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Pain Interventions: Practice Advisory Issued for the Use of Gadolinium-based Contrast Agents

May 20, 2021
With hypersensitivity reactions on the rise, new recommendations help clinicians weigh the risks and better identify patients for nerve blocks and injections.

Iodinated contrast agents are necessary when administering pain interventions, such as nerve blocks and other injections, however many patients have hypersensitivity reactions to these agents. In fact, the incidence of hypersensitivity reactions has increased over the past decade as the use of iodinated contrast agents has increased.1

As a result, many interventional pain physicians are now utilizing gadolinium-based contrast agents (GBCAs) when a patient reports a previous reaction to an iodinated agent.2 However, GBCAs are not always a safe solution. A 2018 FDA safety communication warned that these agents are retained in the body for months to years and should be used with caution.3 Potential dangers include nephrogenic systemic fibrosis (NSF), impaired brain function, and other adverse events, including, in some cases, death.

New practice recommendations released for the use of contrast agents in pain interventions. (iStock)

With this in mind, a team representing 11 multispecialty organizations, including the American Academy of Pain Medicine (AAPM) and the American Society of Regional Anesthesia and Pain Medicine, developed a practice advisory, published in March 2021.2 The advisory offers recommendations for the use of contrast agents in pain interventions.

“In 2019 a high-profile case was published describing a catastrophic patient death after inadvertent intrathecal injection of gadolinium-based contrast media,” explained Ariana Nelson, MD, associate clinical professor of anesthesiology at the University of California Irvine, one of the authors of the advisory. “As this is often a pain physician’s preferred option if a patient reports an allergy to iodinated contrast dye, this event completely upturned the existing algorithm for selecting contrast media for fluoroscopically guided procedures.”

Why issue recommendations now? Dr. Nelson noted, “Given the need for wide-spread revision, this was the optimal time to produce an integrated set of guidelines related to use of contrast agents with systematic input from physicians from multiple disciplines and pain societies.”


Pain Interventions: The Best Available Evidence for GBCAs

The practice advisory panel was divided into four groups to review existing clinical information on:

  • nephrogenic systemic fibrosis
  • gadolinium deposition/retention the brain
  • encephalopathy from unintentional IT gadolinium injection
  • hypersensitivity reactions to contrast agents.

Each group included at least one pain medicine physician, a rehabilitation specialist, and either an anesthesiologist, radiologist, or a PM&R specialist. The group that drafted the initial recommendations on hypersensitivity reactions included an allergist. 

Based on a recent JAMA viewpoint article (supported by the Agency for Healthcare Research and Quality) that compared evidence-based and consensus-based medicine, the advisory panel chose to use the “best available evidence” (which incorporates observational studies, case reports, and clinician experience in addition to meta-analyses and RCTs) to support their recommendations.2 They used the Delphi process to reach a consensus.

Pain Intervention Recommendations for Contrast Agents

Recommendations regarding each of the four topics are highlighted below.

Nephrogenic Systemic Fibrosis (NSF)

Consistent with the Canadian Association of Radiologists (CAR), American College of Radiology (ACR), and European Society of Urogenital Radiology (ESUR) guidelines, the practice advisory states that low-risk macrocyclic and medium-risk linear ionic agents may be administered in patients with chronic kidney disease (CKD) Stage 3. These agents may also be used with caution in patients with Stage 4 or 5 CKD, as well as in patients on dialysis. The advisory states that following a GBCA-enhanced procedure patients with mild renal failure are not at risk for developing NSF, and patients with moderate renal impairment are at very low risk.

The group added that “though the risk of contrast-induced acute kidney injury is lower than previously thought, the lowest possible doses should still be administered in patients at higher risk for contrast-induced acute kidney injury.”2

Gadolinium deposition/retention the brain

The team tasked with assess the risks of gadolinium retention in the brain found that no definite clinical consequences of GABA retention have been proven. However, they warned that physicians should be aware when patients have had multiple previous procedures that used GBCAs, use the GBCAs only when necessary, and carefully weigh the clinical benefit of the procedure against the potential unknown risks of the contrast agent. The team noted that their recommendations “balance the need for contrast injection with the low risk of gadolinium brain deposition from small extravascular injections and the lack of clinical significance of these brain depositions.”2

Encephalopathy from unintentional IT gadolinium injection

This risk of unintentional IT injection of gadolinium in interventional pain procedures has been identified only recently, so there are not many controlled studies. However, the reported cases have led to serious adverse outcomes and even death. There have also been reports of encephalopathy after IT gadolinium injection in non-pain management procedures. The group urgespain physicians to “observe every precaution to prevent unintentional IT injections of gadolinium.”2

In addition, clinicians are encouraged to identify patients in whom there is a heightened risk of unintentional IT injection, such as patients with spinal stenosis, kyphoscoliosis, or previous spine surgery. GBCA use is not recommended in epidural injections via an inter-laminar approach, including epidurograms nor is it recommended in transforaminal epidural injections. If gadolinium is used, the group recommends considering digital subtraction imaging guidance to increase the detection of intrathecal spread and allow the safer use of a lower molar concentration of GBCA.

Hypersensitivity reactions to contrast agents

The greatest risk for hypersensitivity appears to be in patients with a previous history of hypersensitivity reactions to contrast agents. Other conditions that increase hypersensitivity reactions risk include asthma, atopy, severe cardiovascular disease, being female, and having drug allergies. Seafood allergies did not appear to increase risk. Reactions are less likely to occur with GBCAs than with iodinated contrast media, and reactions to GBCAs are generally mild. The group noted the importance of rigorously verifying a history of HR to contrast agents, as the notation in the medical record can affect care for the rest of the patient’s life.

Patients who have a history of mild hypersensitivity reactions may be given an appropriate pre-treatment and, if it is known which contrast medium caused the previous reaction, a different contrast medium. For patients with a history of moderate to severe HR, the guidelines suggest considering referral to an allergist. These patients may also be referred to an allergist for evaluation and explanation before the procedure. The recommendations also offered guidance for monitoring patients post-procedure and for responding to adverse reactions.

“There is no ideal GBCA,” the advisory panel concluded. Making careful patient selection for procedures, being aware of any comorbidities, and choosing the appropriate contrast medium for each situation are crucial to using CBCAs safely in interventional pain procedures.”

Last updated on: May 20, 2021
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