Can Iodixanol Prevent Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis? A Prospective, Randomized, Controlled Trial.

BACKGROUND: It is yet not clear whether differences in the contrast medium may affect post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). AIM: The aim of this study was to evaluate the rate of PEP between high osmolality contrast medium (HOCM) and iso osmolar medium (IOCM) in a prospective, randomized, controlled trial. METHODS: Patients who were scheduled to undergo a diagnostic or therapeutic procedure under ERCP guidance were included. Patients were excluded from this study if they (1) were < 20 years old; (2) had acute or active pancreatitis; (3) had previously undergone ERCP; (4) had surgical altered upper gastrointestinal tract anatomy; or (5) refused to be involved in this study. RESULTS: Seventy-five patients were randomly assigned to the IOCM group, and 71 patients were assigned to the HOCM group. PEP occurred in 27 patients (18.5%). Although there were no significant differences, the severe grade of PEP was more frequent in the HOCM group than in the IOCM group (p = 0.08). The results of the multivariate analyses for PEP were not identified as independent risk factors. Also, independent risk factors of hyperamylasemia were performing pre-cut. In subgroup analyses, HOCM was an independent risk factor for hyperamylasemia. CONCLUSIONS: In conclusion, HOCM may play a role in the development of PEP and in PEP severity grade.

Iodixanol versus Iopromide at Coronary CT Angiography: Lumen Opacification and Effect on Heart Rhythm-the Randomized IsoCOR Trial.

Purpose To show that equal coronary lumen opacification can be achieved with iso- and low-osmolar contrast media when it is injected at the same iodine delivery rate with contemporary cardiac computed tomographic (CT) protocols and to investigate the cardiovascular effect of iso-osmolar contrast media and the image quality achieved. Materials and Methods Institutional review board approval and written informed consent were obtained for the Effect of Iso-osmolar Contrast Medium on Coronary Opacification and Heart Rhythm in Coronary CT Angiography, or IsoCOR, trial. Between November 2015 and August 2016, 306 patients (167 [55%] women) at least 18 years old (weight range, 50-125 kg), were prospectively randomized to receive iso-osmolar iodixanol 270 or low-osmolar iopromide 300 contrast media. All coronary segments were assessed for intraluminal opacification and image quality and were compared by using the Student t test. Heart rate, arrhythmia, patient discomfort, and adverse events also were monitored. Results Mean measured coronary attenuation values ± standard deviation were comparable between the iodixanol 270 and iopromide 300 contrast media groups (469 HU ± 167 vs 447 HU ± 166, respectively [P = .241]; 95% confidence interval: -15.1, 60.0), including those from subanalyses. Adjusted for the lower iodine concentration, the mean iodixanol 270 bolus was larger compared with that of iopromide 300 (76.8 mL ± 11.6 vs 69.7 mL ± 10.8, respectively; P < .001). The higher injection rate was associated with higher pressure (777 kPa ± 308 vs 630 kPa ± 252, respectively; P < .001). Although in the iodixanol 270 group patients experienced less heat discomfort (72% vs 86%, respectively; P < .001), no differences in heart rate or rhythm were observed. Conclusion If injected at comparable iodine delivery rates, the iso-osmolar contrast medium iodixanol 270 is not inferior to low-osmolar contrast medium iopromide 300 for assessment of coronary opacification. Iodixanol 270 was associated with less heat discomfort, but did not affect heart rate differently compared with iopromide 300. © RSNA, 2017 Online supplemental material is available for this article.

Is Intravenous Administration of Iodixanol Associated with Increased Risk of Acute Kidney Injury, Dialysis, or Mortality? A Propensity Score-adjusted Study.

Purpose To compare the rates of acute kidney injury (AKI), emergent dialysis, and short-term mortality between patients who underwent intravenous administration of the iso-osmolar contrast material (IOCM) iodixanol 320 and patients who underwent a noncontrast computed tomography (CT) examination. Materials and Methods Study design and implementation were overseen by an institutional review board and conformed to HIPAA guidelines on patient data integrity. All patients who underwent an iodixanol-enhanced (IOCM group) or a noncontrast (noncontrast group) CT examination from January 2003 to December 2014 were identified. Patients were subdivided into subgroups of those with stage 1-2 chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR], ≥ 60 mL/min/1.73 m2), those with stage 3 CKD (eGFR, 30-59 mL/min/1.73 m2), and those with stage 4-5 CKD (eGFR < 30 mL/min/1.73 m2) and separately underwent propensity score stratification and matching. Rates of AKI, emergent dialysis, and mortality were compared between IOCM and noncontrast groups. Additional analyses incorporating intravenous fluid administration, including additional CT studies at other sites within a single institution, and a paired analysis of patients who underwent both IOCM and noncontrast CT studies during the study time frame, were also performed. Results A total of 5758 patients (1538 with stage 1-2 CKD, 2899 with stage 3 CKD, and 1321 with stage 4-5 CKD) were included in the study. After propensity score adjustment, rates of AKI, dialysis, and mortality were not significantly higher in the IOCM group compared with the noncontrast group for all CKD subgroups (AKI odds ratios [ORs], 0.74-0.91, P = .16-0.69; dialysis ORs, 0.74-2.00, P = .42-.76; mortality ORs, 0.98-1.24, P = .39-.88). Sensitivity analyses yielded similar results. Conclusion Among patients at the highest perceived risk of postcontrast AKI, intravenous administration of iodixanol for contrast material enhanced CT was not an independent risk factor for AKI, dialysis, or mortality. © RSNA, 2017 Online supplemental material is available for this article.

Bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels for targeted X-ray computed tomography imaging and chemotherapy of breast tumors.

Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of 'personalized medicine'. Here, we designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90nm, bright green fluoresence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. Notably, paclitaxel (PTX)-loaded HAI-NGs showed a fast glutathione-responsive drug release. Confocal microscopy displayed efficient uptake of HAI-NGs by CD44 overexpressing MCF-7 cells via a receptor-mediated mechanism. MTT assays revealed that HAI-NGs were nontoxic to MCF-7 cells even at a high concentration of 1mg/mL whereas PTX-loaded HAI-NGs exhibited strong inhibition of MCF-7 cells. The in vivo pharmcokinetics, near-infrared imaging and biodistribution studies revealed that HAI-NGs significantly prolonged the blood circulation time and enhanced tumor accumulation of PTX. Interestingly, significantly enhanced CT imaging was observed for MCF-7 breast tumors in nude mice via either intratumoral or intravenous injection of HAI-NGs as compared to iodixanol. HAI-NGs fluoresence was distributed thoughout the whole tumor indicating deep tumor penetration. PTX-loaded HAI-NGs showed effective suppression of tumor growth with little systemic toxicity. HAI-NGs appear as a "smart" theranostic nanoplatform for the treatment of CD44 positive tumors.

The incidence and significance of acute kidney injury following emergent contrast administration in patients with STEMI and stroke.

The authors have investigated the incidence of acute kidney injury (AKI) and short-term mortality following an activated STEMI and stroke alert at a tertiary referral and academic center. A single center, retrospective chart review of STEMI and stroke activation patients from January 2010 to March 2012. Data was collected and reviewed from an institutional database following IRB-approval. Inclusion criteria were STEMI patients taken for cardiac catheterization, excluding patients receiving hemodialysis due to end-stage renal disease (ESRD). Primary outcome measures were the incidence of AKI using the RIFLE criteria and short-term mortality. 745 patients were included (488 stroke, 257 STEMI). The median age was 65, and 39 % were female. Overall inpatient mortality was 7.0 %. 5.4 % (40/745) of patients experienced some degree of AKI (8.6 % of STEMI, 3.7 % of stroke patients). Overall, 30 % of patients with AKI died during their hospitalization. AKI was associated with a 7.1-fold (95 % CI 3.4-15.1) increase in mortality in the entire cohort. Among STEMI patients, AKI was associated with a 66.6-fold (95 % CI 12.9-343.4) increase in mortality. These findings follow similar trends published among critically ill patients with AKI. The risk of death with concomitant AKI in this hospital population is significant and deserves future study. Early recognition and awareness in the emergency department is paramount to the patient's survival. Future studies should focus on modalities to improve early recognition and preventative therapies.

Stereotactic radiofrequency ablation (SRFA) of liver lesions: technique effectiveness, safety, and interoperator performance.

PURPOSE: To evaluate technique effectiveness, safety, and interoperator performance of stereotactic radiofrequency ablation (SRFA) of liver lesions. METHODS: Retrospective review including 90 consecutive patients from January 2008 to January 2010 with 106 computed tomography-guided SRFA sessions using both single and multiple electrodes for the treatment of 177 lesions: 72 hepatocellular carcinoma (HCC) and 105 metastases with a mean size of 2.9 cm (range 0.5-11 cm). Technique effectiveness and 1-year local recurrence were evaluated by computed tomographic scans. Complications, mortality, and hospital days were recorded. The performance between an experienced and inexperienced interventional radiologist was compared. RESULTS: The overall technique effectiveness after a single SRFA was 95.5% (93.1% for HCC and 97.1% for metastases). Four of the eight unsuccessfully treated lesions could be retreated (secondary technique effectiveness of 97.7%). Local recurrence at 1 year was 2.9%. Technique effectiveness was significantly different for lesions<5 cm (96.7%) and >5 cm (87.5%) (P=0.044) but not for lesions<3 cm (95.9%) and 3-5 cm (100%). Compared to clear parenchymal property (97.3%), vessel vicinity (93.3%) (P=0.349) and subcapsular (95.2%) (P=0.532) had no, but hollow viscera vicinity (83.3%) had a significantly lower technique effectiveness (P=0.020). Mortality rate was 0.9%. Major complications and hospital days were higher for cirrhosis Child-Pugh B (20%, 7.2 days) than Child-Pugh A (3.1%, 4.7 days) patients and for metastases (5.1%, 4.3 days). There was no significant difference in interoperator performance. CONCLUSION: SRFA allowed for efficient, reliable, and safe ablation of large-volume liver disease.

Nonionic iodinated intravenous contrast material-related reactions: incidence in large urban children's hospital--retrospective analysis of data in 12,494 patients.

PURPOSE: To examine the incidence and severity of nonionic intravenous contrast material reactions in a large pediatric patient population. MATERIALS AND METHODS: Electronic records on all consecutive patients at a tertiary care pediatric hospital who received ioversol contrast material over a 7-year period for computed tomographic or excretory urographic studies were reviewed, yielding individual contrast material injection events in 12,494 patients up to 21 years of age. There were 6600 male patients and 5894 female patients. Contrast material reactions were categorized as mild, moderate, or severe according to American College of Radiology guidelines. Logistic regression analysis was performed to evaluate effects of age, sex, season, and study year on the presence of an intravenous contrast material reaction. RESULTS: There were 57 adverse events related to nonionic iodinated intravenous contrast material in 12,494 consecutive pediatric and young adult patients. Incidence of a contrast material reaction was 0.46% (57 of 12,494), or one in 200 patients. Incidence of a type I (mild) contrast material reaction was 0.38% (47 of 12,494), or one in 250 patients. Incidence of a type II (moderate) reaction was 0.08% (10 of 12,494), or one in 1000 patients. There were no severe (type III) reactions. The average age of patients with a contrast material reaction (12.9 years +/- 4.3 [standard deviation]) was 3.4 years older (P < .001) than the average age of all patients in the study (9.5 years +/- 5.9). There was a significant relationship between patient age and incidence of contrast material reaction per 1000 studies (P = .003), independent of sex, season, and year of study. CONCLUSION: Adverse reactions to intravenous administration of a nonionic contrast material (ioversol) are rare in children and increase in frequency with advancing age. The great majority of reactions in children are mild.

Contrast enhancement hyperdensity after endovascular coiling of intracranial aneurysms.

BACKGROUND AND PURPOSE: Endovascular coil embolization is used increasingly to treat cerebral aneurysms. The purpose of our study was to quantify the incidence of CT-detectable abnormalities after aneurysm coiling and map the radiographic and clinical progression. MATERIALS AND METHODS: We reviewed the radiographic and clinical sequelae of 30 consecutive patients with aneurysms who underwent endosaccular coiling followed by head CT scans. Patients with CT abnormalities received follow-up scans at 4 to 6 hours and 20 to 25 hours. Contrast enhancement was defined as CT hyperdensities with progressive resolution over 25 hours and a Hounsfield unit (HU) of less than 70. The incidence of CT abnormalities was recorded and correlated with amount of contrast used, use of antiplatelet agents, procedure time, and clinical sequelae. RESULTS: Seven patients (23%) had new hyperdensities on CT scan. Four showed gyral hyperattenuation; 1 showed basal ganglia hyperattenuation, and 2 showed a combination of these patterns. All were asymptomatic and were consistent with contrast enhancement, with complete resolution in 5 of 7 and partial resolution in 2 of 7 by 20 to 25 hours. Antithrombotic or antiplatelet medication was continued in all cases. The amount of contrast used (P = .014) and the use of antiplatelet medication (P = .029) were statistically correlated with the presence of hyperattenuation after aneurysm coiling, whereas the length of the procedure was not (P = .162). CONCLUSION: Contrast enhancement, unlike contrast extravasation, is a fairly common and clinically benign finding after aneurysm coiling. The enhancement resolves by 25 hours in most cases, regardless of the continuation of antithrombotic or antiplatelet therapy.

Recent clinical trials of iodixanol.

In patients with well-preserved renal function, the choice of contrast agent appears to have little impact on the development of contrast-induced nephropathy (CIN). However, in patients with underlying renal insufficiency and diabetes mellitus, it has been shown that the use of low-osmolar media is associated with a lower incidence of CIN compared with high-osmolar agents. Previously, it was unknown whether further benefit would be derived from the use of iso-osmolar contrast media. Recent studies, including Nephrotoxicity in High-Risk Patients Study of Iso-osmolar and Low-Osmolar Nonionic Contrast Media (NEPHRIC), have shown a reduction in the incidence of CIN with the iso-osmolar contrast agent iodixanol compared with low-osmolar agents in patients with renal insufficiency and diabetes. The peak rise in serum creatinine was significantly reduced with iodixanol (0.13 mg/dL vs 0.55 mg/dL, P <.001). The incidence of CIN, defined as a peak rise > 0.5 mg/dL, was decreased from 26% to 3%, P <.0002 when iodixanol was used. An ongoing, multicenter, prospective, double-blind, randomized study (Visipaque Angiography/Interventions with Laboratory Outcomes for Renal Insufficiency [VALOR]) is evaluating the potential benefit of iodixanol in reducing CIN in patients with preexisting renal impairment. Accumulating evidence suggests that the use of iso-osmolar contrast agents in conjunction with other proven measures, especially adequate intravenous hydration and contrast dosage limitation, can reduce the morbidity and mortality associated with CIN. These measures have the potential for a significant reduction in health care costs.

A randomized prospective trial of ioxaglate 320 (Hexabrix) vs. iodixanol 320 (Visipaque) in patients undergoing percutaneous coronary intervention.

We performed a randomized, prospective, double blind trial comparing the use of the ionic dimer contrast agent ioxaglate 320 (Hexabrix) with the nonionic dimer contrast agent iodixanol 320 (Visipaque) in 618 patients undergoing percutaneous coronary intervention (PCI) for stable or unstable coronary artery syndromes. The aim was to determine whether the different anticoagulant and antiplatelet properties of these two contrast agents resulted in a significant difference in the incidence of a combined endpoint comprising the major complications of PCI. Procedural success rates were marginally higher in the Visipaque group compared to the Hexabrix group, although this did not reach statistical significance (96.7% vs. 93.9%; P = 0.09). There was a borderline statistically significant higher requirement for bailout stenting in the Visipaque group compared to the Hexabrix group (6.8% vs. 3.2%; P = 0.05), although this was not a predefined endpoint. The incidence of the combined primary endpoint of failed catheter laboratory outcome/requirement for bailout stenting/requirement for abciximab/myocardial infarction/death before hospital discharge was higher in the Visipaque group compared to the Hexabrix group (17.9% vs. 14.8%), although this did not reach statistical significance (P = 0.29). When subgroup analysis was performed, the incidence of the combined endpoint in patients with stable coronary artery disease randomized to receive either Visipaque or Hexabrix was identical (13.7%). In patients with an acute coronary syndrome, there was a trend toward a reduced incidence of the combined endpoint in the Hexabrix compared to the Visipaque group, although this did not reach statistical significance (17.2% vs. 24.8%; P = 0.17). More adverse reactions occurred in the Hexabrix group compared to the Visipaque group (8.7% vs. 4.9%; P = 0.06). We conclude that there is no clear advantage with the use of an ionic contrast agent in a large population of patients undergoing PCI for both stable and unstable coronary artery disease. Although the study was underpowered to detect significant differences with the use of either agent when patients with either stable or unstable coronary disease were studied, it is highly unlikely that the ionicity of the contrast agent confers any advantage for patients with stable coronary disease. There remains a possibility that ionic agents do have advantages for patients with unstable coronary artery disease undergoing PCI, although a larger study than ours would be required to confirm or refute this.

Antithrombotic effects of ionic and non-ionic contrast media in nonhuman primates.

Thromboembolic complications have been attributed to the use of radiographic contrast media (CM) during interventional procedures for arterial revascularization. However, due to the low frequency of adverse events, comparisons between different CM have been difficult to perform, although it has been suggested that ionic (vs. non-ionic) CM may be associated with fewer thrombotic events. The present study was undertaken using well-characterized baboon thrombosis models in order to compare different CM under physiologically relevant and controlled conditions of blood flow, exposure time, and CM concentration. Three CM were studied: ioxaglate, iohexol, and iodixanol. CM were locally infused into the proximal segment of femoral arteriovenous shunts. Palmaz-Schatz stents (4 mm i.d.) and expanded tubular segments (9 mm i.d.), which exhibited venous-type flow recirculation and stasis, were deployed into the shunts distally. Saline was infused in identical control studies. Blood flow was maintained at 100 ml/min. Thrombosis was measured over a blood exposure period of 2 hours by gamma camera imaging of 111In-platelets and by gamma counting of deposited 125I-fibrin. CM concentrations within the flowfield were predicted using computational fluid dynamics. At infusion rates of 0.1 and 0.3 ml/min, the low-osmolar ionic CM ioxaglate reduced both platelet and fibrin deposition on the stents by 75-80% (p <0.005), while both iohexol and iodixanol reduced platelet deposition by 30-50% (p <0.05). In the regions of low shear flow, ioxaglate (0.3 ml/min) also reduced platelet deposition significantly (by 52% vs. control results; p <0.05). Thus the three agents evaluated--ioxaglate, iohexol, and iodixanol--all produced anticoagulant and antiplatelet effects and were inherently antithrombotic in vivo. The most striking effects were seen with the low osmolarity, ionic contrast agent ioxaglate.

Influence of a nonionic, iso-osmolar contrast medium (iodixanol) versus an ionic, low-osmolar contrast medium (ioxaglate) on major adverse cardiac events in patients undergoing percutaneous transluminal coronary angioplasty: A multicenter, randomized, double-blind study. Visipaque in Percutaneous Transluminal Coronary Angioplasty [VIP] Trial Investigators.

BACKGROUND: The potential merits and disadvantages of the use of ionic or nonionic contrast media in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) have been the subjects of controversy. The present study was designed to evaluate the possible influence of both types of contrast media on major adverse cardiac events (MACE) in patients undergoing PTCA. METHODS AND RESULTS: In a randomized, parallel-group, double-blind study, 1411 patients received either iodixanol (a nonionic, iso-osmolar contrast medium) or ioxaglate (an ionic, low-osmolar contrast medium) during PTCA. A standardized anticoagulation regimen was followed. Patients were monitored in the hospital for 2 days and followed-up at 1 month. The primary end point, a composite of MACE (death, stroke, myocardial infarction, coronary artery bypass grafting, and re-PTCA) after 2 days, occurred in 4.3% of the total population, with no statistically significant difference between groups (iodixanol, 4.7%; ioxaglate, 3.9%; P=0.45). Further, between 2-day and 1-month follow-ups, no significant difference (P=0.27) existed between the groups in the rates of MACE. Hypersensitivity reactions (P=0.007) and adverse drug reactions (P=0.002) were significantly less frequent in the iodixanol group. The only significant predicting factors for the occurrence of MACE were dissection/abrupt closure and country. CONCLUSIONS: No significant differences were observed between the iodixanol and ioxaglate groups with regard to MACE, although hypersensitivity and adverse drug reactions were significantly less frequent in patients who received iodixanol.

Iodixanol. A review of its pharmacodynamic and pharmacokinetic properties and diagnostic use as an x-ray contrast medium.

Iodixanol is an iso-osmolal nonionic dimeric hydrophilic contrast agent. It has similar diagnostic efficacy to that of other iodinated contrast media. Because of its physical properties, iodixanol would be expected to produce a lower incidence of adverse events than other nondimeric contrast media. Indeed, pharmacodynamic studies indicate that iodixanol has fewer cardiovascular effects, causes less renal damage and is associated with similar or smaller changes to the blood-brain barrier and neurological function when compared with nondimeric nonionic contrast media. In clinical trials, iodixanol had a similar tolerability profile to other nonionic contrast media but induced fewer adverse events than ioxaglate. Iodixanol appears to have an advantage over other contrast media in that it generally causes less frequent and less intense discomfort on injection. However, in common with other newer, and usually nonionic, contrast media, iodixanol is expensive. Studies investigating other nonionic contrast media (but not iodixanol) have shown that it is not cost-effective in all patients to replace older, usually ionic, contrast media with the more costly newer alternatives. Nonetheless, in selected patients who are considered at increased risk of contrast medium-associated adverse events, nonionic agents should be used. Iodixanol, with its lower intensity (and possibly frequency) of discomfort, may be a preferred option in these patients.

Polysorbate 80 and low-osmolality water-soluble contrast medium enema in diagnosis and treatment of faecal obstruction in malignant phaeochromocytoma. Report of a case.

Stercoral obstruction in a young woman with disseminated phaeochromocytoma was diagnosed and treated successfully using an enema of isosmolar iohexol (Omnipaque) and 1% polysorbate 80 (Tween 80) without complication. Surgical intervention was thus avoided. A low osmolality water-soluble contrast medium (iohexol 150 mg I/ml) with a wetting agent (1% Tween 80) was used because a barium suspension would have inspissated, exacerbating the constipation and a hyperosmolar contrast medium might have precipitated a hypertensive crisis and destabilized her critical salt and water balance.