Post-Tonsillectomy Bleeding: Ibuprofen Versus Acetaminophen

Abstract

Source: Diercks GR, Comins J, Bennett K, et al. Comparison of ibuprofen vs acetaminophen and severe bleeding risk after pediatric tonsillectomy: a noninferiority randomized clinical trial. JAMA Otolaryngol Head Neck Surg. 2019; 145(6): 494– 500; doi: 10.1001/jamaoto.2019.0269Investigators conducted a multicenter, randomized, double-blind, noninferiority trial to compare the effect of ibuprofen to that of acetaminophen on post-tonsillectomy bleeding (PTB) in children. Children aged 2–18 years who presented to 1 of 4 study institutions for extracapsular tonsillectomy for sleep-disordered breathing or obstructive sleep apnea, adenotonsillar hypertrophy, or infectious tonsillitis were eligible. Children with known personal or family history of a bleeding disorder were excluded.Participants were randomized to receive either 15 mg/kg of acetaminophen every 6 hours or 10 mg/kg of ibuprofen every 6 hours for the first 9 postoperative days for analgesia. Participants, parents, and clinicians were all blinded to treatment, with acetaminophen and ibuprofen prepared in identical packaging, of equal volume, and as grape flavored. Participants completed daily postoperative study medication dosage questionnaires to track their compliance, as well as a questionnaire about PTB in the 14 days after their tonsillectomy, which was supplemented by medical record review. PTB was categorized by severity: type 1 was bleeding observed at home or evaluated in the ED, type 2 was bleeding requiring readmission for observation, and type 3 was bleeding requiring return to the operating room for control of hemorrhage.The primary outcome was type 3 PTB. The investigators conducted an intention-to-treat analysis to assess whether the rate of type 3 PTB differed between the 2 treatment groups. The noninferiority margin was set at 3%, which required that the ibuprofen group have no more than a 3% absolute increase over the acetaminophen group in the rate of type 3 PTB (and the upper limit of the 97.5% CI) to be considered noninferior to acetaminophen.There were 688 participants included in analyses: 345 in the ibuprofen group and 343 in the acetaminophen group. Overall, 44% of participants had missing postoperative dosage data on their daily questionnaires. In the ibuprofen group, 38 participants had PTB, including 10 (26.3%) with type 3. In the acetaminophen group, 27 participants had PTB, including 4 (14.8%) with type 3. Overall, the type 3 PTB rate was 1.2% in the acetaminophen group and 2.9% in the ibuprofen group (difference, 1.7%; 97.5% CI upper limit, 3.8%).The investigators conclude that ibuprofen did not meet the criteria for noninferiority with acetaminophen and, therefore, may increase the risk of severe bleeding after tonsillectomy.Dr Chung has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Tonsillectomy is a common surgical procedure performed in children. The results of the current study are a reminder that ibuprofen and other NSAIDs interfere with platelet aggregation and may pose a risk for postoperative bleeding. Although the risk of PTB is low, with a mean rate of 4.5%, severe bleeding occurs in some children.1 Whether ibuprofen poses an increased risk for PTB has been studied previously. The most recent Cochrane review on this subject concluded that there was insufficient evidence to exclude an increased risk of PTB.2 Stokes et al3 demonstrated a significantly increased OR of 1.38 for PTB associated with ibuprofen use when compared to other analgesics and placebos.In 2017, the US Food and Drug Administration deemed codeine to be contraindicated as an analgesic and antitussive agent in all children <12 years after earlier reports of an increased risk of life-threatening events and death associated with use of codeine after tonsillectomy in patients who were ultra-rapid metabolizers.4 Today, ibuprofen is widely available over-the-counter, and clinicians and parents alike commonly use this agent. The investigators in the current study compared ibuprofen 10 mg/kg per dose with acetaminophen 15 mg/kg per dose every 6 hours and allowed for supplemental use of oxycodone. However, they provide information neither about pain control nor use of oxycodone among the comparison groups, nor do they provide information about post-tonsillectomy nausea and vomiting, symptoms found less commonly with use of ibuprofen than with use of other analgesics or placebo.5 Such information would have been useful for readers interested in weighing the risk-benefit ratio of using ibuprofen over acetaminophen. This study, nonetheless, is a well-designed, randomized, double-blind trial across multiple centers. The investigators conclude that use of ibuprofen when compared to acetaminophen may increase the risk of severe bleeding.Use caution when determining which analgesic to use after tonsillectomy because there may be an increased risk of severe bleeding in children receiving ibuprofen when compared to that in those receiving acetaminophen.