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CORR Insights®

No Clinically Important Difference in Pain Scores After THA Between Periarticular Analgesic Injection and Placebo

A Randomized Trial

Post, Zachary D. MD

Clinical Orthopaedics and Related Research®: September 2018 - Volume 476 - Issue 9 - p 1846–1847
doi: 10.1097/CORR.0000000000000401

Z. D. Post, Associate Professor, Rothman Institute Thomas Jefferson University, Department of Orthopaedic Surgery, Philadelphia, PA, USA

Zachary D. Post MD, Rothman Institute Thomas Jefferson University, Department of Orthopaedic Surgery, 925 Chestnut St., Philadelphia, PA 19107 USA, Email:

This CORR Insights® is a commentary on the article “No Clinically Important Difference in Pain Scores After THA Between Periarticular Analgesic Injection and Placebo: A Randomized Trial” by Hirasawa and colleagues available at: DOI: 10.1097/CORR.0000000000000374.

The author certifies that neither he, nor any members of his immediate family, have any commercial associations (such as consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

The opinions expressed are those of the writers, and do not reflect the opinion or policy of CORR® or The Association of Bone and Joint Surgeons®.

This CORR Insights® comment refers to the article available at DOI: 10.1097/CORR.0000000000000374.

Received June 13, 2018

Accepted June 20, 2018

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Where Are We Now?

The evidence base about periarticular injection (PAI) in hip and knee replacement includes a substantial number of studies proclaiming its benefits [2, 9], although others have questioned its value [4, 5]. Not long ago, before the advent of multimodal pain control and rapid-recovery protocols for hip and knee replacement, postoperative pain was an expected, even accepted, part of recovery. Acute pain was a leading cause of delayed discharge [10] with hospital stays routinely exceeding 3 days. Pain management has improved substantially among arthroplasty patients over the last decade, and lengths of stay have decreased correspondingly, with many high-volume centers typically discharging patients the same day or the day after surgery. In addition to multimodal pain control (including PAI), systematic use of early mobilization, tranexamic acid, and less-aggressive anticoagulation have transformed postoperative recovery after joint replacement. But which of these factors has had the greatest effect?

In the current study, Hirasawa and colleagues [6] perform a randomized, double-blind, placebo-controlled trial to evaluate the effect of PAI on VAS-measured pain after THA. This rare Level-1 (yet brilliantly simple) study takes place in the context of one surgeon performing bilateral surgery with patients randomized to get PAI in one hip and placebo in the other. While there was a difference in VAS pain scores, the difference did not achieve the predetermined minimum clinically important difference (MCID) of > 20 mm out of 100 on the VAS scale. This was true at all measured time points, up to 24 hours. There were no complications in either group. The authors correctly conclude that the expense of PAI did not justify its use. Perhaps PAI is not as valuable as we may have thought.

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Where Do We Need To Go?

While Hirasawa and colleagues [6] demonstrate important shortcomings as to the clinical efficacy of PAI, their study also raises three important questions that remain unanswered: (1) Which medications typically used in PAI are valuable and which are not? (2) Are systemic medications administered locally having an effect on the contralateral hip? (3) Do patients perceive the difference in the hip treated with PAI versus placebo and is this difference valuable to the patient?

In the current study, the authors use a complex mixture of medications for PAI, including ropivacaine, morphine, methylprednisolone, ketoprofen, and epinephrine. This combination includes many medications frequently found in cocktail formulations for PAI [3, 12]. Still, other surgeons use medications not discussed in the current study, sometimes with little to support why each medication is used. Future studies with more-complex study designs should isolate the effectiveness of each medication. Additionally, methylprednisolone, morphine, and ketoprofen are each known to have systemic effects when administered intramuscularly. Without question, these medications contributed to the overall pain perception of the hip treated with placebo, thereby muddying the comparison of PAI- and placebo-treated hips. The current study has emphasized our need to better understand the effect medications used for PAI are having and how to best use them.

The authors of this study, based on a previous knee study [8], set a difference of > 20 mm on the VAS as the MCID. Recovery after THA requires adequate pain control to enable early ambulation and a return to activities of daily living. Undoubtedly, there is a cumulative effect from preoperative analgesia, local intraoperative injections, regional anesthesia, and postoperative pain medications. Future studies should ask patients if they felt more mobile on or able to use one hip versus the other to understand the clinical value of PAI from a patient’s perspective.

One final question that remains is the effect of newer medications like liposomal bupivacaine [1] on the effectiveness of PAI—a controversial subject [11] as most joint replacement surgeons remain hopeful but unsure of the value of these medications.

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How Do We Get There?

Level 1 studies are a joy to read but difficult to execute, as is evident from their scarcity. Hirasawa and colleagues have shown us the way forward. To better understand the effect of PAI on postoperative pain, we must understand which medications are working and what effects they have. More randomized, double-blind, well-controlled studies can help us get there. An even simpler study design, isolating specific medications, performed in a regimented way, could answer these questions. Additionally, we need larger studies; it is often smaller studies that miss a dangerous outcome [7], particularly when medications are combined and used in a patient population that frequently has issues with polypharmacy. Often in our rush to improve our patients’ outcomes we fail to completely understand what we have done or why it works. This is likely true of PAI with its many iterations of cocktails described. It is perhaps time to step back just a bit to more fully understand how PAI is working and in the process, standardize its use and delivery.

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