Effect of Over-the-counter Analgesics on Postoperative Pain

In 2011, a randomized controlled trial compared acetaminophen, acetaminophen + ibuprofen, and acetaminophen + codeine for post-operative pain relief after Mohs surgery. In this study, the combination of acetaminophen + ibuprofen was shown to be superior to the other treatment groups at controlling postoperative pain. The study also detailed the timing at which patients experienced pain after cutaneous reconstruction, with peak pain scores occurring at 4 hours post-op for all three groups. Since its publication, the as needed dosage of acetaminophen alternated with ibuprofen has become the standard of care for most patients undergoing cutaneous reconstructive surgery. Additionally, studies from multiple disciplines including cutaneous surgery, emergency medicine, otolaryngology and obstetrics have found that use of non-steroidal anti-inflammatories pose no greater incidence of side effects.

Given that peak pain levels occur approximately four hours after cutaneous reconstruction, likely due to the cessation of lidocaine or other local numbing medications, patients may benefit from additional pain relief during this critical time period. However, it is standard practice to start acetaminophen and ibuprofen only as needed when pain begins. Further, given the short half-life of ibuprofen (2 hours), it is unlikely that this medication taken in the immediate postoperative period would be of benefit at the four hour time mark. Therefore, we theorize that the one-time dosage of a long-acting non-steroidal anti-inflammatory taken upon completion of cutaneous surgery may be superior to the as needed dosing of acetaminophen and ibuprofen.

Study Overview

• Status: Completed
• Conditions: Pain Management
• Intervention / Treatment: Drug: Naproxen; Drug: Acetaminophen (Standard of Care); Drug: ibuprofen

Detailed Description

Upon completion of informed consent, enrolled participants will be randomized to one of two treatment groups.

Group 1 (intervention group): will receive a one-time, mandatory dose of Naproxen sodium 440 mg immediately following completion of cutaneous reconstruction. For a period of 24 hours after surgery, patients will then be instructed to use acetaminophen as needed per manufacturer instructions not to exceed 4 g in a 24 hour period. Patients will not be permitted to use additional nonsteroidal analgesics during the 24 hour period. Patients will be asked to record pain scales in a pain diary at time points 0, 2, 4, 6, 8, 10 and 24 hours after surgery as well as the amount and timing of breakthrough pain medication (acetaminophen). Patients will be contacted the day following their procedure by the Principal Investigator and their responses will be recorded. Upon recording of the patient's pain diary, their enrollment in the study is complete.

Group 2 (control group): will not receive any mandatory dose of postoperative analgesic. As is considered standard of care, these patients will be instructed to alternate use of ibuprofen and acetaminophen on an as needed basis per manufacturer instructions. The dose of acetaminophen is not to exceed 4 g in a 24 hour period. The dose of ibuprofen is not to exceed 1200 mg in a 24 hour period. Patients will be asked to record pain scales in a pain diary at time points 0, 2, 4, 6, 8, 10 and 24 hours after surgery as well as the amount and timing of breakthrough pain medication (acetaminophen or ibuprofen). Patients will be contacted the day following their procedure by the Principal Investigator and their responses will be recorded. Upon recording of the patient's pain diary, their enrollment in the study is complete.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Clairton, Pennsylvania, United States, 15025
      • Zitelli & Brodland Skin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients undergoing Mohs micrographic surgery with same-day reconstruction on the head/neck

Exclusion Criteria:

• Second intention wound healing Operative site not on head and neck Self-described allergies to acetaminophen or any non-steroidal anti-inflammatory medication Pre-existing pain condition requiring analgesics History of bleeding or clotting disorder Recent history of upper gastrointestinal bleeding or ulcers Advanced liver disease or renal impairment Pregnancy Current use of anticoagulant (examples: aspirin, clopidogrel, warfarin, apixaban)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Naproxen; These patients receive a one-time dose of naproxen at surgery completion. They are instructed to take acetaminophen as needed for additional pain	Drug: Naproxen; Naproxen given immediately post-operatively following Mohs surgery reconstruction; Drug: Acetaminophen (Standard of Care); Acetaminophen alternated with ibuprofen on an as needed, patient directed basis
Active Comparator: Control; These patients received 'standard of care' use of ibuprofen in combination with acetaminophen in a patient directed manner for pain control	Drug: Acetaminophen (Standard of Care); Acetaminophen alternated with ibuprofen on an as needed, patient directed basis; Drug: ibuprofen; Ibuprofen alternated with acetaminophen in a patient directed manner for as needed pain control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported pain score	Recorded using a visual analog scale and taken at defined time intervals during postoperative period	10 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional pain medication used	Amount of as-needed dosing taken by patients for pain control	10 hours

Collaborators and Investigators

• Sponsor: Zitelli & Brodland Skin Cancer Center

Publications and helpful links

General Publications

• Watson H, Hildebolt C, Rowland K. Pain Relief with Combination Acetaminophen/Codeine or Ibuprofen following Third-Molar Extraction: A Systematic Review and Meta-Analysis. Pain Med. 2022 May 30;23(6):1176-1185. doi: 10.1093/pm/pnab334.
• Sniezek PJ, Brodland DG, Zitelli JA. A randomized controlled trial comparing acetaminophen, acetaminophen and ibuprofen, and acetaminophen and codeine for postoperative pain relief after Mohs surgery and cutaneous reconstruction. Dermatol Surg. 2011 Jul;37(7):1007-13. doi: 10.1111/j.1524-4725.2011.02022.x. Epub 2011 May 11.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: April 21, 2025
• First Submitted That Met QC Criteria: April 21, 2025
• First Posted (Actual): April 29, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Gout Suppressants; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Acetaminophen; Naproxen; Ibuprofen
• Other Study ID Numbers: 1344913

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No