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

Honorio T. Benzon, MD; Timothy P. Maus, MD; Hye-Ryun Kang, MD; David A. Provenzano, MD; Anuj Bhatia, MD; Felix Diehn, MD; Ariana Nelson, MD; Zachary L. McCormick, MD; Benjamin P. Liu, MD; Javier de Andres Ares, MD; Magdalena Anitescu, MD; Kristine Blackham, MD; Arun Bhaskar, MD; Silviu Brill, MD; Jeremy Collins, MD; Ashish Gulve, MD; Robert W. Hurley, MD; Young Hoon Jeon, MD; Jee Youn Moon, MD; Richard L. Rauck, MD; Meghan Rodes, MD; Ryan K. Lee, MD; Vinil Shah, MD; Harsha Shanthanna, MD; Jan van Zundert, MD, PhD; Marc Huntoon, MD; James P. Rathmell, MD; Mario Sanchez Borges, MD; Steven P. Cohen, MD; Paul A. Greenberger, MD


Anesth Analg. 2021;133(2):535-552. 

In This Article

Abstract and Introduction


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 an 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.


Contrast agents are obligatory in interventional pain procedures to ensure delivery of the diagnostic and/or therapeutic agent to the target tissue or anatomic space, and to exclude off-target delivery (intravascular, subarachnoid), which may incur patient risk or diminish the efficacy or specificity of the procedure. The primary contrast agents used for this purpose have historically been iodinated contrast medium (ICM) due to their long history in medicine and ability to delineate vascular and tissue structures under fluoroscopic observation. Patients may describe a hypersensitivity reaction (HR) during prior administration of ICM, ranging from hives to laryngeal edema or even cardiovascular collapse. In these circumstances, the physician must choose either to not perform the procedure, proceed without injecting a contrast agent, premedicate the patient to lessen the likelihood of a serious adverse event, or use an alternative contrast agent, most commonly a gadolinium-based contrast agent (GBCA). Although these latter agents were developed for intravascular enhancement during magnetic resonance imaging (MRI) studies, they also exhibit radiopacity (although to a lesser degree than ICM) and can be used to document on-target delivery and exclude off-target delivery. They do not appear to exhibit hypersensitivity cross-reactivity with ICM.

GBCAs represent a significant advancement in clinical medicine. Their use allows the detection of lesions in the brain on MRI, led to contrast-enhanced MR angiography, and enables the assessment of tissue perfusion.[1] Early clinical reports of the use of GBCAs appeared in 1984, and their clinical use was approved by the Food and Drug Administration (FDA) in 1988. The GBCAs differ in their structure and ionicity (Table 1). GBCAs have since been used in >300 million patients worldwide.[2]

Three recent developments impact the continued use of GBCAs as an alternative to ICM during interventional pain procedures. These include nephrogenic systemic fibrosis (NSF) in patients with preexisting renal disease,[3,4] gadolinium deposition/retention in the brain from repeated administration of GBCAs,[5–7] and encephalopathy from unintentional intrathecal (IT) injection of GBCA.[8–10] Appearance of these new reports of previously unrecognized adverse events resulted in calls for caution in the continued use of GBCA,[9–11] an informed discussion with the patient,[12] and the creation of a guideline.[13] These developments, together with the recent finding of rare breakthrough HRs (HR after exposure to the culprit contrast medium) in interventional pain procedures,[14] prompted a group of concerned investigators and organizations to develop a Practice Advisory (PA) on contrast agents.