Effect of iohexol and diatrizoate on pulmonary arterial pressure following pulmonary angiography. A clinical comparison in man

A clinical comparison of the effects on pulmonary arterial pressure produced by iohexol and diatrizoate, following selective pulmonary angiography, was made in 17 patients with a normal pressure before the injection of the contrast medium. A double blind crossover study was performed and each contrast medium was administered in random order. The pulmonary arterial pressure was continuously recorded before, during and after the injection for 3 minutes. The effect of iohexol on the pulmonary arterial pressure was significantly less than that of diatrizoate. The results indicated that iohexol should be better tolerated than diatrizoate and therefore a safer contrast medium for selective pulmonary angiography.     

Comparison of iohexol 300 mg I/ml and Hexabrix 320 mg I/ml in central angiography

Summary Iohexol 300 mg I/ml and Hexabrix 320 mg I/ml have been compared in a randomized, double blind, parallel study, to evaluate hemodynamic parameters, diagnostic information and adverse reactions. A total of 55 patients entered the study, one of them was later excluded, bacause both contrast media were given by mistake. In the included material, 21 patients were given iohexol 300 mg I/ml in 55 selective injections and 23 patients Hexabrix 320 mg I/ml in 65 selective injections. The median total dose was 52 (12–88) ml in the iohexol group and 51 (13–118) ml in the Hexabrix group. No changes in heart rate were seen. Angiograms of good or excellent quality were obtained, and no difference between the two media was shown. No serious adverse reaction accured, and no statistical significant difference was found between the two media with respect to subjective patient reactions. The results indicate that the non-ionic, low-osmotic contrast medium iohexol is well tolerated in cerebral angiography with respect to the parameters tested. No statistical significant difference was found in any of these parameters between iohexol and Hexabrix.     

Systemic, pulmonary and renal haemodynamic effects of intravenously infused iopentol. A comparison in the pig of a new low osmolar non-ionic medium with saline and iohexol

The central, peripheral and renal haemodynamic effects after intravenous infusion (1 ml/s) of high doses (4 mg I/kg) of two low osmolar, chemically and physically similar non-ionic contrast media (iohexol and iopentol) were investigated in 16 pigs. Both contrast media induced a significant increase of mean arterial, mean right atrial, mean pulmonary arterial and mean pulmonary arterial occlusion pressure along with an increase in cardiac output. The systemic vascular and pulmonary vascular resistances were decreased. Renal venous blood flow and renal vascular resistance were not significantly changed after infusion of contrast media. There were no differences in haemodynamic effects between the two media studied.     

A comparison of the systemic responses to rapid intravenous injections of ioxilan, iohexol, and diatrizoate in rabbits

Rapid intravenous injections of contrast media are used for angiocardiography, intravenous digital subtraction angiography (DSA), and rapid scan computed tomography procedures. These rapid intravenous injections have been shown to produce significant hemodynamic changes that appear related to contrast media osmolality. In this study the systemic responses to 2-second injections at a dose of 1.5 mL/kg were compared for a new nonionic agent, ioxilan (350 mgI/mL), and for iohexol (350 mgI/mL), meglumine/sodium diatrizoate (370 mgI/mL), and saline. Ioxilan has a lower osmolality and viscosity than iohexol and is formulated with a 3 mM sodium citrate as a buffer and anticoagulant. All of the test solutions produced statistically significant changes in arterial pressure and respiratory rate (P less than .05, Student's t-test). The decrease in arterial pressure seen with diatrizoate (20.1%) was significantly greater than the decrease seen with either ioxilan (10.2%) or iohexol (10.2%). All of the responses observed were transient and would not be of clinical concern in a healthy patient. Ioxilan, which contains the calcium binding agent, sodium citrate, and iohexol appear to cause less systemic effects then diatrizoate.     

Preclinical evaluation of iotrolan as a contrast medium for angiography and urography]

Efficacy and tolerability of iotrolan, a nonionic isotonic dimer, as a contrast medium for angiography and urography were investigated in animals. In the arteriography of rabbit femur, the efficacy of iotrolan 280 mgI/ml was as good as iopamidol 300 mgI/ml and better than meglumine diatrizoate 306 mgI/ml. In rat urography, the efficacy of iotrolan 280 mgI/ml was better than both iopamidol 370 mgI/ml and iohexol 350 mgI/ml. Vascular pain was less with iotrolan 280 mgI/ml than with iohexol 300 mgI/ml in rats. Effect of iotrolan on the pulmo-cardiovascular parameters, arterial pO2, hematocrit and plasma osmolality was less than iopamidol and diatrizoate in rabbits. Iotrolan induced no renal dysfunction and diuresis where iopamidol induced diuresis in rats. Effect of iotrolan on the blood coagulation was similar to nonionic monomers and less than diatrizoate in rabbits. Because of its isotonicity, iotrolan induced little water shift in the blood vessel and urinary tract, which would result in good efficacy and tolerability. These results suggest that iotrolan is superior to ionic and nonionic monomers for angiography and urography.     

Iohexol and ioxaglate in peripheral angiography

A double-blind, cross-over trial of the non-ionic, low-osmolar contrast medium iohexol (Omnipaque) and the ionic, low-osmolar medium ioxaglate (Hexabrix) at concentrations of 300 mg I/ml was carried out in 107 consecutive patients with arterial insufficiency of the lower limbs. The purpose of the study was to observe possible 'carry-over' effects from any of the contrast media, and to evaluate patient discomfort such as pain, adverse reactions, or effect on peripheral blood pressure. No carry-over effect was seen. Ioxaglate caused less injection pain and heat sensations than iohexol, and showed less effect on the systemic blood pressure.     

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.     

Comparative double-blind investigation of meglumine metrizoate, metrizamide, and iohexol in carotid angiography

The new nonionic contrast medium iohexol (Omnipaque) was compared with its predecessor metrizamide (Amipaque) and with the conventional ionic medium meglumine metrizoate (Isopaque Cerebral) in carotid angiography using a double-blind crossover technique. The results indicated that iohexol and metrizamide caused less discomfort than the ionic medium. The circulatory effects of the three media were generally mild, and the diagnostic effectiveness was comparable when the iodine concentration was kept in the range of 280-300 mg I/ml.     

Ioxaglate versus diatrizoate in selective pulmonary angiography. II. Cardiovascular responses

A clinical comparison of ioxaglate and diatrizoate with regard to the cardiovascular effects following selective pulmonary angiography was performed in 20 patients with normal pulmonary arterial pressure. Ioxaglate produced a significantly less marked effect on systemic blood pressure (p less than 0.001), pulmonary arterial pressure (p less than 0.001), and heart rate (p less than 0.05-0.01), as compared with diatrizoate.     

Glucose alters the susceptibility of mesangial cells to contrast media

RATIONALE AND OBJECTIVES: Diabetic patients frequently suffer contrast media-induced nephropathy. Hyperglycemia in diabetes mellitus causes gradual deterioration of glomerular mesangial cells (MCs) in the kidney. In this study, the authors investigated the response of rat MCs cultured in high-glucose medium to diatrizoate and iohexol, high- and low-osmolar contrast media, respectively. METHODS: Isolated rat MCs were precultured under basal-glucose (5.5 mmol/L) and high-glucose (30 and 55 mmol/L) conditions for 24 hours to mimic hyperglycemia in diabetes mellitus and then were exposed to diatrizoate (40 and 80 mg I/mL) and iohexol (80, 120, 160 mg I/mL) for 2 hours. The cytotoxic effects of diatrizoate and iohexol were monitored by neutral red uptake in MCs. The protective effects of an antioxidant, d-alpha-tocopherol (Toc), on cytotoxicity of the contrast media were determined when MCs were precultured with Toc under high-glucose conditions or were exposed to the contrast media together with Toc. Peroxide levels in the cells exposed to the contrast media were analyzed by flow cytometry using dichlorofluorescin diacetate. RESULTS: Exposure to both contrast media (diatrizoate and iohexol) induced a concentration-dependent decrease in viability of the cells precultured under basal-glucose conditions (5.5 mmol/L). Preculture under high-glucose conditions (30 and 55 mmol/L) augmented the cytotoxic effects of both contrast media. An increase in the intracellular peroxide level was detected after exposure to both contrast media. Preculture with Toc prevented augmentation of the cytotoxic effects of diatrizoate by the higher glucose concentration (55 mmol/L). The exposure to diatrizoate together with Toc also attenuated its cytotoxic effects. Toc showed no such protective effects against iohexol exposure. CONCLUSIONS: These findings suggest that high-glucose conditions enhance the susceptibility of MCs to the cytotoxic effects of both contrast media; the enhanced susceptibility was in part attributable to oxidative stress caused by high-glucose conditions; diatrizoate exerted the cytotoxic effects by means of oxidative stress; and iohexol appeared to exert its cytotoxicity in a manner different from diatrizoate.     

Ioxaglate versus diatrizoate in selective pulmonary angiography. I. Subjective reactions

In selective pulmonary angiography, a low osmolality contrast medium, ioxaglate, was compared with diatrizoate from the aspects of subjective discomfort and angiographic information. A cross-over analysis was done in 40 cases. The intensity of local heat sensation during and after the injection of ioxaglate was significantly lower than with diatrizoate. With ioxaglate, no cough was experienced even in patients with subtotal atelectasis or massive pleurisy. The quality of the arterial phase was essentially identical, with both media, while in the venous ioxaglate series the quality was significantly superior to that of diatrizoate.     

Intra-arterial digital subtraction angiography with isotonic dimeric (iodixanol) and monomeric (iohexol) nonionic contrast media: radiographic,clinical and neurophysiological evaluation

Monomeric (iohexol 300 mg I/ml) and dimeric (iodixanol 270 mg I/ml) nonionic contrast media were compared in a double-blind, randomised, parallel group trial. Safety and efficacy of the media in intra-arterial cerebral digital subtraction angiography were evaluated by assessing adverse events, discomfort, EEG, heart rate and quality of radiodiagnostic information. Seventy-six patients underwent selective injection of the carotid and/or vertebral arteries. Both contrast media were well tolerated. No serious adverse events occurred. No effects on heart rate and EEG were evident. The arteriograms were of high quality and overall diagnostic information was optimal in 94% of the examinations. No clinically important differences between the two contrast media were found.     

Opiate involvement in contrast media-induced blood pressure changes

The intravenous administration of contrast media (CM) often alters blood pressure (BP). Osmolality plays a role, but the magnitude and even direction of change varies under similar (osmotic) conditions, indicating the involvement of other mechanisms. Male Wistar rats, anesthetized with pentobarbital, received sodium/meglumine diatrizoate, iohexol, or normal saline, 4 ml/kg, via a tail vein, while blood pressure was recorded continuously. Additional groups were pretreated with the opiate antagonist, naloxone (1 mg/kg, IV), or with an equal volume of normal saline 5 minutes prior to the diatrizoate injection. Comparisons of BP change were made with the Student's t-test. Diatrizoate caused a significant (P less than .0002) increase in BP relative to the saline control group, iohexol did not. Thus, the increase with diatrizoate was significantly greater than with iohexol (P less than .00006). Neither the saline nor naloxone pretreatment altered BP significantly. Saline pretreatment did not alter the significant increase in BP produced by the diatrizoate. However, the diatrizoate-induced increase in BP was prevented by the naloxone pretreatment and was significantly less than after the saline pretreatment (P less than .0001). Based on these and previous results, the authors hypothesize that release of endogenous opioids may play a role in BP changes caused by intravenous CM and that significant CM-induced changes may be prevented pharmacologically with the selective opiate blocker, naloxone.     

Nitric oxide protects against contrast media-increased pulmonary vascular permeability in rats

RATIONALE AND OBJECTIVES: Nitric oxide (NO) regulation of endothelial function is involved in the development of acute lung injury. The role of NO in contrast media-induced increases in pulmonary vascular permeability was investigated in a rat model. METHODS: Nonionic (iohexol) and ionic (ioxaglate) contrast media were intravenously injected at 1.5 mL/min in rats. Pulmonary vascular permeability was evaluated by measuring the amount of Evans blue dye uptake as a quantitative marker of albumin extravasation in lung tissue. RESULTS: Intravenous injections of contrast media at doses of 4 and 6 g I/kg induced a dose-dependent increase in pulmonary vascular permeability. L-Arginine (an NO synthase substrate) and N(G)-nitro-L-arginine (L-NNA) (an NO synthase inhibitor) prevented and aggravated, respectively, the increase in pulmonary vascular permeability induced by the contrast medium. An aggravating action of L-NNA was confirmed by morphological and histological observations, this action being blocked by L-arginine (300 mg/kg) but not by D-arginine. Isosorbide dinitrate (1-20 mg/kg), an NO donor, had a dose-dependent protective effect on ioxaglate-increased vascular permeability. CONCLUSIONS: Our experimental findings suggest that contrast media at high doses produce pulmonary edema by inhibiting endothelial NO production, and nitrovasodilators protect against this adverse effect in rats.     

Comparison of iohexol 300 and diatrizoate meglumine 60 for body CT: image quality, adverse reactions, and aborted/repeated examinations.

Six hundred patients were prospectively randomized and given either diatrizoate meglumine 60 or iohexol 300 during dynamic contrast-enhanced body CT in order to compare image quality, contrast reactions, and the number of aborted studies or studies in which images had to be repeated. Three hundred two patients received iohexol 300, and 298 patients received diatrizoate meglumine 60. Thirty-nine percent (119/302) of the patients given iohexol 300 and 63% (188/298) of the patients given diatrizoate meglumine 60 had at least one adverse reaction thought to be related to contrast material during, or within 24 hr of, the body CT scan. When reactions of discomfort (heat or warmth, flushing, bad taste) were excluded, 16% (48/302) of the patients who received iohexol and 33% (99/298) of the patients who were given diatrizoate meglumine 60 had at least one adverse reaction. The differences in both types of reactions between the two agents were significant (p less than .001). Among scans evaluated for study quality, 71% (214/302) of the iohexol 300 group and 62% (184/298) of the diatrizoate meglumine 60 group had optimal enhancement (p = .02). However, when the optimal and adequate categories were combined, 301 of 302 patients given iohexol 300 and 292 of 298 patients given diatrizoate meglumine 60 had diagnostic-quality studies (no statistical difference). Studies were not terminated nor were images repeated in 97% (292/302) of the patients given iohexol 300 and in 94% (280/298) of those given diatrizoate meglumine 60. The CT study was repeated because of movement during the contrast injection or aborted because of contrast-related reactions in 0.7% of the patients given iohexol 300 and in 3.0% of the patients given diatrizoate meglumine 60. This difference was statistically significant (p = .04). Our results suggest that the difference in image quality, number of adverse reactions, and number of aborted/repeated CT scans performed with iohexol 300 or diatrizoate meglumine 60 are not sufficiently different to warrant conversion to nonionic agents for body CT scans.     

Nephrotoxicity of cyclosporin A and contrast media. A comparison between diatrizoate and iohexol in rats

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 22 h or 8 days after intravenous injection of diatrizoate, iohexol or saline in 30 adult Wistar rats in which nephrotoxicity was induced by daily peroral administration of 25 mg/kg body weight cyclosporin A over a 14-day period. Another 10 rats which had the vehicle of the cyclosporin A solution (placebo) and saline injected intravenously served as controls. The effect of iohexol and saline on the albumin excretion was similar, whereas diatrizoate increased it significantly. Both contrast media caused significantly increased excretion of all three enzymes. The contrast media had no effect on the excretion of glucose and sodium. Except for the fact that the excretion of NAG was significantly higher following iohexol than following diatrizoate 24 to 46 h after injection no significant differences between the two media were found from 24 h after injection among the rats given cyclosporin A. No contrast medium related changes were found by light microscopy of the kidneys. Neither iohexol nor diatrizoate potentiate acute cyclosporin A nephrotoxicity.     

Intravenous urography with a new non-ionic contrast media in a clinical phase III study: iopentol vs iohexol

The safety and diagnostic efficacy of iopentol 300 mg I/ml were compared with iohexol 300 mg I/ml in 300 patients submitted for urography. The study was carried out as a double-blind, randomised parallel study where 149 patients received iopentol and 150 patients iohexol. There were no significant differences between the patients receiving the two contrast media with regard to demographic parameters, rate of injection or total dose of injected contrast media. No changes in blood pressure and no clinically important changes in heart rate were detected in the two groups. No serious adverse effects occurred. Seven patients (5%) in the iohexol and 12 patients (8%) in the iopentol group experienced adverse effects other than a sensation of warmth. Fourteen iohexol patients (9%) and 18 iopentol patients (12%) experienced warmth related to the contrast injection. Excellent films were obtained in most patients and no difference in diagnostic quality between iopentol and iohexol was observed.     

The toxicity of the non-ionic water-soluble contrast media iohexol and metrizamide (Amipaque) in selective vertebral angiography

Summary Selective left vertebral angiography was carried out in 25 rabbits comparing the toxic effects of iohexol and metrizamide (Amipaque). The iodine concentration for iohexol was 280 and 350 mg/ml and for metrizamide 350 mg/ml. Short general convulsions were seen in many of the animals with iohexol in the concentration of 350 mg iodine/ml. Cardiovascular reactions were seen with both contrast media, but were more marked with iohexol than with metrizamide in the concentration of 350 mg iodine/ml. Both iohexol and metrizamide are far less toxic than the ionic contrast medium metrizoate, but metrizamide seems to be less toxic than iohexol in vertebral angiography.     

Excretory urography with iohexol: evaluation in children

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.     

High dose urography in patients with renal failure. A double blind investigation of iohexol and metrizoate

The new non-ionic contrast medium iohexol 350 mg I/ml was compared with the ionic contrast medium metrizoate 350 mg I/ml in a double blind, two-group urographic study performed on 20 patients with stable, impaired renal function. A dose of contrast medium of 500 mg I/kg body weight was given to each patient. Iohexol resulted in significantly fewer subjective adverse reactions than metrizoate. A similar image quality was obtained with the two contrast media. No clinically significant difference existed between the two contrast media with respect to influence on blood pressure, pulse or clinical chemical parameters. A tendency to deterioration of renal function after urography was found in both groups, but no difference of statistical significance existed between the two contrast media with respect to possible nephrotoxicity. Inadequate hydration may have been partly responsible for the nephrotoxic effect of the urographic procedure.