Janet H. Friday, MD, John T. Kanegaye, MD, Ian McCaslin, MD, MPH, Amy Zheng, MD, and Jim R. Harley, MD, MPH. Ibuprofen Provides Analgesia Equivalent to Acetaminophen–Codeine in the Treatment of Acute Pain in Children with Extremity Injuries: A Randomized Clinical Trial. Academic Emergency Medicine
This study compared the analgesic effectiveness of acetaminophen–codeine with that of ibuprofen for children with acute traumatic extremity pain, with the hypothesis that the two medications would demonstrate equivalent reduction in pain scores in an emergency department (ED) setting.
This was a randomized, double-blinded equivalence trial. Pediatric ED patients 5 to 17 years of age with acute traumatic extremity pain received acetaminophen–codeine (1 mg⁄ kg as codeine, maximum 60 mg) or ibuprofen (10 mg⁄ kg, maximum 400 mg). The patients provided Color Analog Scale (CAS) pain scores at baseline and at 20, 40, and 60 minutes after medication administration. The primary outcome measured was the difference in changes in pain score at 40 minutes, compared to a previously described minimal clinically significant change in pain score of 2 cm. The difference was defined as (change in ibuprofen CAS score from baseline) – (change in acetaminophen–codeine CAS score from baseline); negative values thus favor the ibuprofen group. Additional outcomes included need for rescue medication and adverse effects.
The 32 acetaminophen–codeine and the 34 ibuprofen recipients in our convenience sample had indistinguishable pain scores at baseline. The intergroup differences in pain score change at 20 minutes ()0.6, 95% confidence interval [CI] = )1.5 to 0.3), 40 minutes ()0.4, 95% CI = )1.4 to 0.6), and 60 minutes (0.2, 95% CI = )0.8 to 1.2) were all less than 2 cm. Adverse effects were minimal: vomiting (one patient after acetaminophen–codeine), nausea (one patient after ibuprofen), and pruritus (one after acetaminophen– codeine). The three patients in each group who received rescue medications all had radiographically demonstrated fractures or dislocations.
This study found similar performance of acetaminophen–codeine and ibuprofen in analgesic effectiveness among ED patients aged 5–17 years with acute traumatic extremity pain. Both drugs provided measurable analgesia. Patients tolerated them well, with few treatment failures and minimal adverse effects.
Study #2: A Randomized Clinical Trial of Ibuprofen Versus Acetaminophen With Codeine for Acute Pediatric Arm Fracture Pain.
Drendel AL, Gorelick MH, Weisman SJ, Lyon R, Brousseau DC, Kim MK. A Randomized Clinical Trial of Ibuprofen Versus Acetaminophen With Codeine for Acute Pediatric Arm Fracture Pain. Ann Emerg Med. Oct 2009. Volume 54, p553.
To compare the treatment of pain in children with arm fractures by ibuprofen 10 mg/kg versus acetaminophen with codeine 1 mg/kg/dose (codeine component).
This was a randomized, double-blind, clinical trial of children during the first 3 days after discharge from the emergency department (ED). The primary outcome was failure of the oral study medication, defined as use of the rescue medication. Pain medication use, pain scores, functional outcomes, adverse effects, and satisfaction were also assessed.
Three hundred thirty-six children were randomized to treatment, 169 to ibuprofen and 167 to acetaminophen with codeine; 244 patients were analyzed. Both groups used a median of 4 doses (interquartile range 2, 6.5). The proportion of treatment failures for ibuprofen (20.3%) was lower than for acetaminophen with codeine (31.0%), though not statistically significant (difference=10.7%; 95% confidence interval -0.2 to 21.6). The proportion of children who had any function (play, sleep, eating, school) affected by pain when pain was analyzed by day after injury was significantly lower for the ibuprofen group. Significantly more children receiving acetaminophen with codeine reported adverse effects and did not want to use it for future fractures.
Ibuprofen was at least as effective as acetaminophen with codeine for outpatient analgesia for children with arm fractures. There was no significant difference in analgesic failure or pain scores, but children receiving ibuprofen had better functional outcomes. Children receiving ibuprofen had significantly fewer adverse effects, and both children and parents were more satisfied with ibuprofen. Ibuprofen is preferable to acetaminophen with codeine for outpatient treatment of children with uncomplicated arm fractures.
Study #3: 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. Epub 2007 Nov 26. A randomized controlled trial comparing acetaminophen plus ibuprofen versus acetaminophen plus codeine plus caffeine after outpatient general surgery. Mitchell A, van Zanten SV, Inglis K, Porter G.
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.
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.
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).
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.
This last study is interesting in that it used a combination of acetaminophen and ibuprofen. In my opinion, a better study would have been to have a 3-arm trial comparing acetaminophen with codeine versus acetaminophen versus ibuprofen. This way there would be a more clear answer of which pain medication was superior. Many surgeons do not recommend ibuprofen post-operatively due to the dogma of increased post-operative bleeding. Larger trials will be necessary to see if ibuprofen can be safely used in these patients as there were only 72 patients in the combination acetaminophen and ibuprofen trial. However, these three studies provide us with some food for thought and some reassurance, that ibuprofen is at least as effective as acetaminophen with codeine with fewer side effects and higher patient and parental satisfaction. The next study would be to compare ibuprofen against hydrocodone and acetaminophen to see if there is any significant difference between these two regimens.