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PubMed1991

Cutaneous ulceration due to contrast extravasation. Experimental assessment of injury and potential antidotes.

Severe cutaneous ulceration may occur as a result of contrast media extravasation. We established a definitive animal model for assessing the cutaneous toxicity of commonly employed agents and used this model to evaluate possible antidotes to the effects of contrast media extravasation. The contrast agents studied were: meglumine/sodium diatrizoate 76%, meglumine iothalamate 60% and 43%, meglumine/sodium ioxaglate 60%, iohexol 350, and iopamidol 370, in varying volumes and osmolalities. Hypertonic saline (950 and 1900 mOsm/kg) also was injected. Agents were injected intradermally into BALB/c mice. The higher osmolality agents produced dose-dependent skin ulcerations. The lower osmolality agents failed to produce any skin lesions after the same volume doses. Hypertonic saline produced skin toxicity in a dose-dependent fashion similar to hyperosmolar contrast agents. Three antidotes were tested: hyaluronidase, topical heat, and topical cold. Hyaluronidase significantly reduced skin toxicity when injected immediately following contrast injection. Cold also significantly reduced skin toxicity, while heat caused no improvement.

Animals↗
PubMed1991

Comparison of the rates of adverse drug reactions. Ionic contrast agents, ionic agents combined with steroids, and nonionic agents.

The influence of ionic agents alone, of diatrizoate plus two oral doses of methylprednisolone premedication, and of a nonionic agent (iohexol) upon the frequency and severity of adverse drug reactions (ADRs) was compared in ten hospitals during three separate time periods from 1985 to 1989. Nonionic agents were found to reduce significantly total ADRs; 52 of 8857 patients receiving nonionic agents experienced reactions, versus 263 of 6006 patients for ionics (P less than .0001). The frequency of reactions classed as mild (2.9% for ionic agents versus 0.476 for nonionic agents: P less than .001), moderate (1.2% versus 0.1%; P less than .001), or severe (0.37% versus 0.01%; P less than .001), also favored nonionic agents. Steroid premedication provided some protection, but iohexol was significantly better with respect to mild reactions (2.9% versus 0.4%, P less than .001), moderate reactions (0.9% versus 0.1%, P less than .01), and severe reactions (0.25% versus 0.01%, P less than .01). The contrast medium was the greatest risk factor for adverse reaction (odds ratio 7.3), while prior contrast reaction (odds ratio 6.25), and hay fever (odds ratio 2.3) were found to be significant independent risks. We conclude that nonionic agents are safer for intravenous use than ionic agents given alone or with corticosteroid premedication.

Diatrizoate Meglumine↗
PubMed1991

Anticoagulant effects of nonionic versus ionic contrast media in angiography syringes.

To determine whether nonionic contrast media present a clotting hazard when plastic or glass injection syringes are contaminated with aspirated blood, we evaluated two nonionic (iohexol and iopamidol) and two ionic (ioxaglate and diatrizoate) contrast agents. We used a blood:contrast media ratio of 2 mL:5 mL and ten normal donors, each studied at 10, 20, 30, and 60 minutes, a parallel study of clotting and fibrinopeptide A (FPA) generation in plastic tubes, and life table analysis to estimate more accurately donor-based early clotting probabilities. While ionic contrast media are stronger anticoagulants, both nonionic and ionic media retard clotting in plastic tubes, and clotting in plastic and glass angiography syringes in comparison to saline controls. A clotting probability of 1% for nonionic agents in plastic syringes was not reached until a time (mean +/- SD) of 21.5 +/- 3.2 minutes. This contrasts with a time of 8.7 +/- 2.5 minutes for saline control. With plastic syringes, no clotting at all was observed at 10 and 20 minutes with either class of agents. Neither class of agents hastened the generation of FPA. We found no evidence, therefore, that nonionic agents either cause clots or are procoagulant.

Angiography↗
PubMed1991

Use of perfluorooctylbromide (PFOB) to detect liver abscesses with computed tomography. Safety and efficacy.

Although perfluorooctylbromide (PFOB) is known to stimulate macrophages, particulates given intravenously (IV) can inhibit the body's response to infection by blocking the reticuloendothelial system. Since PFOB enhances abscesses on computed tomography (CT), the authors evaluated its safety and efficacy by assessing the mortality and abscess volume in 104 rabbits with intrahepatic abscesses given either PFOB or lactated Ringer's (LR), and by comparing its efficacy to that of 76% meglumine sodium diatrizoate (MSD76). Abscesses were produced by injecting a virulent strain of E. coli into the liver. Two days later, five of the rabbits had died. Of the remaining rabbits, 50 were given 5 g/kg PFOB IV, and 49 were given an equal volume of LR. All rabbits had a CT scan at four and at ten days after infusion. They were killed before the second CT scan. Thirty seconds before being killed, 28 rabbits given LR were given a bolus of 2 ml/kg MSD76 IV. Following CT, rabbits were frozen, sliced, and photographed. Abscess volumes were calculated by digitizing the photographs of the anatomic sections and the CT images. MSD76 enhanced the liver by 105 Hounsfield units (HU) more than the liquefied abscess center. The abscess wall enhanced to the same degree as liver, resulting in nonvisualization of three of six abscesses less than 3 mm in size, and a 30% underestimation of true abscess volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Safety considerations in the power injection of contrast media via central venous catheters during computed tomographic examinations.

RATIONALE AND OBJECTIVES: This study addresses the theoretical, experimental, and clinical application of using a central venous catheter system (CVS) for the rapid injection of contrast media during computed tomography (CT). METHODS: Application of Poiseuille's law and the Reynolds equation yielded theoretical data. In-line pressures were measured in experimental models and patients undergoing CT. Diatrizoate meglumine and iohexal contrast media were evaluated. RESULTS: The Reynolds number was consistent with laminar flow, allowing the application of Poiseuille's law. The calculated and experimental catheter tubing-chamber connection pressures were safe for both contrast media, at rates of 1 mL/second for long catheter tubing and 2 mL/second for short tubing. Thirteen patients had measured pressures within safety limits with no complications. CONCLUSIONS: This study establishes that power injection of contrast media via a CVS during CT is a safe procedure. Benefits include no need for peripheral intravenous catheter placement, decreased paramedical staff radiation exposure, and improved CT image quality.

Catheterization, Central Venous↗
PubMed1992

Contrast media-induced renal morphologic changes in rats with acute edematous pancreatitis.

OBJECTIVES: Contrast media (CM)-induced renal morphologic changes were studied in rats during acute edematous pancreatitis. METHODS: The histologically verified, mild pancreatitis was caused in Wistar rats (n = 54) by an injection of peanut oil into the pancreatic duct. After 24 hours, the animals received an intravenous (IV) injection of 1.0 or 3.0 g iodine (I)/kg of high-osmolality diatrizoate, low-osmolality iopromide or iohexol, or 0.2 or 0.6 g/kg of high-osmolality magnetic resonance (MR) CM, gadolinium-DTPA (Gd-DTPA). The controls received physiologic saline. The kidneys were fixed by perfusion after 2 hours, and changes in renal morphology were analyzed semiquantitatively by two independent observers blinded to the treatment. RESULTS: The smaller dose of iohexol and the larger dose of all other CM induced a statistically significant (P less than .05) cytoplasmic vacuolization in the proximal convoluted tubule cells. The changes were most prominent after iohexol (P less than .001). When compared with the authors' earlier findings on healthy rats, the CM-induced renal structural injury was more severe. CONCLUSIONS: Pancreatitis potentiates the renal microstructural changes associated with CM; although the animals' fluid and electrolyte status was not specifically assessed, the enhanced abnormalities may be related to the hypovolemia associated with pancreatitis.

Acute Disease↗
PubMed1993

In vitro histamine release induced by magnetic resonance imaging and iodinated contrast media.

RATIONALE AND OBJECTIVES: To investigate the mechanism of anaphylactoid reactions to contrast media, in vitro histamine release induced by magnetic resonance imaging, and iodinated contrast agents was examined in a dog mastocytoma cell line. METHODS: Two gadolinium (Gd)-based magnetic resonance contrast agents, Gd diethylenetriamine pentaacetic acid (Gd-DTPA), dimeglumine, and Gd-bismorpholide, and two iodinated contrast agents, diatrizoate meglumine and iohexol, were incubated with histamine-containing canine mastocytoma cells. Release of histamine into the supernatant was determined at various contrast-medium concentrations after incubation at 37 degrees C for 30 minutes. RESULTS: Iodinated and Gd-based contrast agents caused release of histamine from mastocytoma cells at similar concentrations (50-150 mM). Mannitol, an osmotic stimulus, caused release of histamine only at concentrations greater than 1,000 mM. CONCLUSIONS: Histamine release from canine mastocytoma cells does not appear to be solely due to osmotic effects, but results from direct stimulation by contrast media. For all agents examined, the concentration at which in vitro histamine release occurs far exceeds the serum contrast media concentration expected in routine clinical application. Direct release of histamine from mast cells does not completely explain the pathogenesis of idiosyncratic anaphylactoid responses to contrast media.

Anaphylaxis↗
PubMed1996

Application of pharmacokinetics to computed tomography: injection rates and schemes: mono-, bi-, or multiphasic?

OBJECTIVE: The objective of the current study was to test whether optimization of dose regimens for detecting focal liver lesions by computed tomography is possible by using the available time-density data of former studies published in the literature and a computer program so that the number of further clinical tests with the exclusive objective of optimizing injection schemes could be reduced. METHODS: Computed tomography enhancement data of the aorta and/or the liver obtained after injecting a conventional ionic and a nonionic contrast agent were used to calculate pharmacokinetic parameters and to simulate the time course of enhancement for a variety of different infusion regimens modifying contrast medium strength, dose, and injection rate. The study consisted of two parts. In the first part, mean relative enhancement curves of the aorta and of liver parenchyma (0 to 300 sec) using meglumine diatrizoate (306 mg iodine per mL, 300 mg iodine per kg) were taken from the literature and their values were approximated using the computer program TOPFIT. In the second part, equivalent data for iohexol including a total of three strengths (240, 300, and 350 mg iodine per kg) and doses from 30 to 45 grams of iodine were used. "Validation" of the simulation method was obtained, first by comparing measured and calculated maximum intensities and times to reach maximum and, second, by using one injection scheme for the simulation of a second and comparing the results with actually measured data. RESULTS: The computer program TOPFIT allowed for excellent curve fitting of the measured density values. The data obtained in the first part of the study showed that after a dose of 300 mg I/kg and a rate of 2 mL/sec maximal enhancement is achieved in the aorta after 30 seconds (approximately 100 HU) and in the liver after 50 seconds (approximately 30 HU). The higher the dose and the rate of infusion were, the higher was the enhancement. The difference in density between aorta and liver was proportional to the infusion rate approaching asymptotically approximately 90 HU at 8 mL/sec for a dose of 300 mg I/kg. Bi- or triphasic infusion schemes did not improve differences in enhancement. The curve fitting obtained in the second part of the study also confirmed the results reported in the literature. A "crossover" prediction of data was possible within the range of interindividual variations of pharmacokinetic parameters and thus validated the chosen approach of computer simulation. Furthermore, data sets selected randomly out of the simulation results could be used--within the limits of interindividual variability--to predict data determined in other clinical trials. CONCLUSION: The computer program TOPFIT appears useful for the optimization of time--density profiles in computed tomography. The number of further clinical studies with the objective of optimization could therefore possibly be reduced.

Aortography↗
PubMed1997

Effect of contrast medium on corpus cavernosum smooth muscle.

RATIONALE AND OBJECTIVES: Changes in contractility of corpus cavernosum (CC) smooth muscle caused by radio contrast medium may result in misinterpretations of cavernosography used diagnostically in erectile dysfunction. METHODS: The authors investigated the direct effect of various contrast media on rabbit CC smooth muscle tissue strips in an in vitro model by adding contrast medium to the tissue in a perfusion bath and recording the resulting contractions. Glucose addition was used as control. RESULTS: Application of high-osmolar, ionic contrast medium diatrizoate-induced CC smooth muscle contractions of 57% of the control potassium chloride (124 mM) induced contractions. The low-osmolar (862 mOsm/kg) nonionic monomer contrast medium, iohexol, and the iso-osmolar (300 mOsm/kg) nonionic-dimer contrast medium, iodixanol, elicited contractions of 34% and 36% of the potassium chloride control contractions, respectively. High- and Iso-osmolar glucose solutions caused contractions of 51%, 38%, and 24% of the control, respectively. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) regulate CC smooth muscle contractions. These are influenced by different drugs including phosphodiesterases (PDEs), forskolin, and 3-morpholinsydnonimine hydrochloride (SIN-1). The nonspecific PDE inhibitors papaverine (0.1 mM) and theophylline (1 mM) reduced the contrast medium-induced contractions to 66% and 69%, respectively. The specific PDE inhibitor milrinone (0.1 mM) reduced the contractions to 69%; 0.1 mM forskolin and SIN-1 reduced the contractions to 34% and 41%, respectively. CONCLUSIONS: Contrast medium induces CC smooth muscle contractions, depending mainly on the osmolality of the solution. The contractions are reduced but not abolished by elevating the intracellular cAMP and cGMP concentrations. The clinical applications in cavernosography are discussed.

Animals↗
PubMed2002

Use of near-infrared reflection spectroscopy to study the effects of X-ray contrast media on renal tolerance in rats: effects of a prostacyclin analogue and of phosphodiesterase inhibitors.

RATIONALE AND OBJECTIVES: Use of near-infrared reflection spectroscopy (NIR-RS) as a new model to assess renal tolerance of contrast agents and determination of the effects of a prostacyclin analogue and of two phosphodiesterase inhibitors on renal tolerance. MATERIALS AND METHODS: NIR-RS was used to measure total hemoglobin, oxygenated hemoglobin and tissue oxygen saturation in the renal cortex of rats and the effect of diatrizoate, iopromide and iotrolan injected at 1 g iodine/kg alone or together with the prostacyclin derivative, iloprost, or the phosphodiesterase inhibitors, rolipram and mesopram, on these parameters. RESULTS: Injection of the contrast media alone resulted in a 10% to 35% depression of total hemoglobin, oxygenated hemoglobin, and tissue oxygen saturation approximately 40 to 100 seconds after administration, whereas saline showed no effect and mannitol solution only a minor effect. Coadministration of iloprost or pretreatment with the phosphodiesterase inhibitors, rolipram or mesopram, significantly attenuated the contrast media-induced effects. CONCLUSION: NIR-RS might be useful for the determination of contrast media-induced side effects. Stable prostacyclin analogues or phosphodiesterase inhibitors have the potential to mitigate these side effects.

Animals↗
PubMed1989

Hypaque and steroids in the treatment of sudden sensorineural hearing loss.

While the origins of sudden sensorineural hearing loss remain unproven and treatment empirical, the most appropriate therapy remains a matter of controversy. In this paper we have analysed the current forms of treatment, i.e. diatrizoate meglumine, steroids and a vasodilator. The results suggest that although several related factors were shown to indicate a good prognosis regardless of the therapy, none of the currently available regimens produces consistently better results than the spontaneous recovery rate of 65% reported by Mattox & Simmons.

Adult↗
PubMed2004

Effects of hyperosmolar ionic and low osmolar non-ionic contrast media on acid base, blood gas and electrolyte status in dogs.

The dogs in groups I, II and III in equal numbers received diatrizoate, iohexol and ioxilan at a dose of 700 mgI/kg intravenously (i.v.) as a bolus, respectively. Blood samples were collected prior to contrast media (CM) administration and thereafter at 3, 15, 30, 60, 90 and 180 min to evaluate acid-base, venous blood gas status (pH, PCO2, PO2, HCO, BE, O2) and electrolytes (Na+, Ca++, K+). Values of pH, PCO2, BE, HCO, Na+ and K+ remained unchanged or within non-significant fluctuations compared with the baseline values. PO2 was significantly different from the baseline values in group 1 up to 90 min after administration, significant alterations were found for O2 saturation in group 1 up to 90 min, and in group II at 3, 60 and 180 min; and for Ca++ in group 1 at all time points except at 90 min, and groups II and II at 3 and 15 min post administration. It was concluded that none of the CM are considered to cause long-lasting and major effects on acid-base, blood gas and electrolyte status.

Animals↗
PubMed2004

Diffusion properties of transurethral intraprostatic injection.

OBJECTIVES: To evaluate the location and extent of diffusion that occurs when liquid is injected transurethrally into the prostate gland, by correlating real-time fluoroscopy and gross pathology, and to quantify the variables that influence intraprostatic diffusion during chemoablation of the prostate. MATERIALS AND METHODS: A solution of diatrizoate meglumine (Hypaque, Nycomed, Princeton, NJ) gentamicin and methylene-blue dye (HGM) was injected transurethrally into the prostate in six dogs, using a passive-deflection needle injection system. The intraprostatic diffusion characteristics were evaluated during each injection using real-time C-arm fluoroscopy, and following each injection by gross examination of methylene blue staining within the prostatic tissues. HGM back-flow into the urethra at the time of injection was assessed by measuring gentamicin levels in the collected bladder irrigant after each injection, using a standard dilution formula. RESULTS: There was variability in the intraprostatic diffusion both fluoroscopically and grossly. The needle occasionally assumed a straighter trajectory than its intended curve. Intraprostatic diffusion was detected in 12 of 36 injections (33%). Using standard manipulations of various devices increased the intraprostatic diffusion in these injections to almost 80%. There was less intraprostatic diffusion when the injection resistance was either extremely high or absent. There was no extraprostatic extravasation of HGM beyond the prostatic capsule. CONCLUSION: Current methods of transurethral intraprostatic injection are variable for both the diffusion of HGM solution and in needle deployment. The gross diffusion patterns with the HGM solution were consistent with the diffusion patterns documented in our previous research using absolute ethanol. These and other factors may partly explain the variability of the lesions produced with ethanol injection. Therefore, more research is needed to further elucidate the diffusion characteristics of solutions injected intraprostatically using the transurethral approach.

Animals↗
PubMed1983

Increased risk of ventricular fibrillation associated with temporary pacemaker use during coronary arteriography.

Each injection of angiographic contrast dye during coronary arteriography represents a "natural experiment" in which the human ventricular fibrillation threshold is transiently reduced. Few factors, however, have been identified which favor the actual occurrence of ventricular fibrillation in this setting. Of 3906 consecutive patients undergoing selective coronary arteriography with sodium meglumine diatrizoate, 66 (1.7 percent) experienced dye-induced ventricular fibrillation, from which all were successfully defibrillated. Analysis of these cases revealed, unexpectedly, that patients in whom temporary right ventricular pacemakers were employed had an incidence of ventricular fibrillation nearly six times that found in the entire group undergoing arteriography (10 percent vs. 1.7 percent, respectively; P less than .001). Those individuals receiving pacemakers were distinguished from other studied patients only by a higher prevalence of conduction abnormalities. Although there is normally a low probability that mechanical stimulation by a pacing catheter can induce ventricular fibrillation, it is postulated that such an occurrence may be more likely after ventricular vulnerability has been increased by contrast dye.

Adult↗
PubMed1983

Intrarenal backflow during retrograde pyelography with graded intrapelvic pressure. A pathoanatomic study.

Histologic examination was performed in 21 baby-pig kidneys after retrograde pyelography with a mixture of meglumine sodium diatrizoate and Ferritin at intrapelvic pressures of either 30-35 or 70-75 mm Hg. In further 4 kidneys light microscopy was done after retrograde pyelography with a mixture of barium sulfate and gelatin at an intrapelvic pressure of 70-75 mm Hg. The primary pathway for intrarenal backflow was canalicular. The contrast material entered the interstitium only by one route: Tubular leakage. Only in the central portions of the kidney leakage was seen. Interstitial Ferritin was found more frequently in areas with intrarenal backflow at an intrapelvic pressure of 70-75 mm Hg than of 30-35 mm Hg.

Animals↗
PubMedDate not supplied

Excretory urography by intraosseous injection of contrast media in a rabbit model.

There are many indications for an intravenous excretory urogram. However, where intravenous access is not available, the intraosseous route to the circulation may be an alternative. We found that safe and diagnostic excretory urograms could be obtained in rabbits following the injection of different contrast media via the intraosseous route. In fact, these excretory urograms were indistinguishable from ones obtained by the conventional intravenous route. While the rabbits did not develop any abnormal clinical signs following the procedure, there were postmortem histologic lesions of osteochondrosis in 5 of 22 (22.7%) tibias receiving an intraosseous needle, but in none of the 14 tibias that did not receive an intraosseous needle. Further, the use of diatrizoate was associated with the development of osteochondrosis while the use of iopamidol was not.

Animals↗
PubMed1986

Use of contrast radiography in the investigation of tenosynovitis and bursitis in horses.

Contrast radiography, using a 25 per cent solution of sodium diatrizoate, has been used for the investigation of tenosynovitis and bursitis in horses. The procedure was undertaken on a series of 32 clinical cases and on specimens obtained at autopsy. Lesions affecting the extensor tendon sheaths at the carpus, the digital sheath, the tarsal sheath and the bursae at the elbow, hock and fetlock were examined by this means. The results showed the procedure offered the clinician useful information about the nature of the interior of these structures, particularly as regards the presence of adhesions and anastomoses between adjacent sheaths and joint capsules. Together with other clinical and laboratory findings, contrast radiography can assist in assessing the prognosis and in formulating appropriate treatment.

Animals↗
PubMed1971

Changes of sodium and urea concentrations in the renal papillary interstitial fluid on dehydration of rats.

1. The isolated renal papillae of a rat were centrifuged in a two tube assembly which allowed fluid from the tissue to separate into the lower tube.2. The papillae were centrifuged for 15 min at 300 g and 1500 g consecutively.3. After intraperitoneal injection of Na (131)I-diatrizoate, the activities of urine, and fluid samples obtained from the papilla, were compared. It was found at 1500 g that the median value for papillary fluid activity was 1.52% of the activity of urine. This is evidence that the papillary fluid was virtually free from any contamination from the terminal collecting ducts.4. It is considered that the fluid sample obtained from the papillae by centrifugation at 1500 g is a representative and reproducible sample of interstitial fluid.5. The method was used to demonstrate changes in solute concentrations in the renal papillary fluid, following dehydration of rats.

Animals↗