Intra-articular (IA) joint and bursa injections are used to treat pain in the joint and surrounding structures. Musculoskeletal system disorders, including osteoarthritis, are some of the most common medical conditions for which patients seek care. Musculoskeletal diseases are associated with high levels of disability and significant economic costs. Osteoarthritis, a noninflammatory rheumatologic condition, is the most prevalent form of arthritis. It is projected that more than 59 million individuals in the United States (18% of the population) will suffer from osteoarthritis by 2020.
In the 1950s, Hollander introduced the IA corticosteroid injection for the treatment of rheumatoid arthritis (RA). In 1958, the first clinical trial for IA joint injections for osteoarthritis was performed. Currently, joint injections continue to be used extensively in a multimodal treatment platform for musculoskeletal conditions. In the updated American College of Rheumatology (ACR) guidelines for the medical management of osteoarthritis, IA injections were recommended as alternative and augmentative treatment approaches to oral medications and physical therapy.
This chapter provides an updated review of IA joint injections. Four major areas are covered: (1) pharmacology of common injectable agents, (2) indications for treatment, (3) image-guided injection techniques, and (4) IA injection-associated adverse effects and complications. The three major joints addressed are the shoulder, hip, and knee. Assessments of the accuracy and therapeutic efficacy of each technique are provided.
Pharmacology of Agents Utilized for Joint Injections
Intra-articular needle placement is routinely used to deliver therapeutic agents to reduce pain and improve function. The three agents routinely employed for IA injections are local anesthetics, corticosteroids, and viscosupplements.
Local Anesthetics
Indications and Mechanism of Action
Local anesthetics (LAs) are often utilized in combination with corticosteroids for IA and extra-articular injections. The rationale for utilizing LAs includes providing pain relief for the needle insertion itself and diagnostic purposes as well as diluting and distributing the steroid preparation within the joint.
Local anesthetics act by reversibly binding to sodium channels on neuronal cell membranes, thereby blocking nerve conduction. Local anesthetics also have transient anti-inflammatory effects and inhibit several leukocyte functions.
Local Anesthetic Agent Selection (Structure and Function)
Local anesthetics commonly employed for joint injections include the short-acting LA, lidocaine, and the long-acting LAs, bupivacaine and ropivacaine.
Adverse Effects and Complications Associated with Local Anesthetic Injection
Local anesthetics are associated with both local and systemic side effects. Local effects of LAs include myotoxicity and chondrotoxicity. Myotoxicity can occur from LA administration in or around muscle tissue, although it is usually not clinically relevant and muscle regeneration occurs. Bupivacaine is more myotoxic than lidocaine and ropivacaine. Local anesthetics produce myonecrosis through the lytic degeneration of the sarcoplasmic reticulum and mitochondria. The addition of corticosteroids to LA injection amplifies the muscle damage and prolongs the recovery phase. Myonecrosis rarely presents any clinically discernible manifestations in the course of routine use of local anesthetics for IA joint injections.
Local anesthetics are also chondrotoxic. Most reported cases of chondrolysis occurred after use of continuous IA local anesthetic infusions to manage postoperative pain rather than single IA injections. In vitro studies have demonstrated that LAs cause mitochondrial dysfunction and apoptosis in human chondrocytes. Chondrotoxic effects are influenced by the LA type and concentration. Grishko and colleagues demonstrated that 2% lidocaine caused massive necrosis of cultured chondrocytes after 24 hours of exposure, whereas 1% lidocaine caused a detectable but insignificant decrease in cell viability. For longer-acting LAs, in vitro studies indicate that 0.5% ropivacaine is significantly less chondrotoxic to cultured human articular cartilage than 0.5% bupivacaine. Similar to myotoxicity, combining LA with corticosteroids amplifies chondrotoxicity. Further studies are needed to determine the clinical significance and exact mechanisms of LA toxicity to cartilage cells.
When combining LA with corticosteroids, flocculation—aggregation of the particles of steroid—may occur. Indeed, dilution with either saline or LA may influence the size of corticosteroid particles. Betamethasone sodium phosphate/betamethasone acetate (Celestone Soluspan) should not be mixed with LAs that contain the excipients methylparaben, propylparaben, or phenol because of an increased risk of flocculation. Flocculation leads to larger particles that may clog smaller bore needles, preventing injection. The effect of flocculation of the injected steroid on its therapeutic effect is unclear; theoretically, the change in the size of the microaggregates of the steroid could significantly alter the bioavailability of the steroid over time as well the distribution within the joint after injection, altering the therapeutic effect.
Systemic effects of LAs include allergic reactions and central nervous system and cardiac toxicity. When appropriate steps are taken to avoid intravascular injection, including frequent aspiration and using small volumes for musculoskeletal injections, the incidence of these occurrences are low. Allergic reactions are more common with amino-ester LAs secondary to the production of metabolites related to para -aminobenzoic acid. Allergic reactions may also be due to the preservatives contained within the carrier solution (e.g., methylparaben). Cross-sensitivity does not exist between LA structural classes. The American Society of Regional Anesthesia published a practice advisory on local anesthetic toxicity and provided a checklist for managing local anesthetic toxicity ( Fig. 71.1 ).
Corticosteroids
Indications and Mechanism of Action
Corticosteroids are often used for pain associated with symptomatic arthritis and soft tissue conditions (e.g., tendinitis, bursitis, and tenosynovitis). Numerous guidelines with specific focus on osteoarthritis of the knee recommend IA corticosteroid injection for short-term pain relief. Intra-articular steroid injections should be part of a multimodal treatment plan that includes aerobic and muscle-strengthening programs. Contraindications to IA injection are shown in Box 71.1 .
Absolute Contraindications
Overlying skin infection
Fracture site
Severely compromised immune status
Suspected bacteremia
Suspected infectious arthritis
Hypersensitivity to previous viscosupplementation
Relative Contraindications
Coagulopathy
Hypersensitivity to avian products (proteins, feather, and egg products) ∗
∗ Consider using nonavian viscosupplementation products.
Joint prosthesis
Poorly controlled diabetes mellitus
Previous lack of efficacy
The exact mechanism of action of corticosteroids in reducing arthritic joint pain has not been completely defined. Corticosteroids placed in the joint exert both local and systemic effects. In individuals with RA, changes in the non-injected knee thermographic index, a quantitative measure of radiated energy from a defined area of the joint surface, have been demonstrated after IA prednisolone and triamcinolone hexacetonide (TH) injection into the symptomatic knee. Intra-articular placement of methylprednisolone acetate (MPA), 40 or 80 mg, resulted in detectable serum levels with peak levels occurring between 2 and 12 hours after injection. Additionally, endogenous serum cortisol levels were suppressed for up to 1 week after injection. The systemic effects are further confirmed by reduction of systemic inflammatory marker levels, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
Corticosteroids have significant anti-inflammatory and immune effects and are active at the cellular level by combining with receptors to alter the rate of messenger RNA synthesis and specific protein production. Specifically, corticosteroids result in increased synthesis of annexin-1 (lipocortin-1). Annexin-1 has phospholipase A 2 -inhibitory activity that reduces production of multiple inflammatory mediators, including eicosanoids, lysosomal enzymes, interleukin-1, leukotrienes, and prostaglandins. The clinical response to IA steroids is accompanied by histologic improvement and decreased expression of genes that are involved in articular cartilage destruction. Additionally, corticosteroids reduce microvascular permeability and synovial perfusion, and they increase synovial fluid viscosity.
Corticosteroids seem to exert greater therapeutic effects with IA injection versus either systemic or intramuscular (IM) administration. Injection of corticosteroid into multiple joints in RA patients greatly improved ACR criteria, patient disease activity, number of tender points, and reduced systemic side effects, when compared to equivalent IM dosing.
Corticosteroid Selection (Structure and Function)
The first steroid used for IA injection was hydrocortisone. Although over the past 50 years pharmacologic developments have resulted in the advancement of steroid preparations, substantial variation still exists for agent selection. However, there remains a paucity of randomized controlled trials comparing the efficacy of different corticosteroids for osteoarthritis. Thus, evidence-based recommendations to guide steroid selection cannot be made. In 1994, a survey of ACR members indicated that agent selection was usually determined empirically and was strongly influenced by the geographic region of training. The three most commonly utilized agents were MPA, TH, and triamcinolone acetonide (TA).
Table 71.1 lists commonly utilized corticosteroids that have been certified by the United States Food and Drug Administration (FDA) for IA injection. The only other corticosteroid approved for IA injection is dexamethasone. Dexamethasone, a highly water soluble, nonparticulate steroid preparation, exerts primarily systemic effects even after IA injection and is not routinely utilized for IA injections.
