent safety profile. Seventy-two children scheduled to undergo tonsillectomy (with or without adenoidectomy) at Children's will be invited to participate in a randomized, prospective, double-blinded study to evaluate the efficacy and side effects of codeine with acetaminophen versus tramadol. Using a 10-day take-home diary, caregivers will be asked to record daily information about their child's postoperative pain and other core outcomes and domains as recommended in the recent consensus statement put forth by the Pediatric Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) (McGrath et al., 2008). This study will offer new information regarding the efficacy and side effects associated with tramadol as compared with codeine/acetaminophen (the current practice standard) in a pediatric population. Hypotheses H1: Children who receive scheduled tramadol following tonsillectomy will report better pain control than children who receive scheduled codeine/acetaminophen. H2: Children who receive scheduled tramadol following tonsillectomy will report fewer side effects than children who receive scheduled codeine/acetaminophen.
Interventions
DRUGCodeine with acetaminophen
Liquid codeine/acetaminophen (Capital® 5mL= 120mg acetaminophen/12 mg codeine) 0.72 mg/kg \[=0.3 mL/kg\] (max. 36 mg) PO Q6h, plus 0.72 mg/kg (max. 36 mg) PO Q3h pro re nata (PRN) (max. of 3 PRN doses/day)
DRUGTramadol suspension
Liquid tramadol 1.05 mg/kg \[=0.3 mL/kg\] (max. 52.5 mg) PO Q6h, plus 1.05 mg/kg (max. 52.5 mg) PO Q3h PRN (max. of 3 PRN doses/day).
Sponsors
Children's Hospitals and Clinics of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Child must be scheduled to undergo tonsillectomy (with or without adenoidectomy). * Child must be between the ages of 4 and 15 at the time of enrollment. * Child and caregiver must be English-speaking. * The same caregiver (e.g., mother) must agree to complete all study assessments with child to ensure consistency.
Exclusion criteria
* Child cannot self-assess pain due to conditions such as developmental delays, chromosomal abnormalities, and other syndromes. * Child had significant adverse effects to codeine, tramadol, or acetaminophen in the past. * Child has a known underlying seizure disorder (not febrile seizure). * Child has known underlying renal or liver dysfunction (with creatinine, aspartate aminotransferase \[AST\]/amino alanine transferase \[ALT\], above normal value for age, respectively). * Child or caregiver is not English-speaking. * The same caregiver (e.g., mother) is unable to complete all follow-up assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Two Different Liquid Pain Medications: Tramadol vs. Codeine/Acetaminophen During the Post-tonsillectomy Recovery Period. | Efficacy was assessed daily during the 10-day postoperative recovery period. | Average number of post-operative days with pain score \>4/10. Pain score assessments were administered once daily by parents using either the Numeric Rating Scale (NRS-11) (with anchors 0=no pain and 10=highest pain imaginable) for children ages 8-15 (von Baeyer et al., 2009) or the Faces Pain Scale-Revised (FPS-R) (with anchors 0=no pain and 10=highest pain imaginable) for children ages 4-10 (Hicks et al., 2001). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Side effects will be observed and recorded daily by caregivers for a total of 10 days in the take-home diary. | Parent-reported side effects entered in 10-day diary. |
Countries
United States
Participant flow
Recruitment details
The study was introduced to 137 potential subjects during or following an outpatient office evaluation with an ear/nose/throat (ENT) surgeon between February 2011 and May 2012.
Pre-assignment details
The study was introduced to 137 potential subjects, and 84 children were enrolled in the study and assigned to one of the two study arms.
Participants by arm
| Arm | Count |
|---|---|
| Capital® With Codeine Suspension Codeine with acetaminophen : Liquid codeine/acetaminophen (Capital® 5mL= 120mg acetaminophen/12 mg codeine) 0.72 mg/kg \[=0.3 mL/kg\] (max. 36 mg) PO Q6h, plus 0.72 mg/kg (max. 36 mg) PO Q3h PRN (max. of 3 PRN doses/day) | 42 |
| Tramadol Suspension Tramadol suspension : Liquid tramadol 1.05 mg/kg \[=0.3 mL/kg\] (max. 52.5 mg) PO Q6h, plus 1.05 mg/kg (max. 52.5 mg) PO Q3h PRN (max. of 3 PRN doses/day). | 42 |
| Total | 84 |
Baseline characteristics
| Characteristic | Tramadol Suspension | Capital® With Codeine Suspension | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 42 Participants | 42 Participants | 84 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 6.6 years STANDARD_DEVIATION 2.3 | 6.4 years STANDARD_DEVIATION 2.3 | 6.5 years STANDARD_DEVIATION 2.3 |
| Region of Enrollment United States | 42 participants | 42 participants | 84 participants |
| Sex: Female, Male Female | 25 Participants | 26 Participants | 51 Participants |
| Sex: Female, Male Male | 17 Participants | 16 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 38 | 35 / 36 |
| serious Total, serious adverse events | 1 / 42 | 1 / 42 |
Outcome results
Primary
Efficacy of Two Different Liquid Pain Medications: Tramadol vs. Codeine/Acetaminophen During the Post-tonsillectomy Recovery Period.
Average number of post-operative days with pain score \>4/10. Pain score assessments were administered once daily by parents using either the Numeric Rating Scale (NRS-11) (with anchors 0=no pain and 10=highest pain imaginable) for children ages 8-15 (von Baeyer et al., 2009) or the Faces Pain Scale-Revised (FPS-R) (with anchors 0=no pain and 10=highest pain imaginable) for children ages 4-10 (Hicks et al., 2001).
Time frame: Efficacy was assessed daily during the 10-day postoperative recovery period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capital® With Codeine Suspension | Efficacy of Two Different Liquid Pain Medications: Tramadol vs. Codeine/Acetaminophen During the Post-tonsillectomy Recovery Period. | 1.5 days |
| Tramadol Suspension | Efficacy of Two Different Liquid Pain Medications: Tramadol vs. Codeine/Acetaminophen During the Post-tonsillectomy Recovery Period. | 1 days |
Secondary
Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period.
Parent-reported side effects entered in 10-day diary.
Time frame: Side effects will be observed and recorded daily by caregivers for a total of 10 days in the take-home diary.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Itching | 5 participants |
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Dizziness | 15 participants |
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Fever | 11 participants |
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Headache | 12 participants |
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Rash | 1 participants |
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Constipation | 21 participants |
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Vomiting | 21 participants |
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Oversedation | 14 participants |
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Sweating | 9 participants |
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Tonsil bleed | 3 participants |
| Capital® With Codeine Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Nausea | 20 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Tonsil bleed | 0 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Nausea | 20 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Vomiting | 18 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Fever | 10 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Itching | 12 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Rash | 1 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Sweating | 7 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Dizziness | 17 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Headache | 17 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Constipation | 21 participants |
| Tramadol Suspension | Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. | Oversedation | 8 participants |