Is Ketorolac Underutilized In Foot And Ankle Surgery?

By Jason Miller, DPM, FACFAS, Benjamin Marder, DPM, AACFAS and Steven Sinclair-Hall, DPM

The postoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) is a large topic of debate within the foot and ankle community, and orthopaedics at large due to the well-documented opioid epidemic.¹ Much of the literature regarding the use of NSAIDs is limited to spinal surgery and animal models with only a scant amount of literature dedicated to foot and ankle procedures. However, recent literature specific to foot and ankle surgeons advocates for the use of ketorolac (Toradol) or ibuprofen within the acute post-operative multimodal pain pathway.^2,3 

Multimodal analgesia describes the use of a variety of analgesic medications and techniques that target different mechanisms of action in the peripheral or central nervous system. These treatments can have an additive or synergistic effect with more pain relief in comparison to a single modality intervention.⁴ The American Pain Society in 2016 published guidelines for management of post operative pain that promote the routine use of non-opioid analgesics, such as NSAIDs and/or acetaminophen, local,regional or neuraxial anesthetic techniques and nonpharmacologic therapies such as cognitive modalities and TENS for postoperative pain control as studies have shown superior pain relief and decreased opioid consumption.⁵ 

What Does The Literature Reveal About NSAIDs In Foot And Ankle Surgery?

Generally speaking, NSAIDs are classified either by their chemical structure or their mechanism of action. However, all NSAIDs function by inhibiting production of cyclooxygenase (COX)-1 and COX-2 in a selective or non-selective fashion. Cyclooxygenase ultimately leads to the production of prostaglandins (PGE), which promote inflammation, protect the stomach lining and support the blood clotting function of platelets.⁶ The interruption of this pathway, as shown by animal studies, has been proposed to play a negative effect on bone healing.^7,8 However, recent clinical research in foot and ankle surgery contests this long-standing evidence. 

Just this year, McDonald and colleagues prospectively evaluated the use of ketorolac within a subset of patients requiring open reduction and internal fixation of ankle fractures.² These authors wanted to evaluate if ketorolac reduced the rate of opioid consumption, improved visual analogue scale (VAS) pain control scores and affected fracture healing. In this prospective, randomized study involving 128 patients who sustained an operative isolated lateral malleolar, bimalleolar or trimalleolar ankle fracture were prospectively randomized, the treatment group had five days of ketorolac 10 mg and 30 tablets of 5/325 oxycodone-acetaminophen (Percocet) in comparison to the control group, who only received 30 tablets of 5/325 oxycodone-acetaminophen (Percocet) post-operatively. 

These authors found significantly less opioid use in the treatment group, who utilized 14 tablets of 5/325 oxycodone-acetaminophen (Percocet) in the first seven days postoperatively in comparison to the control group, who consumed a mean of 19.3 tablets of 5/325 oxycodone-acetaminophen (Percocet).² Furthermore, these authors were able to show no difference in radiographic bone healing between the two groups at 12 weeks with 83 percent of patients in the treatment group and 77 percent in the control group showing signs of healed fractures.

In another recent study, a retrospective review, Hassan and Karlock reviewed 232 patients who were prescribed either ibuprofen, ketorolac, acetaminophen or hydrocodone-acetaminophen (Vicodin) during the first 14 days following surgery.³ Patients in the ibuprofen group received advice to titrate their dosage (200 to 800mg) based on their personal VAS pain score during the postoperative period. With regard to these subgroups, 59 patients used ibuprofen and 62 patients used ketorolac and these groups had 2.9 percent and 1.6 percent non-union rates, respectively. These findings were not statistically significant from those of the control group. 

In his practice, the senior author routinely utilizes a multimodal pain pathway in the form of pre-incision regional anesthesia and five days of ketorolac in combination with a short-acting narcotic pain medication during the postoperative period. In his experience, patients require less systemic narcotics during the post-operative period and report lower VAS pain scores. 

Final Notes

The adverse effects of isolated narcotic analgesia are a common concern among surgeons and society as overconsumption can lead to catastrophic events such as overdose and death. In the literature, researchers have shown that the prescription of adjunctive medications for multimodal pain control decreases the consumption of post-operative narcotic use while providing adequate pain control. Furthermore, recent literature shows limited evidence that NSAIDs play an adverse effect on bone healing following foot and ankle surgery. In light of the recent opioid epidemic, the use of ketorolac or alternative NSAIDs in a multimodal pain approach would be a judicious adjunctive approach to reduce the negative long-term effects of isolated opioid use.  

Dr. Miller is the Director of the Pennsylvania Intensive Lower Extremity Fellowship at Premier Orthopaedics in Malvern, PA.

Dr. Marder is a Fellow with the Pennsylvania Intensive Lower Extremity Fellowship in Malvern, Pa. 

Dr. Sinclair-Hall is a first-year resident with the Phoenixville Hospital/Tower Health Residency Program in Phoenixville, Pa. 

References

1. “What is the U.S. opioid epidemic?” U.S. Department of Health and Human Services. Available at: https://www.hhs.gov/opioids/about-the-epidemic/index.html . Accessed November 22, 2019.
2. McDonald EL, Daniel JN, Rogero RG et al. How does perioperative ketorolac effect opioid consumption and pain management after ankle fracture surgery? Clin Orthop Relat Res. 2019. doi: 10.1097/CORR.0000000000000978. Accessed November 22, 2019.
3. Hassan MK, Karlock LG. The effect of post-operative NSAID administration on bone healing after elective foot and ankle surgery. Foot Ankle Surg. 2019. doi: 10.1016/j.fas.2019.05.016. Accessed November 22, 2019.
4. Elia N, Lysakowski C, Tramer MR. Does multimodal analgesia with acetaminophen, nonsteroidal anti-inflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient controlled analgesia morphine offer advantages over morphine alone? Anesthesiology. 2005;103:1296-1304.
5. Chou R, Gordon DB, de Leon-Casasola OA, et al. Guidelines on the management of postoperative pain. management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131-157.
6. Vuolteenaho K, Moilanen T, Moilanen E. Non-steroidal anti-inflammatory drugs, cyclooxygenase-2 and the bone healing process. Basic Clin Pharmacol Toxicol. 2008;102(1):10–14. 
7. Brown KM, Saunders MM, Kirsch T, Donahue HJ, Reid JS. Effect of COX-2 specific inhibition on fracture-healing in the rat femur. J Bone Surg Am. 2004;86(1):116-123.
8. Goodman SB, Ma T, Mitsunaga L, Miyanishi K, Genovese MC, Smith RL. Temporal effects of a COX-2 selective NSAID on bone in growth. J Biomed Mater Res A. 2005;72(3):279-87.