2017-18 HSC Section 3 Green Book

Reprinted by permission of Laryngoscope. 2014; 124(8):1789-1793.

The Laryngoscope V C 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Perioperative Ketorolac Increases Post-Tonsillectomy Hemorrhage in Adults But Not Children

Dylan K. Chan, MD, PhD; Sanjay R. Parikh, MD

Objectives/Hypothesis: To evaluate the risk of post-tonsillectomy hemorrhage associated with perioperative ketorolac use. Study Design: Systematic review and meta-analysis of primary articles reporting individual-level post-tonsillectomy hemorrhage rates in subjects receiving perioperative ketorolac and matched controls. Retrospective and prospective studies were both included. Methods: PubMed search was performed for “[ketorolac OR toradol] AND tonsillectomy.” Articles fulfilling inclusion cri- teria were subjected to meta-analysis to determine summary relative risk (RR). Results: Adults are at five times increased risk for post-tonsillectomy hemorrhage with ketorolac use (RR: 5.64; 95% confidence interval [CI]: 2.08–15.27; P < .001). In contrast, children under 18 are not at statistically significantly increased risk (RR: 1.39; 95% CI: 0.84–2.30; P 5 .20). Both retrospective and prospective studies yield consistent findings. There is no association of RR with pre- or postoperative administration of ketorolac. Conclusions: Ketorolac can be used safely in children, but is associated with a five-fold increased bleeding risk in adults. Key Words: Tonsillectomy, hemorrhage, ketorolac, obstructive sleep apnea. Level of Evidence: NA Laryngoscope , 124:1789–1793, 2014

INTRODUCTION Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) administered intravenously for analge- sia. It is an alternative or adjunct to narcotics, acet- aminophen, and ibuprofen in the management of perioperative pain, and is of particular interest for use around the time of tonsillectomy. However, ketorolac use is associated with increased risk of postoperative hemorrhage in some settings. 1 A recent 2010 Cochrane review 2 of NSAID use in children undergoing tonsillec- tomy specifically examined six randomized controlled studies and concluded that there is no statistically significantly increased risk of reoperation for post- tonsillectomy hemorrhage in patients who receive ketorolac compared to controls. However, the reported summary odds ratio (3.12, 95% confidence interval [CI]: 0.53-18.38; P 5 .21) was high, and the CI was wide. Though this may suggest an increased risk of From the Division of Pediatric Otolaryngology, Department of Otolaryngology–Head and Neck Surgery ( D . K . C .), University of California, San Francisco, California; and the Division of Pediatric Otolaryngology ( S . R . P .), University of Washington School of Medicine, Seattle Children’s Hospital, Seattle, Washington, U.S.A. Editor’s Note: This Manuscript was accepted for publication December 9, 2013. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Dylan K. Chan, MD, 2233 Post Street, 3rd Floor, Box 1225, San Francisco, CA 94115. E-mail: dylan.chan@ucsf.edu

bleeding with ketorolac, the findings were not statisti- cally significant. Furthermore, recent 2011 American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) guidelines for pediatric tonsillectomy 3 stated that “post-tonsillectomy hemorrhage rates with ketorolac range from 4.4% to 18%, and therefore ketor- olac use should be avoided.” The choice of the Cochrane collaboration to narrowly analyze reoperation, rather than any hemorrhage, lowered the incidence of the analyzed outcome, and subsequently widened the reported CI. In practice, decision making for reoperation may vary between surgeons, and likely did between studies. As the Cochrane protocol limits analysis to prospective, randomized, controlled studies, sample size was limited; retrospective case-control studies, which had larger numbers, were not considered in the final recom- mendation. The AAO-HNS guidelines, although citing the Cochrane review, referred specifically to two studies that found increased rates of post-tonsillectomy hemorrhage associated with ketorolac use, 1,4 both of which predomi- nantly reported results on adults, not children. Given the lack of clarity on this issue in the litera- ture, and the increasing focus on non-narcotic analgesics given the recent US Food and Drug Administration black-box warnings regarding codeine use in children, 5 we have performed an updated systematic review and meta-analysis of retrospective and prospective studies examining the incidence of post-tonsillectomy hemor- rhage with and without ketorolac use in adults and children.

DOI: 10.1002/lary.24555

Laryngoscope 124: August 2014

Chan and Parikh: Ketorolac and Tonsillectomy

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