Ketorolac May Increase Hematoma Risk in Reduction Mammaplasty

A Case-Control Study

Jouseph O. Barkho, MD; Yu Kit Li, MD, FRCSC; Eric Duku, PhD, PStat; Achilleas Thoma, MD, MSc, FRCSC


Plast Reconstr Surg Glob Open. 2018;6(3):e1699 

In This Article

Abstract and Introduction


Background: Ketorolac is a potent nonsteroidal anti-inflammatory drug that has valuable analgesic properties but also a hypothetical risk of increased bleeding due to inhibition of platelet activation. The clinical significance of this risk, however, is unclear when it is used after reduction mammaplasty. Our study objective was to therefore examine the association between ketorolac exposure and hematoma occurrence after breast reduction surgery. We hypothesized that there was no association between ketorolac exposure and hematoma occurrence in breast reduction surgery.

Methods: A case-control design was used. Data from charts of all reduction mammaplasties that developed hematomas requiring surgical evacuation (cases) at our university-based hospitals were retrieved and matched to data from charts of reduction mammaplasty patients who did not indicate this complication (controls). Matching occurred in a 1:1 ratio based on 4 criteria: age, body mass index, institution, and preexisting hypertension. Charts were reviewed for retrospective information on exposure to ketorolac. Odds ratio (OR) was calculated with an OR > 1 favoring an association.

Results: From 2002 to 2016, 40 cases of hematoma met inclusion criteria and were matched with 40 controls (N = 80). Cases had a significantly lower body mass index than controls; however, the other baseline patient demographics were similar between the 2 groups. There was an association between hematoma formation and exposure to ketorolac (OR, 2.4; 95% confidence interval, 0.8–7.4; P = 0.114) and a trend for greater risk of hematoma formation, although this was not statistically significant.

Conclusions: Based on this level 3 evidence, there appears to be an association between perioperative ketorolac exposure and hematoma after breast reduction surgery, but it was not statistically significant. Although this study was adequately powered, the OR of 2.4 was associated with a wide confidence interval. A larger sample size may increase the precision of the results and may also make the association definitive.


Breast reduction mammaplasty is a common plastic surgical procedure in the province of Ontario, Canada, with over 5,000 women in the province undergoing this procedure annually.[1] In the United States, 100,969 women underwent breast reduction in the year 2016.[2] On average, breast reduction patients rate their pain as moderate.[3,4] To further improve patient comfort postoperatively, various interventions have been utilized, including oral or intravenous analgesics, infiltration of local anesthetic as a field block, intercostal block, or wound infusion pumps.[5–7] Although each has shown efficacy, there are disadvantages with each, such as lidocaine toxicity, pneumothorax, increased cost, and medication-related adverse effects.

Among the various interventions, administration of postoperative opioids is routine and ubiquitously used by plastic surgeons. Although opioids are effective, they may induce vomiting, constipation, drowsiness, and in severe cases, respiratory depression. To mitigate these adverse effects, the use of nonsteroidal anti-inflammatory drug (NSAIDs), either as replacement or adjunctive therapy has been described.[8] Ketorolac (Toradol) is one NSAID with intriguing potential because it can decrease opioid requirements by up to 50% when used as an adjunct.[9] Cost analyses show higher immediate costs for ketorolac versus opioids; however, long-term savings may justify its use, as fewer resources will be spent on treating opioid-related side effects and delayed discharge.[10]

Although the analgesic efficacy of ketorolac has been established in pain management, there is concern among plastic surgeons regarding the risk of bleeding in the setting of reduction mammaplasty, due to the agent's antiplatelet properties.[11] Although several studies have suggested a link between ketorolac and breast hematomas postreduction mammaplasty, they have been limited by their retrospective nature, small sample sizes, and failure to control for confounding factors, such as premorbid hypertension.[11,12] The timing of ketorolac administration (ie, intra-versus postoperatively) is also inconsistent, which may also influence the outcome. For example, administering ketorolac in the postoperative period may negate the hypothetical bleeding risk, because platelets will have already been activated and adhered during primary hemostasis. Observational studies investigating ketorolac use after both subglandular breast augmentation and transverse rectus abdominis myocutaneous flap breast reconstruction did not find a correlation between NSAID use and bleeding, although the planes of tissue dissection are notably different compared with reduction mammaplasty.[13,14]

Given that ketorolac is a potent analgesic that can reduce opioid consumption postoperatively, it is of great interest for routine use, but there remains insufficient evidence in the literature to support this decision. The baseline incidence of hematoma after breast reduction is low, estimated at 2.4%,[11] hampering the ability to perform an adequately powered prospective trial. We therefore conducted a case-control study to examine the association of ketorolac exposure among patients who developed a hematoma requiring surgical exploration (cases) to those who had uncomplicated reduction mammaplasty (controls). The research question we aimed to answer was: in breast reduction patients, is there an association between the administration of ketorolac and hematoma formation? Our hypothesis was that there was no association of administration of ketorolac with hematoma formation.