Adenoidectomy, Tonsillectomy
Conditions
Brief summary
Acetaminophen is frequently used as an adjunct for pain management in pediatric surgical patients. The drug is available in an over the counter, inexpensive oral form as well as a considerably more expensive intravenous form. This study will compare opioid requirements and acetaminophen plasma levels post operatively for two dosing regimens to compare oral versus intravenous routes given pre operatively.
Detailed description
The primary purpose of this study is to compare opioid utilization in post-operative patients undergoing tonsillectomy and adenoidectomy, between IV and PO acetaminophen. Secondarily, it will provide information regarding possible cost savings, pharmacokinetics and safety between these two regimens.
Interventions
DRUGAcetaminophen
already included in arm/group descriptions
Sponsors
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patients ages 3 years to 17 years scheduled for tonsillectomy and adenoidectomy for obstructive sleep apnea with or without additional minor procedures such as sleep endoscopy, unilateral or bilateral myringotomy, insertion of tympanostomy tubes and/or ear exam. ( Minor additional procedures that are frequently combined with tonsillectomy and adenoidectomy but are not commonly considered to have pain that is significantly greater than the tonsillectomy and adenoidectomy).
Exclusion criteria
* Patients who meet University of California Davis Children's Hospital (UCDCH) criteria for Pediatric Intensive Care Unit (PICU) admission: on home oxygen pre-operatively, exhibit airway obstruction when awake (stertor above larynx, stridor at larynx), sleep study with apnea hypoxia index greater than 25 or sleep oxygen saturation nadir \<80%, cardiac disease, difficult intubation. * Patients with a known allergy to acetaminophen * Patients with known hepatic insufficiency or severe hepatic disease * Patients with known Glucose-6-phosphate dehydrogenase (G6PD) deficiency * Patients who are malnourished (ie lower levels of glutathione) * Patients with severe renal impairment as defined by calculated creatinine clearance \<20 ml/min (per modified Schwarz equation) * Patients who are pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Dose of Opioid | Within 24hrs | Total dose of opioid, in morphine equivalents, that the patient receives for breakthrough pain in the 24 hour period following surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Severe Pain Score of 7 or Higher | 24 hrs period following surgery | A secondary endpoint is the proportion of patients with pain scores in the severe pain range (7 or higher) on numeric pain rating scale of 0 to 10; higher score more severe. |
| Plasma Acetaminophen Level 1 - End of Surgery | at the end of surgery, about 1 hour after IV Dose | mg/L acetaminophen in the plasma at the end of surgery |
| Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration | Outcome will be measured 3hrs post first IV Dose | mg/L acetaminophen in the plasma 3 hours after IV study drug administration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Acetaminophen Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.
Acetaminophen | 30 |
| Intravenous Acetaminophen Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.
Acetaminophen | 36 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive study medications: red dye allergy | 0 | 1 |
| Overall Study | Did not receive study medications: Study drug not available prior to anesthesia induction | 6 | 0 |
| Overall Study | Did not receive study medications: vomited after ingestion | 1 | 0 |
Baseline characteristics
| Characteristic | Oral Acetaminophen | Intravenous Acetaminophen | Total |
|---|---|---|---|
| Age, Continuous | 4 years | 6 years | 5 years |
| Percentile weight for age | 55.0 percentile | 45.0 percentile | 49.5 percentile |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 15 Participants | 14 Participants | 29 Participants |
| Sex: Female, Male Male | 15 Participants | 22 Participants | 37 Participants |
| Weight (kg) | 19.3 kg | 20.6 kg | 20.2 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 36 |
| other Total, other adverse events | 0 / 30 | 0 / 36 |
| serious Total, serious adverse events | 0 / 30 | 0 / 36 |
Outcome results
Primary
Total Dose of Opioid
Total dose of opioid, in morphine equivalents, that the patient receives for breakthrough pain in the 24 hour period following surgery.
Time frame: Within 24hrs
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Total Dose of Opioid | 147.6 mcg/kg |
| Intravenous Acetaminophen | Total Dose of Opioid | 125.4 mcg/kg |
p-value: 0.12795% CI: [-2.5, 44.2]Wilcoxon (Mann-Whitney)
Secondary
Plasma Acetaminophen Level 1 - End of Surgery
mg/L acetaminophen in the plasma at the end of surgery
Time frame: at the end of surgery, about 1 hour after IV Dose
Population: 2 patients in Oral did not have sample obtained for level; 1 patient in IV had value below 10 mg/L limit of quantification
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Plasma Acetaminophen Level 1 - End of Surgery | 22 mg/L |
| Intravenous Acetaminophen | Plasma Acetaminophen Level 1 - End of Surgery | 20 mg/L |
p-value: 0.10995% CI: [-1, 6]Wilcoxon (Mann-Whitney)
Secondary
Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration
mg/L acetaminophen in the plasma 3 hours after IV study drug administration
Time frame: Outcome will be measured 3hrs post first IV Dose
Population: Acetaminophen plasma levels obtained 3 hours after start of the IV study drug in patients with samples obtained; these were not available for 8 Oral and 9 IV subjects.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration | 18 mg/L |
| Intravenous Acetaminophen | Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration | 11 mg/L |
p-value: 0.000195% CI: [4, 8]Wilcoxon (Mann-Whitney)
Secondary
Proportion of Patients With Severe Pain Score of 7 or Higher
A secondary endpoint is the proportion of patients with pain scores in the severe pain range (7 or higher) on numeric pain rating scale of 0 to 10; higher score more severe.
Time frame: 24 hrs period following surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Acetaminophen | Proportion of Patients With Severe Pain Score of 7 or Higher | 15 Participants |
| Intravenous Acetaminophen | Proportion of Patients With Severe Pain Score of 7 or Higher | 17 Participants |
p-value: 0.851Chi-squared