How Does Perioperative Ketorolac Affect Opioid Consumption and Pain Management After Ankle Fracture Surgery?

Clin Orthop Relat Res. 2020 Jan;478(1):144-151. doi: 10.1097/CORR.0000000000000978.


Background: The investigation of nonnarcotic drug regimens for postoperative pain management is important in addressing the opioid epidemic. NSAIDs can be a powerful adjunct in managing postoperative pain, but the possibility of delayed bone healing is a major concern for orthopaedic surgeons. Our recent retrospective study on ketorolac administration demonstrated that the NSAID is not associated with an increased risk of delayed union or nonunion after ankle fracture surgery.

Questions/purposes: To determine whether postoperative ketorolac (1) reduces opioid consumption, (2) improves VAS pain control, and (3) affects fracture healing after open reduction and internal fixation of ankle fractures.

Methods: Between August 2016 and December 2017, 128 patients undergoing open reduction and internal fixation of an acute ankle fracture were randomized before surgery via simple randomization to treatment with or without ketorolac. No patients changed treatment regimen groups or opted out of randomization. All other aspects of perioperative care were treated identically. A once-daily survey was distributed via email on postoperative Days 1 to 7. Unblinded participants were asked to report their daily opioid consumption, pain level, and sleep interference using the VAS, and pain frequency using a five-point Likert scale, and side effects with the VAS. For VAS pain, > 20 mm/100 mm on the VAS scale was required to be considered "improved." In all, 83% (106 of 128) patients completed all seven postoperative surveys with 14 in the control group and eight in the ketorolac group lost to follow-up. Fifty-six patients were administered ketorolac with opioid medication (treatment group) and 50 were administered opioids alone (control group). Participants were comprised of 42% men (44), and 58% women (62); mean age was 48 years. The treating surgeon assessed clinical healing based on the patient's ability to ambulate comfortably at 12 weeks postoperatively. Radiographic healing was assessed by two fellowship-trained orthopaedic foot and ankle surgeons blinded to the patient's name and time since surgery. The surgeons evaluated randomized standard ankle series (anteroposterior, mortise, and lateral) radiographs for resolution of each fracture line to determine fracture union, with delayed union being defined as fracture lines present on radiographs taken at 12-week postoperative visits. Intention-to-treat analysis was performed.

Results: Patients in the treatment group consumed a mean of 14 opioid pills, which was less than the mean of 19.3 opioids pills consumed by patients in the control group (p = 0.037). Patients with ketorolac had lower median VAS scores for pain (p < 0.035) postoperatively on postoperative Days 1 and 2 than did control patients. By contrast, patient-reported pain scores and scores for sleep did not convincingly show a benefit to the use of ketorolac. For patients whose ankle fractures healed at 12 weeks, there was no difference between the groups in terms of clinical healing (p = 0.575) and radiographic healing (p = 0.961).

Conclusions: In this randomized study, adding ketorolac to the postoperative drug regimen decreased the use of opioid medication after open reduction and internal fixation of ankle fractures in the early postoperative period, and there were mixed, small effects on pain reduction. This NSAID is a valuable tool in helping patients manage postoperative pain with less use of narcotic analgesia. However, our study was underpowered to determine the true safety of this drug in terms of fracture healing and side effects and these questions warrant higher-powered randomized study investigation.

Level of evidence: Level I, therapeutic study.

MeSH terms

  • Adult
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use*
  • Ankle Fractures / surgery*
  • Ankle Joint / surgery*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Female
  • Fracture Fixation, Internal
  • Fracture Healing / drug effects
  • Humans
  • Ketorolac / administration & dosage
  • Ketorolac / therapeutic use*
  • Male
  • Middle Aged
  • Open Fracture Reduction
  • Pain Management / methods*
  • Pain Measurement
  • Pain, Postoperative / drug therapy*
  • Retrospective Studies


  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Ketorolac