Multimodal Periarticular Injection Improves Early Postop Pain Control

    Adding ketorolac, or ketorolac and clonidine, to a periarticular injection of ropivacaine and epinephrine significantly improves pain relief soon after total knee arthroplasty (TKA), a randomized, double-blind, single-center study has demonstrated.

    One of the reasons patients are hesitant to have knee replacement surgery is the perception that it is incredibly painful and involves a lengthy recovery period. “So we started experimenting with different mixtures of medications to try and come up with a mixture that was well tolerated and effective enough to improve patients’ outcome and enhance their recovery,” senior researcher David Dalury, MD, told ICJR.

    He and his colleagues randomly assigned 160 patients who were undergoing primary TKA for osteoarthritis to receive one of four intraoperative periarticular injections:

    • Group A — Ropivacaine 5 mg/mL (49.25 mL), epinephrine 1 mg/mL (0.5 mL), ketorolac 30 mg/mL (1 mL), and clonidine 1 mg/mL (0.08 mg to 0.8 mL)
    • Group B — Same as group A except no clonidine
    • Group C — Same as group A except no ketorolac
    • Group D — (Control) Ropivacaine and epinephrine as in group A

    Normal saline was added to all protocols to total an injection of 100 mL. All patients were hospitalized until POD3, and then were asked to return for a follow-up visit 6 weeks after surgery.

    In the final analysis, which included 150 patients, patients in groups A and B had significantly lower pain scores (visual analog scale) during hospitalization compared with patients in the control group (P < .001 and P = .02, respectively). Pain scores in group C did not differ significantly from those in the control group. Compared with the control group, patients in groups A, B, and C showed no significant differences with respect to range of motion, ambulation, or other functional outcomes.

    “It’s the four drugs together that we think makes the difference,” Dr. Dalury said. “This has been our standard protocol and we wanted to do a double-blind study to confirm our suspicions that it was a combination of the medications that potentiate each other that makes a difference in the patient recovery.”

    He added that with any periarticular injection, the periosteum must be well injected. “I’ll have guys tell me, ‘Well, I tried a cocktail and it worked pretty well.’ But then you ask them how they did (the injection) and they were not meticulous in how they put it in the knee.”

    The researchers noted in their paper that the drugs they used in the injections are readily available and easily administered during surgery, leading them believe their findings can be generalized to any joint reconstruction surgery.

    “The advances in pain management have made an incredible different in patients’ recoveries,” Dr. Dalury concluded. “It really has been one of the most important things that I’ve done over the past 10 years to improve my patients’ outcomes.”

    The early improvements in pain control did not persist at the 6-week follow-up, and neither multimodal regimen was associated with significantly improved postoperative function.

    Dr. Dalury’s team is beginning to research whether additional medications or changes in the medication concentrations in the injection could provide added benefit or long-term functional improvements.


    Kelley TC, Adams MJ, Mulliken BD, Dalury DF. Efficacy of multimodal perioperative analgesia protocol with periarticular medication injection in total knee arthroplasty: a randomized, double-blinded study. J Arthroplasty. 2013;28(8):1274-1277.