Nephrotoxicity of iso-osmolar iodixanol compared with nonionic low-osmolar contrast media: meta-analysis of randomized controlled trials.

PURPOSE: To compare the nephrotoxicity of iso-osmolar iodixanol with that of nonionic low-osmolar contrast media (CM) (LOCM) in randomized clinical trials. MATERIALS AND METHODS: This meta-analysis was conducted with a systematic search of MEDLINE, EMBASE, BIOSIS, Web of Science, ISI Web of Knowledge, Current Contents Medizin, Cochrane Library (until August 2007), trial registers, conference proceedings, and reference lists to identify studies and with requests from all manufacturers of CM for unidentified studies. Randomized controlled trials assessing serum creatinine levels before and after intravascular application of iodixanol or LOCM were included. The primary outcome measures were the incidence of contrast medium-induced nephropathy (CIN) and change in serum creatinine levels. RESULTS: Twenty-five trials were included. Iodixanol did not significantly reduce the risk of CIN (relative risk [RR], 0.80; 95% confidence interval [CI]: 0.61, 1.04; weighted mean difference in serum creatinine increase, 0.01 mg/dL [0.88 mumol/L]; 95% CI: -0.01, 0.03). There was no significant risk reduction after intravenous administration of the CM (RR, 1.08; 95% CI: 0.62, 1.89); subgroup with preexisting renal insufficiency (RR, 1.07; 95% CI: 0.56, 2.02) or after intraarterial administration (RR, 0.68; 95% CI: 0.46, 1.01); subgroup with preexisting renal insufficiency (RR, 0.59; 95% CI: 0.33, 1.07). However, in patients with intraarterial administration and renal insufficiency, the risk of CIN was greater for iohexol than for iodixanol (RR, 0.38; 95% CI: 0.21, 0.68), whereas there was no difference between iodixanol and the other (noniohexol) LOCM (RR, 0.95; 95% CI: 0.50, 1.78). CONCLUSION: Iodixanol is not associated with a significantly reduced risk of CIN compared with the LOCM pooled together. However, in patients with intraarterial administration and renal insufficiency, iodixanol is associated with a reduced risk of CIN compared with iohexol, whereas no significant difference between iodixanol and other LOCM could be found.

Peripheral intravenous power injection of iodinated contrast media: the impact of temperature on maximum injection pressures at different cannula sizes.

RATIONALE AND OBJECTIVES: Modern computed tomographic scanners and examination protocols often require high injection rates of iodinated contrast media (CM). The purpose of this study was to investigate the maximum injection pressures (MIPs) with different CM at different temperatures in the most common intravenous cannula (IVC) sizes. MATERIALS AND METHODS: Three IVC sizes, 22, 20, and 18 gauge, were evaluated. All examinations were performed with a pressure-limited (300 psi) power injector. The MIPs of three different CM (Solutrast 300, Imeron 350, and Imeron 400) were measured at room temperature (20 degrees C) and at 37 degrees C using increasing flow rates (1-9 mL/s). The intactness of the IVCs was checked after injection. RESULTS: Heating the CM led to reductions in injection pressures (P < .001). Using constant flow rates, the difference in MIP between 20-gauge and 22-gauge IVCs was higher than that between 20-gauge and 18-gauge IVCs. By heating the CM, the manufacturer's suggested operating pressure limit was exceeded at higher flow rates, such as with an 18-gauge cannula at 8 mL/s instead of 6 mL/s using warmed iomeprol 400. Even with pressures of up to 159.7 psi, none of the IVCs ruptured. CONCLUSIONS: Heating of CM effectively reduces MIPs using power injection in common IVCs. Although the manufacturer's suggested MIP was exceeded at higher flow rates, safe CM injection seems to be possible even in small cannulas using power injection. The compilation of the obtained data is meant to serve as guidance for future decisions on parameters of the power injection of iodinated CM.

Cytotoxicity of iodinated and gadolinium-based contrast agents in renal tubular cells at angiographic concentrations: in vitro study.

PURPOSE: To test in vitro whether gadolinium-based contrast agents induce fewer toxic effects on renal tubular cells than does an iodinated contrast medium at concentrations used for angiography. MATERIALS AND METHODS: LLC-PK1 cells were incubated with iomeprol, gadopentetate dimeglumine, gadobenate dimeglumine, gadoterate meglumine, gadodiamide, and corresponding mannitol solutions for 24 hours at 37 degrees C in two experimental settings: measurements with equally attenuating solutions and measurements with equimolar solutions. Cytotoxicity was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, trypan blue testing, and an assay to detect apoptosis and necrosis. Data were analyzed with analyses of variance and post hoc tests. RESULTS: Yielding the same x-ray attenuation, iomeprol-300 and iomeprol-150 at concentrations of 2.34-18.75 mg of iodine per milliliter induced significantly (P < .001) lower inhibition of MTT conversion (74%-102% of undamaged control cells) compared with 15.63-125.00 mmol/L concentrations of the gadolinium-based agents (mean percentages of undamaged control cells: 48%-80%, 50%-87%, 60%-95%, and 56%-92% with gadopentetate dimeglumine, gadobenate dimeglumine, gadoterate meglumine, and gadodiamide, respectively). At equimolar concentrations (62.5 mmol/L), iomeprol-190 induced a mean extent of inhibition of MTT conversion (69% of undamaged control cells) similar to that induced by gadoterate meglumine (71%) and gadodiamide (70%), whereas gadopentetate dimeglumine and gadobenate dimeglumine induced stronger effects (63% and 64%, respectively; P < .001). At trypan blue testing, there were more dead cells after incubation with 125 mmol/L gadopentetate dimeglumine than after incubation with iomeprol-190 (57% vs 19%, P < .001). The 125 mmol/L gadopentetate and gadobenate formulations induced more necrosis and apoptosis than did gadoterate meglumine, gadodiamide, and iomeprol (mean percentage difference between treated and untreated control cells: for necrosis, +124%, +95%, +17%, -6%, and +3%, respectively; for apoptosis, +34%, +35%, +13%, +4%, and +5%, respectively; P < .001). CONCLUSION: At angiographic concentrations, gadolinium-based contrast agents do not induce fewer cytotoxic effects on cultured renal tubular cells than does iomeprol.

Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro.

PURPOSE: To compare the cytotoxic effects of dimeric and monomeric iodinated contrast media on renal tubular cells in vitro with regard to osmolality. MATERIALS AND METHODS: LLC-PK1 cells were incubated with ioxithalamate, ioversol, iomeprol-300, iomeprol-150, iodixanol, iotrolan, and hyperosmolar mannitol solutions for 1-24 hours at concentrations from 18.75 to 150 mg of iodine per milliliter. Cytotoxic effects were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Data were analyzed with one-way analysis of variance; post hoc tests were performed. RESULTS: At equal iodine concentrations, ioxithalamate showed stronger cytotoxic effects than did other contrast media (MTT conversion for ioxithalamate was 4% vs that for ioversol of 32%, that for iomeprol-300 of 34%, that for iodixanol of 40%, and that for iotrolan of 41% of undamaged control cells at 75 mg of iodine per milliliter, n = 61-90, P < .001); there was no significant difference between low-osmolar monomeric and iso-osmolar dimeric contrast media (P > .05). At equal molarity, dimeric contrast media induced significantly stronger cytotoxic effects than did low-osmolar monomeric contrast media (40% for iodixanol and 41% for iotrolan vs 64% for ioversol and 59% for iomeprol-300 at 98.5 mmol/L, n = 61-75, P < .001). At equimolar concentrations, both dimeric contrast media showed stronger cytotoxic effects than did iso-osmolar formulation of iomeprol-150 (51% for iodixanol and 50% for iotrolan vs 77% for iomeprol-150 at 98.5 mmol/L, n = 35-40, P < .001). Mannitol solutions induced weaker cytotoxic effects than did corresponding contrast media compounds (74% for mannitol-520 vs 34% for iomeprol-300 and 41% for mannitol-1860 vs 4% for ioxithalamate, P < .001). CONCLUSION: Besides hyperosmolality, direct cytotoxic effects of contrast media molecules contribute to their cytotoxic effects. Results of this study indicate that dimeric contrast media molecules have a greater potential for cytotoxic effects on proximal renal tubular cells in vitro than do monomeric contrast media molecules.