A comparison of Hexabrix and Renografin-60 in knee arthrography

Forty patients were randomized in a double-blind study to compare the safety and diagnostic quality of Hexabrix vs. Renografin-60 without epinephrine in knee arthrography. Hexabrix is a monoacidic dimer of meglumine and sodium salts of ioxaglic acid with a lower osmolality than conventional contrast agents of similar concentration (32% iodine). Initial films were of equally high diagnostic quality for both groups, but delayed films at 20 and 30 min significantly favored Hexabrix for diagnostic quality. Hexabrix proved to be a safe and effective contrast agent for knee arthrography.     

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.     

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.     

Comparison of cellular mechanisms underlying histamine release from rat mast cells induced by ionic and nonionic radiographic contrast media

PURPOSE: To determine the cellular mechanisms underlying mast cell histamine release induced by ionic and nonionic radiographic contrast media. MATERIALS AND METHODS: Histamine release from rat pulmonary mast cells was measured after incubation with various radiographic contrast media. The cellular cAMP content was determined by an enzymatic immunoassay. RESULTS: Both ionic and nonionic contrast media stimulated the histamine release, although the former was more potent than the latter. Dibutyryl cAMP suppressed histamine release evoked by ionic but not nonionic contrast media in a manner dependent on A kinase. The cellular cAMP content was lowered only by ionic contrast media. However, a secretory phospholipase A2 inhibitor p-bromophenacyl bromide inhibited both ionic and nonionic contrast media-evoked histamine releases. CONCLUSION: We demonstrated for the first time the difference and similarity in the cellular mechanisms underlying histamine release induced by ionic and nonionic contrast media, in which the reduction in cAMP was specific for ionic materials and the activation of secretory phospholipase A2 may be common to both agents.     

Dacryocystography: comparison of water-soluble and oil-based contrast agents

Dacryocystography has been widely used in the assessment of the nasolacrimal duct system, particularly in patients with epiphora. Our study was undertaken to evaluate image quality and level of patient discomfort during examinations with water-soluble contrast agents (iohexol [Omnipaque 240], iopamidol [Isovue 200 and 300], and 52.7% diatrizoate meglumine and 26.9% iodipamide meglumine [Sinografin]) compared with the iodized oil-based contrast agent Lipiodol. Fifty-five dacryocystograms were obtained from 41 consecutive patients. The procedure was performed first with a water-soluble contrast agent, then repeated with Lipiodol. A distention technique was used with conventional radiography. Patients were asked to evaluate their level of discomfort (none, mild, moderate, severe). The images were evaluated separately by two radiologists, blinded to which water-soluble agent was employed, and the images were graded on a five-point scale. Images obtained with Lipiodol were significantly better than those with other agents (P less than .02), and image quality deteriorated as iodine concentration decreased. Use of Isovue 300 and Sinografin produced significantly more patient discomfort (P less than .03) than the use of other agents. The authors conclude that, in most instances, Lipiodol is the contrast agent of choice with regard to both highest level of patient comfort and greatest conventional radiographic image quality among the agents compared.     

Criteria for choice and use of contrast media in intra-arterial D.S.A

The authors investigated the optimal characteristics of contrast media for use in intra-arterial DSA. 209 injections in 108 patients were evaluated, most of them in the abdominal and peripheral regions. In order to decrease contrast media osmolarity and obtain an adequate mixing with blood, contrast media with low iodine concentration were injected using the same volumes and flow rates of conventional arteriography. Good results were obtained with ionic contrast media, 100 and 150 mgI/ml. depending on the area investigated. The low concentrations allowed the use of ionic agents with an osmolarity very close to that of the non ionic contrast media: the pain has been eliminated and the heat sensation reduced. Furthermore the comparison with the cost of nonionic agents shows a great saving.     

A clinical trial of a new low osmolality contrast medium. Sodium and meglumine ioxaglate (Hexabrix) compared with meglumine iothalamate (Conray) for carotid arteriography.

The discomfort of cerebral arteriography is due mainly to the osmolality of the contrast medium injection. A new low osmolality contrast medium--Hexabrix (32% iodine)--sodium and meglumine salts of ioxaglic acid was compared with Conray 280 (28% iodine)--meglumine iothalamate for carotid arteriography in 33 conscious patients. 30 patients preferred the ioxaglate solution which caused significantly less sensation of heat. Three patients could not distinguish between the two media. No patient preferred iothalamate. Ioxaglic acid is a newly synthesized mono-acid dimer. Its salts produce the same osmolality as non-ionics (e.g. metrizamide), and one third of the osmolality of currently used mono-valent salts (e.g. meglumine iothalamate) in solutions of the same iodine content. Low osmolality contrast media have significant clinical advantages and will probably become the media of choice for arteriography and venography.     

Cytostatic effects of radiographic contrast media in synchronized cell cultures

The cytostatic effects of conventional high osmolal ionic contrast media (meglumine-calcium metrizoate and Na-metrizoate) and new low osmolal nonionic contrast media (iohexol and iopamidol) in synchronized cell cultures were tested. The cell-cycle prolongation was most pronounced when the contrast media were added in the G1 phase, but there was also a marked effect when the contrast media were added in the S phase or late in the G2 phase. The cytostatic effect even persisted into the first cell cycle following the termination of the exposure. All four contrast media exerted effects stronger than that of equiosmolal saline. Iohexol and iopamidol produced a more severe effect than meglumine-calcium metrizoate and Nametrizoate at equal osmolality. Thus, the cytostatic effect of contrast media cannot be explained only by hypertonicity; the contrast media must have an additional specific cytostatic effect. When the cytostatic effect was related to iodine concentration, the new low osmolal nonionic contrast media influenced the cell cycle less than the conventional high osmolal ionic contrast media.     

Adverse reactions during intravenous urography: are these due to histamine release?

The effects of four different radiographic contrast media (Urovison 58%, Hexabrix 320, Iopamiro 370 and Omnipaque 300) have been examined with respect to histamine release, cardiovascular changes and adverse drug reaction (ADR) in a group of 200 patients undergoing intravenous urography. Each patient received only one of the four agents, which were allocated on a random basis. Urovison produced the greatest number of ADRs. Iopamiro caused the least. No significant correlation between the magnitude of the change in plasma histamine following injection of radiographic contrast medium and the production of a particular ADR could be demonstrated. Heart rate increased significantly following the administration of Urovison, Hexabrix and Iopamiro in the absence of any appreciable change in blood pressure. These results and our earlier findings would favour the use of the low-osmolality contrast media in intravenous urography to minimize ADRs, histamine release and patient discomfort.     

Effect of oral contrast agents on computed tomography-based positron emission tomography attenuation correction in dual-modality positron emission tomography/computed tomography imaging

RATIONALE AND OBJECTIVES: To evaluate the effect of iodine- and barium-based contrast agents on the computed tomography (CT)-based positron emission tomography (PET) attenuation correction in dual-modality PET/CT. METHODS: Experiments were conducted on a Society of Nuclear Medicine/National Electrical Manufacturers Association-PET phantom equipped with cylinders containing [18F]-2-fluoro-2-desoxy-D-glucose. The main compartment was filled with iodine (0.5-10%), barium (0.5-50%), or water (negative control). The error in attenuation correction was determined by comparison of measured tracer quantities in the presence of contrast agents with expected quantities. Contrast agent attenuation was demonstrated to be comparable to in vivo conditions. RESULTS: The presence of contrast agents resulted in an overestimation of the intracylindrical activity concentration on PET images and overestimation directly related to contrast concentrations (iodine 5-38%; barium 15-580%). Iodine and barium concentrations in clinical use resulted in an activity overestimation of 20 +/- 1.8% for iodine and 21 +/- 2.9% for barium. CONCLUSION: An overestimation of the tracer activity concentration is to be expected in the presence of oral contrast agents, if PET attenuation correction is attained CT-based.     

Pharmacology and physiology of the biliary radiographic contrast materials.

(1) Solubilization of Telepaque in the intestine is a limiting factor in the rate of intestinal absorption. Bilopaque and Oragrafin are more water-soluble and appear to be better absorbed than Telepaque. (2) Bile salts in the intestinal lumen increase the solubility of Telepaque. Therefore, a fatty meal administered with the Telepaque is desirable to evacuate bile salts from the gallbladder into the intestine. This is not required for the more water-soluble agents, Biopaque and Oragrafin. (3) The degree of protein binding of the contrast agents can be related to the degree of toxicity. Cholografin is the most highly bound and is the most toxic. (4) Hepatic receptor proteins may specifically bind the biliary contrast agents. This may be the reason that the renal contrast materials are poorly escreted in bile compared to the biliary contrast agents. (5) Telepaque is conjugated in the liver with glucuronide making the compound more soluble in bile. This prevents precipitation of Telepaque in the gallbladder and avoids reabsorpiton from the intestine. (6) The biliary excretion of Telepaque is facilitated by bile salts. Therefore, the administration of a fatty meal with Telepaque not only increases the rate of intestinal absorption of Telepaque but also the rate of biliary excretion. (7) The rate of biliary excretion of both the oral and the intravenous contrast agents appears to be limited by a hepatic transport maximum. Above a certain dose, increased amounts of the contrast agents do not result in more rapid excretion of the agents into bile. Rapid infusion of intravenous contrast agents results in high plasma concentration and greater urinary excretion, without increasing the biliary excretion. It does not appear to be indicated in clinical practice. (8) The biliary concentration of the contrast agents used for intravenous cholangiography is determined by their rate of biliary excretion, the choleretic effect of the contrast agent, and factors that determine the rate of basal bile flow. Fixed coupling of water with the biliary excretion of these contrast agents imposes an inherent limitation on the concentration of the contrast agent in bile. It appears that the biliary concentration of the intravenous contrast materials can be increased by having the patient fast prior to intravenous cholangiography. This decreases the enterohepatic circulation of bile salts and the rate of bile-salt-dependent bile flow. (9) Failure of the gallbladder to visualize after administration of Telepaque when there is adequate biliary excretion may be due to cystic duct obstruction, failure of the inflamed gallbladder mucosa to reabosrb water, or reabsorption or the contrast agent by the diseased gallbladder mucosa. (10) Maximum concentration of Telepaque occurs at 14-19 hr after ingestion. It is at this time that radiographs of the gallbladder should be made. With Bilopaque, peak concentration occurs at 10 hr so radiographs can be made earlier when Bilopaque is used.     

Gadobutrol: an alternative contrast agent for digital subtraction dacryocystography

We report the application of gadobutrol as a contrast medium for digital subtraction dacryocystography (DS-DCG) in patients with known allergy to iodinated contrast agent. Gadobutrol has the double gadolinium concentration (1.0 mmol/ml) of other gadolinium-based contrast agents. Quality of the DS-DCG images obtained with gadobutrol was comparable to DS-DCG images obtained with iodinated contrast medium. Radiodensity measurements using a micro-CT scanner confirmed a high radiodensity of gadobutrol which was comparable to the radiodensity of iopentol with a iodine concentration of 250 mg/ml and only approximately 20% lower than the radiodensity of iopentol with a concentration of 300 mg/l. Gadobutrol is a well-suited substitute for DS-DCG in patients with allergy to iodinated contrast agents.     

Hemodynamic and electrocardiographic effects of ioversol during cardiac angiography. Comparison with iopamidol and diatrizoate

We studied the hemodynamic and electrocardiographic responses to left ventriculography and coronary arteriography with three angiographic contrast agents. Two were nonionic agents (ioversol 32% iodine, 60 patients, and iopamidol 37% iodine, 30 patients). The third was a conventional ionic agent (diatrizoate 37% iodine, 30 patients). Cardiovascular hemodynamics and the electrocardiogram were recorded for 5 minutes after left ventricular injection and for 2 minutes after coronary injections. Following left ventriculography, diatrizoate caused a greater increase in cardiac output, left ventricular end diastolic pressure, and corrected QT interval while causing a greater decrease in arterial pressure than did either ioversol or iopamidol, which were indistinguishable from each other. Following left coronary arteriography, diatrizoate caused a significant decrease in heart rate, prolongation of the corrected QT interval, and increase in T wave amplitude. In contrast, neither ioversol nor iopamidol caused significant changes in any electrocardiographic parameters. Adverse reactions were more common with diatrizoate than with either ioversol or iopamidol. There were no recognizable differences in angiographic image quality among the three agents. We conclude that the angiographic performance of ioversol is equivalent to that of iopamidol and that both cause less hemodynamic and electrocardiographic disturbance than diatrizoate.     

Comparison of vascular opacification after bolus injection of iodixanol-320 iohexol-350.

RATIONALE AND OBJECTIVES. The vascular opacification characteristics of a new nonionic, dimeric contrast agent, iodixanol, have been compared with a nonionic, monomeric agent, iohexol, using ultrafast computed tomography (UFCT). METHODS. In 10 experiments with mongrel dogs, the contrast agents were alternately injected into the animal's left atrium, and UFCT images were obtained at four cross-sectional levels through the carotid arteries. Time-density curves were then obtained for each carotid artery and each agent. The peak height and area under the curves were compared for each agent. RESULTS. Iohexol provided significantly (P < or = .05) greater opacification, determined by paired Student's t tests. CONCLUSION. This result was predicted from the greater iodine concentration of iohexol (350 mg/mL) compared with iodixanol (320 mg/mL); the difference was greater than expected based on iodine content alone.     

Plasma histamine levels following administration of radiographic contrast media

The effect of two conventional high-osmolality and two new low-osmolality contrast media on plasma histamine levels has been examined. The study population included 25 patients undergoing intravenous urography with Urovison 58% (sodium and meglumine diatrizoate), 24 patients receiving intravenous Hexabrix 320 (sodium and meglumine ioxaglate) for urography, 16 patients receiving intravenous Iopamiro 370 (iopamidol) for urography and 12 patients receiving Urografin 76% (sodium and meglumine diatrizoate) for coronary angiography. Seventy-four percent of the 77 patients studied suffered adverse reactions ranging from a feeling of warmth and nausea to laryngeal oedema and bronchospasm. Hexabrix 320 and Iopamiro 370 were associated with the least patient discomfort. All contrast agents usually produced a rise in plasma histamine following injection (Iopamiro 370 causing the least change) and the histamine levels then fell towards preinjection values over a space of about 10 minutes. No relationship was observed between the magnitude of the increase in histamine and the severity of the reaction that occurred. However, a relationship was suggested between the mean peak plasma histamine level achieved and the occurrence of a Grade II reaction (i.e., dry retching/vomiting, mild urticaria or rash). These findings raise the probability that histamine contributes to the more severe grades of reaction to radiographic contrast media.     

In vitro and in vivo release of histamine by contrast media in the rat.

Some contrast media are able to release histamine from isolated mast cells of the rat and produce degranulation of these cells. Such properties are fairly correlated with the ability to increase vascular permeability in vivo and to produce a drop in blood pressure. If histamine is similarly being released in humans many untoward effects of these agents referred to clinically might be thus explained.     

A simplified radioenzymatic method for the study of whole blood histamine release in patients receiving radiographic contrast media.

With the availability of a newly developed, histamine-dependent allergy blood test, the authors studied the effect of ionic and nonionic radiocontrast media (RCM) on the in vitro release of histamine from whole blood obtained from 61 patients undergoing diagnostic arteriography. The ionic RCM, sodium meglumine diatrizoate (60 to 378 mmol/L), induced the release of a significantly (P less than .005) higher amount of histamine from blood compared with the nonionic agents, iopamidol and ioversol. Diatrizoate triggered significantly (P less than .05) more histamine release from the blood of eight patients with a history of adverse reactions to RCM than it did in 53 nonreactors; however, there was no appreciable difference in histamine release between reactive and nonreactive groups when stimulated with iopamidol and ioversol.     

Excretion of contrast media by the immature rabbit. Comparison of Renografin and Iopamidol

The excretion of iodinated contrast media was studied in 13 immature rabbits after the intravenous injection of 2 ml/kg (approximately 600 mg I/kg) of radio-labelled Renografin-60, a high osmolality agent (1510 mOsm/kg), or Iopamidol-300, a new agent with a much lower osmolality (616 mOsm/kg). Renografin, but not Iopamidol, induced an immediate but transient 40% fall in blood pressure, a marked diuresis that was 3.4 times greater at its maximum than for Iopamidol, and a much lower urinary iodine concentration at the time of maximum diuresis (Renografin: 90.3 +/- 9.2 microgram/ml; Iopamidol: 213 +/- 32.9 microgram/ml). No difference between the two contrast media was found for plasma iodine concentration, renal clearance from the plasma, urinary iodine excretion rate or volume of distribution. In five additional rabbit pups, formal clearance studies made using a constant IV infusion of the agents and timed collections of urine and plasma showed that Iopamidol and Renografin were cleared at the same rate by the kidneys (P greater than 0.9).     

Comparison of diatrizoate, iopamidol, and ioxaglate for the contrast enhancement of experimental hepatic tumors in CT

The accumulation of diatrizoate and two new low osmolality contrast agents, iopamidol and ioxaglate, was investigated in three experimental tumors (a well differentiated mammary adenocarcinoma, a poorly differentiated colon carcinoma, and a hepatoma) in the rat. All three tumors were implanted into the liver 12 to 14 days prior to intravenous injection of the contrast agents in a dose of 300 mg iodine per kg. Iodine concentrations were determined in blood, liver, and tumors at 1, 5, 10, and 30 minutes using x-ray energy spectrometry. Ratios between tumor iodine and blood iodine concentrations increased more with time with diatrizoate than either iopamidol or ioxaglate and were at 30 minutes significantly greater for diatrizoate than the other two agents. This suggests that the contrast medium efflux from the vascular compartment into the extravascular compartment of all tumors is greater for diatrizoate than either iopamidol or ioxaglate. Although it is known from clinical experience that the differential enhancement between hypodense hepatic tumors and liver parenchyma decreases rapidly with time after contrast administration, this investigation suggests that the substitution of diatrizoate by either iopamidol or ioxaglate should not affect appreciably the contrast enhancement in this condition in dynamic CT completed within the first minutes after contrast administration. In a later phase, after contrast administration, however, both iopamidol and ioxaglate should conceal hypodense hepatic tumors less than diatrizoate.     

Contrast venography of the leg: diagnostic efficacy, tolerance, and complication rates with ionic and nonionic contrast media

A prospective, three-center study of two contrast agents for leg venography was performed to evaluate both the relative frequency of adverse effects and whether low-osmolality agents provided significant advantages for this procedure. Fifty-four patients were studied with the standard preparation (iothalamate meglumine) and 57 with a nonionic agent (iopamidol). Both were used at an iodine concentration of 200 mg/mL, and there were no differences in volume of contrast material, duration of infusion, percentage of positive studies, or overall diagnostic adequacy. Patient discomfort was less with iopamidol than with iothalamate (18% vs. 44%), although discomfort was generally mild in both groups. By objective follow-up studies, the frequency of postvenographic thrombosis was not significantly different in the two groups (8% vs. 9%). Contrast venography, then, had a low frequency of complications when either a dilute conventional or a low-osmolality agent was employed. Although the frequency of postvenographic thrombosis was low with both agents, patient discomfort was less with the low-osmolality formulation.