New Research in Joint Pain Management

There are few things more satisfying in emergency medicine than employing your technical skill to quickly alleviate a patient’s pain. And there are few things more annoying in modern practice than reading a lit review that relies on animal studies and histology slides to warn you about potential downsides to your skillful, pain-relieving ways. Yet here we are.

A review of literature sheds light on the practice of adding local anesthetics to intra-articular steroid injections

There are few things more satisfying in emergency medicine than employing your technical skill to quickly alleviate a patient’s pain.

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And there are few things more annoying in modern practice than reading a lit review that relies on animal studies and histology slides to warn you about potential downsides to your skillful, pain-relieving ways.

Yet here we are.

We’ve all seen the construction worker with an aching shoulder that wants to get back to the job, or the heavyset woman with knee pain, who needs to be on her feet during the day. These folks have grappled with their chronic pain for ages, trialed OTC meds and even received some opioid prescriptions in the past. Now they’ve come to your ED with an acute flare-up, they can’t get in to see an orthopedist for a week, and you’ve ruled out dangerous pathology.

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A lot of us would use this opportunity to inject something into that joint. And why not? With some practice, and good sterile technique, iatrogenic infection rates are low. Intra-articular steroids are part of the textbook management of osteoarthritis flares, as well as adhesive capsulitis, rheumatoid arthritis, gout, pseudogout and other painful joint disease. Triamcinolone (40mg for hips, knees and shoulders, 20mg of elbows and ankles, 10mg for smaller joints), for instance, has shown extended pain relief in randomized trials for osteoarthritis flares, though no effect on physical functioning, and efficacy varied depending on the joint (Zhang 2007).

Onset of relief in these situations is said to be within 24 hours, and lasts weeks. But waiting up to a day for pain relief after an IA injection can be tough to sell to a suffering patient. And since you’re injecting into the joint capsule anyway, why not add something fast-acting into the mix?

Rheumatologists and orthopedists have been injecting fast-acting local anesthetics into joint spaces for decades. In fact, intra-articular lidocaine already has a good reputation in emergency medicine – in a systematic review of six randomized shoulder reduction trials, reductions with IA lidocaine worked just as IV procedural sedation techniques, with fewer complications and shorter length-of-stay (Fitch 2008).
In the world of orthopedics, intra-articular anesthetics are commonly used to facilitate pain control after during and after joint procedures. Some trials show IA anesthetics permit early ambulation (Dobrydnjov 2011) and reduce length of stay (Andersen 2007) after joint replacement.

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So what’s the harm? Well, reports have been trickling in, in recent years, about devastating cartilage destruction discovered months following intra-articular anesthesia delivered by continuous-infusion pumps (Hansen 2007, Anakwenze 2010). A retrospective review showed that 19% of patients (3 out of 16) with glenohumeral joint infusions of 0.5% bupivacaine pain pumps developed severe cartilage degeneration within a year (Rapley 2009).
No one wants to cause a young person to need a joint replacement – but is there a danger after a single injection of intra-articular anesthetic? That’s where the rats come in – Chu et al found that injecting rat joints with 0.5% bupivacaine led to 50% depletion of chondrocytes within 6 months, compared to saline. And damage was apparent on histology in as little as four weeks (Chu 2010).

After observing a dose- and time-dependent nature of the cartilage toxicity in animal models, Dr. Chu recommended (in an interview to orthopedists) avoiding infusion pumps and minimizing the frequency and dose of IA injections. She also favored lidocaine over bupivacaine.

The danger from a single injection of intra-articular anesthetic in humans remains. It’s been suggested that an inflamed synovium will help increase the clearance of local anesthetics from the joint space, and help minimize damage – and as you might expect, in vivo data also suggests the presence of epinephrine worsens damage (Piper 2011).

While there’s no report of chondrolysis after an ED injection of intra-articular anesthetics, the balance of evidence – basic, animal and human studies – have prompted me to rethink the practice of adding local anesthetics to intra-articular steroid injections.

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Are there other options for rapid pain relief, in those patients who’ve already tried oral opioids or NSAIDs for acute flares of chronic joint pain? Well, in the orthopedic literature, trials and reports abound on the efficacy of intra-articular morphine and other opioid medications. But in reviewing the prior studies for a proposed Cochrane analysis, Zou et al found confounders and methods that were difficult to compare, noting “evidence is still lacking as to whether intra-articular opioids offer clinically relevant pain relief” (Zou 2011).

You can imagine the same can be said for intra-articular magnesium and even IA midazolam (!) – there seems to be slight, short-lived benefit compared to placebo in trials of post-op patients, but the utility of these agents in an ED setting is hardly compelling.

A safer, surer bet is topical diclofenac (Barthel 2010). It’s marketed as a lotion under the name Pennsaid, and a gel form goes by the trade name Voltaren. Topical diclofenac formulations four times daily have shown comparable pain relief to oral diclofenac (and superior to placebo) without the systemic side effects associated with oral NSAIDs (typically, the only adverse reaction reported was site irritation).  

Less commonly used agents are developing a basis for use, as well. Topical capsaicin has shown benefit over placebo after one and two weeks in a Cochrane review of rheumatoid arthritis patients (Richards 2012) – though almost half of recipients developed burning at the application site (go figure). And in a recent review of no less than eighteen trials that met criteria, fifteen studies showed significant analgesic effect of cannabinoids, compared to placebo, in rheumatoid and fibromyalgia pain (sleep was also found to be improved in the cannabinoid groups, and no significant adverse effects were reported) (Lynch 2011).

After ruling out dangerous pathologies, patients with acute flares of chronic joint pain can be difficult to satisfy in the ED, though it’s undoubtedly more frustrating for the patient than the provider. Beyond traditional oral NSAIDs and opioid medications, topical diclofenac and IA steroid injections are safe and established therapies that can provided relief quickly and over time.

Nicholas Genes is faculty in the Emergency Department at the Icahn School of Medicine at Mount Sinai. He is the author of a chapter on EM arthritis presentations for a forthcoming edition of Rosen’s Emergency Medicine textbook.

References

• Zhang W, et al: EULAR evidence based recommendations for the management of osteoarthritis: Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007; 66:377-388.
• Fitch RW, Kuhn JE. Intraarticular lidocaine versus intravenous procedural sedation with narcotics and benzodiazepines for reduction of the dislocated shoulder: a systematic review.  Acad Emerg Med. 2008 Aug;15(8):703-8.
• Dobrydnjov I, Anderberg C, Olsson C, Shapurova O, Angel K, Bergman S. Intraarticular vs. extraarticular ropivacaine infusion following high-dose local infiltration analgesia after total knee arthroplasty: a randomized double-blind study. Acta Orthop. 2011 Dec;82(6):692-8.
• Andersen KV, Pfeiffer-Jensen M, Haraldsted V, Søballe K. Reduced hospital stay and narcotic consumption, and improved mobilization with local and intraarticular infiltration after hip arthroplasty: a randomized clinical trial of an intraarticular technique versus epidural infusion in 80 patients. Acta Orthop. 2007 Apr;78(2):180-6.
• Hansen BP, Beck CL, Beck EP, Townsley RW. Postarthroscopic glenohumeral chondrolysis. Am J Sports Med. 2007 Oct;35(10):1628-34.
• Anakwenze OA, Hosalkar H, Huffman GR. Case reports: two cases of glenohumeral chondrolysis after intraarticular pain pumps. Clin Orthop Relat Res. 2010 Sep;468(9):2545-9.
• Rapley JH, Beavis RC, Barber FA. Glenohumeral chondrolysis after shoulder arthroscopy associated with continuous bupivacaine infusion. Arthroscopy. 2009;25(12):1367-1373.
• Chu CR, Coyle CH, Chu CT, et al. In vivo effects of single intra-articular injection of 0.5% bupivacaine on articular cartilage. J Bone Joint Surg Am. 2010;92(3):599-608.
• Chu interview; http://www.mirm.pitt.edu/news/article.asp?qEmpID=382
• Piper SL, Kramer JD, Kim HT, Feeley BT. Effects of local anesthetics on articular cartilage. Am J Sports Med. 2011 Oct;39(10):2245-53.
• Barthel HR, Axford-Gatley RA. Topical nonsteroidal anti-inflammatory drugs for osteoarthritis. Postgrad Med. 2010 Nov;122(6):98-106.
• Zou Z, An MM, Xie Q, Chen XY, Zhang H, Liu GJ, Shi XY. Single-dose intra-articular morphine for pain control after knee arthroscopy (Protocol). Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD008918.
• Richards BL, Whittle SL, et al. Efficacy and Safety of Neuromodulators in Inflammatory Arthritis: A Cochrane Systematic Review. J Rheumatology 2012(90) 28-33.
• Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials.  Br J Clin Pharmacol. 2011 Nov;72(5):735-44.