The recent global shortage of iodinated contrast agents has disrupted diagnostic and procedural care and has forced urologists to adapt their practice to meet the needs of patients. We will review alternative contrast agents, iodinated contrast conservation strategies, and potential alternatives to iodinated contrasted imaging techniques.

GE Healthcare announced on April 19, 2022 that it would begin limiting its supply of iohexol (Omnipaque™), an iodinated contrast agent.¹ This shortage was due to a COVID-19-related lockdown of 26 million Chinese citizens on March 31, shutting down GE’s primary iohexol manufacturing facility located in Shanghai. The company is the leading supplier of iodinated contrast medium in the U.S. and controls approximately 50% of the market.² GE has since restarted manufacturing in a limited capacity and has moved some production to other iohexol manufacturing facilities. Other companies including Bracco Diagnostics, Bayer, and Guerbet LLC have increased production; however, their actions were unable to prevent a critical shortage of iohexol. Many hospital systems currently have categorized imaging indications into tiers based on medical urgency.³ As a result, nonemergent urological procedures are often placed into low-tiered categories and receive a smaller allocation of the hospital’s contrast supply. This shortage negatively impacts the daily workflow of patient care in hospitals across the world.

Shortage of iodinated contrast for CT scans including CT urograms has disrupted urologic oncologic staging, surveillance, and hematuria evaluations. We seek to describe some key learning points for alternative imaging and contrast agents for both diagnostic and procedural urological imaging to mitigate the clinical setbacks of the current shortage and to plan for future shortages.

Alternative Contrast Agents

Intravascular

Iodinated contrast is currently the preferred agent for enhanced CT scans. Currently, nonionic, low-osmolar contrast such as iohexol is preferred due to the relatively low risk of adverse contrast reactions.⁴ In times of severe or prolonged shortage, use of higher-osmolar iodinated contrast (eg Cystografin^®) or gadolinium-based contrast medium can be employed with the knowledge of their limitations and risks of adverse reactions.⁵ A list of alternative contrast agents is provided in Table 1.

Depending on the indication for imaging, magnetic resonance urography can substitute for CT urography and the use of gadolinium-based contrast medium can obviate the need for iodinated contrast. Gadolinium does produce some enhancement on CT, although not to a sufficient degree for substitution. Due to difference in image quality, gadolinium contrast-enhanced CT requires doses 3-4 times higher than the U.S. Food and Drug Administration-approved dose for MRI. This elevated dosage might raise issues in patients with renal impairment by increasing risk of nephrogenic systemic fibrosis as well as the unknown effects of gadolinium metal deposition.^2,6 For this reason, substitution of gadolinium for enhanced CT is not recommended.

Intraluminal

Intraluminal iodinated contrast medium is utilized by urologists for retrograde urethrogram, retrograde pyelogram, loopogram, cystogram, nephrostogram, and videourodynamics. This is the setting in which the contrast shortage has had the greatest urological impact and for which there are efficacious alternatives. Iodinated contrast agents with higher osmolarity and ionic content have an increased incidence of adverse reactions in intravascular administration. However, there is minimal systemic absorption during intraluminal use and these agents should be considered in this setting. In addition to iodinated contrast, gadolinium-based contrast can also be considered. Of note, gadolinium-based contrasts are typically manufactured at lower concentrations, so larger volumes may be required for sufficient imaging.^1,7 Gadavist^® is manufactured with a concentration twice that of other gadolinium-based contrasts, making it more suitable for retrograde urography.⁷ At our institution, we have utilized undiluted Gadavist for intraluminal use as a substitute for iodinated contrast. An image of a retrograde urethrogram obtained with Gadavist is shown in the Figure. Alternative strategies for diagnostic intraluminal contrast use are shown in Table 2. Of note, gadolinium contrast is visible on CT and can be used to perform CT cystogram or CT loopogram in place of iodinated contrast.

Figure. Retrograde urethrogram performed using gadavist gadolinium contrast.

Iodinated Contrast Conservation Strategies

The first line of iodinated contrast conservation would be to review the necessity of imaging study on a per-patient case basis. If the study is believed to be not acutely necessary, delaying imaging should be considered until the shortage ends. When deferral of imaging is not a viable option, various strategies have been implemented to reduce the amount of iodinated contrast that is used during imaging procedures. In the hospital setting, where patients are receiving intravascular iodinated weight-based dosing protocols, there is evidence that doses can be reduced significantly.^2,8 For single-use vials, there should be consideration to reduce volume used by rounding down 10–20 ml.² Limited supplies of iodinated contrast agents can be split for multiple uses; however, this requires strict guidelines for sterility managed institutionally, in accordance with a statement by the CDC in 2012.⁹

Alternatives to Intraluminal Contrast Use

Additionally, there should be consideration into lesser-known methods such as using gas (eg carbon dioxide or air) as a contrast material. These agents can be advantageous for procedures such as percutaneous nephrostomy placement to help delineate calyceal anatomy. Alternatively, percutaneous nephrostomy placement can be performed by direct pyeloscopic visualization of the access needle to confirm placement. Limitations to this approach include the need for retrograde access and potentially higher risk of complications due to ureteral manipulation.

The international contrast shortage has disrupted urological care and has resulted in the delay of contrast-enhanced scans and urological procedures which require contrast. Equipping the urologist with adaptive strategies and a tool kit of alternatives can help to mitigate the disruption of the current contrast shortage and ready us in the event of future shortages. Moving forward, health systems should be mindful to consider and diversify both the source of manufacturing of critical goods and the means of distribution to avoid critical supply chain lapses.