A randomized controlled trial comparing acetaminophen plus ibuprofen versus acetaminophen plus codeine plus caffeine after outpatient general surgery

J Am Coll Surg. 2008 Mar;206(3):472-9. doi: 10.1016/j.jamcollsurg.2007.09.006. Epub 2007 Nov 26.


Background: Narcotics are used extensively in outpatient general surgery but are often poorly tolerated with variable efficacy. Acetaminophen combined with NSAIDs is a possible alternative. The objective of this study was to compare the efficacy of acetaminophen, codeine, and caffeine (Tylenol No. 3) with acetaminophen and ibuprofen for management of pain after outpatient general surgery procedures.

Study design: A double-blind randomized controlled trial was performed in patients undergoing outpatient inguinal/umbilical/ventral hernia repair or laparoscopic cholecystectomy. Patients were randomized to receive acetaminophen plus codeine plus caffeine (Tylenol No. 3) or acetaminophen plus ibuprofen (AcIBU) 4 times daily for 7 days or until pain-free. Pain intensity, measured four times daily by visual analogue scale, was the primary outcome. Secondary end points included incidence of side effects, patient satisfaction, number of days until patient was pain-free, and use of alternative analgesia.

Results: One hundred forty-six patients were randomized (74 Tylenol No. 3 and 72 AcIBU), and 139 (95%) patients completed the study. No significant differences in mean or maximum daily visual analogue scale scores were identified between the 2 groups, except on postoperative day 2, when pain was improved in AcIBU patients (p = 0.025). During the entire week, mean visual analogue scale score was modestly lower in AcIBU patients (p = 0.018). More patients in the AcIBU group, compared with Tylenol No. 3, were satisfied with their analgesia (83% versus 64%, respectively; p = 0.02). There were more side effects with Tylenol No. 3 (57% versus 41%, p = 0.045), and the discontinuation rate was also higher in Tylenol No. 3-treated patients (11% versus 3%, p = 0.044).

Conclusions: When compared with Tylenol No. 3, AcIBU was not an inferior analgesic and was associated with fewer side effects and higher patient satisfaction. AcIBU is an effective, low-cost, and safe alternative to codeine-based narcotic analgesia for outpatient general surgery procedures.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / administration & dosage*
  • Adolescent
  • Adult
  • Aged
  • Ambulatory Surgical Procedures / adverse effects*
  • Analgesics / administration & dosage*
  • Caffeine / administration & dosage
  • Central Nervous System Stimulants / administration & dosage
  • Codeine / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Ibuprofen / administration & dosage*
  • Male
  • Middle Aged
  • Pain Measurement
  • Pain, Postoperative / drug therapy*
  • Pain, Postoperative / etiology
  • Prospective Studies
  • Treatment Outcome


  • Analgesics
  • Central Nervous System Stimulants
  • Acetaminophen
  • Caffeine
  • Codeine
  • Ibuprofen