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Sunday 24 March 2019
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Sponsored: Managing the risks of contrast agents in imaging

Imaging activity continues to rise across the world, fuelled by growth in technology, screening programmes and disease monitoring. The patient safety implications around radiation are well understood and there is increasing awareness of the contraindications to other imaging procedures, such as magnetic resonance imaging (MRI). However, there are other safety-related concerns associated, not with the imaging technology, but with the drugs introduced to improve visualisation of anatomy. The most high-profile of these are the iodinated contrast agents used in computed tomography (CT), interventional radiology (IR) and cardiology procedures.
 
These contrast media are in fact iodine-based ‘dyes’ that are usually administered either intra-arterially or intravenously to highlight vascular and other anatomical structures on imaging. There are two main concerns with these agents:
  • Allergic reaction to the iodine
  • Acute kidney injury.
 
The risk of severe allergic reaction is rare, only accounting for less than 1 in 100,000 patients,1 with more common minor reactions being nausea, vomiting and urticaria (rash). The actual rate of occurrence of kidney injury following contrast administration is difficult to ascertain, but the risk is acknowledged to be greatest in those patients with unstable and reduced kidney function.2
 
Although there remains ongoing controversy as to its prevalence, authors suggest it could represent between 1% and 20% of patients,3 greater in the acutely unwell patient or when using higher doses of contrast media via an intra-arterial route.1,4,5 This iatrogenic problem has a number of names, including contrast-induced nephropathy (CIN), contrast-induced acute kidney injury (CI-AKI) and, more recently, post-contrast acute kidney injury (PC-AKI). 
 
The latter is a relatively new term,5 but, given the mechanism of kidney injury is not well understood, is accepted as a better representation of the disease.6
 

Reducing and identifying the risks

So, if the contrast agents used can have significant side effects, what are imaging departments doing to reduce, or at least identify, the risks?
 

Screening

International guidance advocates that patients with reduced kidney function should be identified to enable preventative measures to be initiated, including hydration. Because of the volume of patients involved and the limited knowledge of comorbidities, identification of these patients based on clinical history is unreliable. Screening questionnaires are gaining in popularity and allow patients to identify risk factors or pre-existing conditions that might predispose them to complications of the contrast. However, as these forms are completed after arrival at the imaging department, the ability to initiate prophylactic hydration is limited, and this might result in the scan being undertaken without contrast or having the appointment rearranged. As a result, many hospitals still require patients to have a blood test for kidney function in advance of the scan to prevent delays and increase efficiency and safety.
 

Kidney function testing

Most acutely unwell patients have already had a panel of bloods results, including creatinine and estimated glomerular filtration rate (eGFR), measures of kidney function, whereas for out-patients, this is commonly an additional test and requires patients to have an additional intervention, regardless of their co-morbidities or risk status. 
 
Whereas for most clinical specialities serum creatinine and eGFR levels provide a longitudinal comparison to identify trends in renal function, imaging uses this as a single measure to categorise the risk of PC-AKI. Although local and national risk stratification varies, there is agreement that the greatest risk of PC-AKI occurs in those patients with an eGFR below 30ml/min/1.73m2. Table 1 outlines the most common thresholds and actions.
 
Table 1: Risk factors and prophylaxis for intravenous iodinated contrast1,3
 
Although there is no consensus on the time interval between kidney function testing and contrast administration, this is often considered to be acceptable within the preceding three months, unless there is known or suspected kidney dysfunction in which case a result within the last week is advised. Unfortunately, this information is not known until scan day screening and therefore point of care(PoC) testing is finding favour as a troubleshooting tool.
 
Figure 1
Figure 1: Iodinated contrast media utilised in a dual-bolus CT urogram to provide optimal enhancement of the abdominal viscera as vasculature as well as delayed visualisation of the left upper renal tract in a case of haematuria.  
 

PoC testing

Although a common site in other hospital and community settings, PoC blood testing is not used widely within imaging,7 with limited evaluation of its clinical utility in this environment. Research has shown variation between device performance,8,9 although there is strong concordance with laboratory testing and assurance of the performance standards of many different devices.
 
What has not yet been realised is the opportunity to streamline the imaging pathway and only undertake testing on patients with risk factors. This would remove a significant administrative burden from clinicians and imaging departments as well as reduce inappropriate testing. For many departments, this is a fundamental change in procedures and it will take some convincing of the validity of such a change. Research is ongoing to evaluate the implementation of a screening enabled pathway utilising PoC and this will hopefully provide evidence of the challenges and benefits of the innovation.
 
Figure 2a
Figure 2A: Iodinated contrast media being used to guide an interventional angiography stenting procedure of the proximal external iliac artery. 
 
Figure 2b
Figure 2B: Confirmation of good angiographic result post-stent placement.
 

Case studies

A 75-year-old patient was referred for a CT scan of the abdomen. The referring clinician had arranged a kidney function test, which confirmed a normal level of 70ml/min/1.73m2. On the scan day, the patient indicated that she had been unwell in the previous week; therefore a PoC creatinine test was performed. This identified a marked reduction in kidney function to 28ml/min/1.73m2, confirmed on laboratory testing. The early indication enabled appropriate action to be taken, including advice regarding proactive oral hydration. On follow up testing three days later, this had improved to 58ml/min/1.73m2.
 
Another 87-year-old patient with chronic kidney disease whose eGFR over the preceding four months varied between 39 and 44ml/min/1.73m2 had a PoC test on the day of her CT urogram. This showed a marked improvement with an eGFR of 64ml/min/1.73m2 and provided assurance around the administration of contrast. On questioning, the patient had recently been catheterised and had been maintaining her fluid balance.
 
Both of these case studies confirm the benefit of PoC testing for patients whose kidney function may have altered, both to ensure patient safety and to prevent contrast being withheld inappropriately.
 

Conclusions

In the imaging setting, complications from contrast administration are thankfully rare, with a mild allergic reaction being the most commonly encountered. Contrast carries a small, and controversial, risk of PC-AKI, yet current strategies often rely on blanket testing of all patients as a precaution. The use of a screening tool and PoC testing may provide the greatest opportunity to streamline the imaging pathway and provide assurance of patient safety. International consensus on screening tools is required to enable a step change in pathway redesign underpinned by confidence in PoC device performance standards.
 

References

1 Royal Australian & New Zealand College of Radiologists. Iodinated contrast media guideline. Sydney; 2016.
2 Davenport MS et al. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material: risk stratification by using estimated glomerular filtration rate. Radiology 2013;268:719–28.
3 Kooiman J et al. Meta-analysis: serum creatinine changes following contrast enhanced CT imaging. Eur J Radiol 2012;81:2554–61.
4 European Society of Urogenital Radiology. ESUR guidelines on contrast media, 2016. Version 9. www.esur.org/esur-guidelines/ (accessed May 2018).
5 van der Molen AJ et al. Post-contrast acute kidney injury – Part 1: Definition, clinical features, incidence, role of contrast medium and risk factors. Recommendations for updated ESUR Contrast Medium Safety Committee guidelines. Eur Radiol 2018;doi: 10.1007/s00330-017-5246-5. 
6 Aycock RD et al. Acute kidney injury after computed tomography: a meta-analysis. Ann Emerg Med 2017;71:44–53.
7 Harris MA et al. Strategies for assessing renal function prior to outpatient contrast-enhanced CT: a UK survey. Br J Radiol 2016;89(1067):20160077. 
8 Snaith B et al. Point-of-care creatinine testing for kidney function measurement prior to contrast-enhanced diagnostic imaging: evaluation of the performance of three systems for clinical utility. CCLM 2018; doi:10.1515/cclm-2018-0128.
9 Korpi-Steiner NL et al. Comparison of three whole blood creatinine methods for estimation of glomerular filtration rate before radiographic contrast administration. Clin Chem 2009;132:920–6. 

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