Waiting times between examinations with intravascularly administered contrast media: a review of contrast media pharmacokinetics and updated ESUR Contrast Media Safety Committee guidelines.

The pharmacokinetics of contrast media (CM) will determine how long safe waiting intervals between successive CT or MRI examinations should be. The Contrast Media Safety Committee has reviewed the data on pharmacokinetics of contrast media to suggest safe waiting intervals between successive contrast-enhanced imaging studies in relation to the renal function of the patient. CLINICAL RELEVANCE STATEMENT: Consider a waiting time between elective contrast-enhanced CT and (coronary) angiography with successive iodine-based contrast media administrations in patients with normal renal function (eGFR > 60 mL/min/1.73 m2) of optimally 12 h (near complete clearance of the previously administered iodine-based contrast media) and minimally 4 h (if clinical indication requires rapid follow-up). KEY POINTS: • Pharmacokinetics of contrast media will guide safe waiting times between successive administrations. • Safe waiting times increase with increasing renal insufficiency. • Iodine-based contrast media influence MRI signal intensities and gadolinium-based contrast agents influence CT attenuation.

Contrast media for hysterosalpingography: systematic search and review providing new guidelines by the Contrast Media Safety Committee of the European Society of Urogenital Radiology.

OBJECTIVES: Hysterosalpingography (HSG) is widely used for evaluating the fallopian tubes; however, controversies regarding the use of water- or oil-based iodine-based contrast media (CM) remain. The aim of this work was (1) to discuss reported pregnancy rates related to the CM type used, (2) to validate the used CM in published literature, (3) to discuss possible complications and side effects of CM in HSG, and (4) to develop guidelines on the use of oil-based CM in HSG. METHODS: A systematic literature search was conducted for original RCT studies or review/meta-analyses on using water-based and oil-based CM in HSG with fertility outcomes and complications. Nine randomized controlled trials (RCTs) and 10 reviews/meta-analyses were analyzed. Grading of the literature was performed based on the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 classification. RESULTS: An approximately 10% higher pregnancy rate is reported for oil-based CM. Side effects are rare, but oil-based CM have potentially more side effects on the maternal thyroid function and the peritoneum. CONCLUSIONS: 1. HSG with oil-based CM gives approximately 10% higher pregnancy rates. 2. External validity is limited, as in five of nine RCTs, the CM used is no longer on the market. 3. Oil-based CM have potentially more side effects on the maternal thyroid function and on the peritoneum. 4. Guideline: Maternal thyroid function should be tested before HSG with oil-based CM and monitored for 6 months after. CLINICAL RELEVANCE STATEMENT: Oil-based CM is associated with an approximately 10% higher chance of pregnancy compared to water-based CM after HSG. Although side effects are rare, higher iodine concentration and slower clearance of oil-based CM may induce maternal thyroid function disturbance and peritoneal inflammation and granuloma formation. KEY POINTS: • It is unknown which type of contrast medium, oil-based or water-based, is the optimal for HSG. • Oil-based contrast media give a 10% higher chance of pregnancy after HSG, compared to water-based contrast media. • From the safety perspective, oil-based CM can cause thyroid dysfunction and an intra-abdominal inflammatory response in the patient.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences.

Safe use of contrast media in myasthenia gravis: systematic review and updated European Society of Urogenital Radiology Contrast Media Safety Committee guidelines.

OBJECTIVES: It is uncertain whether modern iodine-based or gadolinium-based contrast media (CM) administration can lead to increased symptoms in patients with myasthenia gravis. METHODS: A systematic search in Medline was conducted for studies describing the symptomatology of myasthenia gravis patients before and after receiving intravenous (IV) CM and having a matched control group of myasthenia gravis patients who did not receive IV CM. RESULTS: Three retrospective studies were selected with a total of 374 myasthenia gravis patients who received iodine-based CM and a total of 313 myasthenia gravis patients who underwent unenhanced CT and served as controls. Pooling of the data from the three retrospective studies showed that in 23 of 374 patients, increased symptoms after iodine-based CM administration were described (6.1%). Increased symptomatology also occurred in 11 of 313 patients after unenhanced CT (3.5%). When looking more deeply into the data of the three studies, conflicting results were found, as two articles did not find any relationship between CM and myasthenia gravis symptoms. The remaining study only found a significant increase in symptomatology within 1 day after CT scanning: seven patients (6.3%) in the contrast-enhanced CT group and one patient (0.6%) in the unenhanced CT group (p = 0.01). CONCLUSIONS: There is limited evidence on the relationship between CM and myasthenia gravis symptoms. In the vast majority of myasthenia gravis patients, CM are safe. Probably, in less than 5% of the patients, iodine-based CM administration may lead to increased severity of the symptoms within the first 24 h after administration. CLINICAL RELEVANCE STATEMENT: Be aware that intravenous administration of iodine-based contrast media can lead to an increase of symptoms in patients with myasthenia gravis within the first 24 h. This can probably happen in less than 5% of the patients. KEY POINTS: • It is unclear whether modern contrast media can lead to increased symptoms in myasthenia gravis patients after intravenous administration. • There seems to be a small risk of increased myasthenia gravis symptoms within 24 h after intravenous administration of iodine-based contrast media, probably in less than 5% of the administrations. • Gadolinium-based contrast media are safe for patients with myasthenia gravis.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences. CLINICAL RELEVANCE STATEMENT: Contrast Media may interfere with clinical laboratory tests. Awareness of potential interference may prevent unwanted misdiagnosis. KEY POINTS: • Contrast Media may interfere with clinical laboratory tests; therefore awareness of potential interference may prevent unwanted misdiagnosis. • Clinical Laboratory tests should be performed prior to radiological imaging with contrast media or alternatively, blood or urine collection should be delayed, depending on kidney function.

Intravenous contrast medium extravasation: systematic review and updated ESUR Contrast Media Safety Committee Guidelines.

NEED FOR A REVIEW: Guidelines for management and prevention of contrast media extravasation have not been updated recently. In view of emerging research and changing working practices, this review aims to inform update on the current guidelines. AREAS COVERED: In this paper, we review the literature pertaining to the pathophysiology, diagnosis, risk factors and treatments of contrast media extravasation. A suggested protocol and guidelines are recommended based upon the available literature. KEY POINTS: • Risk of extravasation is dependent on scanning technique and patient risk factors. • Diagnosis is mostly clinical, and outcomes are mostly favourable. • Referral to surgery should be based on clinical severity rather than extravasated volume.

Iodine-based contrast media, multiple myeloma and monoclonal gammopathies: literature review and ESUR Contrast Media Safety Committee guidelines.

OBJECTIVES: Many radiologists and clinicians still consider multiple myeloma (MM) and monoclonal gammopathies (MG) a contraindication for using iodine-based contrast media. The ESUR Contrast Media Safety Committee performed a systematic review of the incidence of post-contrast acute kidney injury (PC-AKI) in these patients. METHODS: A systematic search in Medline and Scopus databases was performed for renal function deterioration studies in patients with MM or MG following administration of iodine-based contrast media. Data collection and analysis were performed according to the PRISMA statement 2009. Eligibility criteria and methods of analysis were specified in advance. Cohort and case-control studies reporting changes in renal function were included. RESULTS: Thirteen studies were selected that reported 824 iodine-based contrast medium administrations in 642 patients with MM or MG, in which 12 unconfounded cases of PC-AKI were found (1.6 %). The majority of patients had intravenous urography with high osmolality ionic contrast media after preparatory dehydration and purgation. CONCLUSIONS: MM and MG alone are not risk factors for PC-AKI. However, the risk of PC-AKI may become significant in dehydrated patients with impaired renal function. Hypercalcaemia may increase the risk of kidney damage, and should be corrected before contrast medium administration. Assessment for Bence-Jones proteinuria is not necessary. KEY POINTS: • Monoclonal gammopathies including multiple myeloma are a large spectrum of disorders. • In monoclonal gammopathy with normal renal function, PC-AKI risk is not increased. • Renal function is often reduced in myeloma, increasing the risk of PC-AKI. • Correction of hypercalcaemia is necessary in myeloma before iodine-based contrast medium administration. • Bence-Jones proteinuria assessment in myeloma is unnecessary before iodine-based contrast medium administration.

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.

PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers. AREAS COVERED IN PART 1: Topics reviewed include the terminology used, the best way to measure eGFR, the definition of PC-AKI, and the risk factors for PC-AKI, including whether the risk with intravenous and intra-arterial contrast medium differs. KEY POINTS: • PC-AKI is the preferred term for renal function deterioration after contrast medium. • PC-AKI has many possible causes. • The risk of AKI caused by intravascular contrast medium has been overstated. • Important patient risk factors for PC-AKI are CKD and dehydration.

Post-contrast acute kidney injury. Part 2: risk stratification, role of hydration and other prophylactic measures, patients taking metformin and chronic dialysis patients : Recommendations for updated ESUR Contrast Medium Safety Committee guidelines.

OBJECTIVES: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers. AREAS COVERED IN PART 2: Topics reviewed include stratification of PC-AKI risk, the need to withdraw nephrotoxic medication, PC-AKI prophylaxis with hydration or drugs, the use of metformin in diabetic patients receiving contrast medium and the need to alter dialysis schedules in patients receiving contrast medium. KEY POINTS: • In CKD, hydration reduces the PC-AKI risk • Intravenous normal saline and intravenous sodium bicarbonate provide equally effective prophylaxis • No drugs have been consistently shown to reduce the risk of PC-AKI • Stop metformin from the time of contrast medium administration if eGFR < 30 ml/min/1.73 m 2 • Dialysis schedules need not change when intravascular contrast medium is given.

Inter-observer variation and diagnostic efficacy of apparent diffusion coefficient (ADC) measurements obtained by diffusion-weighted imaging (DWI) in small renal masses.

BACKGROUND: Diffusion-weighted imaging (DWI) is increasingly used to diagnose renal lesion subtypes. Especially in small renal masses, identification of less aggressive tumor types is of clinical interest, as active surveillance strategies can be applied. PURPOSE: To evaluate the inter-observer variation and diagnostic efficacy of apparent diffusion coefficient (ADC) measurements obtained by DWI in small renal masses ≤4 cm (SRM). MATERIAL AND METHODS: This retrospective IRB-approved study included 39 patients (46 SRM: 12 benign, 34 malignant). All underwent a 3 T DWI of SRM prior to surgery. Two radiologists independently analyzed all imaging data by three measurements. Limits of agreement, intraclass correlation coefficients (ICC), group comparisons by t-tests, and ROC analysis were performed. RESULTS: Reliability of ADC measurements was very high with an ICC of >0.9 for both observers. Inter-rater reliability was high with an ICC of 0.82. Limits of agreement for average ADC values between both observers were -23.5% to 38.3% with a mean difference of 7.5% between both observers. No significant differences were found between benign and malignant lesions (P value Observer 1: 0.362, Observer 2: 0.622). Papillary carcinoma showed lower ADC values compared to non-papillary carcinoma (P value Observer 1: 0.008, Observer 2: 0.012). Consequently, ROC analysis revealed a significant (P < 0.001, respectively) area under the ROC curve of 0.853 (Observer 1) and 0.837 (Observer 2) without significant differences between both readers (P = 0.772). CONCLUSION: ADC measurements of SRM at 3 T show a high reproducibility and differentiate papillary from non-papillary carcinoma subtypes. However, measurement variability may limit the application of fixed ADC thresholds for lesion diagnosis.

Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR Contrast Medium Safety Committee guidelines.

PURPOSE: To update the guidelines of the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) on nephrogenic systemic fibrosis and gadolinium-based contrast media. AREAS COVERED: Topics reviewed include the history, clinical features and prevalence of nephrogenic systemic fibrosis and the current understanding of its pathophysiology. The risk factors for NSF are discussed and prophylactic measures are recommended. The stability of the different gadolinium-based contrast media and the potential long-term effects of gadolinium in the body have also been reviewed.

Late adverse reactions to intravascular iodine based contrast media: an update.

DEFINITION: Late adverse reactions (LAR) to contrast media (CM) are defined as reactions occurring 1 h to 1 week after exposure. NEED FOR REVIEW: In view of more prospective studies of LAR and new data about their pathophysiology, the Contrast Medium Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) reviewed the literature on LAR and updated their guidelines. CLINICAL FEATURES AND PATHOLOGY: LAR after CM include symptoms such as nausea, vomiting, headache, itching, skin rash, musculoskeletal pain, and fever. Skin reactions are well-documented LAR to CM with an incidence of approximately 2%-4% after nonionic monomers. LAR are commoner by a factor of three to four after nonionic dimers. The commonest skin reactions are maculopapular rashes, erythema and skin swelling. These reactions are T cell-mediated immune reactions, and the diagnosis may be confirmed using skin tests (patch or delayed reading intradermal). The main risk factors for LAR are a previous reaction to contrast medium, a history of allergy, and interleukin-2 treatment. Most skin reactions are mild or moderate and self-limiting. MANAGEMENT: Management is symptomatic and similar to the management of other drug-induced skin reactions. To reduce the risk of repeat reactions avoidance of the relevant CM and any cross-reacting agents identified by skin testing is recommended.

Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines.

PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml/min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR ≥ 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally.

Enhancement of liver parenchyma after injection of hepatocyte-specific MRI contrast media: a comparison of gadoxetic acid and gadobenate dimeglumine.

PURPOSE: To compare enhancement of liver parenchyma in MR imaging after injection of hepatocyte-specific contrast media. MATERIALS AND METHODS: Patients (n = 295) with known/suspected focal liver lesions randomly received 0.025 mmol gadoxetic acid/kg body weight or 0.05 mmol gadobenate dimeglumine/kg body weight by means of bolus injection. MR imaging was performed before and immediately after injection, and in the delayed phase at approved time points (20 min after injection of gadoxetic acid and 40 min after injection of gadobenate dimeglumine). The relative liver enhancement for the overall population and a cirrhotic subgroup was compared in T1-weighted GRE sequences. An independent radiologist performed signal intensity measurements. Enhancement ratios were compared using confidence intervals (CIs). RESULTS: The relative liver enhancement in the overall population was superior with gadoxetic acid (57.24%) versus gadobenate dimeglumine (32.77%) in the delayed-imaging phase. The enhancement ratio between the contrast media was statistically significant at 1.75 (95% CI: 1.46-2.13). In the delayed phase, the enhancement of cirrhotic liver with gadoxetic acid (57.00%) was comparable to that in the overall population. Enhancement with gadobenate dimeglumine was inferior in cirrhotic liver parenchyma (26.85%). CONCLUSION: In the delayed, hepatocyte-specific phase, liver enhancement after injection of gadoxetic acid was superior to that obtained with gadobenate dimeglumine.

Comparison of 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine-enhanced MRI in 471 patients with known or suspected renal lesions: results of a multicenter, single-blind, interindividual, randomized clinical phase III trial.

The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers ('average reader') was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI.

Reducing the risk of iodine-based and MRI contrast media administration: recommendation for a questionnaire at the time of booking.

This paper presents a practical questionnaire to be used when a contrast medium examination is requested. The questionnaire is based on the guidelines from the European Society of Urogenital Radiology. Its aim is to identify patients at increased risk of clinically relevant renal and non-renal adverse reactions to iodine-based and MRI contrast agents. The questionnaire should be completed by the referring physician when the examination is requested.

Unenhanced MDCT in patients with suspected urinary stone disease: do coronal reformations improve diagnostic performance?

OBJECTIVE: The objectives of our study were to assess whether coronal reformations improve the diagnostic performance of MDCT in patients with acute flank pain and suspected urinary stone disease; and to determine if performing such reformations from 3-mm-thick sections is sufficient or if it is necessary to perform reformations from thinner sections. MATERIALS AND METHODS: We included 147 consecutive patients (72 women and 75 men; mean age +/- SD, 58 +/- 18.1 years) with suspected urinary stone disease who underwent unenhanced MDCT. Scans were obtained with a 4 x 1 mm collimation and were reconstructed with a section thickness of 1.25 and 3 mm. We compared the diagnostic yield of 3-mm axial sections with that of coronal reformations reconstructed from 1.25- and 3-mm axial sections. Imaging data were evaluated in random order by two radiologists. The significance of the difference between the axial sections and coronal multiplanar reformations (MPRs) was tested for the number, size, and location of uroliths and for the presence of alternative diagnoses. The time required for review by both observers was recorded. RESULTS: We found uroliths in 72 patients. There was no difference between 3-mm axial sections and coronal reformations from 1.25-mm sections with regard to the number of detected stones (n = 264 for both protocols), whereas coronal reformations from 3-mm sections revealed significantly fewer calcifications (n = 255, p = 0.016). Coronal reformations did not improve the localization of calcifications. Review time, however, was significantly shorter for coronal reformations than for axial sections (p = 0.001); however, coronal reformations were less sensitive than axial sections for the detection of additional findings suggestive of alternative diagnoses in 16 (30%) of 53 patients. CONCLUSION: Coronal reformations from MDCT do not improve urinary stone detection but may reduce evaluation time; however, there is the danger of missing additional findings. Coronal reformations reconstructed from thick (i.e., 3-5 mm) axial sections may result in reduced detection of small stones and should therefore be avoided.

Applicability of laparoscopic adrenalectomy in a prospective study in 150 consecutive patients.

HYPOTHESIS: Within a decade, laparascopic adrenalectomy has become the new "gold standard" for the surgical treatment of most adrenal lesions. Designed as a single-center project focused on patients with adrenal lesions, this study should provide an indication of the number of patients requiring surgery who can safely undergo laparoscopy, after consideration of such selection criteria as tumor size and benign or malignant lesion status at magnetic resonance imaging. Furthermore, the access-related complications were analyzed. DESIGN: According to a prospective protocol, 150 consecutive patients selected for adrenal surgery were assigned to transperitoneal endoscopic or open adrenalectomy. SETTING: University hospital section of endocrine surgery. RESULTS: One hundred two patients (68%) were selected for a laparoscopic approach that had to be converted to open surgery in 5 patients (5%). Two malignant cortisol-secreting lesions were operated on laparoscopically because of their small size and benign appearance at magnetic resonance imaging. During histological examination, 14 (29%) of 48 patients assigned to transperitoneal open adrenalectomy had lesions deemed malignant (16 [11%] of 150 patients). The laparoscopic group had significantly fewer complications (9%) than did the open group (21%; P =.04). CONCLUSIONS: By applying defined selection criteria for the treatment of adrenal lesions, transperitoneal endoscopic adrenalectomy can be a safe procedure and may be performed in at least two thirds of patients. The choice of endoscopic or open approach in larger tumors should depend on the results of preoperative imaging studies and the endocrine surgeon's experience in endoscopic adrenal surgery.

Surgical strategy in adrenal masses.

OBJECTIVE: Endoscopic adrenalectomy represents the "New Golden Standard" in the surgical treatment of benign adrenal lesions up to 6 cm. Open adrenalectomy is recommended for patients with suspected malignant disease and tumors larger than 6 cm. METHODS AND MATERIAL: The surgical technique of trans- and retroperitoneal adrenalectomy is described. Reviewing literature the importance of the endoscopic approach and its role in the surgical treatment of adrenal lesions is analyzed. RESULTS: As in open adrenalectomy different endoscopic approaches to the adrenals were developed: adrenal tumors can be removed endoscopically using a transperitoneal (patient in a supine or lateral decubitus position) or extraperitoneal route (patient in a lateral decubitus or prone position). Reviewing literature the endoscopic transperitoneal adrenalectomy is documented in 1425 patients. 4.6% (66 patients) had to be converted to an open procedure. Five hundred and forty-four tumors were removed by an extraperitoneal access. The conversion rate was 4.4% (24 patients). CONCLUSION: The basis of excellent results are careful patient selection, evaluation and preoperative preparation in a center with experience in the open techniques and at least 20 endoscopic adrenalectomies per year.