Ketorolac and post T&A bleeding
Lynne G. Maxwell MD and Myron Yaster MD
I probably can’t remember what I had for breakfast this morning, but I can tell you exactly where I was and what I was doing on 9/11. Similarly, I have vivid memories of being let out of school and seeing adults crying on the street and on the subway when President Kennedy was assassinated on November 22, 1963. These shocking events are sometimes called “flashbulb memories”.1 They are memories that we simply do not forget.
We all provide anesthesia successfully on a daily basis, but occasionally something bad occurs, like laryngospasm in a child with a URI or a bleeding tonsil in a patient who was treated with an NSAID. We tend to notice the negative more than the positive and many studies have shown that we are more likely to remember negative experiences than positive ones. Our flashbulb memories.
The August 6, 2024 PAAD: Celecoxib (Celebrex) and post tonsillectomy bleeding (https://ronlitman.substack.com/p/celecoxib-celebrex-and-post-tonsillectomy ) elicited a lot of reader responses, particularly from one of the PAAD’s executive council members, Dr. Lynn Martin. He provided some data from a study undertaken at Seattle Children’s Hospital which retrospectively compared post-tonsillectomy bleeding requiring surgery in patients who received ketorolac compared to those who did not. Today’s PAAD provides further information from that study,2 now published, showing no increased risk of posttonsillectomy hemorrhage (PTH) requiring surgery in T&A patients who received ketorolac. Interestingly, while preparing today’s PAAD, we found an almost identical retrospective database study with the completely opposite conclusion, showing ketorolac use increased the risk of post tonsillectomy (PTH).3 Which one you are going to believe may depend more on your personal flashbulb memories of taking a child with a bleeding tonsil to the OR emergently than the data presented in the articles. Myron Yaster MD
Original article
Shaikh N, Kais A, Dewey J, Jaffal H. Effect of perioperative ketorolac on postoperative bleeding after pediatric tonsillectomy. Int J Pediatr Otorhinolaryngol. 2024 May;180:111953. doi: 10.1016/j.ijporl.2024.111953. Epub 2024 Apr 15. PMID: 38653108.
Original article
Feldman RM, O'Reilly-Shah V, Dahl JP, Siu J, Newby M, Sutherland TN, Parikh SR, Jiang T, Franz A. Impact of Ketorolac on Reoperation for Hemorrhage After Pediatric Tonsillectomy: A Single-Center Retrospective Propensity-Matched Study. Otolaryngol Head Neck Surg. 2024 Mar;170(3):928-936. doi: 10.1002/ohn.577. Epub 2023 Nov 5. PMID: 37925621.
As Yaster, Monitto, and Martin stated in their August 6, 2024 PAAD, risk tolerance in NSAID prescribing in T&A patients remains variable at different pediatric institutions. Some use ketorolac perioperatively routinely, others do not allow it under almost any circumstances. When dealing with what is almost religious fervor, no amount of data will change the minds of the believers and non-believers. Today’s articles, with diametrically opposite conclusions may not help shed light on this conundrum.
Shaikh et al.3 felt compelled to examine this question because although “multiple systematic reviews with meta-analyses reached the conclusion that ketorolac was safe to use in children but not in adults undergoing tonsillectomy,4 a Cochrane review by Lewis et al.5 did not identify sufficient evidence to exclude elevated bleeding risk with the use of ketorolac in pediatric tonsillectomy. Multiple studies included in the systematic review used different surgical techniques that may confound the bleeding risk assessment of peri-operative use of ketorolac. Intracapsular tonsillectomy is thought to result in less postoperative pain and lower incidences of PTH when compared to extracapsular electro-dissection tonsillectomy.” Shaikh et al. utilized data from a multi-institutional EHR research database (TriNetX) from 2013-2024, propensity-matching 17434 patients who received ketorolac for tonsillectomy with or without adenoidectomy with an equal number who did not receive ketorolac. Although the authors state that the goal of the study was “to assess the risk of posttonsillectomy bleeding requiring operative control associated with the use of ketorolac intraoperatively”, they also state that because of the nature of the database, it was known that the patients received ketorolac on the same day as surgery, but the timing was unknown (at end of surgery vs postoperatively). The authors reported both primary hemorrhage (on the same day as surgery) and secondary hemorrhage (bleeding within 30 days of surgery). They concluded that “receipt of ketorolac the same day as surgery resulted in an increased risk of primary hemorrhage OR 2.158 (95 % CI 1.354, 3.437) and secondary hemorrhage OR 1.374 (95 % CI 1.057, 1.787) requiring operative control.” As pointed out in the Celecoxib PAAD, “when drawing conclusions from this study there are several issues to consider: first, the long-time frame of this retrospective study (11 years) likely coincided with evolution in surgical techniques that could have significant impact on the bleeding rate. In Seattle, the intracapsular technique (n=407) versus all other surgical techniques (n=5,764) has a lower PACU Max Pain Score (3.1 vs 3.8), 30-day all-cause hospital readmission rate (12.3 vs 38.3 per 1000 cases), same day return to OR (0.00% vs 0.17%), and 30-day return to OR (0.0% vs 1.5%).”2 The nature of the TriNetX database “lacks descriptions of tonsillectomy technique,” but they point to a systematic review which “demonstrated a lack of significant effect of operating technique on postoperative complications”.6
Feldman et al.2 from Seattle Children’s Hospital, examined their database, finding 5873 patients less than 18 years of age who had received ketorolac for tonsillectomy (K+) with or without adenoidectomy and a propensity-matched cohort of 4694 patients who did not receive ketorolac (K-). In contrast to the findings of Shaikh et al., they found that "reoperation for hemorrhage within 30 days occurred in 1.9% of K+ patients and 1.6% of K− patients (P = 0.455) in the full cohort and 1.9% of K+ patients and 1.7% of K− patients (odds ratio [OR] 1.10, 95% confidence interval [CI] 0.72-1.69, P = 0.662) in the propensity-matched cohort. Reoperation within 48 hours occurred in 0.65% of K+ patients and 0.53% of K− patients (P = 0.679) in the full cohort and 0.68% of K+ patients and 0.51% of K− patients (OR 1.33, 95% CI 0.63-2.81, P = 0.451) in the propensity-matched cohort. There was no association between perioperative ketorolac administration and reoperation for hemorrhage in any of the other analyses.” Interestingly, “among all comers, the rate of reoperation for hemorrhage within 30 days was higher in teenagers (n = 17/500, 3.4%) than in children (n = 87/5373, 1.6%, P=0.007). Notably, teenagers were more likely to undergo tonsillectomy for an inflammatory/other indication (n = 144/500, 28.8%) than children (n = 613/5373, 11.4%, P<0.001). After stratifying by ketorolac administration, differences in hemorrhage within 30 days were significant in the nonketorolac group (teenagers 3.9% vs children 1.4%, P = 0.004) but not the ketorolac group (teenagers 2.7% versus children 1.9%, P = 0.53). No differences were observed between children and teens for the 48‐hour outcome.”
Clear as mud? Do your OLHN surgeons allow ketorolac to be used in patients having tonsillectomy intra- or post-operatively? Do you use it in your practice? Send your responses and comments to Myron who will post them in a Friday reader response.
References
1. Hirst W, Phelps EA, Meksin R, et al. A ten-year follow-up of a study of memory for the attack of September 11, 2001: Flashbulb memories and memories for flashbulb events. J Exp Psychol Gen 2015;144(3):604-23. (In eng). DOI: 10.1037/xge0000055.
2. Feldman RM, O'Reilly-Shah V, Dahl JP, et al. Impact of Ketorolac on Reoperation for Hemorrhage After Pediatric Tonsillectomy: A Single-Center Retrospective Propensity-Matched Study. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 2024;170(3):928-936. (In eng). DOI: 10.1002/ohn.577.
3. Shaikh N, Kais A, Dewey J, Jaffal H. Effect of perioperative ketorolac on postoperative bleeding after pediatric tonsillectomy. International journal of pediatric otorhinolaryngology 2024;180:111953. (In eng). DOI: 10.1016/j.ijporl.2024.111953.
4. Riggin L, Ramakrishna J, Sommer DD, Koren G. A 2013 updated systematic review & meta-analysis of 36 randomized controlled trials; no apparent effects of non steroidal anti-inflammatory agents on the risk of bleeding after tonsillectomy. Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery 2013;38(2):115-29. (In eng). DOI: 10.1111/coa.12106.
5. Lewis SR, Nicholson A, Cardwell ME, Siviter G, Smith AF. Nonsteroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy. The Cochrane database of systematic reviews 2013;2013(7):Cd003591. (In eng). DOI: 10.1002/14651858.CD003591.pub3.
6. Lee YC, Hsin LJ, Lin WN, Fang TJ, Tsai YT, Luo CM. Adolescents and Adults Undergoing Temperature-Controlled Surgical Instruments vs Electrocautery in Tonsillectomy: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Otolaryngol Head Neck Surg 2020;146(4):339-346. (In eng). DOI: 10.1001/jamaoto.2019.4605.