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Targeted Muscle Reinnervation Helps Reduce—and Prevent—Pain in Amputees

Symptomatic neuromas have long been a problem for amputees, interfering with prosthetic comfort and causing residual pain that often requires treatment. During the last 15 to 20 years, surgeons have used targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) procedures to improve symptoms from neuromas. In TMR, surgeons transfer a mixed or sensory nerve to a “target” transected motor nerve to prevent disorganized axonal growth. RPNI is a less complicated procedure during which the free nerve end is implanted into a denervated free muscle graft, again to decrease disorganized sprouting of axons.

Advances in amputee care at US military centers, driven largely by recent overseas conflicts, have shown anecdotally that TMR and RPNI prevent neuroma formation when used prophylactically during initial amputation, and that they also relieve pain when used as secondary treatment for existing neuromas. In the April 22, 2021 issue of The Journal, Hoyt et al. reviewed records from Walter Reed National Military Medical Center to evaluate changes in pain scores, symptom resolution, and frequency of complications when TMR and/or RPNI were utilized.

The authors analyzed 87 nerve interface interventions in 80 lower extremity amputations that had at least 6 months of follow-up. Fifty-nine of the procedures (68%) were done to treat symptomatic neuromas at a median of 6.5 years after amputation, while 28 procedures (32%) were done for primary prophylaxis. Hoyt et al. found that the sciatic nerve was most likely to develop symptomatic neuromas after amputations at or above the knee, while the tibial and peroneal nerve distributions were most commonly symptomatic after amputations distal to the knee. TMR was utilized alone in 85% of the cases, and surgeons used RPNI most frequently to prevent pain in the sural and saphenous nerves.

Overall, symptom resolution after all procedures was 92% at the final follow-up. VAS pain scores improved from 4.3 to 1.7 points in the delayed-treatment group and did not vary by amputation level. The final mean pain score in the primary-prophylaxis group was 1.0 ±1.9. There were no significant differences in pain outcomes between the primary and delayed groups, but 6 patients in the delayed cohort required revision for residual limb or phantom limb pain. In patients with transtibial amputations, failure to address an asymptomatic tibial nerve during delayed TMR resulted in an increased risk of revision surgery.

Although retrospective in nature, this study shows some encouraging early data to support the primary and secondary use of TMR/RPNI in amputee care. More research is required to determine whether these results in wounded warriors can be replicated in a civilian amputee population.

Click here for a Commentary on this study by Ann R. Schwentker, MD.

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

Better 24-Hour Pain Control with Periarticular vs. IV Steroids in TKA

Corticosteroids are commonly used in total knee arthroplasty (TKA) to reduce pain and prevent nausea. But are the effects of steroids different when administered locally rather than systemically? Hatayama et al. investigate this question in JBJS, where they report on a randomized controlled trial comparing periarticular injection with intravenous (IV) administration of corticosteroids. The authors assessed the drugs’ effects on pain control, the prevention of postoperative nausea, and inflammation and thromboembolism markers following TKA.

The 100 included patients were 50 to 85 years of age and underwent primary, unilateral TKA for osteoarthritis. Fifty patients were randomized to the intravenous group (10 mg dexamethasone IV 1 hour pre- and 24 hours postoperatively, along with periarticular placebo injection during the procedure), and 50 were randomized to the periarticular injection group (a 40-mg injection of triamcinolone acetonide during surgery, along with IV placebo 1 hour pre- and 24 hours postoperatively).

Patients in the periarticular injection group experienced better pain control at 24 hours postoperatively, both at rest and during walking. The antiemetic effect was similar and notable in both groups. The IV group showed a better anti-thromboembolic effect, as measured by prothrombin fragment 1.2 levels, but the incidence of deep venous thrombosis was low overall, each group having only 2 cases.

The authors also reported that, at 24 and 48 hours, interleukin-6 levels did not differ between the groups, while C-reactive protein (CRP) levels were significantly lower in the IV group. In contrast, 1 week after surgery, patients in the periarticular group had a significantly lower CRP. These inflammatory-marker findings lead Hatayama et al. to postulate that “the better [24-hour] pain control in the periarticular injection group was not because of reduced inflammation,” and they note that locally administered corticosteroids directly inhibit signal transmission in nociceptive fibers.

What’s New in Adult Reconstructive Knee Surgery 2021

Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all such OrthoBuzz specialty-update summaries.

This month, author Michael J. Taunton, MD summarizes the 5 most compelling findings from the 130 studies highlighted in the January 20, 2021 “What’s New in Adult Reconstructive Knee Surgery.”

Waiting for a Knee Replacement
–Patient wait times for joint arthroplasty, exacerbated in many places by the COVID-19 pandemic, continue to increase. As measured by the EQ-5D, the health among 12% of 2,168 patients awaiting total knee arthroplasty (TKA) in a recent cross-sectional analysis was rated as “worse than death.”1 Joint-specific function and various comorbidities were associated with these findings.

UKA vs TKA
–The multicenter randomized TOPKAT trial2 compared unicompartmental knee arthroplasty (UKA) with TKA for treating medial compartment osteoarthritis. At the 5-year follow-up, there was no between-group difference in Oxford knee scores, but UKA was more cost-effective and provided an additional 0.24 quality-adjusted life year.

Perioperative Patient Optimization
–An observational study analyzing >1,000 total joint arthroplasties3 found that implementing a “perioperative orthopaedic surgical home”—a surgeon-led screening and optimization initiative targeting 8 common modifiable comorbidities—resulted in a 1.6% 30-day readmission rate (versus 5.3% among patients not involved in the initiative).

Pain Management and Opioids
–A randomized controlled trial of >300 patients undergoing primary total knee or hip arthroplasty4 demonstrated that reducing the number of 5-mg oxycodone pills prescribed at discharge from 90 to 30 resulted in the following findings 30 days postoperatively:

  • Similar between-group pain scores
  • No between-group differences in patient-reported outcomes
  • Significant reductions in unused opioid pills and in pain pills taken in the 30-pill group

Periprosthetic Joint Infection
–Patients undergoing primary TKA who had a history of periprosthetic joint infection (PJI) in another joint had a significantly higher risk of PJI after the primary TKA, compared with the risk among a matched cohort with no history of PJI.5

References

  1. Scott CEH, MacDonald DJ, Howie CR. ‘Worse than death’ and waiting for a joint arthroplasty. Bone Joint J.2019 Aug;101-B(8):941-50.
  2. Beard DJ, Davies LJ, Cook JA, MacLennan G, Price A, Kent S, Hudson J, Carr A, Leal J, Campbell H, Fitzpatrick R, Arden N, Murray D, Campbell MK; TOPKAT Study Group. The clinical and cost-effectiveness of total versus partial knee replacement in patients with medial compartment osteoarthritis (TOPKAT): 5-year outcomes of a randomised controlled trial. 2019 Aug 31;394(10200):746-56. Epub 2019 Jul 17.
  3. Kim KY, Anoushiravani AA, Chen KK, Li R, Bosco JA, Slover JD, Iorio R. Perioperative orthopedic surgical home: optimizing total joint arthroplasty candidates and preventing readmission. J Arthroplasty.2019 Jul;34(7S):S91-6. Epub 2019 Jan 18.
  4. Hannon CP, Calkins TE, Li J, Culvern C, Darrith B, Nam D, Gerlinger TL, Buvanendran A, Della Valle CJ. The James A. Rand Young Investigator’s Award: large opioid prescriptions are unnecessary after total joint arthroplasty: a randomized controlled trial. J Arthroplasty.2019 Jul;34(7S):S4-10. Epub 2019 Feb 4.
  5. Chalmers BP, Weston JT, Osmon DR, Hanssen AD, Berry DJ, Abdel MP. Prior hip or knee prosthetic joint infection in another joint increases risk three-fold of prosthetic joint infection after primary total knee arthroplasty: a matched control study. Bone Joint J.2019 Jul;101-B(7_Supple_C):91-7.

Postop Dexamethasone Cuts Opioid Use after AIS Surgery

OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Impact Science, in response to a recent article in JBJS.

Pain management is an important aspect of postoperative care after posterior spinal fusion for the treatment of adolescent idiopathic scoliosis (AIS). Opioid medications, while highly effective and commonly used for postoperative analgesia, have many well-documented adverse effects. Several recent studies have suggested that dexamethasone, a glucocorticoid, is an effective adjunct for postoperative pain management after many adult orthopaedic procedures, but its use after AIS surgery has not been well studied.

Beginning in 2017, doctors at Children’s Healthcare of Atlanta added dexamethasone to their postoperative pain control pathway for adolescent spinal-fusion patients. In the October 21, 2020 issue of The Journal of Bone & Joint Surgery, Fletcher et al. report findings from a cohort study that investigated the postoperative outcomes of 113 patients (median age of 14 years) who underwent posterior spinal fusion between 2015 and 2018. The main outcome of interest—opioid consumption while hospitalized—was determined by converting all postoperative opioids given into morphine milligram equivalents (MME).

Because dexamethasone entered their institution’s standardized pathway for this operation in 2017, it was easy for the authors to divide these patients into two groups; 65 of the study patients did not receive postoperative steroids, while 48 patients were managed with 3 doses of steroids postoperatively. Relative to the former group, the latter group showed a 39.6% decrease in total MME used and a 29.5% decrease in weight-based MME. Patients who received postoperative dexamethasone were also more likely to walk at the time of initial physical therapy evaluation. Notably, the authors found no differences between the groups with regard to wound dihescence or 90-day infection rates—2 complications that have been associated with chronic use of perioperative steroids.

In commenting on these findings, Amy L. McIntosh, MD from Texas Scottish Rite Hospital for Children writes that she was so impressed that she plans “on adding dexamethasone to our institution’s standardized AIS care pathway.”

Impact Science is a team of highly specialized subject-area experts (Life Sciences, Physical Sciences, Medicine & Humanities), who collaborate with authors, societies, libraries, universities, and various other stakeholders for services to enhance research impact. Through research engagement and science communication, Impact Science aims at democratizing science by making research-backed content accessible to the world.

Cannabis Users Should Disclose Prior to Surgery

Although many patients believe marijuana is an effective agent to treat chronic and nerve pain, the effect of cannabis on acute musculoskeletal pain has been questioned. In an OrthoBuzz post from 2019, we reported findings published in JBJS indicating that, compared with “never users,” patients who reported using marijuana during recovery from a traumatic musculoskeletal injury experienced increases in both total prescribed opioids and duration of opioid use.

At the 2020 annual meeting of the American Society of Anesthesiologists, researchers reported parallel findings. Among 118 patients who underwent open reduction and internal fixation to repair a tibial fracture, 25% reported using cannabis prior to surgery. When researchers compared the patients who had used cannabis with those who had not, they found the following perioperative and postoperative results among the users:

  • A higher intraoperative requirement for inhalation anesthetic
  • Higher reported pain scores while in the postacute care unit after surgery
  • Higher in-hospital postoperative opioid consumption

In a press release about this study, lead author Ian Holmen, MD is quoted as saying, “…it is important for patients to tell their physician anesthesiologist if they have used cannabis products prior to surgery to ensure they receive the best anesthesia and pain control possible.”

JBJS Webinar-Sept. 23: Opioid Use Challenges and Solutions

Amid the current backdrop of opioid misuse, overdose, and addiction, conducting robust studies to investigate management of musculoskeletal pain is uniquely challenging. Last November, a JBJS-convened symposium, supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, explored those challenges. From that meeting came a 12-article JBJS Supplement published in May 2020.

On Wednesday, September 23, 2020 at 8 PM EDT, a one-hour live JBJS webinar will focus on 2 of the most salient solutions arising from the symposium.

Jeffrey Katz, MD, MSc will examine how to overcome study-design challenges such as quantifying opioid use, confounding by indication, and distinguishing between nationwide “secular changes” in opioid prescribing and the true effects from studied interventions.

Seoyoung Kim, MD, ScD, MSCE will emphasize that careful attention to methods is crucial when designing and conducting observational studies based on claims databases and patient registries. Widely accepted definitions of many common terms, such as “persistent opioid use,” do not exist.

Moderated by James Heckman, MD, Editor Emeritus of JBJS, the webinar will feature additional expert commentaries on the two author-led presentations. Andrew Schoenfeld, MD will weigh in on Dr. Katz’s paper and Nicholas Bedard, MD will comment on Dr. Kim’s paper.

The webinar will conclude with a 15-minute live Q&A session during which attendees can ask questions of all the panelists.

Seats are limited–so Register Today!

Opioid Use Challenges and Solutions: JBJS Webinar-Sept. 23

Amid the current backdrop of opioid misuse, overdose, and addiction, conducting robust studies to investigate management of musculoskeletal pain is uniquely challenging. Last November, a JBJS-convened symposium, supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, explored those challenges, and from that meeting came a 12-article JBJS Supplement published in May 2020.

On Wednesday, September 23, 2020 at 8 PM EDT, a one-hour live JBJS webinar will focus on 2 of the most salient solutions arising from the symposium.

Jeffrey Katz, MD, MSc will examine how to overcome study-design challenges such as quantifying opioid use, confounding by indication, and distinguishing between nationwide “secular changes” in opioid prescribing and the true effects from studied interventions.

Seoyoung Kim, MD, ScD, MSCE will emphasize that careful attention to methods is crucial when designing and conducting observational studies based on claims databases and patient registries, because widely accepted definitions of many common terms, such as “persistent opioid use,” do not exist.

Moderated by James Heckman, MD, Editor Emeritus of JBJS, the webinar will feature additional expert commentaries on the two author-led presentations. Andrew Schoenfeld, MD will weigh in on Dr. Katz’s paper and Nicholas Bedard, MD will comment on Dr. Kim’s paper.

The webinar will conclude with a 15-minute live Q&A session during which attendees can ask questions of all the panelists.

Seats are limited–so Register Today!

The NSAID-Fracture Nonunion Debate Continues

Many animal studies have investigated the impact of nonselective NSAIDs and selective COX-2 inhibitors on fracture healing. Nearly all those experiments focused on chronic drug administration following simulated long-bone fractures. One concern regarding the clinical relevance of those animal studies is that the “fractures” are often created by open means, which results in cortical devascularization and which may not accurately simulate the most common long-bone fracture pathophysiology in humans. Nevertheless, many orthopaedic surgeons have used the results of those animal studies to limit—or even stop—their use of NSAIDs to treat postfracture pain.

In the July 15, 2020 issue of The Journal, George et al. use a large private-insurance database to investigate the association between postfracture prescriptions filled for NSAIDS (both selective COX-2 inhibitors and nonselective types) and the subsequent diagnosis of a nonunion at 1 year postinjury. Administrative database research is more useful for generating hypotheses than for proving or disproving them, and these authors (along with Commentary writer Willem-Jan Metsemakers, MD, PhD) rightly point out that adequately powered randomized trials are needed to more fully address this issue.

Still, I was a bit surprised by the finding that nonselective NSAIDs were not associated with the diagnosis of nonunion while selective COX-2 inhibitors were. It seems to me that, given the sparse and conflicting clinical evidence today, a brief course of NSAIDs for fracture-related pain management should be included for patients while we await answers from studies with more robust research designs.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

Predictors of Prolonged Analgesic Use after Joint Replacement

OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Eric Secrist, MD in response to a recent study in Arthritis Research & Therapy.

There has been a proliferation of research regarding postoperative opioid usage after joint arthroplasty due to the widespread opioid epidemic. But Rajamäki and colleagues from Tampere University in Finland took the unique approach of also analyzing acetaminophen and NSAID usage in addition to opioids. The authors used robust data from Finland’s nationwide Drug Prescription Register, which contains reliable information on all medications dispensed from pharmacies, including over-the-counter drugs.

After excluding patients who underwent revision surgery or had their knee or hip replaced for a diagnosis other than osteoarthritis, the authors analyzed 6,238 hip replacements in 5,657 patients and 7,501 knee replacements in 6,791 patients, all performed between 2002 and 2013. The mean patient age was 68.7 years and the mean BMI was 29.

One year postoperatively, 26.1% of patients were still filling prescriptions for one or more analgesics, including NSAIDs (15.5%), acetaminophen (10.1%), and opioids (6.7%). Obesity and preoperative analgesic use were the strongest predictors of prolonged analgesic medication usage 1 year following total joint arthroplasty. Other predictors of ongoing analgesic usage included older age, female gender, and higher number of comorbidities. Patients who underwent knee replacement used the 3 analgesics more often than those who underwent hip replacement.

This study had all of the limitations inherent in retrospective database analyses. Additionally, it was not possible for the authors to determine whether patients took analgesic medications for postoperative knee or hip pain or for pain elsewhere in their body. Finally, the authors utilized antidepressant reimbursement data as a surrogate marker for depression and other medications as a surrogate for a Charlson Comorbidity Index.

Figure 2 from this study (shown below) reveals 2 important findings. First, total joint arthroplasty resulted in a significant decrease in the proportion of patients taking an analgesic medication, regardless of BMI. Second, patients in lower BMI categories were less likely to use analgesics both preoperatively and postoperatively.

The findings from this study may be most useful during preoperative counseling for obese patients, who often present with severe joint pain but are frequently told they need to delay surgery to lose weight and improve their complication-risk profile. Based on this study, those patients can be counseled that losing weight will not only decrease their complication risk, but also decrease their reliance on medications for the pain that led them to seek surgery in the first place.

Eric Secrist, MD is a fourth-year orthopaedic resident at Atrium Health in Charlotte, North Carolina.

Open-Access JBJS Supplement: Pain Management Research

In November 2019, OrthoBuzz promised readers more details from the Pain Management Research Symposium held that month (see related post), which was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Those details are now available in the form of a JBJS Supplement containing 12 articles generated from that convening of > 30 orthopaedic researchers and journal editors. The Symposium focused on the unique challenges of designing studies that will answer pressing questions about pain management related to musculoskeletal conditions and procedures.

The content of this open-access Supplement ranges from subspecialty-specific considerations in pain management to “complementary medicine” approaches. It culminates in 7 key “Recommendations for Pain Management Research,” all targeted to identifying effective pain-management strategies, not just elimination of opioids. Among those recommendations are the following:

  • Define all terms (such as “long-term opioid use”) precisely.
  • Quantify opioid use in morphine milligram equivalents (MMEs), and state how MMEs were calculated.
  • Precisely define the study population (including age, sex, and socioeconomic and cultural characteristics).
  • Mental/emotional risk factors–including depression, catastrophizing, expectations, and coping ability–should be studied.
  • Outcome measures should be patient-related, not just the number of pills taken.

JBJS would again like to thank NIAMS for its support and all Symposium participants and Supplement authors for their time and energy.