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.     

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.     

Iohexol vs. metrizamide: study of efficacy and morbidity in cervical myelography

A double-blind study was conducted in 60 patients undergoing either cervical or more complete myelography via C1-C2 puncture. Patients received either iohexol or metrizamide at a 300 mg l/ml concentration. The contrast media were equally efficacious in the production of high-quality radiographs and CT scans. However, the incidence of adverse reactions differed markedly. Of patients receiving metrizamide, 68% had some type of adverse reaction, whereas only 26% receiving iohexol had symptoms. The incidence of headache (metrizamide, 34%; iohexol, 26%) was not statistically different, but the quality of the headache differed: half of the metrizamide headaches were moderate or severe, whereas all iohexol headaches were mild. Nausea (31%) and vomiting (28%) were common with metrizamide but unusual (3% nausea) with iohexol. Of the metrizamide patients, 21% had overt psychologic changes that did not occur in the iohexol group.     

Comparison of intravenous contrast agents for CT studies in children.

One hundred and eighty children undergoing CT examination were randomly allocated to receive meglumine diatrizoate, iohexol, or iopamidol as their i.v. contrast agent. Minor side effects were detected in 85% of children receiving meglumine diatrizoate, in 18% of those receiving iohexol, and in 36% of those receiving iopamidol. Because many of these minor side effects cause patient motion or delay scanning after contrast medium injection, they potentially degrade image quality. These findings are an indication for the use of low osmolarity contrast agents for i.v. use in pediatric CT imaging.     

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.     

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.     

Contrast medium precipitation during abdominal CT

Abdominal computed tomography (CT) scans of 55 patients who had ingested Gastrografin (meglumine diatrizoate and diatrizoate sodium) diluted to 2% with tap water and flavored with a commercial fruit juice base were reviewed. Twenty patients (36%) demonstrated intraluminal precipitation of Gastrografin shown by focal areas of markedly increased attenuation within the gastric lumen or trapped within gastric folds. Beam-hardening artifact produced by precipitation was observed, which limited the diagnostic value of some examinations. In vitro CT scans of the same Gastrografin solution titrated with hydrochloric acid or sodium hydroxide showed that by raising the pH of the solution, precipitation was virtually eliminated. Fifty-one CT scans of the abdomen using a buffered Gastrografin solution demonstrated precipitation in only five patients. Properly buffered dilute oral Gastrografin solutions should significantly decrease the prevalence of precipitation during abdominal CT examinations.     

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.     

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.     

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.     

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.     

A comparison of iohexol and diatrizoate-meglumine in children undergoing cardiac catheterization

Iohexol (Omnipaque) and meglumine and sodium diatrizoate (Renografin-76) were compared in a double-blind, randomized study for their efficacy, safety, and hemodynamic effects as angiographic contrast agents in children. Forty-four children were randomly allocated to receive either iohexol or diatrizoate as a component of their routine or emergency cardiovascular evaluation. Following age stratification, baseline physiologic parameters were not significantly different between patients receiving either iohexol or diatrizoate. After systemic ventricular injection, iohexol produced significantly less hemodynamic alteration in systemic systolic blood pressure, systemic ventricular end-diastolic pressure, and dP/dt. Less alteration in heart rate and significantly less effect on the QT interval were seen with iohexol. Image quality was comparable, although significantly more patient mobility was associated with diatrizoate-meglumine. This study shows that iohexol, a nonionic contrast medium, causes less hemodynamic disturbance than diatrizoate-meglumine in children. Therefore, its use to be preferred in these potentially high-risk patients.     

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.     

Drip infusion urography with meglumine iodamide.

In a double-blind study of 283 patients (140 given iodamide and 143 diatrizoate), meglumine iodamide 24% produced a significantly greater degree of opacification than meglumine diatrizoate 30% (P less than 0.01 to P less than 0.001) in the renal calyces during the early phase of drip infusion pyelography. The agents were infused at a dose of 4.5 ml/kg, up to a maximum volume of 300 ml, over a period of about 10 min. The incidence and nature of laboratory abnormalities and clinical adverse reactions produced by the drugs were similar. No severe reactions occurred. The apparent superiority of the iodamide solution in the early stage of excretion, despite its lower iodine content, may be due to the partial secretion of iodamide by the renal tubules, as observed in other studies.     

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.     

Effects in vivo of iohexol and diatrizoate on human plasma acetyl- and butyryl-cholinesterase activity

PURPOSE: The aim of this study was to evaluate the effects of two iodinate contrast agents (CA), iohexol and diatrizoate, on human plasma acetyl-(AC) and butyrylcholinesterase(BC) activity. MATERIAL AND METHODS: Forty-eight patients (24 males and 24 females) scheduled for intravenous pyelography were randomly divided into four groups of 6 males and 6 females each, receiving as CA, respectively: iohexol (Omnipaque, Schering) 0.6 ml/kg body weight (G1); iohexol 1.2 mg/kg (G2); sodium and meglumine diatrizoate 58% (Urografin, Schering) 0.6 ml/kg (G3); sodium and meglumine diatrizoate 58% 1.2 ml/kg (G4). Blood samples were taken before and 5, 10, and 20 min after the injection. Enzymatic activity of AC and BC were measured by spectrophotometry. Plasma concentration of K, Na, Ca, and Mg was measured in all blood samples; blood pressure and plasma pH were measured after each sample collection. Statistical analysis was performed by Student's test. RESULTS: In G1 a reversible decrease of AC (12.9%) and BC (8.2%) plasma activity was observed at 10 min. In G2 a progressive decrease of AC (13.9%) and BC (18.4%) plasma activity was observed with a maximum at 20 min. In G3 a modest reversible decrease of BC plasma activity (5.4%) was observed. In G4 a modest progressive decrease of AC (7.3%) and BC (6.5%) plasma activities was observed. In all cases, AC and BC plasma activities remained within the normal range of values. Plasma concentration of K, Na, Ca, and Mg, as well as pH and systolic and diastolic pressure, did not show any change. No adverse effects was observed in our patients. CONCLUSIONS: Iohexol and diatrizoate induce in vivo a significant decrease of AC and BC plasma activities. The decrease is more pronounced for iohexol, a non ionic CA, which has a lower pharmacotoxicity than diatrizoate and adverse effects rate. No inference can be drawn about the relationship between plasma cholinesterase activity and adverse effects.     

Extravascular extravasation of radiographic contrast media. Effects of conventional and low-osmolar agents in the rat thigh

We compared the damage resulting from intradermal injection of four commonly used radiographic contrast media in laboratory rats. Sixty percent meglumine diatrizoate (Reno M 60) and ioxaglate (Hexabrix) produced significantly more ulceration and crusting on gross inspection and more necrosis, edema, and hemorrhage on histologic evaluation than iopamidol 300 (Isovue) or 0.9% (normal) saline. Thirty percent meglumine diatrizoate (Reno M Dip) had an intermediate toxicity, resulting in significantly more visible swelling and more microscopically detected hemorrhage than iopamidol or saline, but less ulceration/crusting and necrosis than Reno M 60 and ioxaglate. Since the three contrast agents of similar osmolality produced different degrees of tissue damage, our results suggest that factors other than high osmolality are partially responsible for determining the severity of injuries from extravasated contrast media.     

Knee arthrography: effects of various contrast media and epinephrine on synovial fluid

Changes in synovial fluid leukocytes, total protein, and total complement were studied in 58 patients after they underwent single contrast material-enhanced knee arthrography with ionic (sodium iothalamate, sodium meglumine diatrizoate, meglumine iothalamate) and nonionic (iopamidol, iohexol) contrast media. In 30 of 58 cases, 0.3 mg epinephrine was also injected. In patients examined without epinephrine, a significant increase in the number of leukocytes was observed when sodium iothalamate and sodium meglumine diatrizoate were used. When administered with epinephrine all ionic compounds produced significant leukocytosis; articular reactions were most evident in patients examined with sodium salts. No inflammatory changes in the synovial fluid were observed when nonionic compounds were used. These data suggest that sodium-containing compounds produce a greater reaction in the joint compared with other contrast media, nonionic compounds are better tolerated by the joint, and epinephrine increases the articular reaction to ionic contrast media.     

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.     

Gastrografin versus dilute barium for colonic CT examination: a blind, randomized study

Fifty patients receiving oral contrast medium the day of their CT examinations were studied to evaluate colonic opacification. Two groups were given small volumes (20 versus 30 ml) of nondilute diatrizoate meglumine/diatrizoate sodium (Gastrografin) the night prior to examination and were compared with groups receiving no contrast medium (control) or a large volume (600 ml) of dilute barium the night prior to examination. Frequency of total colonic opacification was as follows: 30 ml Gastrografin, 92%; 20 ml Gastrografin, 71%; dilute barium, 46%; and control, 9%. Significant artifact was infrequent in all groups. Administration of small volumes of nondilute Gastrografin is a well tolerated, inexpensive, and effective method for opacifying the colon for CT.