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.     

Granulocyte adherence is inhibited by radiographic contrast media in vitro.

Different amounts of diatrizoate, ioxaglate, iohexol, iodixanol, NaCl 1,000 mOsm/kg, mannitol 1,098 mOsm/kg, and meglumine (meglumine concentrations corresponding to the content in the diatrizoate solutions) were added to either whole blood or a suspension of granulocytes in autologous plasma, and the adherence to nylon fibers was determined. At high concentrations all the investigated contrast media (CM) inhibited granulocyte adherence. The degree of inhibition was significantly greater when the ionic CM diatrizoate and ioxaglate were used, as compared with the nonionic media. Meglumine solutions at high concentrations also inhibited adherence but significantly less than diatrizoate solutions containing the same amount of meglumine. Diatrizoate showed the greatest inhibitory effect on granulocyte adherence, and significant inhibition could be detected even with a 1.25% solution.     

Electrolyte disturbances caused by intravenous contrast media.

The changes in serum electrolytes (sodium, potassium, ionized calcium, and total calcium) produced by high-dose (3 ml/kg) intravenous contrast media were investigated in Japanese white rabbits. The test solutions included sodium/meglumine diatrizoate (370 mgI/ml), sodium/meglumine ioxaglate (320 mgI/ml), iohexol (350 mgI/ml), iopamidol (370 mgI/ml), 20% mannitol, and isotonic saline. The alterations in serum ionized calcium were relatively small and transient, and correlated with changes in the hematocrit. Diatrizoate caused a significant decrease in ionized calcium in comparison with other contrast media and mannitol. The ratio of ionized calcium to total calcium showed no significant decrease in any group. The changes in potassium did not correlate with those in hematocrit. Diatrizoate caused a smaller decrease in potassium than low-osmolality contrast media, which may suggest that diatrizoate caused a shift in potassium from extravascular space to intravascular space. In conclusion, intravenous infusion of high doses of low-osmolality contrast media did not cause clinically significant alterations in serum electrolytes.     

Iohexol inhibits adenylate cyclase

Previous studies demonstrated that the intravenous administration of the ionic radiographic contrast agent, diatrizoate, and the nonionic agent, iohexol, causes a decrease in the rate of cerebrospinal fluid (CSF) production. Evidence suggests that adrenergic-mediated adenylate cyclase (AC) activity controls CSF production. Diatrizoate was found to inhibit AC activity. The authors now report that iohexol inhibits activity of this enzyme. Adenylate cyclase activity was measured in membrane fractions of bovine choroid plexus in the presence of various concentrations of iohexol. A concentration-dependent inhibition of basal and adrenergic-stimulated AC activity by the contrast agent was observed. The concentration of iohexol that produced a 50% inhibition was about 2.3 mM. This is similar to the concentration of diatrizoate that produced equivalent enzyme inhibition. These results support the contention that one mechanism for the action of contrast media in reducing CSF production involves inhibition of AC activity.     

High- and low-osmolar contrast agents in urography: a comparison of the appearances with respect to pyelotubular opacification and renal length

The incidence of pyelotubular opacification and the change in renal length during intravenous urography with iohexol (Omnipaque) was compared with sodium/meglumine diatrizoate (Urografin). Pyelotubular opacification was seen in 14 out of 29 urograms performed with iohexol compared with one out of 28 urograms performed with sodium/meglumine diatrizoate. This increased incidence is statistically significant and has not been previously documented. The increase in renal length following intravenous contrast medium was similar for both iohexol and sodium/meglumine diatrizoate. The significance of these findings with respect to the interpretation of urograms performed with iohexol is discussed.     

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.     

Effects of intrathecal injection of diatrizoate on dopamine receptors

RATIONALE AND OBJECTIVES: The authors performed this study to determine whether adverse reactions similar to those that occur in patients receiving antipsychotic medication may occur after inadvertent intrathecal injections of some contrast material. MATERIALS AND METHODS: Recombinant human dopamine-2 (D-2) receptors were incubated together with tritiated (hydrogen 3) spiperone, a D-2 receptor agonist commonly used in binding studies, and three types of contrast material (sodium/meglumine diatrizoate; meglumine iothalamate; and iohexol) in different concentrations to determine competitive binding potentials. Nonspecific binding was also assessed. Membranes were washed, filtered, and counted in a scintillation counter. RESULTS: At several different concentrations, diatrizoate demonstrated a potential to displace the binding of spiperone to the D-2 receptors, whereas the other two contrast materials tested (iothalamate meglumine and iohexol) showed only weak binding potentials. CONCLUSION: Diatrizoate, which has been incriminated in most adverse reactions resulting from the inadvertent intrathecal injection of a contrast material, may produce symptoms similar to those of the neuroleptic malignant syndrome by blocking neurotransmission through dopamine receptors. Although antipsychotic drugs produce this parkinsonism-like effect only after prolonged use, it is probable that diatrizoate produces the effect immediately by virtue of the high concentrations that may accumulate at the base of the brain after myelography. Also worthy of note is the fact that the two other contrast materials that have produced a number of reported adverse reactions share a molecular similarity to diatrizoate that is not found with other contrast materials.     

Omnipaque and Urografin in left ventriculography and coronary arteriography. A randomised, double blind study

In order to compare tolerability and radiographic properties of Omnipaque (iohexol) 350 mg I/ml and Urografin (sodium meglumine diatrizoate) 76% (370 mg I/ml) in left ventriculography and coronary arteriography, a randomised, double-blind parallel study was conducted. ECG, heart rate, blood pressure, cardiac output, oxygen saturation, CK-MB, adverse reactions and opacification were recorded. Twenty-five patients received Omnipaque and 24 Urografin and all patients were included in the final material. Omnipaque was found to have less influence on haemodynamics than Urografin. Few adverse reactions were encountered in the entire study, but fewer after injections of Omnipaque than after Urografin. Equally good opacification was demonstrated for both media. Omnipaque was found well suited for cardioangiography and superior to standard ionic media.     

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.     

Pain in peripheral arteriography: an assessment of conventional versus ionic and non-ionic low-osmolality contrast agents

Two low-osmolality contrast agents, ioxaglate meglumine/sodium and iohexol were compared with diatrizoate meglumine/sodium in a controlled double blind study of 126 patients undergoing arteriography for peripheral vascular disease to determine which caused the least pain. Discomfort was assessed by means of a visual analog scale rating pain from 0 to 100. Average values for pain were 39 +/- 27 for diatrizoate, 14 +/- 15 for ioxaglate and 21 +/- 22 for iohexol. We found that both low-osmolality agents caused significantly less pain in peripheral arteriography than the traditional agent. The p values were p less than 0.0005 for ioxaglate and p less than 0.005 for iohexol versus diatrizoate. In addition, ioxaglate was found to cause significantly less pain than iohexol (p less than 0.05) in this patient group.     

Neuroangiography with iohexol

Iohexol is a new, nonionic water-soluble contrast agent undergoing early clinical trials in the United States. Using a double-blind, parallel format, iohexol was compared with meglumine iothalamate (60 patients) for selective cerebral angiography, and with sodium meglumine diatrizoate (40 patients) for arch aortography. Iohexol produced significantly less pain than meglumine iothalamate or sodium meglumine diatrizoate. There were no significant differences in terms of heart rate, blood pressure, or electrocardiogram (ECG) changes. Both produced a transient tachycardia and hypotension after arch aortography, but significantly less so with iohexol. No significant complications occurred. Film quality was comparable between contrast agents except for diminished motion artifacts with iohexol. Iohexol appears to be a superior neuroangiographic contrast agent to current ionic drugs.     

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.     

Comparison of hepatic damage from direct injections of iodinated contrast agents and carbon dioxide.

PURPOSE: This study guides the choice of contrast agent for localization of portal veins during transjugular intrahepatic portosystemic shunt (TIPS) placement or use in percutaneous transhepatic cholangiography (PTC) by providing gross anatomic and histologic comparison of effects from parenchymal injections of iodinated contrast agents and carbon dioxide. MATERIALS AND METHODS: Eighteen New Zealand White rabbits received direct injections of 2-5 mL of either the nonionic contrast agent iohexol 300 mgI or the ionic contrast agent diatrizoate meglumine 60% into one lobe of the liver and the same volume of CO2 into the other lobe. The rabbits were killed at 2-7 days for gross and histologic evaluation of the livers. RESULTS: At the time of injection, the diatrizoate and iohexol sites showed persistent dark discoloration, whereas CO2 sites showed minimal visible changes. On gross examination at death, all diatrizoate sites showed severe scarring and also commonly showed areas of necrosis. CO2 and iohexol sites showed only minimal discoloration and needle-puncture scars (P < .0001). The histologic grade for diatrizoate sites was significantly more severe than paired CO2 sites (P < .016). Iohexol sites showed mild histologic changes similar to paired CO2 sites (P = .375). CONCLUSION: Iohexol and CO2 produce less severe hepatic damage and are preferred to meglumine diatrizoate for hepatic injection.     

The effects of water soluble contrast agents on the respiratory tract

The water soluble contrast agents Gastrografin (Sodium diatrizoate and meglumine diatrizoate, Schering, Berlin), Iopamiro 300 (Iopamidol, Schering, Berlin), and Dionosil Aqueous (propyliodone BP, Glaxo, England) were instilled into the tracheobronchial tree of rats in doses of either 0.1 ml and 0.25 ml. Rats being used as controls, underwent sham operations with the instillation of air instead of contrast agent. In all, 85 rats were used. All rats that had not already died from the effects of contrast agent were sacrificed 30 minutes after instillation. The relative effects of the contrast agents were measured by comparing: 1. survival time; 2. radiographic effects of the contrast agents on the lungs and; 3. pathological changes as estimated by post mortem lung section and microscopy. The least toxic agent was the one with the lowest osmotic activity, namely Aqueous Dionosil. It is therefore recommended that Aqueous Dionosil be used in preference to Gastrografin or Iopamidol for studies of the oesophagus whenever there is a danger of aspiration of contrast agent into the tracheobronchial tree.     

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.     

The effect of radiographic contrast media on ultrasonically detectable red blood cell aggregation in vitro

We investigated the effect of radiographic contrast media (RCM) on red blood cell (RBC) aggregation by analyzing echogenicity of flowing blood before and after the addition of 2%, 20%, 50% or 95% volume of undiluted meglumine diatrizoate, iohexol, sodium meglumine ioxaglate, or iopamidol and equiosmolar volume concentration of saline. This was done both by stepwise increasing the concentration with minimal mixing and by stepwise decreasing the concentrations with more efficient mixing. All contrast media caused a drop in blood echogenicity after a proper mixing when compared with saline addition. After minimal stirring, both meglumine diatrozoate and iohexol caused a significant increase in blood echogenicity at volume concentrations over 50%. The paper demonstrates that earlier findings of both increased and decreased RBC aggregation following exposure to RCM can be reproduced and that the result depends on experimental setup. In diatrizoate and iohexol RBC aggregates disappear after mixing (increasing the shear rate) or when the RCM/blood mixture is diluted. After dispersement, the abnormal RBC aggregates will not reform.     

Effect of an iso-osmolar contrast medium on pulmonary arterial pressure at pulmonary angiography

A clinical comparison of the effects on pulmonary arterial pressure induced by contrast media with various osmolalities, iohexol 140 mg I/ml (300 mosm/kg H2O), iohexol 300 mg I/ml (690 mosm/kg H2O), and diatrizoate 292 mg I/ml (1480 mosm/kg H2O) following selective pulmonary angiography was made in 12 patients with normal pulmonary arterial pressure. A double-blind crossover study was performed and the contrast media were administered in random order. The pulmonary arterial pressure was recorded continuously before, during, and for 3 min after the injection. The effect of iohexol 140 on the pulmonary arterial pressure was significantly less marked than that of diatrizoate 292, whereas no statistical significance was shown between iohexol 140 and iohexol 300. These results indicate that iso-osmolar contrast medium (iohexol 140), as well as iohexol 300, would be better tolerated than diatrizoate 292, and is therefore a safer contrast medium for selective pulmonary angiography.     

Incompatibility of water-soluble contrast media and intravascular pharmacologic agents. An in vitro study.

In vitro incompatibilities between nine water-soluble contrast media and 21 intravascular pharmacologic agents were investigated using naked-eye observation and a centrifuge. Most of the previously reported incompatibilities were verified, and a few new incompatibilities were discovered: phentolamine mesylate with diatrizoate sodium, diatrizoate meglumine, ioxaglate, and iothalamate; diatrizoate meglumine with diazepam and meperidine hydrochloride; and diatrizoate sodium with meperidine hydrochloride. There were no incompatibilities when the pharmacologic agents investigated were mixed with ioxithalamate, iopromide, iopamidol, and iohexol.     

Effect of ionic and non-ionic contrast media on aggregation of red blood cells in vitro. A preliminary report

Fresh human blood without additives, and contrast medium were mixed and examined immediately by light microscopy in a non-flowing state. Sodium meglumine diatrizoate, meglumine diatrizoate, meglumine iodamide, sodium meglumine ioxaglate, iopromide, iopamidol, iohexol, and metrizamide were tested in concentrations of 300 mg I/ml. Physiologic saline and 5% glucose were used as controls. All media were tested in a randomized order with blood samples from 23 volunteers. No aggregation was detected in physiologic saline, and few rouleaux were found in ionic contrast media. Irregular red cell aggregates were found in all low-osmolal contrast media: in 17 per cent of the specimens in ioxaglate, in 52 per cent in metrizamide, and in 78 to 100 per cent in other non-ionic media. Irregular aggregates were seen in all specimens with glucose. It remains to be demonstrated whether or not the irregular aggregation of human red cells in non-ionic contrast media has clinical significance. Iohexol was also tested with blood samples from several laboratory animals, but in nearly every case no aggregates were found. Results of animal experiments or tests with animal blood seem to be poorly applicable to man.     

High dose brain CT with ioxaglate and diatrizoate adverse reactions and effects on urine protein tests

Sodium meglumine ioxaglate (320 or 306 mg I/ml) and meglumine diatrizoate (306 mg I/ml) in an intravenous dose of 2 ml/kg were compared in a randomized double-blind test on the brain CT of 209 patients. Side effects were noted in 56% of the ioxaglate group and 90% of the diatrizoate group. Diatrizoate caused a sensation of heat significantly more often and more intensely, but the frequencies of other side effects did not differ significantly. No severe reactions occurred. The quality of the CT scans was equal. Neither ioxaglate nor diatrizoate impaired renal function. False-positive strip tests and falsely elevated protein values measured by the biuretic method were found in particular in the ioxaglate group. The results of urine protein measurements and strip tests are misleading on the day of the examination with both ioxaglate and diatrizoate.