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This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.


Nature of interventional pain procedures

Contrast medium is used to document on-target tissue delivery and to exclude flow to off-target tissue in procedures including but not limited to epidural, paravertebral, intravertebral (kyphoplasty), joint (eg, facet, sacroiliac, hip, and knee), sympathetic nerve or ganglia (stellate ganglion, lumbar sympathetic plexus, and visceral sympathetic blocks), and deep muscle (piriformis) injections. These procedures are performed frequently; approximately 2 million epidural injections were performed annually in the US Medicare population alone from 2008 to 2014. In most instances, the volume of contrast injected is between 1.5 and 3 mL and may be repeated. These injection procedures are distinct from diagnostic radiologic studies such as computed tomography (CT) or MRI in which large volumes of contrast are injected intravascularly. Most patients seen in a pain clinic are referred, and their medical issues have been identified and treated. Injections are usually not performed on an emergency basis as the patient’s pain can be partially controlled with medications and other nonpharmacologic alternatives until a procedure can be scheduled. Although injections for pain may be repeated, it is typically after a 2–4 weeks observation of the patient’s response.

Our statements and recommendations pertain to interventional pain procedures where fractionated doses totaling ≤10 mL of contrast medium are injected in the extravascular space unless the needle tip is unintentionally positioned in an intravascular compartment.



Eleven multispecialty organizations were involved in the formulation of this PA. These include the American Academy of Pain Medicine, the American Society of Neuroradiology, the American Society of Regional Anesthesia and Pain Medicine, the British Pain Society, the Canadian Pain Society, the European Pain Federation (EFIC), the Korean Pain Society, the Society for Interventional Radiology, the Spine Intervention Society, the World Allergy Organization, and the World Institute of Pain. Representatives of each society are listed in the Appendix. Conflicts of interest were noted for each participant. In addition, experts who have published on the topic were invited as thought leaders.

These practice recommendations followed due process for development of practice advisories including identification of the literature on specific clinical questions, selection and grading of the available evidence, use of the Delphi process to reach consensus on the PA, and development and grading of the strength of the recommendations. Each of the 4 topics was appointed a leader and 2–3 additional members, inclusive of at least 1 pain medicine physician, either an anesthesiologist, radiologist, or a physical medicine and rehabilitation specialist. Additionally, an allergist was part of the group that drafted the initial statements and recommendations on HRs to contrast media. Each group searched the literature (PubMed; EMBASE; Cochrane Central Register of Controlled Trials; relevant references from articles, reviews, and book chapters) based on key terms and concepts from the development group and the Writing Committee. Medical subject heading (MeSH) terms included “nephrogenic systemic fibrosis,” “brain deposition/retention from gadolinium,” “encephalopathy from IT gadolinium,” and “HRs to contrast media.” The modified Delphi process was followed in the formulation of the PA. We used a modified version of the US Preventive Services Task Force (USPSTF) classification when grading the statements and recommendations (Supplemental Digital Content, Table, The initial statements and recommendations were defined by each section and discussed with the PA co-leaders (H.T.B. and T.P.M.), then sent to participants for voting.

For the statements receiving negative votes, a discussion ensued with the dissenters, the result of which was either reversal of the dissenting vote or revision of the statement in question with subsequent revote by all the participants. All of the participants voted on all statements except for the representatives of the World Allergy Organization who voted only on the statements and recommendations relevant to HRs to contrast media. One organization, the American Society of Neuroradiology, joined after the statements were approved. Their representatives vetted the statements on gadolinium brain deposition/retention and their Board of Directors (BOD) approved the statements and recommendations on that topic.

Randomized clinical trials are considered the gold standard in judging whether an intervention does more good than harm. Clinicians and developers of guidelines have considered randomized trials and meta-analyses as primary sources on which they base their levels of evidence and strength of their recommendation. However, as early as 1996, Sackett et al18 recommended the integration of individual clinical expertise with the best available external evidence found on a systematic search of the literature, in making decisions. By individual clinical experience, they meant the competence and judgment clinicians acquire through their clinical practice and clinical experience. Recently, the evidence-based medicine (EBM) group refined their definition of “evidence-based” to “best available evidence.”

They concluded that best available evidence includes the use of observational studies, case reports, and clinician experience in making recommendations consistent with “the circumstances and their values.”

They noted that deliberate interpretations are essential regardless of the type of evidence and that optimal decisions balance benefits and harms, rather than to only grade the quality of available evidence. For this reason, we used “best available evidence” in providing levels of certainty in some of our recommendations when randomized clinical trials or meta-analyses did not exist, but the evidence suggested obvious and significant clinical benefit.



The statements and recommendations for NSF, gadolinium brain deposition/retention, and encephalopathy after unintentional IT injection of gadolinium were approved after 1 revision while the HRs to contrast media required 3 revisions (Tables 2–5). The final statements and recommendations for all 4 topics were unanimously approved by all participants. The BODs or Executive Committee of each organization approved the final recommendations.


Read the full paper here: The Use of Contrast Agents in Interventional Pain Procedures: A Multispecialty and Multisociety Practice Advisory on Nephrogenic Systemic Fibrosis, Gadolinium Deposition in the Brain, Encephalopathy After Unintentional Intrathecal Gadolinium Injection, and Hypersensitivity Reactions