1. OVERVIEW AND DESCRIPTION
Steroid injections play a prominent role in musculoskeletal care and pain management in PM&R; this article will review steroid pharmacology, various types of steroids, indications, basic techniques, adverse effects and complications.
Naturally occurring corticosteroids can be classified as mineralocorticoids, glucocorticoids, and adrenal androgens. The primary glucocorticoid found in humans is cortisol and is produced by the adrenal cortex under the regulation of the hypothalamic-pituitary-adrenal axis1. Normal production is approximately 5-10 mg/m2 per day, which is roughly equivalent to 20-30 mg/day of hydrocortisone or 5-7 mg/day of oral prednisone2,3. Synthetically produced cortisol analogues are commonly used for injections.
Steroids act as powerful anti-inflammatories primarily through reducing the transcription of genes involved in inflammation but also through the increased synthesis of phospholipase A2 inhibitors, decreasing bradykinin, histamine, prostaglandins and leukotrienes and directly stabilizing neural membranes and inhibiting C-fiber transmission 4,5,6.
The most commonly used synthetic corticosteroids are derivatives of prednisolone; methylation of prednisolone produces methylprednisolone, while fluorination of prednisolone produces triamcinolone, betamethasone and dexamethasone. Fluorination may also lead to increased absorption and potency6,7.
2. RELEVANCE TO CLINICAL PRACTICE
Potency, Solubility, Size, and Duration
There are numerous corticosteroids available, both particulate and non-particulate, all with varying potency, solubility, and duration. Particulate steroids like methylprednisolone and triamcinolone must undergo hydrolysis, lowering their solubility and theoretically lasting longer at the injection site when compared to non-particulate steroids like dexamethasone.
Particulate preparations, while commonly used for peripheral injections, may have serious adverse events when used for axial spine injections, including blood vessel injury or spasm or even embolization through vessels causing spinal cord infarction. Methylprednisolone has significantly higher percentage of large particles and may occlude vessels. Light microscopy studies have demonstrated that the particles in these steroid preparations are either larger than red blood cells or form aggregates larger than red blood cells8. Triamcinolone preparations have an intermediate particle size and betamethasone has the smallest particle size of the particulate steroids8,9.
CHART 1: Potency, Solubility and Preparations*
|Common Injectable Steroids|
|Equivalent Dose (mg)||Relative Glucocorticoid Potency||Solubility||Preparations (mg/mL)||Particulate (Yes/No)||Duration of Action (hours)|
Methylprednisolone sodium succinate
betamethasone sodium phosphate
|Dexamethasone sodium phosphate|
*Reproduced and adapted from 5,6,9,10
Steroids are frequently used both for diagnostic and therapeutic purposes and to control inflammation when more conservative measures (i.e. oral NSAIDs, rest, ice, compression, elevation) have been exhausted5. Typically, steroids can provide short-term pain relief (from weeks to months); few injections are associated with long-term relief of symptoms.
A steroid injection is contraindicated in the setting of overlying soft tissue sepsis, bacteremia, anatomic inaccessibility, an uncooperative patient, articular instability, septic arthritis, avascular necrosis, osteonecrosis, and Charcot joints. A joint with a surgical implant would be a relative contraindication5.
Before injection, the steroid is frequently diluted with an equal volume of anesthetic. The immediate analgesic response may help confirm placement and also may increase the spread of steroid, potentially increasing its efficacy. In addition, it may decrease the risk of atrophy when placed in smaller or superficial structures such as the hand. Dilution does increase the risk of infection, especially when using multidose vials. In addition, the parabens in local anesthetics such as lidocaine may lead to flocculation, or precipitation of the steroid mixture in the syringe11.
Common Injection Procedures
- Thoroughly cleanse skin with alcohol, betadine or chlorhexidine.
- Use a 21-27 gauge needle (larger diameter and 2” length for larger joints, smaller diameter and shorter length for superficial injections).
- Aspirate prior to injection.
- Negative aspiration cannot rule out intravascular injection.
- Synovial fluid aspiration is ideal as it confirms needle placement, fluid should be yellow and clear and any changes from the norm should prompt further investigation including fluid analysis, culture and sensitivities. Steroid should not be injected if there is a risk of infection.
- The injectate should flow relatively easy into the intraarticular or bursal space; if resistance is encountered, repositioning should be attempted5.
Chart 2: Suggested guidelines for maximum amounts with intraarticular injections5,11:
dose (mg) or equivalent
|Medium joint||Shoulder, knee||40|
|Very Small joint||Metacarpophalangeal joints||5-10|
|Small bursa||Anserine, retrocalcaneal||1-5|
Steroids have been increasingly utilized in spinal interventions and steroid selection (particulate versus non-particulate) can help reduce risk of injury to the patient. Central nervous system injuries have been attributed to blood vessel injury, spasm or embolization of particulate steroid through vessels. Blood vessel injury can be attributed to direct needle trauma or effects of dye. Embolization, however, can cause segmental infarct directly related to effects of particulate size in various steroid formulations. Methylprednisolone has significantly higher percentage of large particles, large enough to occlude vessels. Light microscopy studies have demonstrated that the particles in these steroid preparations are either larger than red blood cells or form aggregates larger than red blood cells8. Betamethasone has the smallest particle size, followed by triamcinolone9. Particulate steroids are typically utilized for lumbosacral, sacroiliac, and facet injections. For cervical procedures, dexamethasone, a non-particulate steroid, is preferred as an inadvertent intravascular injection with a particulate steroid could have life threatening consequences.
Chart 3: Typical steroid selection and dosing for interventional spine procedures*
|Dexamethasone||10||4 cc of preservative|
free saline, 1% lidocaine or 0.25% bupivacaine
|Interlaminar ESI||MPA or equivalent||80||4 cc of preservative|
free saline, 1% lidocaine or 0.25% bupivacaine
|Transforaminal ESI||MPA or equivalent||10||0.5-1 cc of 1% lidocaine|
|Facet joints, intraarticular||MPA or equivalent||80 (divided between joints)||1:1 steroid-local mixture (0.25% bupivacaine typically)|
|Sacroiliac Joint, intra-articular||MPA or equivalent||80 (single or split between both joints)||1:1 mixture of 1% lidocaine or 0.25% bupivicaine|
*Adapted from 12,13.
Dosing for diabetics is typically lower than the numbers presented.
ESI: Epidural steroid injection
MPA: Methylprednisolone acetate
- Insoluble steroids have been linked to increased side effects because of their longer duration in tissue.
- Local side effects
- infection (rare as evidenced by one study that found an infection incidence of 0.005% in more than 400,000 consecutive injections14)
- post-injection flare (2-6% of patients, crystal induced synovitis causing inflammation, typically lasts up to 12-48 hours and is treated with NSAIDs and ice5)
- skin changes/hypopigmentation
- tissue/fat atrophy
- tendon rupture
- avascular necrosis
- Systemic Side Effects
- steroid presence in bloodstream (intraarticular methylprednisolone acetate of either 40 or 80 mg led to detectable levels in the serum with peak levels at 2 and 12 hours post-injection)
- suppressed endogenous serum cortisol level for 1 week post-injection15
- acute hyperglycemia, persisting for up to 3 days with a peak glucose level of 300 mg/dL16
- facial flushing (up to 15% of patients, most frequently associated with triamcinolone9,16)
The maximum number and frequency of steroid injections is uncertain. Most studies have evaluated safety in the context of rheumatoid arthritis and osteoarthritis.
In rheumatoid arthritis, studies have shown no change in joint arthroplasty rates between patients who received four or more injections annually versus those receiving less frequent injections9,11.
In osteoarthritis, intraarticular steroid knee injections versus saline injections every 3 months for 2 years produced no significant difference with regards to cartilage thickness, suggesting that steroids in osteoarthritis patients were neither chondrodestructive nor chondroprotective17. Osteoarthritis patients tend to have a shorter duration of action with most of the benefit lasting a maximum of 6 weeks.
These potential side effects have led to general recommendations that steroid injections be performed no more than 3-4 times annually8, although rheumatoid patients may be able to tolerate more frequent injections11.
In 2012 there was an outbreak of fungal meningitis associated with methylprednisolone from a specific compounding pharmacy. As compounding pharmacies are not registered with the FDA, consider using a pharmacy that participates in voluntary accreditation with the Pharmacy Compounding Accreditation Board6.
4. GAPS IN KNOWLEDGE / EVIDENCE BASE
Past studies have demonstrated non-statistically significant superiority of particulate over non-particulate steroids in the short-term treatment of lumbar radicular pain but newer studies have failed to demonstrate any difference over longer follow up periods19. Based on the paucity of literature, the Spine Intervention Society currently recommends that physicians continue to make risk-benefit calculations with regards to particulate versus non-particulate steroids. Overall, further studies are needed to help clarify optimal steroid selection, dosing and frequency and the efficacy of landmark guided versus ultrasound guided peripheral joint injections19,20.
5. CUTTING EDGE/UNIQUE CONCEPTS/EMERGING ISSUES
Ultrasound guidance is becoming increasingly popular in both peripheral and axial injections as a means of improving accuracy without the radiation exposure of fluoroscopy. Further studies are needed to determine if efficacy/functional outcomes are improved.
Some physicians have started using intrathecal betamethasone in cancer patients, especially those with vertebral bone metastases, when conservative options have been exhausted. Intrathecal steroid injection was found to provide long lasting analgesia without any apparent complications in pelvic and perineal cancer patients18.
It has also been speculated that complications from intrathecal steroid injection stem from chemical additives such as antioxidants and preservatives13.
- Orth DN, Kovacs WJ. The adrenal cortex. In: Wilson, J, ed. Williams Textbook of Endocrinology. 9th Philadelphia, PA: Saunders; 1998:517-665.
- Williams GH, Dluhy RG. Disorders of the adrenal cortex. In: Harrison T, Braunwald E, eds. Harrison’s Principles of Internal Medicine. 15th New York, NY: McGraw-Hill; 2001:2084-2105.
- Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002;287:236-240.
- Qin C, Greenwood B, Myers DA. Corticosterone acts directly at the amygdala to alter spinal neuronal activity in response to colorectal distension. J Neurophysiol. 2003;89(3):1343-1352.
- Walsh N, Eckmann M. Pharmacology for the Interventional Pain Physician. In: Gans B, Walsh N, Robinson L, eds. Delisa’s Physical Medicine & Rehabilitation: Principles and Practice. 5th Philadelphia, PA: Lippincott Williams & Wilkins; 2010:1852-1854.
- Anitescu M, Benzon H. Pharmacology for the Interventional Pain Physician. In: Benzon H, et al, eds. Practical management of pain. 5th Philadelphia, PA: Saunders; 2014:596-614.
- Cole BJ, Schumacher HR. Injectable corticosteroids in modern practice. J Am Acad Othop Surg. 2005;13:37-46.
- Derby R, Lee SH, Date ES, Lee JH, Lee CH. Size and aggregation of corticosteroids used for epidural injections. Pain Med. 2008; 9:227-34.
- Lento P, Ihm J, Kennedy D, Visco C. Peripheral Joint and Soft Tissue Injection Techniques. In Chan L, et al, eds. Braddom’s Physical Medicine & Rehabilitation. 4th Philadelphia, PA: Saunders; 2011:517-540.
- Provenzano D, Chandwani K. Joint Injections. In: Benzon H, et al, eds. Practical management of pain. 5th Philadelphia, PA: Saunders; 2014:966-980.
- Roberts, WN. Intraarticular and soft tissue injections: What agent(s) to inject and how frequently? In: UpToDate, Furst DE (ed), UpToDate, Waltham, MA. (Accessed on September 25, 2015).
- Kang S, Hwang B, Son H, et al. The Dosages of Corticosteroid in Transforaminal Epidural Steroid Injections for Lumbar Radicular Pain Due to a Herniated Disc. Pain Physician. 2011;14:361-370.
- Rathmell J. Atlas of Image Guided Intervention in Regional Anesthesia and Pain Medicine. 2nd Philadelphia, PA: Lippincott Williams & Wilkins; 2012.
- Hollander JL, Jessar RA. Intra-synovial corticosteroid therapy: a decade of use. Bull Rheum Dis. 1961;11:239.
- Armstrong, RD, English J. Serum methylprednisolone levels following intra-articular injection of methylprednisolone acetate. Ann Rheum Dis. 1981;40:571-74.
- Gray RG, Tenebaum J. Local corticosteroid injection treatment in rheumatic disorders. Semin Arthritis Rheum. 1981;10:231.
- Raynauld JP, Buckland-Wright C. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2003;48:370.
- Raj P. Neural Blockade with Local Anesthetics and Steroids in the Management of Cancer Pain. In Waldman S, ed. Pain Management. 2nd Philadelphia, PA: Saunders; 2011:319-323.
- MacVicar J et al. The effectiveness of lumbar transforaminal injection of steroids: a comprehensive review with systematic analysis of the published data. Pain Med. 2013; 14:14-28.
- Particulates vs. Non-Particulates: Steroid Choice for Lumbar Tranforaminal Injections Factfinder. Spine Intervention Society website. http://www.spinalinjection.org/?page=PVNPLFF Accessed February 28, 2016.
Creamer P. Intra-articular corticosteroid treatment in osteoarthritis. Curr Opin Rheumatol. 1999;11(5):417-421.
Habib GS. Systemic effects of intra-articular corticosteroids. Clin Rheumatol. 2009;28:749-756.
Hollander JL, Jessar RA. Intra-synovial corticosteroid therapy: a decade of use. Bull Rheum Dis. 1961; 11:239.
McCarty DJ. Treatment of rheumatoid joint inflammation with triamcinolone hexacetonide. Arthritis Rhem. 1972;15:157.
Friedman DM, Moore ME. The efficacy of intraarticular steroids in osteoarthritis: a double-blind study. J Rheumatol. 1980;7:850.
David Haustein, MD
Nothing to Disclose
Daren Subnaik, DO
Nothing to Disclose