Joint Injections

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Joint Injections David A. Provenzano | Kailash Chandwani

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.1,2 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 2020.3 In the 1950s, Hollander introduced the IA corticosteroid injection for the treatment of rheumatoid arthritis (RA).4-6 In 1958, the first clinical trial for IA joint injections for osteoarthritis was performed.7 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.8 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

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nerve conduction.9 Local anesthetics also have transient anti-inflammatory effects and inhibit several leukocyte functions.10 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.11 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.12 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.13-17 Most reported cases of chondrolysis occurred after use of continuous IA local anesthetic infusions to manage postoperative pain rather than single IA injections.17 In vitro studies have demonstrated that LAs cause mitochondrial dysfunction and apoptosis in human chondrocytes.14 Chondrotoxic effects are influenced by the LA type and concentration. Grishko and colleagues14 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.15 Similar to myotoxicity, combining LA with corticosteroids amplifies chondrotoxicity.18 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.19 Indeed, dilution with either saline or LA may influence the size of corticosteroid particles.20 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.19 Flocculation leads to larger particles that may

CHAPTER 71 — JOINT INJECTIONS

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.9 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.8,21,22 Intra-articular steroid injections should be part of a multimodal treatment plan that includes aerobic and musclestrengthening programs. Contraindications to IA injection are shown in Box 71.1. 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.19,23 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.23,24 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.25 The systemic effects are further confirmed by reduction of systemic inflammatory marker levels, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).19 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 A2-inhibitory activity that reduces production of multiple inflammatory mediators, including eicosanoids, lysosomal enzymes, interleukin-1, leukotrienes, and prostaglandins.26-28 The clinical response to IA steroids is accompanied by histologic improvement and decreased expression of genes that are involved in articular cartilage destruction.29 Additionally,

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corticosteroids reduce microvascular permeability and synovial perfusion, and they increase synovial fluid viscosity.30 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.31 CORTICOSTEROID SELECTION (STRUCTURE AND FUNCTION) The first steroid used for IA injection was hydrocortisone.5,6 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).32 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.19,20 The selection of a depot corticosteroid can be based on cost and multiple pharmacologic properties including solubility as well as crystal and molecular structure. Chemical structures important to depot steroids include the presence of an ester group and the addition of a fluorine group. Ester groups decrease corticosteroid solubility.33 Inserted fluorine groups increase corticosteroid absorption and increase steroid potency.19 Corticosteroid solubility may influence duration of action, although published studies are conflicting. Triamcinolone hexacetonide is the most insoluble injectable corticosteroid. Some IA injection studies have demonstrated prolonged duration of activity with TH compared to other corticosteroids with higher solubility. Derendorf and associates34 demonstrated that TH was associated with lower levels of systemic absorption and higher synovial levels than similar IA administration of TA. Comparison of TH and MPA for knee osteoarthritis did not support steroid solubility as the only factor influencing drug duration of action and therapeutic efficacy.35 After 3 weeks, TH was more effective but at 8 weeks only MPA resulted in continued improvement in pain and disability scores. Another study comparing TH and MPA for RA treatment demonstrated a longer therapeutic effect with TH.36 Thus, available data are conflicting. The adverse-effect profile of a corticosteroid should also be considered. Methylprednisolone acetate may be utilized for both joint and soft tissue injections, whereas TH is not recommended for soft tissue injections because of the higher risk of calcification, necrosis, and atrophy of soft tissues.9,33,37

AMERICAN SOCIETY OF REGIONAL ANESTHESIA AND PAIN MEDICINE Checklist for Treatmentof Local Anesthetic Systemic Toxicity The Pharmacologic Treatment of Local Anesthetic Systemic Toxicity (LAST) Is Different from Other Cardiac Arrest Scenarios Get Help Initial Focus Airway management: ventilate with 100% oxygen Seizure suppression: benzodiazepines are preferred; AVOID propofol in patients having signs of cardiovascular instability Alert the nearest facility having cardiopulmonary bypass capability Management of Cardiac Arrhythmias Basic and Advanced Cardiac Life Support (ACLS) will require adjustment of medications and perhaps prolonged effort AVOID vasopressin, calcium channel blockers, beta blockers, or local anesthetic REDUCE individual epinephrine doses to <1 mcg/kg Lipid Emulsion (20%) Therapy (values in parentheses are for 70 kg patient) Bolus 1.5 mL/kg (lean body mass) intravenously over 1 minute (~100 mL) Continuous infusion 0.25 mL/kg/min (~18 mL/min; adjust by roller clamp) Repeat bolus once or twice for persistent cardiovascular collapse Double the infusion rate to 0.5 mL/kg/min if blood pressure remains low Continue infusion for at least 10 minutes after attaining circulatory stability Recommended upper limit: Approximately 10 mL/kg lipid emulsion over the first 30 minutes Post LAST events at www.lipidrescue.org and report use of lipid to www.lipidregistry.org BE PREPARED • We strongly advise that those using local anesthetics (LAs) in doses sufficient to produce local anesthetic systemic toxicity (LAST) establish a plan for managing this complication. Making a Local Anesthetic Toxicity Kit and posting instructions for its use are encouraged. RISK REDUCTION (BE SENSIBLE) • Use the least dose of LA necessary to achieve the desired extent and duration of block. • Local anesthetic blood levels are influenced by site of injection and dose. Factors that can increase the likelihood of LAST include: advanced age, heart failure, ischemic heart disease, conduction abnormalities, metabolic (e.g., mitochondrial) disease, liver disease, low plasma protein concentration, metabolic or respiratory acidosis, medications that inhibit sodium channels. Patients with severe cardiac dysfunction, particularly very low ejection fraction, are more sensitive to LAST and also more prone to “stacked” injections (with resulting elevated LA tissue concentrations) due to slowed circulation time. • Consider using a pharmacologic marker and/or test dose, e.g. epinephrine 5 mcg/mL of LA. Know the expected response, onset, duration, and limitations of “test dose” in identifying intravascular injection. • Aspirate the syringe prior to each injection while observing for blood. • Inject incrementally, while observing for signs and querying for symptoms of toxicity between each injection. DETECTION (BE VIGILANT) • Use standard American Society of Anesthesiologists (ASA) monitors. • Monitor the patient during and after completing injection as clinical toxicity can be delayed up to 30 minutes. • Communicate frequently with the patient to query for symptoms of toxicity. • Consider LAST in any patient with altered mental status, neurological symptoms or cardiovascular instability after a regional anesthetic. • Central nervous system signs (may be subtle or absent)

Depression (drowsiness, obtundation, coma or apnea) Non-specific (metallic taste, circumoral numbness, diplopia, tinnitus, dizziness) • Cardiovascular signs (often the only manifestation of severe LAST) Initially may be hyperdynamic (hypertension, tachycardia, ventricular arrhythmias), then Progressive hypotension Conduction block, bradycardia or asystole Ventricular arrhythmia (ventricular tachycardia, torsades de pointes, ventricular fibrillation) • Sedative hypnotic drugs reduce seizure risk but even light sedation may abolish the patient’s ability to recognize or report symptoms of rising LA concentrations. TREATMENT • Timing of lipid infusion in LAST is controversial. The most conservative approach, waiting until after ACLS has proven unsuccessful, is unreasonable because early treatment can prevent cardiovascular collapse. Infusing lipid at the earliest sign of LAST can result in unnecessary treatment since only a fraction of patients will progress to severe toxicity. The most reasonable approach is to implement lipid therapy on the basis of clinical severity and rate of progression of LAST. • There is laboratory evidence that epinephrine can impair resuscitation from LAST and reduce the efficacy of lipid rescue. Therefore it is recommended to avoid high doses of epinephrine and use smaller doses, e.g., <1 mcg/kg, for treating hypotension. • Propofol should not be used when there are signs of cardiovascular instability. Propofol is a cardiovascular depressant with lipid content too low to provide benefit. Its use is discouraged when there is a risk of progression to cardiovascular collapse. • Prolonged monitoring (>12 hours) is recommended after any signs of systemic LA toxicity, since cardiovascular depression due to local anesthetics can persist or recur after treatment. © 2012. The American Society of Regional Anesthesia and Pain Medicine.

ASRA hereby grants practitioners the right to reproduce this document as a tool for the care of patients who receive potentially toxic doses of LAs. Publication of these recommendations requires Excitation (agitation, confusion, muscle twitching, seizure) permission from ASRA. Figure 71.1  American Society of Regional Anesthesia (ASRA) checklist for treatment of local anesthetic toxicity. (Reprinted with permission from Neal JM, Mulroy MF, Weinberg GL. American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic toxicity: 2012 version. Reg Anesth Pain Med. 2012;37:16-18.) Continued

CHAPTER 71 — JOINT INJECTIONS The ASRA Practice Advisory on Local Anesthetic Toxicity is published in the society’s official publication Regional Anesthesia and Pain Medicine, and can be downloaded from the journal website at www.rapm.org. Neal JM, Bernards CM, Butterworth JF, Di Gregorio G, Drasner K, Hejtmanck MR, Mulroy MF, Rosenquist RW, Weinberg GL. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med 2010;35:152-161. Figure 71.1, cont’d.

Box 71.1 Absolute and Relative

Contraindications for Intra-articular Joint Injections with Corticosteroids or Viscosupplementation

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)* Joint prosthesis Poorly controlled diabetes mellitus Previous lack of efficacy *Consider using nonavian viscosupplementation products.

CORTICOSTEROID DOSING AND POSTINJECTION PROTOCOLS Corticosteroid dosing ranges for various joints are listed in Table 71.1. Evidence-based recommendations for dosing and the maximum injection frequency do not exist. Standard recommendations for weight-bearing joints include a maximum of three to four injections per year, typically with 3 to 4 months between injections.30,33 Long-term corticosteroid safety was studied by Raynauld and colleagues 38 in a randomized, double-blind, placebo-controlled trial that compared IA knee injections of TA or saline every 3 months for up to 2 years. No detrimental effects or joint space destruction was observed on radiographs. Balch and coworkers39 found no radiographic evidence of ­corticosteroid-induced joint destruction after long-term repeated IA injections (from 4 to 15 years) on knee joints affected by RA and osteoarthritis. Following IA corticosteroid injection, patients are often advised to avoid overusing the joint for 2 to 3 days postinjection.40 Studies investigating potential benefits of rest following corticosteroid injections have reported conflicting results.19 Chakravarty and colleagues41 demonstrated additional improvement in individuals who rested for 24 hours after IA injection whereas Chatham and associates42 found no benefit in individuals who rested for 48 hours. If an individual is going to undergo a total hip or knee joint replacement in the near future, caution should be exercised

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in performing IA injections close to the surgical date.43 Retrospective comparative studies demonstrated increased risk for deep infection in individuals who received IA corticosteroid injections shortly before the surgical replacement procedure.44,45 However, Joshy and colleagues46 did not observe increased deep infection rates for individuals who underwent IA injections shortly prior to total knee replacement. ADVERSE EFFECTS AND COMPLICATIONS ASSOCIATED WITH CORTICOSTEROID INJECTION The adverse effects and complications of corticosteroid injections can be divided into local and systemic effects. Local adverse effects include tissue (skin or fat) atrophy, Nicolau’s syndrome, tendon rupture, cartilage damage, postinjection flare, hemarthrosis, joint destruction, avascular necrosis, and septic arthritis.9,33,47,48 Local tissue atrophy is one of the most common local adverse effects occurring in 1% to 8% of cases and is often associated with superficial injection, inaccurate placement, and less soluble agents (e.g., triamcinolone compounds). Skin atrophy typically develops between 1 and 4 months after injection.30,47 Methylprednisolone acetate is less frequently associated with soft tissue atrophy. Another common adverse effect is postinjection flare in pain, with a prevalence of 2% to 25%. Postinjection flare typically presents within a few hours of injection and resolves within 1 to 3 days.33 Concern also exists for corticosteroid-specific effects on cartilage, tendon, and bone. Current data on corticosteroid effects on cartilage are conflicting. Animal studies have been inconsistent, with some demonstrating cartilage destruction and others revealing a cartilage-protective effect during acute inflammatory events.49-55 Clinical studies suggest that cartilage loss may occur more frequently with repeated injections in large numbers.9 Avascular necrosis has also been reported after joint injections, with the hip being the most commonly affected joint. This complication typically occurs after multiple joint injections within a short period of time and is seen more often in individuals who are concurrently taking oral steroids.47 Tendon disruption has also occurred following corticosteroid injection and care should be taken to avoid direct injection within tendons.47,56 Hemarthrosis and septic arthritis are two infrequent complications that carry significant morbidity. No specific guidelines exist for performance of IA steroid injections in individuals on anticoagulants, and surveys have demonstrated substantial practice variation.57 A small study demonstrated a low risk of hemorrhage in individuals taking warfarin sodium who received IA injections.58 Septic arthritis has a reported incidence ranging from 1 in 3000 to 1 in 50,000.19,59,60 To limit this adverse event it is important to understand contraindications to injection (see Box 71.1) and utilize a stringent aseptic technique. When performing a joint injection, if synovial fluid appears abnormal, the aspirated fluid should be sent for a complete white blood cell (WBC) count including differential, crystal analysis, Gram stain, and culture. Steroid should not be placed until the synovial fluid analysis (Table 71.2) has been reviewed and interpreted. Septic arthritis is a medical emergency and can result in cartilage destruction, septicemia, and death within a few days if untreated. When septic arthritis is suspected, orthopedic surgery and infectious disease specialists should

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PART 7 — INTERVENTIONAL TECHNIQUES

Table 71.1 Common Corticosteroid Preparations for Intra-articular and Periarticular Injections. Equivalent Dosage (mg)*

Anti-Inflammatory Potency†

3 mg BSP/3 mg BA per 1 mL

0.75

25

20, 40, 80 mg/mL

4

10, 40 mg/mL 5, 20 mg/mL

Preparation

How Supplied

Betamethasone sodium phosphate/ betamethasone acetate (BSP/BA) Methylprednisolone acetate (MPA) Triamcinolone acetonide (TA) Triamcinolone hexacetonide (TH)

Solubility (%wt/vol)

Fluorinated

Dose Based on Joint Size

Not mentioned‡

Yes

Large: 1-2 mL Medium: 0.5-1 mL Small: 0.25-0.5 mL

5

0.001

No

4

5

0.004

Yes

4

5

0.0002

Yes

Large: 20-80 mg Medium: 10-40 mg Small: 4-10 mg Large: 5-15 mg Small: 2.5-5 mg Large: 10-20 mg Small: 2-6 mg

 

*Equivalent to 5 mg prednisone. For TA and TH the specific dosing for medium-sized joints was not mentioned. †Relative potencies based on equivalent milligram doses with hydrocortisone being the relative baseline with a potency of 1. ‡The betamethasone preparation consists of the highly soluble ester BSP, which is devoid of particles, and the less soluble BA. (Data from references 19, 28, 30, 33, and 40.)

Table 71.2 Synovial Fluid Analysis Diagnosis

Color

Clarity

Normal Noninflammatory Inflammatory (crystalline) Septic arthritis Pseudosepsis

Clear Straw Yellow Yellow NA

Transparent Translucent Cloudy Cloudy NA

WBC Count per mm3

% Neutrophils

<200 200-2000 2000-100,000 >25,000-50,000 5000-80,000*

<25 <25 >50 >75 NA

Gram Stain Negative Negative Negative Variable Negative

 

NA, not available *Unlike septic arthritis, aspirate from joints with suspected pseudosepsis may contain an elevated eosinophil count suggestive of an immune-mediated inflammatory reaction.82 (Data from references 170-172.)

be consulted immediately. Arthrocentesis and synovial fluid analysis (see Table 71.2) are mandatory for diagnosis and to guide treatment. Blood tests including a WBC, erythrocyte sedimentation rate, and CRP are neither sensitive nor specific in diagnosing or excluding septic arthritis.61 Broadspectrum antibiotics are initially started after obtaining the synovial fluid, and antibiotic selection is further guided by culture and sensitivity results. Septic arthritis has also been reported following viscosupplementation injections.62 Systemic adverse effects of IA corticosteroids include endocrine, metabolic, and vascular effects.63 The most common and predictable endocrine effect is rapid suppression of endogenous cortisol production. Maximal suppression of serum cortisol levels occur by 24 to 48 hours after IA injection; adrenocorticotropic hormone (ACTH) levels typically return to normal between 1 and 4 weeks, indicating recovery of normal endogenous steroid production.25,63,64 Metabolic effects include elevation of blood glucose levels in diabetic patients.65 In diabetics with appropriate glucose control, acute hyperglycemia may persist for 2 to 3 days with peak glucose levels reaching 300 mg/dL.63,66 Facial flushing is an unpleasant adverse effect seen in 15% to 40% of patients.9 The effect occurs, on average, 19 hours after injection and is self-limiting, lasting approximately 36

hours. Triamcinolone administration is associated with a higher rate of facial flushing.63

VISCOSUPPLEMENTATION INDICATIONS AND MECHANISM OF ACTION Viscosupplementation refers to IA administration of synthetic hyaluronic acid (HA). Intra-articular HA administration (IAHA) is recommended by numerous specialty guidelines, including the ACR, Osteoarthritis Research Society International (OARSI), and European League Against Rheumatism (EULAR), as a treatment option for the management of knee osteoarthritis.8,67,68 Intra-articular HA administration is approved by the FDA only for knee osteoarthritis. Off-label application of IAHA has been reported for the shoulder, hip, and ankle. Selection criteria include unresponsiveness to standard noninvasive treatment programs with clinical and radiologic signs of knee osteoarthritis.8,69 Osteoarthritis severity may be an important predictor in determining the magnitude of clinical response to IAHA injection. In general, IAHA seems most beneficial in individuals with early osteoarthritis and radiographic evidence of joint space preservation.70-72 Contraindications to IAHA injection are shown in Box 71.1.

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Table 71.3 Commonly Used Hyaluronic Acid Preparations for IA Viscosupplementation. Product Structure

Product Name

Cross linked

Synvisc Synvisc-One Supartz

Non–cross linked

Hyalgan Orthovisc Euflexxa

Origin Sodium hyaluronate Sodium hyaluronate Sodium hyaluronate (naturally derived) Sodium hyaluronate (naturally derived) Bacterial fermentation (nonavian) Bacterial fermentation (nonavian)

Molecular Weight (kDa)

Injection Interval

Dosing Volume

Recommended Dosing Regimen*

6000 6000 620-1170

1 week N/A 1 week

2 ml 6 ml 2.5 ml

3 Once 3 or 5*

500-730

1 week

2 ml

3 or 5*

1000-2900

1 week

2 ml

3-4*

2400-3600

1 week

2 ml

3

 

*Treatment schedule: Please refer to manufacturers’ specific recommendations. kDa, kilodalton. N/A, not applicable.

Although the exact mechanism of action is unknown, the treatment goal is to restore the viscoelastic properties of synovial fluid.73 Observed treatment benefits are not entirely explained by IA residence time, which is considerably shorter than the duration of clinical benefit. Several in vitro and preclinical studies have proposed additional mechanisms of action for IAHA, including inhibition of inflammation and cartilage degradation, reduction of pain mediators, and induction of in vivo HA synthesis.74,75 VISCOSUPPLEMENTATION AGENT SELECTION (STRUCTURE AND FUNCTION) Viscosupplementation formulations differ in their origin, method of production, molecular weight, treatment schedule, and physicochemical properties.75 Six hyaluronic acid preparations are approved for knee osteoarthritis in the United States (Table 71.3). Formulations are classified as cross-linked or non-cross-linked and are further defined by chemical modifications and production method (avianversus non-avian-derived products). Non-avian products are produced by bacterial fermentation. All available avian preparations are derived from rooster combs and are purified natural products. The sole exception is hylan G-F 20, which is chemically modified (cross-linked HA) to increase the molecular weight to more closely replicate the properties of native synovial fluid and to lengthen IA residence half-life.73,76 No conclusive evidence exists that differences in viscosupplement physical properties translate into superior clinical efficacy.77 DOSING AND POSTINJECTION PROTOCOLS The recommended dosing regimens for particular viscosupplementation products are based on the physical properties and the manufacturers’ prescribing recommendations. Currently, there is insufficient evidence to guide the appropriate injection frequency and dosing intervals. Common recommendations are either for a single injection or a total of three to five weekly injections based on the selected product (see Table 71.3), but these are solely based on the manufacturer’s recommendations that arose from the premarketing registry trials for each product.78 Evidence-based recommendations do not exist

for interval timing for repeating treatment. Insurance providers typically require a minimum of 6 months between repeated treatment courses. Pre-injection synovial fluid aspiration and avoidance of excessive weight bearing activities for 48 to 72 hours postinjection may yield better outcomes.70,72,79 ADVERSE EFFECTS AND COMPLICATIONS ASSOCIATED WITH VISCOSUPPLEMENTATION INJECTION In general, viscosupplementation is well tolerated with more local reactions but fewer systemic side effects compared to other medical interventions for the management of knee osteoarthritis.80 Frequently reported local adverse effects include injection site pain, short-term erythema, and joint effusion development. These effects are typically mild and resolve within 24 to 48 hours. Other infrequent local adverse effects include pseudosepsis and pseudogout.81 Pseudosepsis, a severe acute inflammatory reaction (SAIR), is considered an extreme local adverse reaction. It is characterized by a large effusion, severe pain, and cellular infiltration occurring within 24 to 72 hours after the injection. Pseudosepsis often requires clinical intervention such as arthrocentesis, IA corticosteroids, and systemic analgesics.82 Pseudosepsis may be misdiagnosed as septic arthritis.82 The proposed mechanisms of pseudosepsis include an immune reaction to cross-linked products. Inappropriate injectate placement has also been suggested as a causative factor in pseudosepsis.70,83 When pseudosepsis is suspected, it is imperative that other clinical conditions such as septic arthritis are ruled out. Pseudogout is a type of crystal-induced arthropathy characterized by calcium pyrophosphate crystal deposition. Individuals with pseudogout present with acute pain, joint swelling, and decreased function. The pathophysiology leading to pseudogout after IAHA is not clearly understood. Pseudogout occurs more frequently in patients with preexisting chondrocalcinosis; therefore, IAHA should be used with a caution in these individuals.84,85 Pseudogout may also be mislabeled as pseudosepsis. Synovial fluid analysis is helpful in making the correct diagnosis (see Table 71.2).

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JOINT INJECTION TECHNIQUES Three injection techniques (palpation, ultrasound guided, and fluoroscopy guided) may be used for the placement of drugs into the IA space. Palpation-guided IA injections are associated with inappropriate needle placement rates as high as 50% to 60%.86,87 Fluoroscopy- and ultrasound-guided methods have evolved to increase injection accuracy. Although both techniques allow for needle visualization, ultrasound guidance has advantages. Benefits of ultrasound-guided injection include dynamic real-time multiplanar imaging of relevant anatomic structures, direct visualization of injected therapeutic agents, and absence of ionizing radiation. Improved injection accuracy with visually guided techniques ensures correct IA compound placement and may significantly influence clinical outcomes. In a randomized control trial evaluating clinical outcomes in individuals who received either anatomic palpation-guided or ultrasoundguided IA joint injections, the benefit of accurate IA placement was demonstrated.87 A total of 148 joint injections were studied with 95% of injections occurring in large joints (knee, hip, shoulder, elbow, wrist, and ankle). The remaining 5% of the injections occurred in small joints (interphalangeal or metacarpophalangeal joints). Intra-articular knee injections represented the largest category at 42%. Sonographic needle guidance was found to be statistically superior in multiple areas. In comparison to palpation-guided injections, ultrasound-guided injections resulted in a 43% reduction in procedural pain, 58.5% reduction in absolute pain scores at 2 weeks, 26% increase in responder rate, and 62% reduction in the nonresponder rate. Sonographic needle placement also improved detection of joint effusion by 200% and increased aspirated fluid volume by 337%. The authors concluded that sonographic guidance for IA injections is associated with significant short-term clinical advantages. In this section we will describe the injection techniques for the three major joints: shoulder, hip, and knee. Emphasis will be placed on the visual-guided techniques. The efficacy for IA and viscosupplementation will also be discussed. Strict aseptic technique should be utilized for all injections.

SHOULDER ANATOMY The shoulder is a complex anatomic structure allowing multidirectional movement. The shoulder girdle refers to several articulations associated with important muscle groups that provide a wide range of shoulder movement. Three important shoulder joints are the glenohumeral, acromioclavicular, and sternoclavicular. The glenohumeral joint is a ball and socket joint that allows abduction, adduction, flexion, extension, rotation, and circumduction. The acromioclavicular joint is situated superficially between the lateral end of clavicle and acromion process of scapula. The rotator cuff muscles include the supraspinatus, infraspinatus, teres minor, and subscapularis. The subacromial bursa is positioned within the subacromial space between the overlying deltoid muscle and the underlying supraspinatus tendon, and it provides rotator cuff lubrication. Injection techniques for the shoulder include palpation (anatomic landmarks) and visually guided (ultrasound and

fluoroscopy) approaches. We will focus the discussion on visually guided techniques for the three major anatomic locations for shoulder injections: (1) subacromial/subdeltoid bursa, (2) glenohumeral joint, and (3) acromioclavicular (AC) joint. Shoulder injection using only anatomic landmarks may be inaccurate,88-92 which may adversely affect short-term clinical outcomes.88,93

SUBACROMIAL/SUBDELTOID BURSA INJECTIONS INDICATIONS AND MUSCULOSKELETAL PATHOPHYSIOLOGY Subacromial injections are used to diagnose and treat various shoulder conditions including rotator cuff pathology, subacromial bursitis, and subacromial impingement.94,95 Impingement refers to the narrowing of space available for the rotator cuff resulting in compression of rotator cuff tendons against the undersurface of the coracoacromial arch.96 Rotator cuff impingement may result in the development of bursitis, subacromial inflammation, secondary tendinitis, and degenerative tears.97 Clinical outcomes following subacromial injections have been linked to the accuracy of injection, the severity of imaging findings, and the duration of symptoms.88,93,98 Specifically, a magnetic resonance imaging (MRI) finding of isolated bursitis without rotator cuff tear, younger age, and shorter duration of symptoms (less than 1 year) are associated with better postinjection clinical outcomes.98 PALPATION-GUIDED ANATOMIC INJECTION TECHNIQUE Commonly utilized portals for palpation-guided subacromial injections include the posterior-lateral and anterior-lateral approach.89,97,99,100 In the posterior approach, the needle is inserted 1 to 2 cm inferior to the posterior-lateral aspect of the acromion process. The needle is directed anteriorly and cephalad. In the anterior approach, the needle is inserted approximately 1 cm inferior to the anterior/inferior aspect of the acromion process. The needle is directed posteriorly and cephalad. The posterolateral approach is preferred because of the existence of a larger subacromial space.100 FLUOROSCOPY-GUIDED INJECTION TECHNIQUE Limited information exists detailing subacromial joint injections performed under fluoroscopic guidance. The utilization of fluoroscopy with radiographic contrast IA injection has been employed as a confirmatory adjunct to palpationguided injections, to ensure appropriate needle98 and injectate placement.88,99,101 ULTRASOUND-GUIDED INJECTION TECHNIQUE The patient sits in the upright position with the shoulder extended, elbow flexed, and palm of the hand placed over the ipsilateral back pocket (modified Crass position).95,102 Initially the IA portion of the biceps tendon is identified over the anterior shoulder with a high frequency lineararray ultrasound probe. The probe is oriented in the coronal plane and is moved superiorly and posteriorly until it is aligned with the supraspinatus tendon longitudinal axis. The supraspinatus tendon in this position has a typical beakshaped appearance.102 The subacromial-subdeltoid bursa is visualized as a thin hypoechoic band outlined by highly

CHAPTER 71 — JOINT INJECTIONS

D

* * SS

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ACR

H

Figure 71.2  Ultrasound view of the subacromial-subdeltoid bursa along the long axis of the supraspinatus tendon. Asterisks (*) indicate peribursal fat; arrowheads identify the subacromial bursa. ACR, acromion process; D, deltoid; H, humerus; SS, supraspinatus tendon. (Please see text for a detailed description of patient and ultrasound probe positioning.)

reflective lines corresponding to peribursal fat between the deltoid muscle and supraspinatus tendon (Fig. 71.2).95,103 Other structures visualized include the acromion process at the medial end and the greater tuberosity at the lateral end of the scan plane. The lateral end of the transducer is marked for the skin entry. A procedure needle is advanced with an in-plane technique into the subacromial-subdeltoid bursa. After confirming needle position within the bursa, the desired medication is injected slowly while noting the expansion of the bursa.104 Injection without bursa distention suggests intramuscular or intratendinous needle insertion and requires needle tip repositioning.

Figure 71.3  Glenohumeral joint visualization by fluoroscopy. The posterior aspect of the glenohumeral joint space is viewed tangentially under fluoroscopic guidance. The inferomedial quadrant of the humeral head is marked (arrowhead) as the needle entry site. (Please see text for a detailed description of patient positioning.)

Deltoid

GLENOHUMERAL JOINT INJECTIONS INDICATIONS AND MUSCULOSKELETAL PATHOLOGY Glenohumeral joint injections are used as a nonoperative management technique for glenohumeral arthrosis or adhesive capsulitis (frozen shoulder).94 FLUOROSCOPY-GUIDED INJECTION TECHNIQUE The patient is placed in the lateral decubitus position with the head resting on the nontargeted arm with the targeted shoulder in the nondependent position. A bolster is placed in front of the patient and then the patient rotates onto the bolster with the targeted arm internally rotated until the glenohumeral joint space is aligned under the fluoroscopic anterior-posterior view (Fig. 71.3).105 The skin entry site is marked over the inferiomedial quadrant of the humeral head.106 A 22-gauge needle is advanced with a coaxial fluoroscopy-guided technique to the humeral head. After negative aspiration, radiographic contrast is injected to confirm IA needle placement. Although the posterior approach is commonly used, additional fluoroscopic techniques have been described utilizing the anterior107 and rotator cuff interval approaches.108 ULTRASOUND-GUIDED INJECTION TECHNIQUE The patient is placed in either the semiprone position resting on the contralateral shoulder or in an upright sitting

IS H

*

GP

Figure 71.4  Glenohumeral joint visualization by ultrasound. The posterior aspect of the glenohumeral joint space is viewed using ultrasound guidance. Asterisk (*) indicates the glenoid labrum. GP, glenoid process; H, humerus head; IS, infraspinatus muscle. (Please see text for a detailed description of patient and ultrasound probe positioning.)

position with the ipsilateral arm placed on the contralateral shoulder to open up the glenohumeral joint space.91 A high-frequency linear-array probe facilitates visualization of superficial structures including the infraspinatus muscle, glenoid cavity, glenohumeral joint, and associated labrum. The probe is positioned over the infraspinatus fossa inferior and parallel to the scapular spine. The field of view is adjusted to encompass the posterior glenoid rim and the glenohumeral junction (Fig. 71.4). The posterior glenoid labrum appears as a triangular structure. The lateral end

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of the transducer is marked for the skin entry. A 22-gauge needle is advanced with an in-plane approach into the joint deep to the infraspinatus tendon, between the posterior glenoid labrum and the hypoechoic humeral articular cartilage.109 Resistance at the time of injection suggests a needle tip position within articular cartilage or labrum and necessitates needle repositioning. Alternative techniques include the anterior110 and rotator cuff interval approaches.111

A

*

C

ACROMIOCLAVICULAR JOINT INJECTION INDICATIONS AND MUSCULOSKELETAL PATHOLOGY AC joint injections are employed for diagnostic and therapeutic purposes for AC joint arthritis.94,112 FLUOROSCOPY-GUIDED INJECTION TECHNIQUE Few reports exist describing fluoroscopically guided AC joint injections. With the patient in the supine position, a 25-gauge needle is advanced into the AC joint using either an anterior or superior approach. Less than 0.5 mL of radiographic contrast is utilized to confirm IA placement.113,114 ULTRASOUND-GUIDED INJECTION TECHNIQUE Both in-plane115 and out-of-plane95,104,116 ultrasound-guided techniques have been described. However, the out-of-plane technique is preferred due to this joint’s small size and superficial location.95 The patient is positioned in the sitting position, and a high-frequency linear-array probe is placed in an anatomic coronal plane over the superficially located AC joint (Fig. 71.5). The acromion process, clavicle, joint capsule, and wedge-shaped fibrocartilaginous disk are visualized. A 25-gauge needle is advanced using an out-of-plane technique. Because of the shallow AC joint depth, needle insertion must be carefully controlled to avoid misplacement into the subacromial space.95,112

GENERAL EFFICACY OF SHOULDER INJECTIONS GENERAL EFFICACY OF SUBACROMIAL/SUBDELTOID BURSA INJECTIONS Evidence for the efficacy of subacromial/subdeltoid bursa injections is conflicting. This incongruity may correlate with the lack of selection of specific shoulder diagnoses in some study populations or inaccurate injectate placement.93,98,117 A randomized controlled trial of palpation-guided subacromial injections demonstrated greater short-term pain reduction and functional outcome improvement at 1 and 6 weeks with the combined subacromial injection and exercise protocol versus exercise alone.118 However, the study did not demonstrate continued differences in clinical outcomes at 12 weeks. Predictors of success following subacromial injections have been investigated. MRI findings consistent with low-grade impingement and bursitis without evidence of a rotator cuff tear are positive predictors of injection response.98 GENERAL EFFICACY OF GLENOHUMERAL JOINT INJECTIONS The majority of available evidence for therapeutic glenohumeral joint injection relates to adhesive capsulitis.117 A systematic review evaluated the efficacy of repeated IA corticosteroid injections in treating adhesive capsulitis.119 Nine

Figure 71.5  Ultrasound view of the acromioclavicular joint. Asterisk (*) indicates the acromioclavicular joint. C, clavicle; A, acromion. (Please see text for a detailed description of patient and ultrasound probe positioning.)

randomized controlled trials were included in this review. This review concluded that multiple injections improve pain and range of motion in the short term (6 to 16 weeks). Another systematic review investigated the efficacy of IA glenohumeral joint corticosteroid injection compared to other treatments including oral corticosteroid, subacromial injection, joint manipulation, joint distension, and physical therapy. This review concluded that IA corticosteroid injection improves pain and range of motion in the short term, with no significant long-term differences in comparison to other treatments.120 Limitations to the studies included in these reviews were use of diverse outcome measures, injection techniques (palpation versus image guidance), injection site (concurrent subacromial and AC joint injection in some studies), drug types and preparations, and physical therapy regimens. Future studies with improved design are required to definitively assess IA glenohumeral injection efficacy for shoulder joint disorders. GENERAL EFFICACY OF ACROMIOCLAVICULAR JOINT INJECTIONS To date, no randomized controlled trials have been published evaluating the effectiveness of AC joint injections. Retrospective case series and prospective cohort studies reported short-term improvement.121,122 In studies examining pain relief beyond 3 months, decreasing levels of efficacy were documented with only 14% to 19% of patients reporting sustained pain relief.123,124 In one study, a predictor of short-term procedural success was capsular hypertrophy (more than 3 mm) on MRI.114

COMPARISONS OF ACCURACY AND EFFICACY FOR SPECIFIC SHOULDER JOINT INJECTION TECHNIQUES ACCURACY AND EFFICACY OF SUBACROMIAL/ SUBDELTOID BURSA INJECTION TECHNIQUES When directly comparing visually guided techniques to palpation-guided techniques, Naredo and associates93 demonstrated improved technique accuracy and outcomes

CHAPTER 71 — JOINT INJECTIONS

(shoulder functional assessment) with ultrasound-guided injection versus palpation-guided injection. Palpation-guided injection resulted in a 30% accuracy rate when validated with ultrasound confirmation of injectate placement. Although fluoroscopic confirmation of injectate placement has been described in other clinical studies, no direct comparative data have been presented with regard to fluoroscopy- versus ­palpation-guided injection techniques.88,98,99,101 In a systematic review, image-guided (fluoroscopy or ultrasound) injection had an average accuracy rate of 100% compared to an average accuracy rate of 72% for palpation-guided injections.125 When examining individual studies for palpationguided anatomic injection techniques, clinical and cadaveric studies have reported variable accuracy rates in the range of 29% to 91%.88-90, 99,101,126 Improved injection accuracy resulting from ultrasound guidance93 or fluoroscopic confirmation88 positively affects short-term clinical outcomes Studies directly comparing the efficacy and safety of various image-guided techniques have not been conducted. However, Mathews and coworkers127 questioned the reliability of fluoroscopy-guided injections in a cadaveric study. Approximately 7% of injections considered to be accurately placed under fluoroscopic guidance were found to be placed inaccurately on subsequent cadaveric dissection. Because of the complex soft tissue anatomic structures of the shoulder joint, fluoroscopic guidance may not guarantee accurate needle placement in the subacromial space. Better visualization of soft tissues using ultrasound guidance potentially favors this method for subacromial joint injections and diagnostic shoulder imaging.93,97,102 Diagnostic evaluation of rotator cuff tears with high-resolution ultrasound has been shown to be comparable in utility to MRI.102,128 COMPARISON OF ACCURACY AND EFFICACY FOR GLENOHUMERAL INJECTION TECHNIQUES When directly comparing ultrasound-guided techniques to palpation-guided techniques, Cunnington and colleagues129 demonstrated that junior trainees with basic ultrasound skills achieved higher IA injection accuracy rates using ultrasound-guided (63%) compared to palpation-guided (40%) approaches. No studies exist that directly compare fluoroscopy- versus palpation-guided glenohumeral injection techniques. In one review, image guidance (fluoroscopy, ultrasound, and MRI) had an average accuracy rate of 95% compared to an average accuracy rate of 79% with palpation guidance.125 When examining individual studies for palpation-guided anatomic injection techniques, clinical and cadaveric studies have reported variable glenohumeral injection accuracy rates in the range of 27% to 100%.88,126,130-132 Improved glenohumeral injection accuracy resulting from ultrasound guidance129,133 or fluoroscopic confirmation88,129 significantly enhances short-term clinical outcome. In a study involving multijoint interventions, Sibbitt and colleagues87 demonstrated that ultrasound guidance significantly improves clinical outcome. When directly comparing ultrasound guidance with fluoroscopic guidance, Rutten and coworkers91 demonstrated that ultrasound guidance improved procedural outcomes. Ultrasound guidance resulted in a first pass accuracy rate of 94% compared to 72% obtained with fluoroscopic guidance, and it also comparatively reduced procedural time and patient discomfort levels.

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COMPARISON OF ACCURACY AND EFFICACY FOR ACROMIOCLAVICULAR JOINT INJECTION TECHNIQUES Because of the small size and variable morphology of the AC joint, needle placement into the joint is often difficult and inaccurate.90,123 In a direct comparison cadaveric study, ultrasound-guided AC injections using in-plane technique demonstrated a 100% accuracy rate compared with the 40% accuracy rate for palpation-guided injections.115 No direct comparative data have been generated between fluoroscopyversus palpation-guided injection techniques. For anatomically guided palpation techniques, clinical and cadaveric studies have reported variable accuracy rates in the range of 40% to 66% when confirmation of needle or injectate placement was validated with fluoroscopy or cadaveric dissection.90,123,134 Sabeti-Aschraf and associates116 observed similar clinical outcomes following palpation-guided and ultrasound-guided AC injections when performed by experienced physicians.

HIP ANATOMY The hip joint is a ball-and-socket type of synovial joint situated deeply within the pelvis. Hip joint stability is attributed to the articulation of the convex femoral head (ball) into the concave acetabulum (socket), with additional reinforcement arising from the articular capsule and surrounding muscles and ligaments. The fibrous articular capsule extends from the acetabular rim across the joint to the base of the femoral neck. This capsular anatomy allows for accurate IA injectate placement into the capsule at the femoral head/neck junction without going directly into the joint space. The femoral neurovascular bundle lies medially to the hip joint in the femoral triangle. INDICATIONS AND MUSCULOSKELETAL PATHOLOGY Intra-articular injections are used to diagnose and treat the symptoms of inflammatory and noninflammatory arthritis of the hip joint. Osteoarthritis is a significant cause of hip pain and disability. Intra-articular hip injections are used as a nonoperative treatment for hip osteoarthritis. Intraarticular hip injections are also utilized for diagnostic purposes to assist in determining and distinguishing IA hip pathology from extra-articular sources of pain.135 Clinical predictors of a successful response include the presence of joint effusion136 and lack of an atrophic radiologic pattern.137 The radiographic severity of hip arthritis does not predict pain relief outcome for therapeutic IA hip injection. PALPATION-GUIDED ANATOMIC INJECTION TECHNIQUE Multiple hip joint injection techniques are described in literature including palpation- (anatomic landmarks) and visually (fluoroscopy and ultrasound) guided techniques. Palpation-guided injections include both anterior and lateral approaches. Intra-articular hip injections using anatomic landmarks are often inaccurate due to the joint’s deep location.138,139 Here we focus on descriptions of visually guided techniques, which are associated with improved injection accuracy.140-142

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* *

H

F

*

Figure 71.6  Fluoroscopy-guided lateral-approach hip joint injection. An anteroposterior fluoroscopy-guided view used to position the needle for a lateral-approach hip joint injection. The needle tip is positioned at the lateral femoral head/neck junction. Injection of radiographic contrast medium confirms accurate intracapsular needle placement. The arrows point to the needle. Asterisk (*) outlines the intracapsular radiographic contrast agent spread. (Please see text for a detailed description of patient positioning.)

FLUOROSCOPY-GUIDED INTRA-ARTICULAR HIP INJECTION TECHNIQUES Anterior Approach

The patient is placed in the supine position on the fluoroscopy table. First, the femoral artery is identified with palpation along the inguinal crease.143 With fluoroscopy under an anterior-posterior view, the lateral aspect of the femoral head/neck junction is identified.113 A needle is then directed coaxially under fluoroscopic guidance to the lateral femoral head/neck junction while avoiding the previously marked femoral artery. After reaching the lateral aspect of the femoral head/neck junction, the needle is slightly withdrawn. Following negative aspiration, radiographic contrast agent is injected to confirm intracapsular needle placement. Corticosteroids, often with local anesthetics, are then injected (see Table 71.1). Lateral Approach

The patient is placed in the lateral decubitus position on the fluoroscopy table with the targeted hip in the nondependent position. The skin entry point is identified immediately proximal to greater trochanter. The center of the hip joint often corresponds to midplane between the anterior and posterior aspects of the thigh.144 In the anterior-posterior view, the needle is advanced to the lateral aspect of the femoral head/neck junction (Fig. 71.6). Care is taken to avoid an anterior or posterior needle trajectory to the femoral head/neck junction. On the fluoroscopy image, if the needle has passed the femoral head/neck junction without

Figure 71.7  Ultrasound-guided intra-articular hip injection. The arrows indicate the needle tip accurately placed within the synovial recess at the femoral head/neck junction. F, femoral shaft; H, femoral head. (Please see text for a detailed description of patient and ultrasound probe positioning.)

contacting bone the needle needs to be repositioned to ensure intracapsular injection. Corticosteroids, often with local anesthetics, are then administered (see Table 71.1). Proposed advantages of the lateral approach include a skin entry distant from the femoral neurovascular bundle and visualization of the needle throughout placement.143 ULTRASOUND-GUIDED INTRA-ARTICULAR HIP INJECTION TECHNIQUES The patient is placed in the supine position on the procedure table. Typically, a low frequency curvilinear probe is employed to allow for adequate penetration and a larger field of view.145 The femoral neurovascular bundle is identified in the short axis view. Then, the probe is moved laterally and oriented to align it parallel to the long axis of the femoral neck. In the anterior-oblique-sagittal (anterior-longitudinal) view, the femoral neck, femoral head, acetabular rim, and anterior synovial recess should be visualized.142,145,146 The anterior synovial recess, at the femoral head/neck junction, is the target location. In this view, the femoral neurovascular bundle is located 20 to 30 mm medial to the desired needle trajectory.146 Power or color Doppler is utilized to identify any overlying vascular structures such as the ascending branch of lateral femoral circumflex artery.147 The ultrasound view is adjusted to provide a needle trajectory that is clear of any vascular structures. A 22-gauge needle is advanced with an in-plane approach into the anterior synovial recess (Fig. 71.7). After confirming needle position within the synovial recess, the medication is injected slowly while noting expansion of anterior hip capsule.

EFFICACY OF INTRA-ARTICULAR HIP INJECTIONS Limited data exist that evaluate the efficacy of IA hip injections for osteoarthritis. Efficacy data for IA knee injections cannot be extrapolated to the IA hip injections because of differences in anatomic and functional characteristics. Three prospective randomized controlled studies suggest short-term efficacy for pain relief and functional outcome with visually guided (ultrasound or fluoroscopy) administration of corticosteroids.136,148,149

CHAPTER 71 — JOINT INJECTIONS

ACCURACY AND EFFICACY FOR INJECTION TECHNIQUE COMPARISONS Although multiple studies have recommended image guidance to improve accuracy, no studies to date have directly compared image-guided versus palpation-guided techniques.137,138,140-142 Conventional palpation-guided IA injections may result in inaccurate needle placement. The femoral neurovascular bundle is the primary anatomic structure at risk of injury.138 Accuracy rates of 60% to 80% for IA injectate placement have been documented with palpation-guided techniques.138-140,150 Ultrasound-guided IA hip injections have demonstrated accuracy rates of 97% to 100%, which are comparable to the accuracy rates associated with computed tomography (CT)- or fluoroscopy-guided injections.142,150 Given the paucity of clinical outcome studies, no conclusive relationship can be established between improved accuracy rates and clinical and functional outcomes. One study demonstrated that ultrasound guidance significantly improved performance and clinical outcomes for small and large joint IA injections.87 Further evaluation is warranted regarding the safety and efficacy of IA hip injections, with direct comparison necessary between fluoroscopy- and ultrasound-guided techniques.

KNEE ANATOMY The knee joint is a synovial joint composed of three bones: the patella, femur, and tibia. The four major ligaments providing stability to the knee are the anterior cruciate, posterior cruciate, medial collateral, and lateral collateral.151,152 The medial and lateral menisci are fibrocartilaginous structures that provide stability, lubrication, and nutrition to the joint space. Meniscal tears occur three times more frequently in the medial meniscus. Knee flexion and extension are the main motion planes. The knee is divided into three major compartments: medial, lateral, and patellofemoral. Knee arthritis typically occurs in two or more compartments.152,153 INDICATIONS AND MUSCULOSKELETAL PATHOLOGY Intra-articular knee injections with either corticosteroids or viscosupplements are part of nonoperative management of knee osteoarthritis. In 1997, viscosupplementation was approved in the United States to treat knee osteoarthritis. For knee osteoarthritis, clinical predictors of a positive response to IA corticosteroids have not been conclusively identified.154 Multiple attempts have been made to identify clinical predictors of response to IA corticosteroids. Jones and Doherty154 were not able to identify clinical predictors. Gaffney and colleagues155 reported greater improvements in pain relief when there was clinical evidence of an effusion and aspiration of synovial fluid at the time of injection. Based on these data, it is difficult to determine whether an effusion predicts clinical response or if synovial fluid is just a surrogate marker for appropriate needle placement. PALPATION-GUIDED ANATOMIC KNEE INJECTION TECHNIQUES Commonly utilized knee portals for IA injections include superior anteromedial, superior anterolateral, inferior

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anteromedial, inferior anterolateral, and lateral and medial midpatellar approaches. Multiple studies have examined different injection techniques in specific populations. In individuals without knee effusions, confirmation of appropriate needle placement can be difficult when using a palpationguided technique. Jackson and colleagues156 demonstrated that the lateral midpatellar approach resulted in a higher accuracy rate (93%) in comparison with both the anteromedial (75% accuracy) and anterolateral (71% accuracy) approaches. The anteromedial and anterolateral injections were performed inferior to the patella with the affected leg over the side of the examination table and the knee flexed to approximately 90 degrees. A cadaver study compared four different IA injection sites (anteromedial, anterolateral, lateral midpatellar, and medial midpatellar).157 The midpatellar approaches were performed with the knee extended on an examination table. The anteromedial and anterolateral injections were performed inferior to the patella with the leg over the side of the examination table and the knee flexed to approximately 90 degrees. The accuracy rate was highest for the anterolateral approach (85%) and lowest in the medial midpatellar approach (56%). Wind and Smolinski158 examined injection portals superior to the patella (superolateral and superomedial) for low-volume (2 to 3 mL) injections, consistent with viscosupplementation treatment. Injections were performed with the knee extended. In this study, the lateral joint line injection was unreliable and resulted in IA placement less than 50% of the time. FLUOROSCOPY-GUIDED KNEE INJECTION TECHNIQUES Techniques have been described for both fluoroscopic needle advancement and fluoroscopic confirmation of appropriate injectate location following palpation-guided IA injection.113,159 The fluoroscopy-guided injection technique can be performed above (Fig. 71.8), below, or at the level of the patella. When the injection is performed at the patellofemoral joint with either a medial or lateral approach, the patella is manually displaced away from the needle and the needle is advanced into the joint.113 In individuals with severe patellofemoral joint arthritis, access into the joint may be difficult with this technique. Anterior approaches have also been described.160,161 Moser and associates161 assessed the infrapatellar anterolateral and anterior paramedian needle insertion approaches for technical success and patient tolerance levels during knee arthrography. For the anterior paramedian approach, the knee is flexed to 60 degrees and the needle is introduced just lateral to the inferior patellar ligament and directed cephalad and medial toward the femoral notch. For the anterolateral approach, the knee is flexed to 90 degrees and the joint space is located. The needle is placed at the joint line and directed posteriorly and slightly medial toward the lateral femoral articular condyle. For the fluoroscopy-guided techniques, radiographic contrast agent may be injected to confirm appropriate needle placement. If radiographic contrast cannot be utilized, IA placement has also been verified by mini-air arthrography.159 For the superior patellar approach, miniair arthrography is able to confirm IA placement when

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QT

P

QFP

*

*

* PFP

F

Figure 71.9  Long-axis view of the suprapatellar synovial recess. P indicates patella; F, femur; PFP, prefemoral fat pad; QFP, quadriceps fat pad; QT, quadriceps tendon. Asterisk (*) indicates the outline of the suprapatellar synovial recess communicating with the intra-articular joint space. (Please see text for a detailed description of patient and ultrasound probe positioning.) Figure 71.8  Fluoroscopy-guided lateral approach for suprapatellar intra-articular knee injection. Accurate needle tip placement in the suprapatellar synovial recess is confirmed by appropriate localization of injected radiographic contrast medium. (Please see text for a detailed description of patient positioning.) QFP

a sharply defined shadow of air is found in the suprapatellar pouch after 0.5 to 5 mL of air is injected.159,162 Extra-­articular placement is suggested when the air is found diffusely in the surrounding tissues. Although air arthrography has been suggested as a safe procedure, the Doppler function for ultrasound or a negative aspiration for fluoroscopy-guided injections should be utilized prior to injecting air to prevent an intravascular injection and the possible development of an air embolism. ULTRASOUND-GUIDED INJECTION TECHNIQUES Ultrasound-guided approaches include the midpatellar lateral,162 the midpatellar medial,163 and the suprapatellar synovial recess164 approaches. With both the medial and lateral midpatellar approaches, the patella prevents direct visualization of the needle and injectate in the IA space. Therefore, the preferred technique is the suprapatellar synovial recess approach. This approach also minimizes the risk to soft tissue structures and the articular cartilage.164 One disadvantage of this approach is that the suprapatellar synovial recess can be difficult to visualize in individuals without knee effusions. For the suprapatellar approach, the patient is in the sitting or supine position with the knee flexed approximately 20 to 30 degrees.165 The knee can be supported with a pillow. A high-frequency linear-array probe is utilized. First the knee is scanned with the transducer parallel to the longitudinal axis of the quadriceps tendon (Fig. 71.9). Then the skin and subcutaneous tissues, quadriceps tendon, patella, quadriceps fat pad, prefemoral fat pad, femur, and suprapatellar synovial recess are identified. The suprapatellar synovial recess is located between the prefemoral and quadriceps

PFP

Figure 71.10  Short-axis (transverse) view of the suprapatellar synovial recess. The needle was accurately placed in the suprapatellar synovial recess between the prefemoral fat pad (PFP) and quadriceps fat pad (QFP). (Please see text for a detailed description of patient and ultrasound probe positioning.)

fat pads, and it communicates directly with the knee joint. It is important that transducer pressure is minimized to prevent compression of the synovial recess. In some individuals, a significant effusion will be visualized in the synovial recess. Next the transducer is rotated 90 degrees to the axial (transverse) plane for the short axis view (Fig. 71.10), and the same structures are identified. The needle is advanced in the short axis view with an in-plane technique from lateral to medial into the suprapatellar synovial recess. Synovial fluid may be aspirated. Then the injectate is placed into the joint under direct ultrasound visualization. The Doppler function can also be utilized to enhance visualization of the injected fluid. The suprapatellar synovial recess injection may also be performed with the ultrasound transducer along the

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longitudinal axis.164 With this technique, the superior margin of the patella is the inferior landmark of the suprapatellar synovial recess. The transducer is moved laterally to avoid insertion into the quadriceps tendon. The cephalad end of the transducer is positioned more laterally than the caudal end. The needle is advanced in-plane in the long axis. This approach may be advantageous when it is difficult to view the suprapatellar synovial recess in the short axis (transverse) plane. GENERAL EFFICACY OF INTRA-ARTICULAR KNEE INJECTIONS One review evaluated the efficacy of IA-injected corticosteroids for treating knee osteoarthritis.166 Twenty-eight trials were included in the analysis. Corticosteroids were compared to placebo, viscosupplementation (hyaluronan and hylan derivatives), and joint lavage. For pain relief at 1 week, injected corticosteroids were found to be superior to placebo with a number needed to treat (NNT) of three. Increased pain reduction by injection versus placebo lasted up to 3 weeks. From 4 to 24 weeks there was a lack of evidence to support prolonged therapeutic efficacy. Functional outcomes were difficult to evaluate secondary to a lack of data. Corticosteroid injection and viscosupplementation benefits were similar between 1 and 4 weeks postinjection. From weeks 5 to 13, viscosupplementation was assessed as superior, with improvements maintained in functional and pain outcomes. A systematic review of viscosupplementation for the treatment of osteoarthritis evaluated 76 trials.80 In comparison to placebo, viscosupplementation was found to be superior. From 5 to 13 weeks postinjection, viscosupplementation improved pain relief from baseline by 28% to 54%, and enhanced function by 9% to 32%. Although slower in onset, viscosupplementation appears to have a more prolonged therapeutic effect than IA corticosteroids.167 Comparisons between different formulations of viscosupplementation could not be made secondary to differences in study designs and outcome measures.80 COMPARISONS OF ACCURACY AND EFFICACY FOR INTRA-ARTICULAR KNEE INJECTION TECHNIQUES In direct comparison of visually guided techniques to palpation-guided techniques for IA knee injections, numerous studies have demonstrated greater accuracy with visually guided methods.87,163-165,168 For the suprapatellar approach, ultrasound-guided IA injection resulted in greater accuracy rates (96% to 100%) than palpationguided injections (55% to 84% accuracy).164,165 For the medial patellar portal, injection accuracy increased from 77% for blind injections to 96% for ultrasound-guided injections.163 Improvement in accuracy from ultrasound needle guidance positively and significantly influences clinical outcomes and cost effectiveness.87,168 Improvement in outcomes using ultrasound guidance for arthrocentesis of the effusive knee included a 48% reduction in procedural pain and a 183% increase in aspirated synovial fluid volumes.169 Short-term pain outcomes were also improved at 2 weeks postinjection. Although fluoroscopic guidance assists with needle placement, data have not yet been presented that demonstrate improvements in clinical or functional outcomes.

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CONCLUSION Joint injections are an important part of multimodal treatment for painful musculoskeletal conditions. Ultrasoundand fluoroscopy-guided IA injections assist in improving the accuracy of needle placement. Ultrasound is particularly helpful for interventional musculoskeletal procedures, offering advantages for specific procedures due to its ability to visualize periarticular soft tissues and provide real-time needle tracking without using ionizing radiation. The improvement in the accuracy of needle placement with ultrasound guidance for some joints is associated with significant clinical outcome benefits when compared with palpation-guided techniques. Future comparative studies are needed to develop guidelines for selecting the most appropriate IA corticosteroid and viscosupplementation agents and selecting the best methods to deliver these agents. Particular attention must be paid to the efficacy and adverse effects associated with treatment of each particular joint and underlying musculoskeletal condition. Furthermore, optimal protocols for the timing of injection, postprocedure activity, and specific dosing regimens need to be defined. For some joint injections, larger-scale studies are needed to directly compare the safety and efficacy of ultrasound-guided IA techniques with traditional landmark-based and fluoroscopy-guided techniques. KEY POINTS • Musculoskeletal diseases, including symptomatic arthritis and soft tissue conditions, are associated with high levels of disability and significant economic costs. Osteoarthritis is the most prevalent form of arthritis. • When joint injections are used, they should be incorporated into a multimodal treatment plan. • Agents utilized for joint injections include corticosteroids, local anesthetics, and viscosupplements. • Multiple corticosteroid and viscosupplementation formulations exist with differing pharmacologic properties. • Viscosupplementation seems to have a more prolonged analgesic effect than intra-articular corticosteroids. • It is important to understand the adverse effects and complications associated with each injectate class. Appropriate management strategies should be employed when these events occur. • Joint injections may be performed with palpation, ultrasound-guided, or fluoroscopically guided injection techniques. • Visually guided techniques (ultrasound and fluoroscopy) have been shown to improve the accuracy of needle placement. • Ultrasound offers advantages for specific procedures because of its ability to visualize periarticular soft tissues and to provide real-time needle tracking without ionizing radiation. • Appropriate intra-articular placement with ultrasound has been shown to positively influence clinical and economic outcomes.

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SUGGESTED READINGS Bannuru RR, Natov NS, Obadan IE, et al. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthritis Rheum. 2009;61:1704-1711. Bellamy N, Campbell J, Robinson V, et al. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006:CD005321. Bellamy N, Campbell J, Robinson V, et al. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006:CD005328. Bum Park Y, Ah Choi W, Kim YK, et al. Accuracy of blind versus ultrasound-guided suprapatellar bursal injection. J Clin Ultrasound. 2011;40:20-25. Cole BJ, Schumacher HR Jr. Injectable corticosteroids in modern practice. J Am Acad Orthop Surg. 2005;13:37-46. Habib GS. Systemic effects of intra-articular corticosteroids. Clin Rheumatol. 2009;28:749-756. Habib GS, Saliba W, Nashashibi M. Local effects of intra-articular corticosteroids. Clin Rheumatol. 2010;29:347-356. MacMahon PJ, Eustace SJ, Kavanagh EC. Injectable corticosteroid and local anesthetic preparations: a review for radiologists. Radiology. 2009;252:647-661.

Peng PW, Cheng P. Ultrasound-guided interventional procedures in pain medicine: a review of anatomy, sonoanatomy, and procedures, part III: shoulder. Reg Anesth Pain Med. 2011;36:592-605. Peterson C, Hodler J. Evidence-based radiology (part 2): is there sufficient research to support the use of therapeutic injections into the peripheral joints? Skeletal Radiol. 2010;39:11-18. Rutten MJ, Collins JM, Maresch BJ, et al. Glenohumeral joint injection: a comparative study of ultrasound and fluoroscopically guided techniques before MR arthrography. Eur Radiol. 2009;19:722-730. Sibbitt WL Jr, Peisajovich A, Michael AA, et al. Does sonographic needle guidance affect the clinical outcome of intraarticular injections? J Rheumatol. 2009;36:1892-1902. Zhang W, Moskowitz RW, Nuki G. OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidencebased, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16: 137-162.

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