Cochrane Review: Nonsteroidal anti‐inflammatory drugs and perioperative bleeding in paediatric tonsillectomy

Abstract

BackgroundNonsteroidal anti‐inflammatory drugs (NSAIDs) are used for pain relief following tonsillectomy in children. However, as they inhibit platelet aggregation and prolong bleeding time, they could cause increased perioperative bleeding. The overall risk remains unclear. This review was originally published in 2004 and was updated in 2010.ObjectivesThe primary objective of this review was to assess the effects of NSAIDs on bleeding with paediatric tonsillectomy. Our secondary outcome was to establish whether NSAIDs affect the incidence of other postoperative complications when compared to other forms of analgesia.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 6); MEDLINE (inception until May 2010); EMBASE (inception until May 2010); Current Problems (produced by the UK Medicines Control Agency), MedWatch (produced by the US Food and Drug Administration) and the Australian Adverse Drug Reactions Bulletins (to May 2010). The original search was performed in August 2004. We also contacted manufacturers and researchers in the field.Selection criteriaWe included randomized controlled trials assessing NSAIDs in children, up to and including 16 years of age, undergoing elective tonsillectomy or adenotonsillectomy.Data collection and analysisTwo authors independently assessed trial quality and extracted the data. We contacted study authors for additional information, where necessary.Main resultsWe included 15 trials that involved 1046 children in this updated review. This included one trial that was added as a result of updating our search and another trial that we had incorrectly excluded from our previous review. All included trials compared NSAIDs with other analgesics or placebo and looked at bleeding requiring surgical intervention. NSAIDs did not significantly alter the number of perioperative bleeding events requiring surgical intervention: Peto odds ratio (OR) 1.32 (95% confidence interval (CI) 0.47 to 3.70). Eight trials involving 532 children looked at bleeding not requiring surgical intervention. NSAIDs did not significantly alter the number of perioperative bleeding events not requiring surgical intervention: Peto OR 1.00 (95% CI 0.39 to 2.53). Twelve trials involving 928 children looked at postoperative nausea and vomiting. There was less nausea and vomiting when NSAIDs were used as part of the analgesic regime than when NSAIDs were not used: OR 0.49 (95% CI 0.29 to 0.83).Authors' conclusionsNSAIDs did not cause any increase in bleeding that required a return to theatre. There was significantly less nausea and vomiting when NSAIDs were used compared to alternative analgesics.Plain Language SummaryNonsteroidal anti‐inflammatory drugs (NSAIDs) do not significantly increase bleeding in children having their tonsils out, and there is less nausea and vomiting when NSAIDs are used.Nonsteroidal anti‐inflammatory drugs (NSAIDs) are used for pain relief following tonsillectomy in children. Bleeding is a recognised complication of this procedure but NSAIDs can interfere with blood clotting so there has been concern that these drugs will increase the risk of bleeding. If bleeding is severe this may result in the child being re‐admitted to hospital, having a blood transfusion or returning to theatre. It was therefore important to establish whether these drugs are safe to use in children having their tonsils out. The review focused on clinically significant bleeding that results in the child requiring additional treatment rather than measured blood loss.We also wanted to establish whether NSAIDs affect the incidence of other postoperative complications when compared to other forms of analgesia.The review found that NSAIDs did not significantly increase bleeding. There were insufficient data to compare the risk of bleeding with each individual type of NSAID. However, we were able to compare ketorolac, which has been perceived as having a greater risk of bleeding, with the other NSAIDs and found no increased risk of bleeding. There was less nausea and vomiting when NSAIDs were used as part of the analgesic regime than when NSAIDs were not used.The main limitation of our review is that bleeding following tonsillectomy is an uncommon event (occurring in 3% to 5% of children). We found all the data that are currently available (15 trials studying approximately 1000 children) but a very large number of participants are required to provide an adequate number of events to give a significant result. It is possible that the numbers of participants are too small to establish whether NSAIDs increase bleeding. However, currently there is no evidence to support withholding NSAIDs for paediatric tonsillectomy.

Does Celecoxib Prescription for Pain Management Affect Post-tonsillectomy Hemorrhage Requiring Surgery? A Retrospective Observational Cohort Study

“…A large randomized controlled trial was unable to exclude an increased risk of severe bleeding with ibuprofen compared with acetaminophen after tonsillectomy, 27 and recently a prospective study demonstrated a reduction in post-tonsillectomy hemorrhage rates from 5% to less than 1% by increasing the dosing interval of oral ibuprofen (10 mg/kg) from 6 to 8 h. 45 Systematic reviews are equivocal regarding NSAIDs after tonsillectomy and are limited by a number of factors including: insufficient pediatric subjects, heterogeneity in diagnostic indication for adenotonsillectomy, surgical approach and technique, and variable NSAID type, dose, and perioperative timing studied, among others. 16,18,46–48 Finally, a recent meta-analysis of ibuprofen concluded an increased post-tonsillectomy hemorrhage odds ratio of 1.38 (95% CI, 1.11 to 1.72). 49 Given the uncertain risk of bleeding with nonselective NSAIDs, the benefits of COX-2–specific inhibitors in terms of analgesic efficacy and platelet sparing effects, even at supra-therapeutic plasma levels, 19 are noteworthy and have been the focus of a recent meta-analysis 21 and demonstrated in five randomized controlled trials.…”

“…11,12 Although small cohort studies support the use of nonselective NSAIDs, reporting no changes in frequency of bleeding, 13 evidence suggests they may increase post-tonsillectomy hemorrhage severity. 14 Additionally, systematic reviews cite insufficient evidence to discount bleeding risks in children 15,16 due to inadequate sample sizes to assess rare (less than 5%) bleeding events 15–17 or inclusion of both children and adults in larger cohort studies. 18 Given that nonselective NSAID safety is unclear, there is interest in studying other agents, including COX-2 selective inhibitors ( e.g.…”

The efficacy and safety of selective COX-2 inhibitors for postoperative pain management in patients after total knee/hip arthroplasty: a meta-analysis

“…This may lead to high heterogeneity and ultimately affect the results. (9) The primary endpoints were analyzed at 24, 48, and 72 h after operation. However, given that the included studies did not mention the time point at which adverse reactions were recorded, subgroup analysis of secondary endpoints was not conducted according to time (Fig.…”

“…It is one of the key enzymes that initiate inflammatory reactions and promote inflammatory response leading to tissue injury [8]. NSAIDs, therefore, simultaneously exert anti-inflammation and analgesic effects which also increases the risk of perioperative bleeding and digestive tract symptoms [9]. Selective COX-2 inhibitors not only prevent inflammation and exert analgesic and antipyretic effects, but also protect the gastrointestinal mucosa and are widely used in orthopedic postoperative analgesia [10].…”