Best Practice Recommendations for Stroke Vascular Imaging During Iodinated Contrast Shortage

Abstract

GE Healthcare^© announced on April 19, 2022, that their main factory and distributor of iodinated contrast had experienced a temporary shutdown because of COVID-19 outbreak in Shanghai, China. This, along with other supply chain issues, led to a worldwide shortage of iodinated contrast agents, Omnipaque and Visipaque. Our Comprehensive Stroke Center was confronted with the cascading effect of this iodinated contrast material shortage. We took immediate steps to revise our protocols and processes to continue to provide high-quality care to our stroke patients. A multidisciplinary working group comprised of representatives of our stroke center, including vascular neurology, diagnostic neuroradiology, and neurovascular surgery, urgently met to brainstorm how to mitigate the shortage. We established parameters and local guidelines for the use of CT angiography, CT perfusion, and digital subtraction angiography for stroke patients. In this article, we propose “best practice” recommendations from a single Joint Commission approved Comprehensive Stroke Center that can be used as blueprint by other hospital systems when navigating potential future supply chain issues, to provide consistent high-quality stroke care.

GE Healthcare^© announced on April 19, 2022, that their production facility for iodinated contrast experienced a temporary shutdown because of a lockdown imposed by the local authorities to contain the most recent outbreak of COVID-19 in Shanghai, China. This, along with other supply chain issues, led to a worldwide shortage of iodinated contrast agents, Omnipaque and Visipaque. These 2 contrast agents facilitate a significant proportion of medical imaging and radiologic procedures including CT and digital subtraction angiography (DSA). Stroke centers particularly rely on CT angiography (CTA) and DSA studies in the evaluation and management of cerebrovascular disease. Given the shortage, many facilities were redirecting or postponing contrast-enhanced studies in some prioritized fashion.

When our Comprehensive Stroke Center was confronted with the cascading effect of this iodinated contrast material shortage on April 29, 2022, we took immediate steps to revise our protocols and processes to continue to provide high-quality care to our stroke patients. Representatives of our stroke center, including vascular neurology, diagnostic neuroradiology, and neurointerventional surgery, urgently met to brainstorm how to mitigate the shortage. These member representatives formed a multidisciplinary working group comprised 12 members to establish parameters and local guidelines for the use of CTA, CT perfusion, and DSA for stroke patients. A draft of proposed protocol changes was outlined, and then, daily meetings were held over 72 hours to revise and finalize the protocol.

In this article, we propose bulleted “best practice” recommendations from a single Joint Commission–approved Comprehensive Stroke Center that can be used as blueprint by other hospital systems when navigating potential future supply chain issues, to provide consistent high-quality stroke care.

We focus on recommendations for each specific imaging modality and clinical scenario in the stroke continuum of care from the hyperacute emergency setting to elective diagnostic studies for outpatient workup of stroke and cerebrovascular disease. We propose an appropriate algorithm as preparedness for future shortages, natural, or health disasters. We hope to encourage discussion and correspondence with other stroke centers and colleagues to support additional efforts to navigate the iodinated contrast shortage and consider future situations requiring collective resource utilization in stroke care.

Emergent, Hyperacute Imaging in Acute Stroke

CT Angiogram Head and Neck

Acute stroke is an emergency and priority vessel imaging with CTA head and neck should be used in the following stroke alert or code stroke patients (≤24 hours from last known well).

• All patients who qualify for IV thrombolytic treatment with recombinant tissue plasminogen activator (rtPA) or tenecteplase (TNK) with clinical suspicion of large vessel occlusion (LVO) (Figure 1): cortical signs (e.g., aphasia, gaze preference or deviation, visual field deficit, and neglect) and/or National Institutes of Health Stroke Scale (NIHSS) score of ≥6 points.^1,2

• All patients who qualify for emergent stroke thrombectomy, except those with hyperdense vessel sign on noncontrast CT head who can proceed directly to neurointerventional suite.³

• Patients whose noncontrast CT head imaging shows subarachnoid hemorrhage (SAH) or lobar or multifocal intracerebral hemorrhage or there is MRI or lumbar puncture evidence of SAH suggesting the possibility of an intracranial aneurysm, arteriovenous malformation, or dural arteriovenous fistula.

Figure 1. Stroke Vascular Imaging Algorithm During Contrast Media Shortage.

*Clinical suspicion for LVO: cortical signs and/or NIHSS ≥6, **Cortical signs (e.g., aphasia, gaze preference or deviation, visual field deficit, and neglect). NIHSS = National Institutes of Health Stroke Scale; ASPECTS = Alberta Stroke Programme Early CT Score; CSC = comprehensive stroke center; CTA = CT angiogram; CTP = CT perfusion; DSA = digital subtraction angiogram; DWI = diffusion-weighted imaging; ED = emergency department; LKW = last known well; LVO = large vessel occlusion; MRA = MR angiogram; MRV = MR venogram; NCCT = noncontrast CT; PSC = Primary Stroke Center; rtPA = recombinant tissue plasminogen activator; SAH = subarachnoid hemorrhage; TNK = tenecteplase.

Direct to Neurointerventional Suite

• Clinical suspicion of LVO with hyperdense vessel sign on noncontrast CT head (middle cerebral artery, anterior cerebral artery, or basilar artery) and noncontrast CT Alberta Stroke Programme Early CT Score (ASPECTS)⁴ score ≥6 does not require additional vascular imaging studies before stroke thrombectomy.^3,5,6

Acute Stroke Imaging for Wake-Up or Extended Window Stroke Patients (4.5–24 Hours From Last Known Well)

The American Heart Association Acute Stroke Guidelines¹ recommend advanced imaging in stroke patients with LVO in the 6–24-hour window from LKW time to determine eligibility for stroke thrombectomy. Advanced imaging with CT perfusion (CTP), diffusion-weighted imaging (DWI) MRI, or MR perfusion is recommended to demonstrate clinical imaging mismatch⁷ or perfusion core mismatch⁸ to aid in patient selection for stroke thrombectomy. CT perfusion is the most commonly performed diagnostic test to demonstrate this mismatch because it is fast and easy, but it uses approximately 80–100 mL iodinated contrast per scan.⁹ Hospital systems capable of performing MR perfusion imaging to guide eligibility for stroke thrombectomy⁸ will not be affected by the iodinated contrast shortage.

• Avoid CT perfusion particularly in the following scenarios given the additional iodinated contrast requirement.

• For patients presenting with a wake-up or unclear onset of stroke obtain “WAKE-UP” Stroke MRI protocol¹⁰ (Figure 2) including DWI, fluid attenuated inversion recovery (FLAIR), and susceptibility-weighted imaging (SWI) sequences; use the DWI-FLAIR mismatch volume (i.e., abnormal signal on DWI and no visible change on FLAIR) as a surrogate for salvageable penumbra to guide eligibility for IV thrombolysis^1,10 for patients who are ≤4.5 hours from symptom onset or to calculate DWI stroke volume for stroke thrombectomy in patients with LVO.^7,8

• Patients presenting 6–24 hours from last known well (LKW) with an LVO syndrome consider using a clinical-radiologic mismatch with the DWI imaging obtained using the WAKE-UP stroke MRI protocol to determine eligibility for stroke thrombectomy.⁷

• In hospital systems where rapid MRI is not available or in patients who cannot get an MRI because of metal in the body or a pacemaker or other intracardiac device, consider noncontrast CT ASPECTS score of ≥6 to guide eligibility for stroke thrombectomy in patients with acute LVO^5,6 and in those with ASPECTS score <6, CTP may still need to be considered to determine eligibility for stroke thrombectomy.

Figure 2. “WAKE-UP” Stroke MRI Protocol.

DWI = diffusion-weighted imaging; FLAIR = fluid attenuated inversion recovery; SWI = susceptibility-weighted imaging.

“WAKE-UP” Stroke MRI Protocol

• Wake-Up Stroke MRI sequence: Axial DWI, FLAIR, and SWI (Figure 2).¹⁰

• MRI department to prioritize the Wake-Up Stroke MRI.

• MRI Screening form to be completed by stroke team member and emergency department (ED) nurse. To complete the MRI screening form: (1) obtain history from patient or family member, (2) Emergency Medical Services to obtain family member' and nearest contact's phone number to facilitate the process, and (3) emergent screening x-ray of orbits, chest, and abdomen if patient or family unable to provide history or if family is unavailable.

• Pharmacy and ED nurse to accompany patient to the MRI scanner along with the stroke team.

Stroke Thrombectomy in Transfer Patients

American Heart Association/American Stroke Association best practice recommendation suggest an ideal goal of ≤90 minutes in 50% or more of acute ischemic stroke patients transferred to higher level of care.¹¹

• Repeat vascular imaging is not necessary for stable patients without lengthy transfer times.

• Repeat MRA head and neck in patients with resolved deficits or significantly improved NIHSS score.

• WAKE-UP MRI protocol (Figure 2) and use DWI to calculate stroke volume instead of CTP in patients with delayed transfer times.

Telestroke Sites, Primary Stroke Centers, and Other Non–Thrombectomy-Capable Stroke Centers

Our protocol is also applicable to the less resourced hospitals such as primary stroke centers and critical access hospitals. Modern stroke care is typically modeled as “Hub and Spoke” systems of care,¹² and vascular neurology consult is generally sought in acute stroke patients. Our guidance applies specifically to the hub and spoke telestroke model. We would encourage contacting an on-call stroke neurologist and using telemedicine for accurate assessments early on to make appropriate imaging choices.

• Hub hospitals (i.e., thrombectomy-capable and comprehensive stroke centers) to coordinate with their spoke telestroke and other referring hospital sites to better understand the supply chain of iodinated contrast in regional stroke systems of care; hospitals contracting with vendors of other commercially available contrast agents, including Isovue, may not be directly affected by the shortage but may need to ration supply given increased demand overall.

• For those spoke hospitals with a healthy supply of iodinated contrast, encourage them to obtain CTA head and neck before transfer of acute stroke patients when indicated.

• Telemedicine on-call vascular neurologist usually determines transfer eligibility for stroke thrombectomy to a hub hospital based on LVO detection on CTA and a good ASPECTS score (≥6) on noncontrast head CT.^1,5 Occasionally, the ASPECTS score maybe too low, and in those situations, perfusion imaging might help with triage decisions. For spoke hospitals that do not have the capability of performing rapid MRI or MR perfusion but have available CT perfusion, CT perfusion may still be necessary to make important triage decisions for transfer to a hub facility for this subset of patients with LVO.^1,5,7,8

Nonemergent, Subacute Imaging in Acute Stroke

Subacute imaging refers to vascular imaging that can be performed nonemergently and can be ordered as “routine” rather than “urgent” or “stat.”

MR Angiogram Head and Neck

Patients in whom MR Angiogram (MRA) head and neck should be considered include the following:

• Post-IV rtPA or TNK treated patients with low NIHSS (NIHSS <6) and low clinical suspicion of LVO.

• Stroke onset ≤4.5 hours from LKW time, but

◦ Complete resolution of symptoms

◦ Clinical suspicion of stroke mimic

◦ Nondisabling deficits

◦ No fluctuation or progression of symptoms

• Stroke onset time 4.5–24 hours from LKW time and no clinical suspicion of LVO.

• Stroke onset time >24 hours from LKW time.

In Setting of Abnormal MRA

Consider DSA or CTA if deemed necessary for determining secondary stroke prevention plan. A multidisciplinary discussion among the stroke team members is helpful to determine the next best diagnostic test. If there seems to be higher likelihood of therapeutic intervention, we would recommend direct DSA.

Examples:

• Determine the severity and anatomy of carotid stenosis for consideration and planning of carotid revascularization.

• Suspicion of intraluminal thrombus on MRA requiring confirmation and better characterization. Occasionally, a filling defect or lack of flow signal on MRA could be an artifact, a plaque, or a thrombus. CTA confirmation would help with formulating a treatment plan.

• Suspicion of cerebral vasculopathy on MRA, such as cerebral vasculitis, reversible cerebral vasoconstriction syndrome, or cerebral vasospasm, requiring confirmation and/or treatment with intra-arterial calcium channel blocker therapy.

Neurosonology

Transcranial Doppler (TCD) and carotid duplex are established screening modalities for proximal steno-occlusive disorders in acute stroke and vasospasm after subarachnoid hemorrhage. Although most institutions do not have neurosonology emergently available, some that do can use TCD and carotid ultrasound as a potential alternative to CTA in the acute setting. Carotid duplex ultrasonography can be performed as nonemergent diagnostic workup for carotid stenosis in an anterior circulation ischemic stroke as an alternative to MRA.¹³

Outpatient Imaging or Nonacute ED Neurovascualar Consultation

All elective CTA or DSA studies should be postponed or triaged until the iodinated contrast shortage is resolved. An institutional exception process may be developed for iodinated contrast studies when appropriate and approved by the standing hospital contrast shortage triage committee.

• Eliminate obtaining CTA for low probability nonemergent, nonlocalizing neurologic conditions such as headaches, altered mental status, seizures, and syncope.

• MRI and MR venogram may be obtained to rule out cerebral venous sinus thrombosis.

• MRI with dissection protocol (T1 fat-saturated sequences in the neck) and MRA head and neck may be obtained to rule out cervical artery dissection.¹⁴

• MRA head and neck (with vessel wall imaging techniques if available) may be obtained to assess for cerebral vasculopathy/vasculitis.¹⁵

• MRA neck or carotid duplex ultrasound may be obtained to rule out extracranial carotid artery stenosis in an anterior circulation ischemic stroke.

• MRA head should be used in the routine monitoring of unruptured intracranial aneurysms and other stable vascular malformations.

Communication Script

As stroke providers, we need to have a clear and honest communication with our patients regarding the situation. A standard script of communication should be outlined to provide a consistent message for patients from all team members regarding the triaging of contrast-based studies. Although we did not create a specific script for patients, we did include the following institutionally approved language in medical documentation and radiology reports during the shortage.

Inserted language in radiology reports: “This patient was evaluated during a time of global shortage of iodinated contrast media. Based on guidance from professional societies, best practices, and local institutional approaches, an alternative path for evaluating and managing the patient may have been used to provide appropriate care during this shortage.”

Discussion

The most recent international shortage of iodinated contrast supply was another extraordinary situation in health care, stemming as an additional downstream consequence of the COVID-19 pandemic. During the COVID-19 pandemic, we witnessed some uncertain times in medicine and instead of being reactive, having this kind of preparedness before any future events is truly important. As such, stroke centers need to urgently revise and implement processes to ration iodinated contrast use and minimize wasteful resource utilization. The situation was dynamic, and the critical shortage was expected to have an effect on hospital operations from May 2022 over a duration of several months and would have extended longer if current supplies were overutilized and the supply chain not restored. In the month of May, which was the peak of contrast shortage, there was low utilization of CTA and CTP for stroke workup followed by a tiered recovery in June 2022, as the supply was gradually restored (Table). Although the contrast shortage in many areas is less of a concern than it had been in the prior couple of months, it is still important in this day and age to have protocols to pivot public health emergencies and shortages. Future shortages could not only apply clinical factors as we describe but could also apply business model for multimodal CT imaging in stroke care as suggested by Bammer et al.¹⁶ Situations such as these need to be monitored daily, during which time we need to be cognizant of the shortage and consider alternate means of neurovascular imaging as detailed in the proposed temporary recommendations above.

Table.

Volume of CT Angiograms and CT Perfusion Preiodinated and Postiodinated Contrast Shortage

Implementing the above necessary guidelines will most certainly place an additional burden on MRI services, in addition to the potential for delayed inpatient imaging because of the longer time requirements for MRI/MRA studies. It is essential to have radiology be an integral part of the discussions to expedite inpatient stroke imaging. Stroke team members should also work across service lines with other high usage disease specialties, including emergent cardiovascular and aortic disease, where CTA and conventional angiography are also ubiquitous in clinical practice guidelines.

Stroke centers may also review alternatives until supply balances out demand. Collaborative efforts can be made to contact surrounding facilities who may be experiencing less of a shortage of iodinated contrast because they may have contracts with different vendors to see whether they can accommodate triage of elective studies and procedures. Physician leaders and hospital administration need to work together to determine the distribution of supply, interfacility partnerships, and pooling of resources.

This recent contrast shortage and our summary recommendations highlight the importance of appropriate resource allocation in acute stroke care, particularly when it comes to addressing health disparities. However, we advocate for continuing to follow evidence-based guidelines pertaining to acute stroke imaging when an adequate supply of contrast is available.¹ In addition multiple studies have demonstrated the safety of iodinated contrast in acute stroke patients with no correlation between dye administration and kidney disease at a population level.^17-19

Because stroke is a clinical diagnosis, we should continue to rely on our clinical examination and acumen to diagnose stroke syndromes and other cerebrovascular emergencies and recommend appropriately partitioned neurovascular imaging as necessary. We anticipate these to be temporary measures to be lifted once the contrast supply is restored. The limitation of the proposed recommendations is that this is single-center protocol. Nonetheless, as we attempt to delineate alternative pathways for neurovascular imaging to maintain high-quality care to our stroke patients, these unusual circumstances force us to consider the provision of neurovascular imaging in all settings going forward.

Appendix. Authors

Study Funding

The authors report no targeted funding.

Disclosure

R. Bhole, N.J. Solenski, J.H. Donahue, R.T. Kellogg, N.N. Roach, and S.N.Chapman report no disclosures relevant to the manuscript. B.B. Worral is an Associate Editor of Neurology. A.J. Evans, S.H. Patel, S.Mukherjee, and M.S. Park report no disclosures relevant to the manuscript. A.M. Southerland discloses research support from the AHA/ASA, NSF, Diffusion Pharmaceuticals, and AbbVie Pharmaceuticals. He performs expert legal consultation in cases related to acute stroke and cerebrovascular disease. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.