Renal toxicity evaluation and comparison between visipaque (iodixanol) and hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial.

OBJECTIVES: This study sought to compare the nephrotoxicity of iodixanol and ioxaglate in patients with renal impairment undergoing coronary angiography. BACKGROUND: Iodixanol, a nonionic, dimeric, iso-osmolar contrast medium (IOCM), may be less nephrotoxic than low-osmolar contrast media (LOCM) in high-risk patients. METHODS: In a prospective, randomized trial in 300 adults with creatinine clearance (CrCl) < or =60 ml/min, patients received either iodixanol or ioxaglate and underwent coronary angiography with or without percutaneous coronary intervention. The primary end point was the incidence of contrast-induced nephropathy (CIN) (an increase in serum creatinine [SCr] > or =25% or > or =0.5 mg/dl [> or =44.2 mumol/l]). The incidence of CIN in patients with severe renal impairment at baseline (CrCl <30 ml/min) or diabetes and in those receiving large doses (> or =140 ml) of contrast medium was also determined. RESULTS: The incidence of CIN was significantly lower with iodixanol (7.9%) than with ioxaglate (17.0%; p = 0.021), corresponding to an odds ratio (OR) of CIN of 0.415 (95% confidence interval [CI] 0.194 to 0.889) for iodixanol. The incidence of CIN was also significantly lower with iodixanol in patients with severe renal impairment (p = 0.023) or concomitant diabetes (p = 0.041), or in patients given > or =140 ml of contrast media (p = 0.038). Multivariate analysis identified use of ioxaglate (OR 2.65, 95% CI 1.11 to 6.33, p = 0.028), baseline SCr, mg/dl (OR 2.0, 95% CI 1.04 to 3.85, p = 0.038), and left ventricular ejection fraction, % (OR 0.97, 95% CI 0.94 to 0.99, p = 0.019) as independent risk factors for CIN. CONCLUSIONS: The IOCM iodixanol was significantly less nephrotoxic than ioxaglate, an ionic, dimeric LOCM. (The RECOVER Trial; http://clinicaltrials.gov; NCT00247325).

Serum pancreastatin levels predict response to hepatic artery chemoembolization and somatostatin analogue therapy in metastatic neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors often metastasize to the liver and present with disabling hormonal symptoms. Hepatic artery chemoembolization (HACE) combined with somatostatin therapy, pre-embolization, peri-embolization and post-embolization, at doses to control symptoms, is an aggressive approach that can relieve hormonal symptoms with minimal morbidity and mortality. METHODS: Chemoembolization was performed using 30 mg of adriamycin, 50 mg of mitomycin, 12 ml of hexabrix, 10 ml of ethiodol, and 360-500-microm particles. Pancreastatin, a split product of chromogranin A, was measured pre-HACE and post-HACE in all patients. RESULTS: Forty-three chemoebolization procedures were performed in 34 symptomatic patients from December 1995 to August 1999. Seventeen patients had intestinal primaries (50%), seven had pancreatic primaries (20%), five had bronchial primaries (15%), and five had unknown primaries (15%). Systemic pancreastatin levels were improved or stable in 31 patients (78%). Symptoms were improved in these 31 patients (78%). Systemic serotonin levels were improved or stable in 24 patients (60%). Radiographic improvement or stability was seen in 18 patients (45%). Procedural related morbidity included pain, fevers, nausea, vomiting, and transient elevations of liver function studies in 75-100% of patients. There was one procedural related mortality (2%). Less than 20% improvement in pancreastatin levels from baseline was associated with death in five of five patients (100%). This was not observed with serotonin levels. CONCLUSION: Measurement of serum pancreastatin levels is an easy and useful method to predict success in patients who undergo HACE plus somatostatin therapy for metastatic neuroendocrine tumors to the liver. This therapeutic approach is effective in relieving symptoms in 78% of patients, with minimal major morbidity or mortality.

Current usage of contrast agents, anticoagulant and antiplatelet drugs in angiography and angioplasty in the UK.

Currently, there is no consensus in the UK on what constitutes best angiographic practice. To provide a basis for discussion a questionnaire was sent to all Radiology and Cardiology departments in the UK. Information was requested on practice during diagnostic angiography and angioplasty regarding the type of contrast agent used, whether and how flush solution or contrast agents themselves were heparinised, and whether bolus doses of heparin were administered. The use of other supplementary drugs including corticosteroids was also explored. Two hundred of 353 (57%) of questionnaires were returned. Over 80% who replied used non-ionic contrast agents for all angiographic procedures. The majority of the smaller group, using ionic contrast agents for uncomplicated procedures, resorted to non-ionic contrast agents in a range of circumstances in both diagnostic angiography and angioplasty. Heparinized flush solutions were used by over 75% for both types of angiographic procedures, but employing a wide range of doses. Bolus doses of heparin were administered by over 80% performing angioplasty, again in a wide range of doses, with only (a few) cardiologists monitoring the anticoagulant effect by measuring the activated whole blood clotting time in the angiographic suite. Over 70% used aspirin or dipyridamole as supplementary agents, at the time of the angioplasty and, subsequently, continued these medications for a variable period. Corticosteroid prophylaxis for high risk patients, very variably defined, was felt necessary by 58%. A wide range of regimes of both dose and timing was noted.

Cardiac hemodynamic effects of iodixanol, iopamidol, and ioxaglate following left coronary injections in anesthetized dogs.

RATIONALE AND OBJECTIVES: Iodixanol, a dimeric, nonionic X-ray contrast medium, has been formulated at 320 mg iodine per milliliter and supplemented with Na+, Ca2+, and Cl- to produce an osmolality that approximates that of plasma. We compared the effects of left main coronary artery injections of iodixanol, ioxaglate, and iopamidol on cardiac mechanical function in dogs. METHODS: Six mixed-breed dogs were anesthetized and prepared for recordings for electrocardiogram, aortic and left ventricular pressures, and the first derivative of left ventricular pressure, dP/dt. The test solutions and saline were injected into the left coronary artery in a randomized order. The series of four injections were repeated three times in each animal for a total of 12 injections per dog. RESULTS: Iodixanol caused significantly lower (p < .05) reduction in peak left ventricular pressure (-1.7 +/- 0.9% vs -0.7 +/- 2.0%), in diastolic aortic pressure (-1.3 +/- 1.1% vs -9 +/- 1.3%), and in left ventricular dP/dt (0.3 +/- 1.3% vs -13.2 +/- 2.4%) than did ioxaglate. Iodixanol also produced smaller cardiovascular effects than did iopamidol, but the differences were not statistically significant. Injections of both iopamidol and ioxaglate caused significant decreases from baseline parameter values; however, the changes with iodixanol were not significant. CONCLUSION: The isotonic formulation of iodixanol caused smaller cardiovascular hemodynamic effects than did iopamidol and ioxaglate and may offer increased safety in patients with severe cardiac disease.

Selective injection of contrast media: inflammatory effects on rabbit fallopian tubes.

The inflammatory effects of fallopian tube catheterization and selective injection of seven contrast agents (ethiodized oil, diatrizoate meglumine 52%, diatrizoate meglumine 66%, iothalamate meglumine 60%, iopamidol, ioxitol, and ioxaglate) were evaluated in 88 rabbits. The contrast agent used was randomly selected and selectively injected after unilateral catheterization; the contralateral side was used for control. Pathologic inspection of right and left uteri with attached fallopian tubes and ovaries was done without knowledge of side of catheterization or duration of time since catheterization. The degree and location of inflammation were noted. Inflammation disappeared by 4 days in five of seven contrast agents. Iothalamate meglumine 60% and iopamidol required 2 weeks for disappearance of inflammation. Essentially no inflammation was associated at any time with ioxaglate. These findings suggest that all of these contrast agents would be clinically acceptable for direct injection into the human fallopian tube.

Systemic, pulmonary and renal haemodynamic effects of large intravenous doses of high and low osmolar contrast media. An investigation in the pig of ratio 1.5 and ratio 3 media.

The central, peripheral and renal haemodynamic effects of intravenous infusion (1 ml/s) of large doses (4 ml/kg body weight) of non-ionic (iohexol) and ionic (metrizoate and ioxaglate) contrast media were studied in 24 anaesthetized pigs. All contrast media showed marked haemodynamic effects with an increase of mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary occlusion pressure, cardiac output and stroke volume. The response of the pulmonary circulation to contrast media was a fall rather than a rise in pulmonary vascular resistance. No significant changes were detected in the renal circulation after infusion of contrast media.

Incompatibility of contrast agents with intravascular medications. Work in progress.

In vitro and in vivo precipitation of iodinated contrast agents when ioxaglate and papaverine are given together has been reported. To verify these reports and to investigate other medications not previously tested, the authors analyzed mixtures of contrast agents and medications in vitro with a light spectrophotometer and observed them for visible precipitates for up to 120 minutes. Previously reported incompatibilities between ionic or low-osmolality contrast media and medications were verified, and several new incompatibilities were discovered. No incompatibilities were found when the drugs tested were mixed with the new nonionic contrast media.

High-dose clinical urography with the low-osmolality contrast agent Hexabrix: comparison with a conventional contrast agent.

A double-blind clinical trial was performed in 60 patients to compare Hexabrix (ioxaglate meglumine and ioxaglate sodium) and Renografin-60 (diatrizoate meglumine and diatrizoate sodium). Use of Hexabrix produced higher urinary iodine concentrations, lower urine volumes at 30 minutes, and excretory urograms significantly better in diagnostic quality, as rated by four independent observers. There was no difference in nephrogram quality between contrast agents. Patients receiving Hexabrix had less of an increase in heart rate and demonstrated a slight rise in mean arterial blood pressure, rather than the biphasic rise then fall seen with Renografin-60. There was no significant change for up to 96 hours after urography in results of hematology, clinical chemistry, or urinalysis, except for an increase of 0.005 in urine specific gravity with Renografin-60. Patients reported significantly less body heat, heat in the injection arm, and overall discomfort with Hexabrix. There was a similar amount of nausea and vomiting in the two groups. Hexabrix also caused histaminic-type reactions in three patients.