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PubMed2001

Safety of magnetic resonance contrast media.

Intravenous contrast media, specifically the gadolinium chelates, are well accepted for use in the clinical practice of magnetic resonance imaging. The gadolinium chelates are considered to be very safe and lack (in intravenous use) the nephrotoxicity found with iodinated contrast media. Minor adverse reactions, including nausea and hives, occur in a low percentage of cases. The four agents currently available in the United States cannot be differentiated on the basis of these adverse reactions. Severe anaphylactoid reactions are also known to occur with all agents, although these are uncommon. This review discusses the safety issues involved with intravenous administration of the gadolinium chelates and off-label use. The latter is common in clinical practice and permits broader application of these agents.

Anaphylaxis↗
PubMed1989

Histamine release from canine lung and liver mast cells induced by radiographic contrast media.

Radiographic contrast media are commonly used diagnostic aids to improve imaging, e.g. in computerized tomography. However, the routine application of these agents may cause adverse allergic/pseudoallergic reactions. In order to understand more completely the underlying mechanisms involved in these reactions, experiments on histamine release both in vivo and in vitro are necessary. Using canine mast cell suspensions from lung and liver, we have investigated the histamine release caused by six commonly used preparations. The dog is an ideal model for both in vitro and in vivo studies not only by virtue of its size but also because of its similarity to man with respect to e.g. cardiovascular reactions after drug-induced histamine release. The two non-ionic preparations (Solutrast, Ultravist) released little histamine from both cell types (ca. 4-6%). The ionic contrast media (Angiographin, Hexabrix, Telebrix, Rayvist) dose-dependently released histamine from the liver cells and pulmonary cells (maximum release between 18-35%). The liver cells (the liver is the shock organ in the dog) reacted more strongly to these agents than the pulmonary cells, thus providing further evidence for mast cell heterogeneity and the importance of selecting the appropriate mast cell model for the investigation.

Animals↗
PubMed1985

[Contrast media in magnetic resonance tomography. A review. 1. Physicochemical and pharmacological bases of MR contrast media using gadolinium-DTPA as an example].

The principles underlying contrast media for MR tomography are totally different from those for conventional contrast media. Substances suitable for MR tomography are paramagnetic complexes which alter the relaxation times of the tissues. Signal intensity on the MR images are influenced correspondingly. The mode of action of MR contrast media is explained. Gadolinium-DTPA, the first MR contrast medium in clinical use by means of intravenous injection, is described. Its tolerance has been investigated by animal experiments and its effectiveness as an contrast agent has been studied in normal individuals. In the second part of the paper, early results from the use of gadolinium DTPA are given. The additional information which can be obtained by using MR contrast media is discussed.

Animals↗
PubMed1995

Vasoconstriction of isolated arteries induced by angiographic contrast media. A comparison of ionic and non-ionic contrast media iso-osmolar with plasma.

Angiographic contrast media (CM) may cause both vasodilatation and vasoconstriction, effects that can only be partly be explained by the media's hyperosmolality. The present study describes a CM-induced vasoconstriction of isolated rabbit coronary arteries that depends on chemotoxicity and ion content of the CM. Rings of arteries were mounted in tissue baths and the constrictions induced by different CM were measured. Iotrolan and iodixanol (non-ionic dimers) caused the most powerful constrictions followed by iohexol (non-ionic monomer) and mannitol. Ioxaglate (ionic dimer) and diatrizoate (ionic monomer) caused no or weak constrictions. By comparing these findings with previous studies, it is concluded that non-ionic media cause vasoconstriction due to depolarization of the smooth muscle cells, an effect that for iohexol can be counteracted by addition of 30 mM NaCl. The ionic media seem to cause hyperpolarization of the cells. This difference between non-ionic and ionic CM might be one of the reasons for the lower tendency of non-ionic CM to cause vasodilatation clinically.

Angiography↗
PubMedDate not supplied

Ionic and non-ionic contrast media used for contrast-enhanced computed tomography in experimental pancreatitis.

Contrast enhancement of the pancreas was studied in pigs using dynamic computed tomography in experimental oedematous and haemorrhagic/necrotizing pancreatitis during the first two minutes after injection of an intravenous bolus of non-ionic contrast medium (iohexol). The prospects of separating the two forms of the disease, known to be possible with ionic contrast media, were tested with a non-ionic contrast medium. In the oedematous form, contrast enhancement after 5 hours of the disease was significantly higher than in the haemorrhagic/necrotizing form. Contrast enhancement after 30 hours of disease tended to vary with the severity of the disease, showing that the course of oedematous pancreatitis is dynamic. Intermediate forms occur and follow-up studies are needed during the disease. A non-ionic contrast medium proved as good for separating the two forms of the disease in the early phase as were ionic contrast media. In severely ill patients, non-ionic contrast media should therefore be used.

Animals↗
PubMed1997

Deaths related to iodinated contrast media reported spontaneously to the U.S. Food and Drug Administration, 1978-1994: effect of the availability of low-osmolality contrast media.

PURPOSE: To determine whether reports of iodinated contrast medium-related deaths have decreased since low-osmolality contrast media (LOCM) became widely available in the United States. MATERIALS AND METHODS: With use of reports to the U.S. Food and Drug Administration Spontaneous Reporting System, data on iodinated contrast medium-related deaths after LOCM became available (1987-1994) were compared with data on deaths in the period before (1978-1986) and with data on deaths in an even earlier period (1967-1977). RESULTS: In 1967-1994, more than 1,000 contrast medium-related deaths were reported, 850 occurring during 1978-1994. Excluding 22 myelography-related deaths, 37% [corrected] more deaths were reported each year in 1987-1994 than in 1978-1986. Most of this increase was associated with the use of nonionic contrast media. In 1966-1977, 228 deaths were reported; in 1978-1986, 376; and in 1987-1994, 474. In 1987-1994, 220 deaths were associated with use of high-osmolality contrast media alone, 32 with ionic LOCM alone, 214 with nonionic LOCM alone, and eight with combinations of contrast media. CONCLUSION: Despite the availability of LOCM in the United States, data for 1978-1994 do not show a marked decrease in contrast medium-related deaths. Since 1990, more deaths have been associated with LOCM than with conventional contrast media. Although these data have substantial limitations, they shed some light on contrast medium use and safety.

Adverse Drug Reaction Reporting Systems↗
PubMed1980

Adverse reactions to contrast media: a report from the Committee on Safety of Contrast Media of the International Society of Radiology.

More than 300,000 case reports have been collected in a prospective survey of adverse reactions to intravascular contrast media. The reports were provided by radiologists in the United States, Canada, Europe, and Australia and represent the largest survey of its type to date. The overall incidence of reactions was about 5%, lower than any rate reported in the recent literature, and was strikingly similar in all participating countries.

Age Factors↗
PubMed1987

Penetration of the brain by nonionic water soluble tri- and hexaiodinated contrast media. Experimental autoradiographic study of two contrast media: Iotrol and Iopamidol labelled with iodine 125.

After suboccipital injection of Iotrol and Iopamidol labelled with iodine 125 in rabbits, we measured residual radioactivity in the whole brain and optical density on autoradiographs of brain sections obtained 2, 8 and 24 h after injection. Residual radioactivity is higher with Iotrol than with Iopamidol after 8 h and 24 h. At densitometry, while the penetration of the cortex is the same with both media at 2 h (although subcortical passage of Iotrol is greater), by 8 h the concentration of Iopamidol is twice that of Iotrol, and at 24 h it is three times as high. A similar pattern was seen in the subcortical region. These densitometric findings are in agreement with previous electrophysiological studies, in which changes were less severe and more transient with Iotrol than with Iohexol. There is nevertheless an apparent lack of agreement between the studies of radioactivity and the electrical findings. The lower neurotoxicity of Iotrol may be explained by: a longer half-life in the subarachnoid space; its larger molecules, which inhibit diffusion in the extracellular fluid, and its more hydrophilic nature, which reduces intracellular penetration.

Absorptiometry, Photon↗
PubMed1994

Systemic and pulmonary haemodynamic effects of intravenous infusion of non-ionic isoosmolar dimeric contrast media. An investigation in the pig of two ratio 6 contrast media.

The systemic and pulmonary haemodynamic effects of i.v. infusion (1 ml/s) of high doses (4 ml/kg) of 2 non-ionic, isoosmolar dimeric contrast media (CM) were investigated in 17 female pigs. The 2 CM were iodixanol and iotrolan. Both CM induced a significant increase of the following parameters: mean arterial, mean right atrial, mean pulmonary arterial, mean pulmonary arterial occlusion pressure, cardiac output, stroke volume, and diuresis. The plasma concentration of atrial natriuretic peptide was significantly increased following infusion of the 2 CM. A significant decrease was seen in the systemic and pulmonary vascular resistance.

Animals↗
PubMedDate not supplied

Contrast enhancement pharmacokinetics of six ionic and nonionic contrast media.

The contrast enhancement of six contrast media (CM) was compared in 13 tissues of the rat after rapid intravenous bolus injection. The rats were sacrificed at 0 and 40 seconds and 2, 5, and 15 minutes after contrast injection. 125I labeled diatrizoate, metrizamide, ioxaglate, iohexol, iopamidol, and a nonionic dimer, iodecol, were each injected at a dose of 612 mg iodine per kg body weight, and iodine concentration (IC) and contrast enhancement were calculated from radioactivity measurements. Higher blood IC values were obtained with the nonionic CM; similar enhancement patterns were seen in the spleen, heart, lungs, and brain. Renal IC was directly related to the number of iodine atoms per ion or molecule of CM. In consequence, renal IC was inversely related to the CM osmolality, but no such correlation was seen with the blood IC. Metrizamide produced the greatest IC in the organs of the gastrointestinal tract. There was no apparent correlation of IC with molecular structure of physicochemical parameters of the CM in any of the other tissues studied.

Animals↗
PubMed2005

New pharmacological protocols to prevent or reduce contrast media nephropathy.

Contrast media associated acute renal failure represents the third cause of in-hospital renal function deterioration after decreased renal perfusion and post-operative renal insufficiency. Although generally benign, this complication shows a mortality rate ranging from 3.8% to 64%, depending on the increase of creatinine concentration. The mechanism by which contrast-induced renal failure occurs is not well understood. Contrast agent-associated nephrotoxicity appears to be a result of direct contrast induced renal tubular epithelial cell toxicity and renal medullary ischemia. Furthermore, a key mechanism seems to be alteration in renal dynamics, probably caused by imbalances between vasodilator and vasoconstrictor factors, including the activities of nitric oxide, prostaglandins, endothelin and reactive oxygen species. Recommendations to prevent contrast-associated nephrotoxicity are: 1) periprocedural hydration, 2) use of a low osmolality contrast, and 3) limiting the amount of contrast agent. Recently, considerable interest has resulted from the preliminary positive data on the effectiveness of prophylactic administration of antioxidant compounds (such as acetylcysteine and ascorbic acid) and fenoldopam.

Acetylcysteine↗
PubMed2003

Contrast-enhanced magnetic resonance angiography: development and optimization of techniques for paramagnetic and hyperpolarized contrast media.

Contrast-enhanced magnetic resonance angiography (CE-MRA) is a diagnostic method for imaging of vascular structures based on nuclear magnetic resonance. Vascular enhancement is achieved by injection of a contrast medium (CM). Studies were performed using two different types of CM: conventional paramagnetic CM, and a new type of CM based on hyperpolarized (HP) nuclei. The effects of varying CM concentration with time during image acquisition were studied by means of computer simulations using two different models. It was shown that a rapid concentration variation during encoding of the central parts of k-space could result in signal loss and severe image artifacts. The results were confirmed qualitatively with phantom experiments. A postprocessing method was developed to address problems with simultaneous enhancement of arteries and veins in CE-MRA of the lower extremities. The method was based on the difference in flow-induced phase in the two vessel types. Evaluation of the method was performed with flow phantom measurements and with CE-MRA in two volunteers using standard pulse sequences. The flow-induced phase in the vessels of interest was sufficient to distinguish arteries from veins in the superior-inferior direction. Using this method, the venous enhancement could be extinguished. The possibility of using HP nuclei as CM for CE-MRA was evaluated. Signal expressions for a flow of HP CM imaged with a gradient echo sequence were derived. These signal expressions were confirmed in phantom experiments using HP 129Xe dissolved in ethanol. Studies were also performed with a new CM based on HP 13C. The CM had very long relaxation times (T1, in vivo/T2, in vivo approximately 38/1.3 s). The long relaxation times were utilized in imaging with a fully balanced steady-state free precession pulse sequence (trueFISP), where the optimal flip angle was found to be 180 degrees. CE-MRA with the 13C-based CM in rats resulted in images with high vascular SNR (approximately 500). CE-MRA is a useful clinical tool for diagnosing vascular disease. With the development of new contrast media, based on hyperpolarized nuclei for example, there is a potential for further improvement in the signal levels that can be achieved, enabling a standard of imaging of vessels that is not possible today.

Animals↗
PubMed1998

Influence of contrast media on the response of rat renal arteries to endothelin and nitric oxide: influence of contrast media.

RATIONALE AND OBJECTIVES: Contrast media (CM) such as diatrizoate meglumine (DTZ) or iohexol can cause renal vasoconstriction in vivo, and this may initiate CM-induced nephropathy. Endothelin-1 (ET-1), a vasoconstrictor, and nitric oxide, a vasodilator, are key modulators of renal circulation. We tested the hypothesis that CM enhances arterial responses to ET-1, or diminishes responses to nitric oxide. METHODS: A video dimension analyzer continuously recorded changes in diameter of isolated, pressurized rat interlobar renal arteries (200-400 microm diameter) superfused with combinations of CM, ET-1, nitric oxide, and other vasoactive agents. RESULTS: Superfusion of arteries with 3.3% DTZ, but not with 3.3% iohexol, enhanced their sensitivity to ET-1 by approximately twofold, as assessed by shifts in concentration-response curves. Both DTZ and iohexol decreased the sensitivity of arteries to nitric oxide by approximately threefold. Neither DTZ nor iohexol affected arterial sensitivity to other vasoconstrictors (phenylephrine, potassium) or vasodilators (forskolin, diltiazem). CONCLUSIONS: Diatrizoate meglumine and iohexol may induce or augment renal vasoconstriction in part by causing selective alterations in arterial sensitivity to ET-1 and to nitric oxide.

Analysis of Variance↗
PubMed2002

[Allergy to iodinated contrast media].

Iodinated contrast media are responsible for immediate or delayed adverse reactions. Because of the wide use of these products, one must consider them as drugs. The delay and nature of the undesirable events must be carefully recorded because in some selected cases, a true allergic mechanism can be proved. Cutaneous skin tests identify the culprit drug and find safe alternative for the patient.

Anaphylaxis↗
PubMed1991

Plasma osmolality, iodine concentration and urographic images following high and low osmolar contrast media.

Three contrast media (sodium iothalamate, iopamidol and sodium/methylglucamine ioxaglate) in a dose of 240 mg iodine per kilogram of body weight were compared in clinical urography. The ionic monomer sodium iothalamate was the only medium to significantly elevate the plasma osmolality though it returned to normal values within 4 min. All three media exhibited first order linear kinetics. When corrected for the effects of diuresis, sodium iothalamate was shown to give the highest urinary iodine concentrations. On visual scoring sodium iothalamate produced better nephrograms and overall urograms than either of the low osmolar agents.

Contrast Media↗