Significance of a nonionic renographic contrast medium (Iopamidol 300) in the roentgen diagnosis of the kidneys and urinary tract in children

The ionic contrast media used so far have been associated with considerable risks in infants and children. The high osmolality of these media did not always permit a dosage sufficient for kidney imaging in the nephrographic and in the pyelographic phase. The new non-ionic contrast media have largely reduced these risks so that their general application in infants and young children should be recommended. Intravenous urographies using the non-ionic contrast medium Iopamidol 300 (Solutrast 300) were performed in 195 children aged one day to 12 years. Good to superior urograms were obtained in 85% of the investigations. No adverse reactions caused by the osmolality of the contrast media had been observed in spite of the relative high dosage. As a result of their low osmolality and non-ionic property a safe application of high doses was possible.     

New and old contrast agents: Pharmacology,tissue opacification,and excretory urography

In equivalent doses for intravenous urograms conventional ionic contrast agents give iodine concentrations in the urine of approximately 30 mg iodine/ml, nonionic contrast media provide approximately 50 mg iodine/ml, and the ionic dimer Hexabrix approximately 70 mg iodine/mL. These new low osmolality, contrast media provide significantly higher urinary iodine concentrations than conventional ionic contrast media, provide better diagnostic quality excretory urograms, better patient tolerance, and fewer adverse side-effects and serious reactions. These new low osmolality, contrast media have significant advantages in intravenous urography in both safety and efficacy when compared to conventional higher osmolality contrast media.     

Central and renal haemodynamic effects of intravenous infusion of non-ionic and ionic contrast media. An experimental investigation in the pig

The central and renal haemodynamic effects after intravenous infusion (1 ml/s) of a non-ionic (iohexol) and an ionic (metrizoate) contrast medium were investigated in 16 pigs. The injected contrast media induced marked haemodynamic changes compared with normal saline. However, there were no significant differences between the ionic and the non-ionic media. It was concluded that the effects were only partially caused by an increase in the blood volume due to the injected volume. In addition, the effects related to the viscosity, the osmolality and other not specified pharmacodynamic properties of the media are proposed to be of importance.     

Influence of two non-ionic radiographic contrast media with different osmolalities on coagulation in invasive cardiology. A prospective,randomised comparative study

PURPOSE: To investigate the influence of two non-ionic radiographic contrast media with different osmolality on thrombocytic function and the plasmatic coagulation system. MATERIAL AND METHODS: The study was carried out as a randomised, prospective, comparative study with two contrast media in a heart catheter laboratory. RESULTS: Activating influences on platelet aggregation, procoagulatory or profibrinolytic functions or injury to the endothelium could be ruled out. Apparently, also differences in substance properties, such as the media's ionic character or osmolality had no demonstrable influence on the interaction with haemostatis and blood vessels. An adjuvant, antithrombotic therapy was carried out, which consisted of platelet aggregation inhibitors and heparins. CONCLUSION: Our findings agree with the results of recent clinical trials, which demonstrated no relevant disadvantage of non-ionic contrast media as regards thrombotic complications.     

The effects of angiographic contrast media on the aggregation and morphology of red cells in vitro

The effects of four angiographic contrast media on the aggregation and morphology of human red cells in vitro, using microscopic observations were studied. The media included an ionic contrast medium, sodium meglumine amidotrizoate (amidotrizoate); non-ionic low-osmolal contrast media, iopamidol and iohexol; and an ionic low-osmolal contrast medium, sodium meglumine ioxaglate (ioxaglate). Strong, large aggregates formed in the control blood, without media, where aggregation of red cells was inhibited by contrast media mixed with the blood in a ratio of 2:1. Almost no aggregates were observed for amidotrizoate, an ionic contrast medium, while there were a few rouleaux formed in the presence of ioxaglate. Nearly all of the red cells aggregated in the presence of iopamidol and iohexol; iohexol produced the greater aggregation of the two. Besides rouleaux, irregular aggregates were formed with iohexol. When the contrast media were mixed with blood in a ratio of 1:2, their inhibitory effects on aggregation declined. These results clearly indicate that contrast media inhibit the in vitro aggregation of red cells, and ionic-contrast media produced more potent inhibitory effects than non-ionic media. With added NaCl and meglumine, iohexol did not induce red cell aggregation. This suggests that ionic-contrast media have greater inhibitory effects on aggregation than non-ionic media, a result of their ionic properties. Red cells were morphologically quite normal in the presence of ioxaglate, where most red cells were crenated in the presence of iopamidol and iohexol, and shrank in the presence of amidotrizoate. In the presence of iopamidol and iohexol with the osmolality adjusted to that of a saline solution, both normal red cells and crenation were observed. This suggests that non-ionic contrast media may directly effect morphological changes in red blood cells. These results revealed that ioxaglate, an ionic contrast medium, was the best in vitro medium, to prevent aggregation of red cells and crenation deformity of erythrocytes.     

Advantages of non-ionic contrast media in vascular applications

The use of non-ionic contrast media for vascular applications is currently under investigation. Initial studies in the United States have demonstrated non-ionic contrast media have several advantages when compared to conventional ionic contrast media. A comparison of the ionic and non-ionic contrast media, including their physiologic effects, is presented to familiarize the radiologic technologist with this new product.     

Effect of various contrast media on platelet aggregation--an in vivo study

Recently, some radiologists using non-ionic contrast media for angiography have noted the increased tendency of thrombus formation in the injection syringe or angiographic catheter contaminated with blood. In vitro studies by some authors have shown that non-ionic contrast media had only a slight anticoagulative effect as compared with ionic contrast media. But the in vivo studies comparing the anticoagulative effect of both ionic and non-ionic contrast media have not been performed previously. We investigated the effect of non-ionic and ionic contrast media on platelet aggregation in 40 patients undergoing angiography. The in vivo study revealed a negligible influence of both non-ionic and ionic contrast media on systemic platelet aggregation. The dose of contrast media also showed no significant correlation with platelet aggregation. Our study suggests that the data from in vitro experiments cannot be extended to in vivo study as for the relationship between contrast media and their anticoagulant effect.     

Blood clot formation in angiographic catheters. In vitro tests with various contrast media

Human blood was injected into angiographic catheters filled with contrast media or flushing media. The catheters were allowed to stand at 37 degrees C for 10, 20 or 30 min. Physiologic saline was then injected through the catheters, the catheter contents were shaken and filtered, and any clots were identified. Diatrizoate, ioxaglate, iohexol, iopamidol and iopromide were tested. Physiologic and heparinized saline were used as controls. At 10 min, clots were found in 65 per cent of the catheters filled with physiologic saline, in 25 per cent with non-ionic media, in 19 per cent with heparinized saline, and in 4 per cent with ionic contrast media. At 30 min, all catheters with physiologic saline, 85 per cent with non-ionic contrast media, 46 per cent with heparinized saline and 23 per cent with ionic contrast media contained a clot. Although all the contrast media were anticoagulants, a more careful angiographic technique is needed for non-ionic media. All the non-ionic agents showed equal results. Physiologic saline without heparin is not suitable for flushing during angiography.     

A survey of contrast media used in coronary angiography

In recent years, various contrast media have been developed for use in coronary angiography. These contrast media may be divided into ionic contrast media of high osmolality, those of low osmolality, and nonionic contrast materials. We conducted our own clinical studies with 40 patients. In random succession a standard contrast medium (ionic, of high osmolality) and a new-generation contrast medium (either nonionic or ionic with low osmolality) were injected into the right and left coronary arteries. After each injection we measured the systolic and diastolic blood pressure using a liquid-filled coronary catherter. In addition, the change in the length of the cardiac cycle was registered in terms of the R-R interval (in ms) and at the same time, leads I, II, and III of the ECG were recorded. We studied the influence of the various contrast media on the activity of ATPase in in vitro experiments, using Lasser and Lang's [30]. When ionic contrast media of low osmolality and nonionic contrast media were utilized the heart rate showed no change. Disturbances of rhythm such as ventricular tachycardia or fibrillation were not observed. All of the contrast media used produced the same ECG changes. These changes can be ascribed to the inhibition of ATPase. The arterial blood pressure was lowered significantly only by ionic contrast media of high osmolality only.     

Contrast agents used for myelography: an historical perspective

Radiographers often lack a sense of historical perspective, but lack of knowledge of the past can obstruct further advances. This article summarizes the history of myelographic contrast agents used in the 60 years prior to the introduction of water-soluble, non-ionic, low osmolar compounds currently employed. These media have either been negative or positive; water-soluble or insoluble; ionic or non-ionic; very hypertonic or relatively less so.     

Preston M. Hickey memorial lecture. Ionic and nonionic iodinated contrast media: evolution and strategies for use

The search for better radiopaque iodinated contrast material for intravascular use is continuing, but the recent development of new lower osmolality contrast media (LOCM), both ionic and nonionic, has dramatically affected the practice of radiology. The major issue retarding the introduction of LOCM into clinical practice in this country has been the increased cost of the media. Numerous preliminary assumptions and probabilities about the tolerance, efficacy, and overall safety of LOCM have been documented in scientific studies. The lower osmolality, reduced chemotoxicity, and high hydrophilicity of new compounds, particularly the nonionic variety compared with conventional high osmolality ionic agents (HOCM), offer a significant margin of safety to patients with known risk factors. Mounting data suggest that low or no risk patients are benefited as well, perhaps to an even greater degree. Costly trade-offs to the universal use of LOCM exist, therefore careful consideration of the advantages and disadvantages of LOCM for intravascular administration is required. This article, presented as the Preston M. Hickey Memorial Lecture to the Michigan Radiological Society in March of 1990, explores the historical development of iodinated intravascular contrast media, especially LOCM, and cites existing data that form the basis for various strategies for their use, that is, selective, universal, or nonvascular use. Better, safer, and less expensive contrast media are a realistic expectation in this new decade of technological promise. Reducing adverse side effects from the use of any new drug or technology must be our continued, collective goal.     

Safety and tolerability of iodixanol in healthy volunteers with reference to two monomeric X-ray contrast media.

The low osmolar, non-ionic X-ray contrast media have shown a lower frequency of adverse events than the older ionic ones. In this study changes in routine clinical-chemical parameters in blood and urine, vital signs and adverse events were recorded in six groups of 10 healthy male volunteers receiving either iodixanol, a new non-ionic, dimeric X-ray contrast medium for general vascular use, or one of the two non-ionic, monomeric contrast media iopentol and iopamidol. Minor decreases were observed in the values for haemoglobin, haematocrit and erythrocytes 5 min and 3 days after injection of iodixanol. A minor increase was seen in platelets and total protein after 3 days. A transient increase in serum osmolality was seen 5 min after the injections of iopentol and iopamidol. This was not seen in any iodixanol group. The level of thyrotropin showed an increase in all groups at 3 days. It was back to normal within 21 days. No changes of clinical importance were seen regarding blood pressure, heart rate or ECG in any volunteer. No severe adverse events were reported. All events were of short duration, and of mild or moderate intensity. The results, however, may indicate a lower frequency of adverse events/discomfort after the administration of the dimeric iodixanol than the 2 monomeric contrast media iopentol and iopamidol.     

The old and the new: a study of five contrast media for urography

Five contrast media, Conray 280 and 420, Urografin 370, Uromiro Sodium 300 and Niopam 370, were compared in a randomised trial involving a total of 482 patients. The best urographic agent was Conray 420 and the worst Conray 280, these control agents defining the ends of the scoring system. Uromiro Sodium 300 was very nearly as good as Conray 420. A non-ionic agent, Niopam 370, scored nearly equal with Urografin 370; both were rather better than Conray 280. There was little difference in minor reactions between the media. No reason was found to prefer non-ionic to ionic agents for general use in urography; indeed for a diagnostic examination the sodium salt of an ionic agent is preferable.     

Effects of contrast media on cultured myocardial cells

To quantify and characterize mechanisms of negative inotropic effects of ionic and nonionic angiographic contrast media, spontaneously contracting monolayers of cultured chick ventricular cells were studied using the Renografin-76 and iohexol as characteristic ionic and nonionic contrast agents. Utilizing microscopic video-motion detector techniques the effect of each contrast agent on contraction amplitude was measured. Also, the effect of changes in the ionized calcium concentration and osmolality induced by the contrast agents was evaluated. The study demonstrated a linear depression of contractility by increasing contrast concentrations. The negative inotropic effect of Renografin-76 was significantly greater than that of iohexol. Renografin-76 demonstrated significant calcium binding, whereas iohexol had none. Correction for calcium binding by Renografin-76 partially reversed the negative inotropic effect of this agent. Hypertonic sugar solutions of equivalent osmolality to the contrast agents demonstrated dose-related negative inotropic effects such that, in this preparation, calcium binding by Renografin-76 and its high osmolality accounted for all its negative inotropic effect. In contrast, iohexol demonstrated an intrinsic negative inotropic effect not completely explained by its osmolality.     

Immunologic basis for adverse reactions to radiographic contrast media

The lymphocyte transformation test (LTT) was used to elucidate whether certain side effects induced by radiographic contrast media have an immunologic etiology. Groups studied were: 8 patients who had previously experienced adverse reactions in association with urography, 6 patients who underwent urography without notable side reactions, 17 occupationally exposed nurses, and 9 unexposed controls. The lymphocytes from 2 hypersensitive patients and from 11 nurses exhibited a positive proliferative response to amidotrizoate. Five nurses who had shown a positive response, had a previous history of hypersensitivity reactions when handling contrast media, whereas the remaining 6 were free of symptoms. Amidotrizoate-specific memory cells were absent in patients who underwent urography without signs of hypersensitivity and in 7/9 of unexposed control subjects. Lymphocytes from patients sensitive to amidotrizoate cross-reacted to structurally related ionic contrast media while non-ionic contrast agents did not induce proliferation of the lymphocytes. Thus, ionic radiographic contrast agents have antigenic properties in man. Irradiated mixtures of radiographic contrast media and serum proteins were, in general, not effective in inducing an LTT response.     

Assessment of non-ionic contrast agents in reducing the risk of side effects: analysis on the basis of voluntary willingness-to-pay measured by the contingent valuation method

The benefit of replacing ionic contrast agents with non-ionic ones was assessed by employing cost-benefit analysis, a method of medical economic analysis. The benefit derived from replacing ionic with non-ionic contrast agents was assessed by a questionnaire survey of patients using the willingness-to-pay method based on the contingent valuation method. This questionnaire survey was conducted on 204 patients in Shimane Medical University Hospital during the period from October to December 1998. The result of analysis showed that when ionic contrast agents are replaced with non-ionic ones, patients' willingness-to-pay stands at a median value of 12,500 yen and a mean value of 17,082 +/- 1,049 yen. These figures are identical with or larger than the NHI-price differences (12,266-14,234 yen; average 13,287 yen), suggesting that patients think the benefit of reduced side effects from non-ionic contrast agents has a value that is equal to or higher than the actual NHI-prices of these agents. Further, analysis of patient profiles indicated that patients' willingness-to-pay went up with age and income but decreased when age exceeded 60 years, a finding which also suggests that the willingness-to-pay amount is closely related to the economic strength of patients.     

Effects of radiographic contrast media on monolayer cell cultures

The relationship between iodine concentration, osmolality, and toxicity for nine different contrast media was studied. High osmolal conventional ionic contrast media (Na-metrizoate, Na-iothalamate, meglumine/Na-diatrizoate, meglumine-calcium-metrizoate) and the new low osmolal nonionic (Metrizamide, iopamidol, iohexol) and ionic dimer (Meglumine/Na-ioxaglate) contrast media were tested. Monolayer cell cultures of human cervical carcinoma in situ cells were used as a test system. The toxicity of contrast media on cell cultures was strongly dependent on the osmolality, and different contrast media with the same osmolality had about similar effects on the cell cultures. However, contrast media seem to have some additional and more specific effects since equiosmolal saline and mannitol were better tolerated. When the toxicity was related solely to iodine concentration it emerged that the new low osmolal contrast media were much better tolerated than the high osmolal conventional contrast media.     

Effect of ionic and non-ionic contrast medium on aortic and pulmonary arterial pressure. An angiocardiographic study in rabbits.

Effects in angiocardiography from injections into the right atrium of rabbit hearts of a new, non-ionic contrast medium (Amipaque) were studied and were compared with the effects from injections of an ionic medium (Isopaque Coronar) at a dose of 3 ml/kg rabbit and concentration of 370 mg I/ml. Forty-seven experiments in 11 rabbits are reported. Amipaque produced a significantly (p less than 0.001) smaller increase in pulmonary arterial pressure (29%) than Isopaque Coronar (82%). Simultaneously (within 12 seconds from the beginning of an injection) Amipaque produced an increase in aortic pressure of 21%. About 10-15 seconds later when the contrast media had reached peripheral vessels Amipaque produced a significantly (p less than 0.001) smaller decrease of aortic pressure (12%) than the decrease produced by Isopaque Coronar (40%). The differences found between the two types of contrast media are believed to be related to, among other factors, their different osmolality. The osmolality of Amipaque was about one third of the osmolality of Isopaque Coronar.     

Direct cardiac effects of an ionic and a non-ionic contrast medium in dogs

Direct cardiac effects of ionic diatrizoate (Uromiro) and non-ionic iopamidol (Iopamiro) were investigated in "in situ" heart-lung preparation of 19 vagotomized dogs. Diatrizoate was found to induce considerably greater alteration in plasma osmolality and subsequent dehydration of the myocardium compared with iopamidol. Myocardial dehydration resulted in a decrease of left ventricular compliance and in that of cardiac performance. Diatrizoate was shown to influence the myocardium not only by its hyperosmolarity but also by a direct action. Heart rate was reduced by both contrast media.     

Effects of intravenous administration of a new nonionic dimeric contrast medium on the coronary circulation. Comparison with monomeric ionic and nonionic media

Contrast media injected into the circulation produce a variety of cardiovascular effects. Agents with low osmolality and low concentrations of cations cause considerably less hemodynamic effects. This study compared the effects of a nonionic dimer, iotrol, which has an osmolality (340 mosm/kg) close to that of serum (290 mosm/kg), with a standard ionic monomer, meglumine diatrizoate, and a nonionic monomer, iosimide. The effects of intravenous bolus injection of these three contrast agents on coronary and systemic hemodynamics were studied in eight anesthetized dogs. The influence of the contrast media on subendocardial and subepicardial perfusion was assessed by injecting radioactive microspheres into the left atrium 30 seconds after injection of the media. Alterations in coronary hemodynamics occurred with both iosimide and meglumine diatrizoate. Iotrol produced minimal changes in coronary hemodynamics. Thus, iotrol is the least perturbing contrast indicator and seems the best for use in quantitative digital subtraction and dynamic computed tomography studies designed to measure myocardial perfusion.