Experimental evaluation of various available contrast agents for use in the gastrointestinal tract in case of suspected leakage. Effects on pleura

Intrapleural injections of seven contrast agents were carried out in experimental rats in order to find a safe contrast agent to use in the radiological examination of the upper gastrointestinal tract in cases where leakage outside the upper gastrointestinal tract into the pleural space could be suspected, particularly post-operatively. The contrast agent in such cases could enter the mediastinum, pleura, peritoneum or lungs and bronchi. Hexabrix (May and Baker) and Gastrografin (Schering AG) produced the least tissue reaction in the pleura. Due to the potential risk of aspiration in such cases Gastrografin is not suitable as it is known to produce significant reaction in the lungs and may even prove to be fatal. Hexabrix, therefore, appears to be the safest contrast agent where leakage into the pleural space may be suspected.     

Esophageal disruption: evaluation with iohexol esophagography

Twenty-six patients with possible esophageal disruption who were also at risk for aspiration or direct communication of the esophagus with the tracheobronchial tree were examined with iohexol esophagography. Fifteen patients had normal studies confirmed by findings at a barium examination performed immediately after. In 11 patients abnormalities were diagnosed on the basis of iohexol esophagograms; the abnormalities included extraluminal extravasation of contrast material (n = 7), aspiration (n = 1), esophageal stricture with intramural diverticulosis (n = 1), edema of the gastroesophageal junction (n = 1), and epiphrenic diverticulum (n = 1). Eight of these patients were immediately reexamined with barium esophagography, which yielded no additional information. Low-osmolality, water-soluble contrast agents are a safe alternative for patients in whom barium esophagography poses a risk of mediastinitis and esophagography with diatrizoate meglumine and diatrizoate sodium (Gastrografin) poses a risk of pulmonary edema.     

Direct effects of contrast media on rat lungs

Despite the widespread use and the assumed safety of Omnipaque (iohexol) and 3% Gastrografin (meglumine diatrizoate) as contrast media for esophagography and computed tomography respectively, their effects on the lung if they are aspirated have never been studied. This information is important because such compounds may inadvertently enter the lungs during the diagnostic procedures. Twenty-four rats were injected intratracheally with 0.15 mL of one of three contrast agents (omnipaque, full-strength Gastrografin and 3% Gastrografin) or normal saline, which was used as a control. Radiographs were then obtained. Equal numbers from each experimental group were sacrificed after 5 minutes, 1 hour and 24 hours, and their lungs were examined pathologically. The rats injected with full-strength Gastrografin all died immediately of gross pulmonary edema. Neither Omnipaque nor 3% Gastrografin was fatal, but Omnipaque produced more edema and alveolar hemorrhage than either normal saline or 3% Gastrografin. Iohexol is, therefore, more irritating to the airways and the lung parenchyma than previously believed.     

Case report: renal excretion of gastrografin following rectal administration.

Renal excretion of water soluble iodinated contrast media following oral administration has often been described but no reports describing renal excretion following rectal administration of such contrast have previously been described. We describe a case of renal excretion of diatrizoate methylglucamine (Gastrografin, Schering) following a diagnostic 'gastrografin enema' in a woman with caecal carcinoma.     

Experimental evaluation of various available contrast agents for use in the upper gastrointestinal tract in case of suspected leakage. Effects on lungs

The reactions of seven contrast agents--pure barium sulphate, Micropaque, Gastrografin, Dionosil, Hytrast, Amipaque and Hexabrix--on the bronchi and lungs of rats were studied. This work was undertaken to find a safe gastrointestinal contrast agent for use in post-operative patients where aspiration may be an accompanying risk. Amipaque and Hexabrix produced no significant histological reaction in the lungs and would, therefore, appear to be suitable for use in such cases.     

Experimental evaluation of various available contrast agents for use in the upper gastrointestinal tract in case of suspected leakage: effects on mediastinum

The tissue reaction of seven contrast agents--pure barium sulphate, Micropaque, Hytrast, Dionosil, Gastrografin, Amipaque and Hexabrix-was evaluated on the mediastinum of rats. This work was undertaken to define the most suitable and safe contrast agent for use in the upper gastrointestinal tract in cases where leakage outside the gut into the mediastinum, pleura or peritoneal cavity may be suspected and aspiration may be an accompanying risk. Keeping in mind the danger of aspiration, Hexabrix and Amipaque appear to be the safest contrast media for the mediastinum.     

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.     

Effects of iopamidol and iohexol in rat lungs following experimental aspiration

Experimental aspiration of water soluble contrast agents was performed on rats via transoral endotracheal injection. Iopamidol, iohexol and diatrizoate were the contrast agents tested. One group of rats received normal saline as a control. Adjusted lung weights were measured at 2 and 24 hours post aspiration. Radiographs were taken at 2 and 24 hours post aspiration and scored for abnormal pulmonary air space density. Diatrizoate alone demonstrated an increase in adjusted lung weights. Diatrizoate, iopamidol and iohexol showed abnormal pulmonary air space disease on radiographs at 2 hours but not at 24 hours. Histopathologic examination of rat lungs following aspiration of all three contrasts showed pulmonary vascular congestion and perivascular edema. Iopamidol showed evidence of acute cellular inflammation. Iohexol provoked a pulmonary alveolar macrophage response.     

Water-soluble contrast media compared with barium in enteric follow-through. Local effects and radiographic efficacy in rats with simple obstruction of the small bowel

The local effects and radiographic efficacy of 4 water-soluble contrast media, barium and saline were evaluated in 86 anaesthetized rats with the distal ileum ligated. The rats were observed for 8 hours after instillation of 3 ml of the test substance via orogastric tube. Radiographs were taken after 1, 4 and 8 hours of observation. After 8 hours the intestines were weighed and biopsied for light microscopy, and blood and urine were sampled for testing. Sodium diatrizoate caused increased fluid influx to the bowel lumen and, like barium, provided poorer radiographic images as compared with iohexol, ioxaglate or iodixanol. Barium showed slower progression through the small bowel than the other agents, while sodium diatrizoate was the most rapidly progressing contrast medium and caused the greatest distension. Correlation to osmolality was obvious. No significant morphologic effects on the small bowel mucosa were seen in any of the groups. Low-osmolar, water-soluble contrast media may have prospects for clinical use in patients with suspected small bowel obstruction.     

Experimental evaluation of various available contrast agents for use in the gastrointestinal tract in case of suspected leakage. Effects on peritoneum

The effects of seven contrast agents were studied on the peritoneum of rats in order to find the most suitable and safe contrast agent in cases where leakage might be expected from the gastrointestinal tract into the peritoneal cavity. Hexabrix appeared to give the least tissue reaction, with Amipaque and Gastrografin in second place (but not significantly different statistically).     

Contrast media in sialography: a comparison of Lipiodol Ultra Fluid and Urografin 290

A prospective, randomized study of 60 patients undergoing sialography was conducted to compare Lipiodol Ultra Fluid (UF) (Ethyl diiodostearate, May & Baker Ltd), with Urografin 290 (meglumine diatrizoate 52.1% w/v and sodium diatrizoate 7.9% w/v, Schering). The quality of the images, the clinical tolerance and the side-effects of contrast were compared. Both agents produced adequate opacification of ducts but poor intra-gland duct filling was seen in two patients examined with Lipiodol UF. There were significantly more side-effects (which were also more severe) in the Lipiodol group. It is concluded that Urografin 290 is the better contrast agent for sialography because of better filling of intra-gland ducts and greater clinical tolerance.     

Effect of B-15,000 (Iopamidol), a new nonionic contrast agent, on cardiac function of the isolated rat heart

The isolated rat heart model was used to examine the effect of a new nonionic contrast agent, B-15,000 (Iopamidol), on cardiac function. Comparative studies were performed with Amipaque, Renografin 60, Renografin 76, and Vascoray. The three ionic contrast agents had significantly greater detrimental effects on cardiac function than either nonionic agent. The results support the continued evaluation of the nonionic agents for use in coronary angiography.     

Iopamidol,a new nonionic contrast medium in peripheral angiography

Iopamidol (B 15,000), a new nonionic contrast medium, was compared to diatrizoate (Urografin 60%) in a controlled clinical trial using aortofemoral runoff angiography in a consecutive series of 50 severely arteriosclerotic patients. Iopamidol was found to be superior to the conventionally used contrast medium, as it significantly reduced the pain and discomfort following injection. Only slight to moderate alterations of aortic blood pressure and pulse rate were observed following the injection of both media. The hemodynamic influence of iopamidol, however, was significantly less pronounced than that of diatrizoate.     

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.     

Iopamidol as a gastrointestinal contrast agent. Lack of peritoneal reactivity

The ideal contrast agent in patients suspected of having gastrointestinal perforation is an iso-osmolar, or nearly iso-osmolar substance, that causes no peritoneal reaction. Iopamidol is a nonionic water-soluble contrast medium that may be considered in such situations. Intraperitoneal injections of ionic and nonionic contrast agents were compared in rats to study potentially harmful peritoneal inflammation. Only intraperitoneal barium injection produced any significant tissue reaction, such as adhesions and ascites. There was no difference between iopamidol and the other water-soluble contrast agents. Iopamidol may satisfy the need for nonreactive and nearly iso-osmolar contrast agents for evaluating patients with possible bowel perforation. However, the high cost of this agent may make its clinical application impractical.     

Contrast media induced pulmonary edema. Comparison of ionic and nonionic agents in an animal model

High intravenous doses of diatrizoate are known to induce pulmonary edema in the rat. The newer generation of contrast media--nonionics and monovalent dimers--are considered less toxic than diatrizoate. In this study we evaluated the degree of pulmonary edema induced by a high dose (6 g I/kg) of these new agents and found that Ioxaglate produced higher lung weights than Renografin 60 and Iopamidol. Iohexol and Amipaque did not induce a significant degree of edema. The model used in this study demonstrates distinct differences in pulmonary toxicity among these new agents, when given in doses exceedingly higher than given in clinical practice.     

Comparison of barium and diatrizoate bowel labelling agents in computed tomography

A new suspension of barium sulphate, E-Z-CAT, for use as a bowel labelling agent in computed tomography (CT) of the abdomen and pelvis, has been compared with diatrizoate (Gastrografin) in 111 patients. The E-Z-CAT labelled the duodenum more efficiently and patients preferred its taste. Both substances are satisfactory bowel-labelling agents.     

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).     

Production and characterization of improved liposomes containing radiographic contrast media

The authors have investigated liposomes prepared by the reverse-phase evaporation method (REVs) and a modification of this technique that employs a microemulsifier (MREVs), for the delivery of radiographic contrast media (RCM) to the liver and spleen. The modification entailed substituting a Microfluidizer (Microfluidics Inc., Newton, MA) for the sonication step of the REV technique. The MREV procedure is amenable to large-scale production and continuous-flow operation and yields products with high RCM encapsulation. Efficiently entrapped are ionic, high-osmolar diatrizoate (24.38 +/- 2.62% versus 8.35 +/- 0.55%; MREV versus REV), and nonionic, low osmolar Iotrolan (Schering AG, Berlin, FRG) (24.84 +/- 2.13% versus 7.25 +/- 1.19%) RCM with iodine-to-lipid ratio of 1.5:1. The MREV procedure, therefore, has practical advantages over the REV method. High liver and spleen uptakes of Iotrolan-containing vesicles were noted in normal rats. The diatrizoate MREVs lost their contents on contact with serum, resulting in urinary excretion of this agent. Computed tomography values of splenic and hepatic sections, 1 hour after intravenous injection of Iotrolan MREV (500 mgI/kg), are 0.78, and 0.08 Hounsfield Units (HU)/mgI/kg, respectively (versus 0.01, and 0.006 HU/mgI/kg for free Iotrolan).     

A new animal model for testing renal tolerance of contrast agents

RATIONALE AND OBJECTIVES: To develop a new animal model for the evaluation of the renal tolerance of contrast agent and its application to diatrizoate and iotrolan injections in comparison to saline and mannitol solution. MATERIALS AND METHODS: The nephrotoxic potential of intravenously injected contrast agents in Beagle dogs was determined from the effects on the pharmacokinetics of creatinine injected immediately after these agents in comparison with the kinetics of creatinine injected alone. The kinetic parameters evaluated included plasma half-life, volume of distribution, and clearance. In a series of studies, the experimental conditions were optimized in terms of creatinine dose and the effects of diatrizoate, iotrolan, saline, and mannitol solution on the pharmacokinetic parameters of creatinine were determined. RESULTS: Bolus injection of creatinine into dogs followed a dose-linear pharmacokinetic behavior with a terminal half-life of 90 minutes (10 mg/kg) and 108 minutes (20 mg/kg), respectively, and a clearance of 5 mL/min/kg. Injection of diatrizoate decreased the clearance and the half-life of creatinine significantly. A mannitol solution with the same osmolality as diatrizoate showed the same effect whereas physiological saline did not affect pharmacokinetic parameters of creatinine. The isotonic iotrolan was intermediate between saline and diatrizoate in its effects on creatinine clearance. CONCLUSION: The effect of contrast agents on pharmacokinetic parameters of creatinine injected immediately after the administration of the agents in dogs might be a useful model for the evaluation of renal tolerance. In a cross-over study, iotrolan was not statistically separable from diatrizoate.