Algemene inleiding

The Radiological Society of The Netherlands (RSTN - NVvR) deemed a set of new guidelines on the Safe Use of Contrast Media (CM) highly necessary and relevant, due to recent publications on many topics concerning contrast safety. Because of recent scientific developments, the recommendations of the most recent CM guideline (CBO, 2007) were in conflict with what should be considered best clinical practice. In order to update this 2007 CBO Guideline, which only covered selected topics on the use of iodine-containing CM, a plan has been developed to make a set of 3 new guidelines covering the safe use of all types of CM in adults.

 

The patient population for which these guidelines are meant consists of adult patients (>18 years) who receive intravascular, oral or intracavitary (intra-articular, intra-vesical, intra-cholangiographic) iodine-containing contrast media both in the clinical setting, as well as for outpatients. The guidelines do not cover radioactive contrast media use in nuclear medicine.

 

The three parts of the Safe Use of Contrast Media guidelines will be produced in three consecutive 2-year projects and will cover the following topics regarding CM safety (part 3 is still in the planning phase, topics to be finalized):

 

Safe Use of Contrast Media - Part 1 (2014-2017):

 

Safe Use of Contrast Media - Part 2 (2016-2019):

 

Safe Use of Contrast Media - Part 3 (2018-2020; still in planning):

 

General Introduction Part 1

This first part will deal with one of the main challenges in the intravenous and intra-arterial use of CM, the prevention of contrast-induced nephropathy (CIN), also called contrast-induced acute kidney injury (CI-AKI). This issue has received large interest in recent years, resulting in strict prevention guidelines for all physicians requesting radiologic or cardiologic diagnostic or interventional studies with iodine-containing CM. The nephrotoxicity of gadolinium-based contrast media and/or microbubble contrast media and the recommendations for measurement of eGFR will be integrated with the guidelines for prevention of Nephrogenic Systemic Fibrosis. These recommendations will be published in the guideline Safe Use of Contrast Media, part 2 (due begin 2019).

 

The mainstay of the current prevention protocols consists of intravenous volume expansion with either normal saline (NaCl 0.9%), lactated Ringer’s solution, or sodium bicarbonate (NaHCO3 1.4%), starting multiple hours before the administration of iodine-containing CM and continuing for multiple hours after iodine-containing CM administration. The time intervals for this preventive hydration normally range from 4-12 hours before and 4-12 hours after iodine-containing contrast administration, but these may have to be individualized and prolonged in patients with severe congestive heart failure or in patients with severe renal failure.

 

Obviously, such protocols present a logistic and financial burden to the hospital system (Kooiman, 2013). To admit all patients at increased risk for AKI in day-hospital wards for intravenous volume expansion is expensive, and the volume expansion itself may lead to complications as well.

 

Despite the large amount of medical literature produced, researchers in the USA in 2006 began to question the causative role of iodine-containing CM in post-contrast acute kidney injury (PC-AKI). They noted that when studies with proper control populations were analysed, the role of intravenously-injected CM as a cause for AKI was largely overestimated, since changes in serum creatinine that fulfilled the definition of contrast-induced nephropathy (CIN) were found at the same frequency in patients who did not receive CM (Bruce, 2009; Katzberg, 2007; Newhouse, 2008; Rao, 2006).

 

Researchers from the Mayo Clinic and the University of Michigan, centres with an extensive focus on CM research by tradition, subsequently performed a number of large retrospective, observational studies with control populations selected by the strict process of propensity-score matching (Austin, 2011; McDonald, 2013), in order to solve this problem. These studies focused on intravenous injection of CM in patients undergoing computed tomography (CT) and showed a much lower risk of PC-AKI than previously expected (Davenport, 2013; McDonald, 2014; McDonald, 2015).

 

Focus of the guideline

This part 1 of the Safe Use of Contrast Media guideline focuses on all adult (18 years and older) patients that receive iodine-containing CM during radiologic or cardiologic studies or interventions.

 

Post-contrast AKI is predominantly an issue of iodine-containing CM and to a lesser degree related to the use of gadolinium-based contrast media for MRI and is no issue for microbubble contrast media for ultrasound.

 

The techniques involved include contrast-enhanced studies in computed tomography, and (coronary) angiography. Magnetic resonance imaging and ultrasound will be discussed in Part 2 of the Safe Use of Contrast Media Guideline.

 

The primary outcome measures in PC-AKI are a decrease in estimated glomerular filtration rate (eGFR) or an increase in serum creatinine (sCr).

 

Secondary measures are the incidence of renal replacement therapy, days of admittance in hospital, associated patient morbidity and mortality and costs.

 

 

 

Terminology and definitions

Because of the recent developments there is confusion about terminology. Terms as post-contrast acute kidney injury, contrast-associated acute kidney injury, and contrast-induced acute kidney injury or contrast-induced nephropathy are incorrectly used interchangeably.

 

Therefore, this guideline will follow the American College of Radiology (ACR) Committee on Drugs and Contrast Media that has published the following suggestion for more uniformity (ACR Manual, 2017):

 

Post-contrast acute kidney injury (PC-AKI) is a general term used to describe a sudden deterioration in renal function that occurs within 48 hours following the intravascular administration of iodine-containing CM. PC-AKI may occur regardless of whether the CM was the cause of the deterioration. PC-AKI is a correlative diagnosis.

 

Contrast-induced acute kidney injury (CI-AKI) or contrast-induced nephropathy (CIN) is a specific term used to describe a sudden deterioration in kidney function that is caused by the intravascular administration of iodine-containing CM; therefore, CI-AKI/CIN is a subgroup of PC-AKI. CI-AKI/CIN is a causative diagnosis.

 

The ACR acknowledges that very few published studies have a suitable control group to permit the separation of CI-AKI/CIN from PC-AKI. Therefore, the incidence of PC-AKI reported in clinical studies and the incidence of PC-AKI observed in clinical practice likely includes a combination of CI-AKI (i.e., AKI caused by CM administration) and AKI unrelated to CM administration (i.e., AKI coincident to but not caused by CM administration).

 

Therefore, PC-AKI and CI-AKI are not interchangeable (ACR Manual, 2017).

 

Clinical Course and Incidence

Post-contrast acute kidney injury (PC-AKI) is an iatrogenic renal injury that follows intravascular administration of contrast media (CM) in susceptible individuals (Rear, 2016).

 

It is difficult to distinguish between different aetiologies of acute kidney injury. In most of cases PC-AKI is mild and reversible with returning of renal function to baseline or near baseline values within 1 to 3 weeks. (Guitterez, 2002; Mehran, 2006) As common for all forms of AKI, the occurrence of PC-AKI has shown to be a marker for increased short- and long-term morbidity and mortality and longer duration of hospital stay (Gruberg, 2000; Gupta, 2005; Kooiman, 2015; Mitchell, 2015).

 

Various studies suggest that the route of administration of CM (intra-arterial versus intravenous) and type of procedure (i.e. catheter-based angiography versus CT imaging) can have a substantial impact on the incidence of PC-AKI (Dong, 2012; Solomon, 2008).

 

Guideline Disclaimers

General

The aim of clinical guidelines is to help clinicians to make informed decisions for their patients. However, adherence to a guideline does not guarantee a successful outcome. Ultimately, healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgement, knowledge and expertise. A guideline cannot replace a physician’s judgment in diagnosing and treatment of particular patients.

 

Guidelines may not be complete or accurate. The Working Group of this guideline and members of their boards, officers and employees disclaim all liability for the accuracy or completeness of a guideline, and disclaim all warranties, express or implied to their incorrect use.

 

Guidelines users always are urged to seek out newer information that might impact the diagnostic and treatment recommendations contained within a guideline.

 

Individualisation

In specific high-risk patient groups (e.g. in patients with high-grade congestive heart failure or end-stage chronic kidney disease) clinicians may have to regress from these general guidelines and decide on individualisation of preventive measures to best fit the needs of their patients.

 

Life-threatening situations or conditions

In acute life-threatening situations or conditions clinicians may have to regress from these general guidelines and decide on individualisation of renal function estimation or preventive measures to best fit the needs of their patients in these situations or conditions.

 

References

American College of Radiology. ACR Manual on Contrast Media, v10.3. Reston, VA: American College of Radiology, 2017.

 Available at: https://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/Contrast-Manual/Contrast_Media.pdf

Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res. 2011;46(3):399-424.

Bruce RJ, Djamali A, Shinki K, et al. Background fluctuation of kidney function versus contrast-induced nephrotoxicity. AJR Am J Roentgenol. 2009;192(3):711-8.

Davenport MS, Khalatbari S, Cohan RH, et al. Contrast medium–induced nephrotoxicity risk assessment in adult inpatients: a comparison of serum creatinine level–and estimated glomerular filtration rate–based screening methods. Radiology. 2013;269(1):92-100.

Dong M, Jiao Z, Liu T, et al. Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controled trials. J Nephrol. 2012;25(3):290-301.

Gruberg L, Mintz GS, Mehran R, et al. The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. J Am Coll Cardiol. 2000;36(5):1542-8.

Guiterrez NV, Diaz A, Timmins GC, et al. Determinants of serum creatinine trajectory in acute contrast nephropathy. J Interv Cardiol 2002; 15(5): 349-54.

Gupta R, Gurm HS, Bhatt DL, et al. Renal failure after percutaneous coronary intervention is associated with high mortality. Cathet Cardiovascular Intervent. 2005;64(4):442-8.

Karlsberg RP, Dohad SY, Sheng R. Iodixanol peripheral computed tomographic angiography study investigator panel. Contrast medium acute kidney injury: comparison of intravenous and intra-arterial administration of iodinated contrast medium. J Vasc Intervent Radiol. 2011;22(8):1159-65.

Katzberg RW, Barrett BJ. Risk of iodinated contrast material–induced nephropathy with intravenous administration. Radiology. 2007;243:622-628.

Kooiman J, van der Molen AJ, Cannegieter SC, et al. [Prevention of contrast-induced nephropathy: time for nuance and a new guideline]. Ned TijdschrGeneesk. 2013;157(12):A5475.

Kooiman J, van de Peppel WR, Sijpkens YW, et al. No increase in Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin excretion following intravenous contrast enhanced-CT. EurRadiol. 2015;25(7):1926-34.

McDonald RJ, McDonald JS, Kalmes DF, et al. Behind the numbers: Propensity Score analysis – A primer for the diagnostic radiologist. Radiology 2013; 269: 640-645

McDonald RJ, McDonald JS, Bida JP, et al. Intravenous contrast material-induced nephropathy: causal or coincident phenomenon? Radiology. 2013 Apr;267(1):106-18. Erratum in: Radiology. 2016 Jan;278(1):306.

McDonald JS, McDonald RJ, Carter RE, et al. Risk of intravenous contrast material–mediated acute kidney injury: a propensity score–matched study stratified by baseline-estimated glomerular filtration rate. Radiology. 2014;271(1):65-73.

McDonald JS, McDonald RJ, Lieske JC, et al. Risk of acute kidney injury, dialysis and mortality in patients with chronic kidney disease after intravenous contrast material exposure. Mayo Clin Proc 2015; 908: 1046-53

Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Intern. 2006;(100):S11-5.

Mitchell AM, Kline JA, Jones AE, et al. Major adverse events one year after acute kidney injury after contrast-enhanced computed tomography. Ann Emerg Med. 2015;66(3):267-274.e4.

Newhouse JH, Kho D, Rao QA, et al. Frequency of serum creatinine changes in the absence of iodinated contrast material: implications for studies of contrast nephrotoxicity. AJR Am J Roentgenol. 2008;191(2):376-82.

Rao QA, Newhouse JH. Newhouse. Risk of nephropathy after intravenous administration of contrast material: a critical literature analysis. Radiology. 2006;239(2):392-7.

Rear R, Bell RM, Hausenloy DJ. Contrast-induced nephropathy following angiography and cardiac interventions. Heart. 2016;102(8):638-48.

Solomon R. Contrast-induced acute kidney injury: is there a risk after intravenous contrast? Clin J Am Soc Nephrol. 2008;3(5):1242-3.