Contrast, coagulation, and fibrinolysis

Some adverse clinical effects of intravascular radiologic contrast agents have been attributed to their interference with the normal hemostatic processes. This study compares the effects of the low osmolality agents with those of the conventional agents by in vitro studies of platelet function, fibrin formation, and fibrinolytic activation. In various degrees, all the contrast agents studied inhibit platelet aggregation and fibrin formation but show virtually no direct activation of fibrinolysis. The new low osmolality agents generally show lesser inhibitory effects on the hemostatic mechanisms. Some clinical implications are discussed.     

Comparison of the acute cardiovascular side effects of iopamidol, metrizamide and amidotrizoate after intracoronary and left ventricular injections

The acute cardiovascular side effects of iopamidol (osmolality: 0.8 osmol/kg), metrizamide (0.6 osmol/kg), and amidotrizoate (2.1 osmol/kg) during coronary arteriography (n = 30) and left ventriculography (n = 9) have been compared in anesthetized closed-chest dogs (n = 5). The influences of these contrast media on hemodynamics, coronary circulation, ECG and physicochemical properties of coronary sinus blood were evaluated. Following intracoronary injection, iopamidol and metrizamide cause positive inotropism while amidotrizoate initially induces cardiodepression. All contrast solutions lead to marked increase of myocardial blood flow. Electrocardiographic changes are greater after amidotrizoate (P less than 0.05). A fall of cationic content in coronary sinus blood is seen after each contrast medium. Amidotrizoate leads to more decrease of potassium (P less than 0.01) and both ionized and total calcium (P less than 0.001). Increase of osmolality and hydrogen ionic content is greater after amidotrizoate than after iopamidol and metrizamide (P less than 0.01). Following left ventricular injection, marked peripheral vasodilation, as seen after amidotrizoate, does not occur after low osmolality compounds. There are no significant differences between iopamidol and metrizamide in spite of the slightly higher osmolality of the former. Thus, both contrast materials should be equivalent with respect to their acute cardiovascular side effects under clinical conditions. Advantages of low osmolality radiological contrast media are discussed.     

Clinical experience with ioxaglate (Hexabrix) in selective coronary arteriography

This prospective nonrandomized study was performed to evaluate the safety and efficacy of, as well as patient tolerance for, a new low osmolality contrast medium, ioxaglate (Hexabrix), in 90 adult patients of both sexes who were referred to our cardiac catheterization laboratory for angiocardiography including selective coronary arteriography. Ioxaglate did not cause any major adverse effects; side effects were rare and mild. Hemodynamic changes were minimal, even in patients with severe coronary artery disease, and no arrhythmias were seen. The radiographic quality of angiograms was scored as good to excellent for each examination, and was equal to that of films performed using a conventional contrast medium. Ioxaglate may be the contrast medium of choice for angiocardiography, especially in patients at high risk, i.e., those with severe coronary artery disease or severe left ventricular dysfunction.     

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.     

A comparative trial of the diagnostic quality of and tolerance for two low concentration low osmolality contrast media for phlebography

We report a prospective randomised double blind study comparing the diagnostic quality of and tolerance for ascending phlebography in 100 patients using two different low osmolality contrast media, ioxaglate and iohexol, at a concentration of 200 mg I/ml. The immediate and delayed side effects were minimal in both groups and the difference between the two media was not statistically significant. All the phlebograms were of diagnostic quality. We conclude that both ioxaglate and iohexol are suitable agents for leg phlebography in low concentrations.     

Contrastes yodados de utilización en Radiología

Iodinated contrast media are widely used in Radiology practices with a very low rate of adverse effects, being contrast-induced nephropathy the most serious one. In the majority of cases it is temporary and reversible, even though it can increase the inhospital morbidity and mortality in patients with risk factors. We will describe the various measures of prevention, being hydration and use of non-ionic contrast low osmolality those which have demonstrated greater effectiveness. Precautions to be taken in some risk situations, as patients treated with metformin or with impaired renal function, are also discussed.     

Advantages of a low-osmolality ionic contrast medium in intra-arterial applications

Osmolality is recognized as a major contributing factor of contrast media related adverse reactions. The development of a new ionic contrast medium has made it possible to retain the ionic nature of contrast agents and have a lower osmolality than non-ionic and conventional ionic contrast media. Studies have indicated that low osmolality ionic contrast media is comparable to non-ionic agents and in some instances has proven to be superior to non-ionic contrast media.     

Radiological contrast media

1. This author believes that the present evidence (water shifts and vasodilatation) strongly indicates that low osmolality is probably the main advantage of the new contrast media. 2. Arteriographic adverse reactions (pain, vasodilatation) are less marked with the contrast medium of the lowest osmolality--i.e. ionic ioxaglate salts. 3. Minor adverse reactions (nausea and vomiting) are less marked with some non-ionic media (e.g. iohexol, iopamidol) than with ioxaglate but there are no data concerning the relative incidence of severe reactions or fatalities. 4. Dr. Lasser's suggestion in 1987, that 12 hours of corticosteroid prophylaxis reduces the adverse reaction rate of intravenous HOCM to the rate of LOCM reactions, awaits confirmation. However, corticosteroid prophylaxis will not reduce the side effects due to hyperosmolality, e.g. vasodilation, hypervolemia, and pain (on arterial injection). 5. Unless and until the necessary finances are available, I suggest LOCM (costing 12 times the price of HOCM in Canada and America) be used on a selective and discriminatory basis in three groups of patients: those undergoing painful procedures (e.g. peripheral arteriography), those undergoing potentially dangerous procedures (e.g. spinal angiography, coronary angioplasty) for patients considered on account of their previous medical history (e.g. asthma, allergy, previous adverse reactions, cardiac failure) to be at greater risk than the normal population.     

Comparison of the side effects of urographic contrast media (iothalamate, diatrizoate, iodamide, iopamidol) within the scope of a CT study

In 1465 patients the side effects of urographic contrast media for enhancement in CT were compared. The results show that the reaction frequency with iotalamate is 5.1%, with diatrizoate 7.0% and with iodamide 8.9%, but only 0.5% with iopamidol. The number of incidents to be expected with iopamidol is one decimal place lower. Obviously this has to do with its low osmolality. On the other hand we interpret the comparatively slightly higher incidence rate when using iodamide as a result of its higher lipophilic nature.     

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.     

Effect of intracarotid injection of iopamidol on local cerebral glucose utilization in rat brain

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of intracarotid injection of a nonionic, low-osmolar contrast medium (iopamidol) on local cerebral glucose utilization in the rat brain. Contrast medium was injected at 20 degrees C and at 37 degrees C, and the relative changes in local cerebral glucose utilization were measured. At 20 degrees C the viscosity of the contrast agent was about twice that of the same solution at 37 degrees C, and resulted in a statistically significant increase in local cerebral glucose utilization in the hemisphere ipsilateral to the side of intracarotid infusion. Saline control studies showed that the metabolic change was not related to either the solution temperature or the osmolality. These findings suggest that increased viscosity of a contrast medium may contribute to its neurotoxic effects during cerebral angiography, hence emphasizing the importance of preheating contrast material to avoid adverse reactions.     

Medicina nuclear y radiofármacos

Nuclear Medicine is a medical specialty that allows modern diagnostics and treatments using radiopharmaceuticals original radiotracers (drugs linked to a radioactive isotope). In Europe, radiopharmaceuticals are considered a special group of drugs and thus their preparation and use are regulated by a set of policies that have been adopted by individual member countries. The radiopharmaceuticals used in diagnostic examinations are administered in very small doses. So, in general, they have no pharmacological action, side effects or serious adverse reactions. The biggest problem associated with their use are the alterations in their biodistribution that may cause diagnostic errors.Nuclear Medicine is growing considerably influenced by the appearance and development of new radiopharmaceuticals in both the diagnostic and therapeutic fields and primarily to the impact of new multimodality imaging techniques (SPECT-CT, PET-CT, PET-MRI, etc.). It's mandatory to know the limitations of these techniques, distribution and eventual physiological alterations of radiopharmaceuticals, contraindications and adverse reactions of radiological contrasts, and the possible interference of both.     

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.     

Influence of contrast media osmolality on isolated rabbit heart performance.

A low osmolality contrast medium (Iopamidol) caused less cardiac disturbance on isolated rabbit heart than a high osmolality medium (Urografin). The same effects were induced by glucose solutions iso-osmolal with the two media. After perfusion with Propranolol (1 microgram/ml) and Cimetidine (1 microgram/ml) the observed effect was unaltered.     

Why choice of contrast medium matters

Three generations of iodinized contrast media (CM) are available for use in visualization of X-ray procedures. The three types of CM are all primarily based on a tri-iodinated benzene ring structure but differ in the structure of the attached side chains. First-generation CM have an ionizing carboxyl group, meaning they dissociate into two particles in solution. Consequently, these CM have a high osmolality that has been found to result in toxic effects such as pain and heat sensation on injection and a significant risk of CM-induced nephropathy (CIN)—an important adverse event associated with CM use. Low-osmolar CM (LOCM) were developed to overcome these toxic effects and are indeed better tolerated than high-osmolar CM (HOCM). In particular, LOCM have been shown to carry a lower risk of CIN, especially in high-risk patients. However, renal failure is still one of the most severe reported adverse events associated with LOCM. Therefore, a third generation of CM has been developed that is iso-osmolar with plasma offering potential benefits with regards to tolerability compared to LOCM. Two studies in high-risk patients have shown that iodixanol is associated with a lesser effect on renal function than the LOCM iohexol. Thus, clinical data have shown that an iso-osmolar CM should be considered in patients at high risk for CIN undergoing CM-enhanced procedures.     

Lumbar myelography with omnipaque (iohexol)

Summary Lumbar myelography with iohexol (Omnipaque) was performed in 103 consecutive adult patients with low back pain or sciatica. The patients were observed for 48 h with registration of possible adverse reactions. Mild or moderate transient side effects were recorded in 24 patients. No serious adverse reactions were noted, and EEG recorded in 25 patients showed no changes.     

Renal tolerance of iodinated low osmolality contrast agents. Clinical and experimental aspects

The low osmolality iodinated contrast agents (ICA), ionic or non ionic are now suggested too replace the usual high osmolality ICA. The main arguments are the better clinical tolerance and a lower renal toxicity. Recent experimental studies have clearly demonstrated that the low osmolality ICA presents a lower renal toxicity. On the rat, we have confirmed that the in vivo renal toxicity of low osmolality ICA, is lower than the high osmolality ICA toxicity. It is clearly demonstrated on man than the enzyme urinary excretion and proteinuria are little or not modified by the low osmolality ICA, but both are increased by high osmolality ICA. These changes are found with a normal glomerular filtration flow. No difference are noted in the creatinine concentration and clearance follow-up. However it is possible that the necessary population of patient to get statistically significative differences between both agents can be superior to the number of patients studied. In clinical practice, we think, that low osmolality ICA must be used for patients presenting one or several risk factors of acute renal failure.     

Effects of contrast media on the RR and QT interval during coronary arteriography

During coronary arteriography, transient prolongation of the RR and QT intervals can be observed to occur. Animal experiments have suggested that low-osmolality contrast media have less effect, but there have been few clinical studies of this phenomenon. We analyzed 95 electrocardiographic records from patients who had undergone coronary arteriography and assessed the maximal prolongation of the RR and QT intervals. The contrast media used for arteriography included meglumine sodium diatrizoate, iopamidol, iohexol, and meglumine sodium ioxaglate. Diatrizoate caused the greatest electrocardiographic changes. Among the low osmolality contrast media, ioxaglate caused the smallest bradycardial effect and iohexol the smallest prolongation of the QT interval. It appears necessary to consider some additional factors for osmolality or ionicity, such as the chemotoxicity of the chemical structure of the iodinated contrast medium moiety, when assessing their potential adverse effect on the cardiac conduction system.     

Ultrasound findings of iodide mumps

Iodide mumps, swelling of salivary glands after contrast medium injection, is a rare adverse reaction. We present a case in a 73-year-old man with advanced gastric cancer. About 10 min after a CT scan performed with intravenous injection of 140 ml of the low osmolality contrast agent Ioxaglate (Hexabrix 320, Guerbet, France), he complained of progressive swelling of the submandibular area. Ultrasound showed diffuse swelling and internal low echoic thick septa in the submandibular glands bilaterally. Approximately 1 h afterwards, the swelling of his submandibular glands started to regress and returned to normal within a day.     

MR imaging of the small bowel with increasing concentrations of an oral osmotic agent

The aim of this study was to assess the quality of MR imaging and level of adverse effects with increasing concentrations of gastrografin. This is a prospective study with 24 healthy volunteers which were randomised into four groups receiving 50%, 25%, 10% and 0% gastrografin. The endpoint was bowel image quality based on distension, signal homogeneity and wall delineation evaluated by three independent radiologists, and the maximum bowel diameter at three different levels. The subjects also scored any adverse events on a 1–5 scale. The interradiologist agreement was relatively good, with kappa values varying between 0.81 and 0.41. Improved bowel distension and image quality were achieved with increasing concentrations. But significant dose-response effects were found between increasing osmolalities and the bowel diameters and also versus the score of adverse events. The most frequent adverse reactions were diarrhea, nausea and lack of palatability. There is a gradient relationship between increasing osmolality of gastrografin and improved image quality and the score of adverse effects. The optimum concentration of gastrografin is dependent of the tolerance of the adverse events.