The recent lockdown in Shanghai, China, has had a serious impact on GE Healthcare’s primary pharmaceutical manufacturing facility for iohexol (Omipaque, GE Healthcare) iodinated contrast media (ICM), which is widely used for imaging in the United States. GE is one of four manufacturers of ICM, and while the factory has since been reopened, GE expects that there will be an 80% reduction in supplies through the end of June.
The other companies supplying ICM to the US have been unable to rapidly scale up production to meet the demand created by the reduction in iohexol supplies. As the problem is not going to be completely solved within the near future, the Radiologic Society of North America (RSNA) issued a special report in the journal Radiology to help clinicians deal with the shortage of ICM in the short term, and also discusses some of the long-term issues and potential solutions to supply chain problems.
“In many ways this feels like ‘deja vu all over again,’ as we are facing issues similar to those we faced in the early days of the COVID pandemic, caused by a limited supply of an important pharmaceutical, critical to our ability to care for our patients,” said Thomas M. Grist, MD, chair of the Department of Radiology at the University of Wisconsin School of Medicine and Public Health in Madison and lead author of the Radiology Special Report. “One important difference, however, is that our hospitals and health systems are more adept at establishing incident command centers to implement rapid responses to the challenges we face and communicating those changes to our patients and referring physicians.”
However, in an interview with Medscape Medical News, Grist pointed out cautiously that the situation may have taken a turn for the better. “My understanding is that the Shanghai facility is now at 60% capacity and the manufacturer has shifted to delivery by air rather than ship, so the trajectory of recovery is going in a positive direction,” he said. “However, there will be a lag in the availability of iohexol for a few weeks due to the time needed for distribution through the US supply chain.
“This is a global shortage that doesn’t impact everyone equally and depends on the source of iodinated contrast that each site uses,” he added.
Strategies for the Shortage
The spike in COVID‐19 cases in Shanghai led to a total lockdown by the Chinese government on March 31, which effectively halted production of GE Healthcare’s primary pharmaceutical manufacturing facility for iohexol. The only other pharmaceutical facility capable of producing iohexol, which is located in Ireland, is currently operating at maximum capacity.
On May 18, a GE Healthcare spokesperson provided an update to the RSNA: “Our priority is delivering for our customers and their patients, and we are working around the clock to expand capacity of our iodinated contrast media products. After having to close our Shanghai manufacturing facility for several weeks due to local COVID policies, we have been able to reopen and are utilizing our other global plants wherever we can. We are working to return to full capacity as soon as local authorities allow.”
In their report, Grist and colleagues offer short-term, midterm, and long-term strategies for coping with the shortage.
In the short term, they recommend establishing an incident command center to direct and monitor ICM usage, delaying elective contrast-enhanced CT exams, converting exams to noncontrast when possible, reducing contrast dose, and substituting other types of exams, such as MRI, ultrasound, or noncontrast PET-CT.
For the midterm, recommended strategies for the coming months include contrast repackaging, multiuse and multiaccess tactics, negotiation with payers on billing and reimbursement, and consistent communication with ordering providers to ensure compliance.
Finally, in the long term, the authors recommend advocating for legislation to facilitate contrast manufacturing plants in the US, improving institutional inventory of contrast supplies, and supporting the vendors to expand manufacturing.
“It is indeed remarkable that the bulk of iodinated contrast for imaging comes from only a few facilities,” said Grist. “We have evolved into a pharmaceutical delivery system, using group purchasing organizations and other distribution channels, that is very low cost and also very fragile. The [profit] margins on making x-ray contrast are slim, and therefore the manufacturing and distribution channels have consolidated globally to give us this result.”
He added that it is “another example of every system producing the results it is designed to achieve, and we need to think more carefully about the impact on our ability to provide healthcare to the patients, who trust us with their lives.”
Feeling the Pain in Pain Management
Another critical aspect the ICM shortage is in pain management, and the American Society of Anesthesiologists (ASA) has warned patients and healthcare providers that the shortage may affect care and patient safety.
Contrast media enhances the differences between body tissues to help clinicians pinpoint the area of concern. “We often use contrast media during diagnostic or therapeutic spinal or epidural injections for back, neck, or extremity pain,” said David Dickerson, MD, chair of the ASA’s Committee on Pain Medicine. “Injection of contrast media helps confirm needle tip location and the absence of communication of the injection with a blood vessel or with an area outside of the intended target. Contrast media is commonly used prior to injecting medication around the spinal nerve roots.”
As this region contains blood vessels, some of which may be critical to the perfusion of the spinal cord, contrast media helps clinicians avoid injecting medications into these vessels and the resultant injury to the nervous system.
Working around the shortage is possible, although Dickerson emphasized that some procedures require contrast to ensure safety. “That said, we have many different forms of image guidance and approaches to deliver targeted treatment to inflamed or dysfunctional parts of the nervous or musculoskeletal system,” he said. “Treatment approaches can incorporate safety steps and alternative approaches that allow for us to reduce the potential for inadvertent injection into a blood vessel or outside of the intended target.”
Dickerson noted that he has yet to hear of procedures being put on hold, but “this is due to clinicians working to find alternative sources for their purchasing of contrast media or through working with their institutions or practices to safely aliquot multiuse vials according to the policies and procedures of their care sites. Without restoration of the supply chain, the shortage could absolutely impact interventional pain clinics.”
He also pointed out that it is sometimes safer to avoid some substitutions, even during a shortage. “Gadolinium, an MRI contrast agent, may seem like a safe alternative to iodinated contrast media, but these medications can cause injury to the central nervous system if inadvertently injected into the spinal fluid,” said Dickerson. “These drugs should be avoided if intrathecal spread of the medication is a possible risk of the procedure.”
Similarly, some formulations of iodinated contrast media are not labeled for intrathecal injection. “Thus, medications labeled for this use should be allocated specifically for use in procedures where intentional spinal fluid or intrathecal injection is planned,” he added. “The majority of our injections are not intrathecal, which makes this strategy feasible.”
Radiology. Published online May 19, 2022. Full text