Research Review By Dr. Shawn Thistle©


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Date Posted:

October 2011

Study Title:

Adverse events from diagnostic and therapeutic joint injections: A literature review


Peterson C & Hodler J

Author's Affiliations:

Radiology Department, Orthopedic University Hospital of Balgrist, Switzerland

Publication Information:

Skeletal Radiology 2011; 40: 5-12.

Background Information:

For most of our readers, the interventions discussed today are not in our scope of practice. However, since our patients turn to us for advice about their treatment options for all varieties of musculoskeletal pain, we as evidence-informed clinicians should be conversant about the potential benefits and risks associated with as many therapeutic interventions as possible. I think today’s topic is particularly important, as it is my experience that many medical professionals recommend diagnostic and therapeutic joint injections frequently, with little or no discussion about the state of the literature on the potential benefits (we’ll leave that for another review) or risks associated with these interventions. I also know that I am not alone, as I have received numerous requests from readers over the years to review the risks associated with injections.

Before getting into this further, I thought it was noteworthy that the lead author of this review paper – Dr. Cynthia Peterson – will be familiar to many Canadian Memorial Chiropractic College graduates as our beloved radiology professor who always took a logical, patient-centered approach to the utilization and integration of imaging in clinical practice. She has since taken her talents to Switzerland, but her popular teaching style and clinical approach shines through in this publication.


Types of Injections:
  1. Diagnostic Injections: These normally involve injection of local anesthetics into spinal or peripheral joints to localize and identify the source of a patient’s pain. A variety of anesthetics can be used, including lidocaine hydrochloride, bupivacaine hydrochloride or ropivacaine hydrochloride, and there is a substantial body of published evidence that supports their value, particularly when conducted under imaging guidance.
  2. Therapeutic Injections: These utilize either a corticosteroid or a hyaluronic acid product (also called viscosupplementation) along with local anesthetics. Although highly utilized for many years, the base of evidence supporting their use is not as strong.
  3. Arthrography: Involves the injection of a contrast agent into a joint to facilitate proper needle placement or for general imaging purposes. This can be done for both diagnostic and therapeutic applications.
Adverse Events Associated with Injections:

It is generally accepted that the risk of adverse events associated with diagnostic and therapeutic injections is low. Roughly 2.4-12% of patients report adverse reactions, the vast majority of which are very mild and self-limiting. Having said that, the goal of this paper was to outline and categorize the possible adverse reactions and make recommendations to reduce the likelihood of these events.

Accuracy of Extra- & Intra-Articular Injections:

Corticosteroid injections are likely the most common type of injection our patients will ask us about as they are utilized for a wide variety of musculoskeletal conditions. Family physicians and specialists commonly prescribe and conduct these procedures in-office but as you’ll see below, this is not a recommended approach. The data on anatomical accuracy may also surprise you and to some degree explain the variability in patient response to injection therapy:
  • Current standards of practice and clinical guidelines recommend that injections be conducted under imaging guidance, including the use of a contrast agent to properly facilitate and visualize needle placement into the target tissue/joint (1). The shoulder and the knee are the most common joints injected without such imaging guidance.
  • Imaging-guided injections are normally performed using ultrasound, fluoroscopy, computed tomography or MRI.
  • Studies examining the accuracy of intra-articular injections performed with and without imaging guidance clearly demonstrate that the accuracy of hitting the intended target is poor if no imaging is used, even when the clinician is confident that the correct structure has been injected.
  • In fact, one study (2) demonstrated that without the use of imaging, only 69-76% of subacromial bursa injections hit the intended target! Further, many of the ‘missed’ injections end up injecting the drug into non-target, extra-articular surrounding structures. Other studies have reported even worse accuracy, ranging from only 27-37% success without imaging (3, 4).
  • The importance of accurate needle placement should be evident, but is further strengthened by studies demonstrating that patient outcomes are significantly better when accuracy is achieved and the likelihood of adverse reactions is significantly lower.
Classification of Adverse Events Associated with Injections:
  • Adverse reactions can occur with both imaging-guided and ‘blind’ (without imaging) injections.
  • Adverse reactions are generally classified into mild, moderate, severe or life-threatening but these is overlap in such a classification system. The adverse reactions listed below are all possible from corticosteroid injections.
Life-Threatening Reactions:
  • Life-threatening adverse reactions are so rare that most research is in the form of case studies. Such reactions require immediate medical care and include: air embolism, anaphylactic reactions, hypotension, vasomotor collapse, laryngeal edema, adrenal insufficiency (only with corticosteroid injections) and apnea. Nervous system or cardiac toxicity can also occur if the substance is injected into the vasculature or thecal sac.
Severe Reactions:
  • Severe reactions are also very uncommon and can include: septic arthritis, seizures, avascular necrosis, Charcot-like arthropathy, tendon tears, reactivation of Complex Regional Pain Syndrome (CRPS), damage to adjacent structures, vessels, nerves or muscles/fascia.
Moderate Reactions:
  • These reactions are also rare and some do not require additional medical attention: elevated blood pressure, elevated blood sugar, transient hypophosphatemia, Cushing’s syndrome, bleeding into a joint, skin necrosis, flare reactions, Tachon syndrome (intense but brief lumbar or thoracic pain immediately after injection), dysphonia, transient steroid-induced psychosis, urticaria, insufficiency fractures, vasovagal reactions, or less severe damage to adjacent structures as above.
Mild Reactions:
  • These reactions are by far the most common and are transient, requiring no medical intervention typically: local pain (most common), pressure in the joint, slight swelling, local tissue atrophy, urticaria, rash, facial or general flushing, hypopigmentation (normally resolves in 12 months), reactivation of herpes zoster, flare reactions, or mild cellulitis.
Septic Arthritis – the most feared adverse reaction:
  • The estimated occurrence of this condition is between 1 in 10000 to 1 in 50000 injections (EDITOR’S NOTE: seems common compared to the risk we have to discuss with our patients every day, doesn’t it?).
  • The rapid and irreversible joint destruction caused by pyogenic micro-organisms classifies this as a serious adverse event.
  • This is a risk of all injections, but it is thought that there is a higher prevalence in those receiving corticosteroid injections due to their inherent immunosuppressive effect.
  • Important: manual medicine practitioners should be aware that there is evidence to suggest that patients who receive intra-articular corticosteroid injections into knees or hips when they are likely to receive joint replacements significantly increase their risk of joint infection post-replacement (reported to be as high as 10% of hip replacement patients who had received an injection prior to surgery versus only 1% in those who haven’t [5]). It is very common for knee or hip OA patients to receive corticosteroid injections to delay surgery or address symptoms prior to surgery – evidence-informed clinicians should be aware of this potential risk and discuss it with their patients (for those who administer these injections, this risk should be communicated in the informed consent process and serious consideration should be given to whether injections should be performed at all in these patients).
Systemic Reactions to Injections:
  • Sometimes, the reactions from injections extend beyond the joint or local tissue.
  • After injection of corticosteroids, blood levels reach their peak within 3-6 hours post-injection.
  • Examples of systemic reactions include:
    1. Hypophospatemia (mentioned above) presents as transient paresthesia and weakness of limbs with associated dysarthria
    2. Secondary Cushing’s Syndrome happens more frequently in pediatric patients with juvenile chronic arthritis who receive repeated injections over a period of time.
    3. Intra-articular and epidural corticosteroid injections have also been associated with a flushing reaction of the face and upper trunk – warmth and redness of the skin occur and this is more common in women (this reaction is self-limiting).
Additional Notes Regarding Viscosupplementation:
  • Viscosupplementation refers to the use of hyaluronic acid derivatives like ‘Synvisc’, which are used for treating osteoarthritis. The reported severe reactions associated with this sort of injection include septic arthritis, seizures, crystal deposition disease, injury to adjacent structures, or reactivation of CRPS. Moderate adverse reactions include pseudoseptic arthritis (same symptoms as septic arthritis without the presence of micro-organisms), granulomatous inflammation, hemarthrosis, vertigo, urticaria, or injury to adjacent structures. Flare reactions and pseudosepsis seem to be more common with viscosupplementation than corticosteroid injections.
  • In the literature, the descriptions of pseudosepsis and flare reactions overlap – some describe the flare reaction as a transient increase in pain post-injection (> 2 points on a VAS) while others also add join pain, warmth, swelling and effusion which are typically associated with pseudo, and actual, sepsis.
  • Another non-infective adverse event seen with viscosupplementation injections is called ‘granulomatous synovitis’ – the descriptions of this in the literature seem to mimic those of flare reactions and pseudosepsis. The last non-infective arthritic adverse event associated with viscosupplementation in particular is acute calcium pyrophosphate dehydrate crystal arthropathy (CPPD or pseudogout) – therefore it is suggested that patients with these conditions not be given such injections.

Clinical Application & Conclusions:

It is prudent for evidence-informed manual medicine providers to be conversant in the risk associated with injections since many of our patients will undergo these procedures at some point. This paper discussed the spectrum of adverse events from the more common, mild reactions to the rare, severe or life-threatening reactions. The authors also offered recommendations for preventing adverse reactions to injection procedures including:
  • Use careful sterile technique – doctors should wear a mask (especially if they have an upper respiratory tract infection), disinfect hands, wear sterile gloves, disinfect skin with iodine or alcohol, drape the area with sterile towels.
  • Avoid injections into areas of skin that are infected, broken or have conditions such as psoriasis.
  • Perhaps avoid injections in patients who are candidates for joint replacement surgeries.
  • Flare reactions may be reduced by using hyaluronic acid preparations that are of lower molecular weight and not derived from animal products.
  • Avoid injecting patients with pre-existing chondrocalcinosis
  • Inform diabetic patients of the likely changes in blood sugar levels post-injection that may last for days (these patients are normally under specialist care anyway).
  • Finally, use imaging guidance to improve clinical outcomes and reduce the risk of adverse reactions.

Study Methods:

This was a narrative literature review.

Additional References:

  1. Malfair D. Therapeutic and diagnostic joint injections. Radiol Clin N Am. 2008; 46: 439–453.
  2. Henkus HE, Lodewijck PJ, Cobben MD, Coerkamp EG, Nelissen RGHH, van Arkel ERA. The accuracy of subacromial injections: a prospective randomized magnetic resonance imaging study. Arthroscopy. 2006; 22: 277–282.
  3. Sethi PM, Kingston S, Elattrache N. Accuracy of anterior intraarticular injection of the glenohumeral joint. Arthroscopy. 2005; 21: 77–80.
  4. Eustace JA, Brophy DP, Gibney RP, Bresnihan B, FitzGerald O. Comparison of the accuracy of steroid placement with clinical outcome in patients with shoulder symptoms. Ann Rheum Dis. 1997; 56: 59–63.
  5. Kaspar S, de V de Beer K. Infection in hip arthroplasty after previous injection of steroid. J Bone Jt Surg (Br). 2005; 87-B: 454–457.

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