Postoperative Pain
Conditions
Keywords
Acetaminophen, Postoperative pain, Sinus Surgery
Brief summary
The comparative efficacy of intravenous (IV) to oral (PO-'per os') acetaminophen in the management of postoperative pain is understudied and largely unknown. In this observer blinded randomized clinical trial, investigators aim to determine the comparative efficacy of PO (preoperative) vs. IV (intraoperative) acetaminophen in a sinus surgery population.
Detailed description
The comparative efficacy of intravenous (IV) to oral (PO-'per os') acetaminophen is understudied and largely unknown. Intravenous acetaminophen has been available since 2010 (http://www.accessdata.fda.gov/drugsatfda\_docs/label/2010/022450lbl.pdf) and has proven superiority over placebo in human clinical trials. It is clearly advantageous in patients who cannot take oral medications. Similarly, oral acetaminophen has proven efficacy in the management of postoperative pain. However, in patients who can receive either formulation the incremental cost of the IV formulation, both to the Health System and patient, is substantial. This incremental cost would be justifiable if there were clear efficacy or safety data to support the preferential use of IV over PO acetaminophen. However, there is no evidence of superior safety and there are only two studies to our knowledge investigating the question of comparative efficacy. Fenlon et al. randomized 130 patients undergoing 3rd molar (i.e., wisdom tooth) removal to IV vs. PO acetaminophen and found that PO acetaminophen was non-inferior to IV acetaminophen. The primary endpoint was postoperative pain score 1h after surgery. No safety concerns were identified in either group. Pettersson et al. randomized cardiac surgery patients to IV or PO acetaminophen, starting immediately postoperatively through the following morning, and found a significant opioid sparing effect of IV acetaminophen but no difference in pain scores or nausea. IV acetaminophen avoids first-pass hepatic metabolism and therefore generates higher serum and cerebrospinal fluid (CSF)/brain levels than does PO acetaminophen (http://ofirmev.com/Pharmacokinetics/). Based on the pharmacokinetic data, one can hypothesize that IV acetaminophen would be superior to PO acetaminophen at time points where serum and/or cerebrospinal fluid drug levels are higher.
Interventions
1000mg oral acetaminophen + 400mg oral celecoxib given within one hour of incision
400mg oral celecoxib given within one hour of incision + 1000mg IV acetaminophen within one hour prior to anesthetic emergence.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients aged 18 years or older * Undergoing elective sinus surgery at Zale Lipshy Hospital
Exclusion criteria
* Inability of the patient to follow directions or comprehend either English or Spanish language. * Disorders of the liver which would make acetaminophen contraindicated (such as hepatitis, liver failure, prior liver transplant, etc). * Patients with chronic pain manifest by a baseline pain score \> 4/10 * Chronic opioid use (\>2 weeks continuously), or illicit drug abuse * Body weight \< 50 kg. * Patients with contraindications to any of the study drugs (such as Malignant Hyperthermia susceptible, celecoxib or sulfa allergy, etc.). * Patients who have taken analgesic medications on the morning of surgery (prior to arrival). * Allergy to acetaminophen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Pain Score on the Scale of 10 (0=No Pain and 10=Worst Pain) | 1-h postoperatively | Pain score on the scale of 10 at 1-h postoperatively in the Post-Anesthesia Care Unit (PACU) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Morphine Equivalents of Postoperative Opioid Usage | an expected average of 6 hours | Total amount of postoperative opioid usage at Postoperative Anesthesia Care Unit (PACU), an expected average of 6 hours |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Acetaminophen Oral Acetaminophen 1-hour before surgery
Oral Acetaminophen: 1000mg oral acetaminophen + 400mg oral celecoxib given within one hour of incision | 55 |
| Intravenous Acetaminophen Intravenous Acetaminophen within 1-hour prior to anesthetic emergence
Intravenous acetaminophen: 400mg oral celecoxib given within one hour of incision + 1000mg IV acetaminophen within one hour prior to anesthetic emergence. | 55 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 4 | 5 |
Baseline characteristics
| Characteristic | Intravenous Acetaminophen | Oral Acetaminophen | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 11 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants | 44 Participants | 86 Participants |
| Age, Continuous | 54.0 years STANDARD_DEVIATION 15.7 | 51.5 years STANDARD_DEVIATION 16.3 | 52.7 years STANDARD_DEVIATION 16 |
| Region of Enrollment United States | 55 participants | 55 participants | 110 participants |
| Sex: Female, Male Female | 20 Participants | 21 Participants | 41 Participants |
| Sex: Female, Male Male | 35 Participants | 34 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 50 |
| other Total, other adverse events | 3 / 51 | 6 / 50 |
| serious Total, serious adverse events | 0 / 51 | 0 / 50 |
Outcome results
Primary
Postoperative Pain Score on the Scale of 10 (0=No Pain and 10=Worst Pain)
Pain score on the scale of 10 at 1-h postoperatively in the Post-Anesthesia Care Unit (PACU)
Time frame: 1-h postoperatively
Population: Subjects undergoing Functional Endoscopic Sinus Surgery were enrolled to the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Postoperative Pain Score on the Scale of 10 (0=No Pain and 10=Worst Pain) | 2 units on a scale |
| Intravenous Acetaminophen | Postoperative Pain Score on the Scale of 10 (0=No Pain and 10=Worst Pain) | 2 units on a scale |
p-value: 0.252Wilcoxon (Mann-Whitney)
Secondary
Morphine Equivalents of Postoperative Opioid Usage
Total amount of postoperative opioid usage at Postoperative Anesthesia Care Unit (PACU), an expected average of 6 hours
Time frame: an expected average of 6 hours
Population: Subjects undergoing Functional Endoscopic Sinus Surgery were enrolled to the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Acetaminophen | Morphine Equivalents of Postoperative Opioid Usage | 5 Morphine equivalent (mg) |
| Intravenous Acetaminophen | Morphine Equivalents of Postoperative Opioid Usage | 5 Morphine equivalent (mg) |
p-value: 0.402Wilcoxon (Mann-Whitney)