Contrast media leakage to the cerebrospinal fluid after intravenous injection. Comparison of stroke patients and controls.

We have tested a method to evaluate leakage of i.v. injected contrast media (CM) through the 3 partitions between blood and cerebrospinal fluid (CSF) in controls and in patients with acute cerebrovascular disease (ACBVD) to detect differences between normal brains and brains with ischemic lesions. High-osmolar (HOCM) and low-osmolar (LOCM) CM were used. In 55 patients and in 41 controls who underwent CT after i.v. contrast administration, lumbar CSF was collected 1 hour after injection and the iodine content in the CSF was measured. The concentration of iodine in CSF was very low, between 0.57 and 11.20 ng/l, and no significant difference could be found between patients and controls or between HOCM and LOCM. We conclude that under the conditions mentioned above, iodine detected in the human lumbar CSF does not reflect the true leakage of contrast agent through the blood-brain barrier.

The effect of various contrast media on the activation of plasminogen by streptokinase or recombinant tissue plasminogen activator in vitro.

RATIONALE AND OBJECTIVES: Radiologic contrast media (CM) may influence processes of coagulation and fibrinolysis. In the current study, the effects of various CM on the formation of plasmin were examined in an in vitro buffer system. METHODS: The effects of three clinically relevant concentrations of seven different iodine-containing CM and gadolinium-DTPA on streptokinase (SK) or recombinant tissue plasminogen activator (rt-PA)-induced plasmin formation was monitored using a plasmin-sensitive chromogenic substrate. RESULTS: Contrast media generally had an inhibitory effect at the plasminogen activation step; this effect was particularly noticeable with the ionic CM. CONCLUSIONS: Contrast media influence plasminogen activation by SK and rt-PA in vitro. Ionic CM have a more pronounced inhibitory effect than the nonionic media. The ionic Gd-DTPA shows a less inhibitory effect than the ionic iodine-containing CM. However, they must be regarded separately because of the different chemical composition of the magnetic resonance imaging and x-ray CM.

Inadvertent intrathecal use of ionic contrast media for myelography.

PURPOSE: To describe instances of inadvertent intrathecal injection of ionic contrast media and to consider treatment approaches, and diagnostic and medicolegal issues. METHODS: Ten cases of inadvertent injection, of which nine were reported to the manufacturers/authors and one appeared in the literature, are related with emphasis on similarity of reactions. RESULTS: Six criteria are enumerated and used to coin the term "ascending tonic-clonic seizure syndrome." CONCLUSIONS: Therapeutic possibilities seem limited, but several methods for controlling seizures are suggested. The importance of identifying the contrast material is underscored. Awareness of the grave possibility of administering the wrong contrast material is the first step in avoiding this problem; awareness of the symptoms is the first step toward therapy.

Effective concentration of bone marrow mononuclear cells using density gradient separation within an automated cell separator.

An effective method for concentrating bone marrow is described. Concentration was achieved using an intermittent flow cell separator. Elimination of mature haemopoietic cells was enhanced by the addition of a density separation medium (Ficoll-metrizoate) which was then removed by washing. All procedures were undertaken using the cell separator, this allowed for standardization of procedure and less manipulation which is associated with enhanced mononuclear cell recovery and less risk of microbial contamination. Mature granulocytes were depleted by 86.8% and red cells by 97.7% whilst mononuclear cells showed a 49% recovery. Marrows processed in this way and subsequently purged and/or cyropreserved were shown to successfully engraft when reinfused.

The spectrum of isolated ocular reactions following intravascular contrast administration.

Five out of 2930 (0.2%) consecutive patients developed ocular adverse reactions following intravascular administration of sodium-meglumine diatrizoate. The adverse reactions included bilateral blurring of vision (2), unilateral orbital oedema (2) and bilateral intense conjunctival congestion (one patient). The latter two phenomena responded to steroid and antihistaminic agents. Contrast medium-induced ocular anaphylactoid response is rare but clinically significant.

Intracellular penetration and accumulation of radiographic contrast media in the rat kidney.

Radiographic iodine-containing contrast media (meglumine calcium metrizoate, iohexol and meglumine sodium ioxaglate) were injected intravenously in rats. At various intervals after exposure, in situ cryofixation of kidneys was performed. Thin, freeze-dried cryosections were examined by electron microscopy and X-ray microanalysis. In endothelial cells, erythrocytes and tubular cells high dry weight concentrations of iodine were found. Twenty-four hours after iohexol was injected, no trace of iodine was found in the plasma, microvilli or the nuclei of the tubular cells. Small organelle-like compartments in the cytoplasm of the proximal tubular cells contained high concentrations of iodine, whereas no iodine was found in the surrounding cytoplasm. Since no metabolism of contrast medium has been demonstrated, the iodine signals must be emitted from contrast medium molecules. Other elements were also measured, with the concentrations being always within the ranges found in tubular cells of control animals. The detection of intracellular contrast thus does not seem to be an artifact due to cell injury, but rather represents a physiological event in healthy cells in the rat kidney. Our results are in contradiction to the prevailing opinion that contrast media do not enter healthy cells. However, previous conclusions have been based on the use of conventional preparation methods, and the highly water soluble contrast molecules may have been lost during the different steps of fixation and processing.

Systemic, pulmonary and renal haemodynamic effects of large intravenous doses of high and low osmolar contrast media. An investigation in the pig of ratio 1.5 and ratio 3 media.

The central, peripheral and renal haemodynamic effects of intravenous infusion (1 ml/s) of large doses (4 ml/kg body weight) of non-ionic (iohexol) and ionic (metrizoate and ioxaglate) contrast media were studied in 24 anaesthetized pigs. All contrast media showed marked haemodynamic effects with an increase of mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary occlusion pressure, cardiac output and stroke volume. The response of the pulmonary circulation to contrast media was a fall rather than a rise in pulmonary vascular resistance. No significant changes were detected in the renal circulation after infusion of contrast media.

A micropuncture assessment of the effects of contrast media of different osmolality.

The pathophysiology of radiographic contrast media-induced acute renal failure is unclear. Different causes are suggested, including hypertonicity, charged molecules, and toxicity of the media. This study deals with hemodynamic changes after injection of contrast media of high osmolarity iohexol, and metrizoate. Proximal tubular free-flow and stop-flow pressure (Psf), (the latter a marker of glomerular capillary pressure) were measured before, during, and afer injection of contrast media into the renal artery, compared with saline injection, in both normal rats and rats with ureteral obstruction (UO). Urine and electrolyte excretion also were examined. Metrizoate caused an initial decrease in Psf, from 37 to 20 mm Hg, followed by an increase to 81 mm Hg, and the value remained high for 10 minutes. During UO, the elevation of Psf was prolonged. Iohexol injection had a less marked effect. The change in glomerular capillary pressure may be dependent on the osmolarity of the contrast agent.

Addition of local anesthetics to contrast media. I. Effects on patient discomfort and hemodynamics in aortofemoral angiography.

Effects of equiosmolar solutions (osmolality 1.35 mol/kg) of the ratio 1.5 contrast medium metrizoate (250 mg I/ml) containing either the local anesthetic mepivacaine or saline were evaluated on subjective discomfort, aortic blood pressure and heart rate in 17 patients referred for aortofemoral angiography due to intermittent claudication. Each patient was injected with 30 ml (15 ml/s) of each solution in random double-blind order. Each patient was then injected with 45 ml (12 ml/s) of the ratio 3 medium ioxaglate (320 mg I/ml, osmolality 0.58 ml/kg). Ioxaglate caused significantly less total discomfort, pain, heat, vocal reactions, involuntary movements and hemodynamic effects than metrizoate-mepivacaine and metrizoate-saline. The effects of the two metrizoate solutions did not differ significantly. Previous contradictory reports on the effects of anesthetics in contrast media were reviewed with regard to experimental design, different osmolality of the test and control solutions, premedication, and pH dependence of local anesthetics. Ratio 3 media are recommended because they produce a more reliable relief of patient discomfort and fewer hemodynamic changes than the addition of local anesthetics to ratio 1.5 media.

Selective injection of iopentol, iohexol and metrizoate into the left coronary artery of the dog. Induction of ventricular fibrillation and decrease of aortic pressure.

In twenty beagle dogs selective injections were made into the left coronary artery with iopentol, iohexol and metrizoate in doses of 4 ml, 8 ml and 16 ml. Thirty-six iopentol injections, 35 iohexol injections and 37 metrizoate injections were made. Frequencies of ventricular fibrillation were significantly lower (p less than 0.05) after iopentol (0%) and iohexol (3%) than after metrizoate (22%). Iopentol and iohexol also produced significantly less decrease in aortic blood pressure than metrizoate at the different doses.

Low dose urography with a low osmolar contrast medium.

In a double blind study of 100 consecutive patients routinely referred for urography, a conventional contrast medium (Isopaque cerebral) was compared at a dose of 180 mg I/kg body weight with a low osmolar contrast medium (Hexabrix 160) at a dose of 90 mg I/kg body weight. In spite of 50 per cent dose reduction, equally good diagnostic effect was achieved with Hexabrix as with the conventional contrast medium.

Demonstration of the renal venous system at routine nephroangiography. A comparison between metrizoate, metrizamide and ioxaglate.

The demonstration of renal veins during routine nephroangiography was retrospectively investigated and blindly scored in 60 patients. Three different types of contrast media were used: one high-osmolar ionic monomeric (metrizoate) and two low-osmolar, the non-ionic monomeric (metrizamide) and the ionic monoacidic dimeric (ioxalate). The renal veins and the inferior vena cava were significantly better and more often demonstrated when ioxaglate was used compared with metrizoate and metrizmide. There was no significant difference between metrizoate and metrizamide. Following semiselective renal artery injection, the main renal veins were demonstrated with a diagnostically acceptable quality with ioxaglate in 76 per cent, with metrizamide in 40 per cent and with metrizoate in 29 per cent. On selective renal artery injection the demonstration of renal veins increased to 85 per cent with ioxaglate and remained unchanged with metrizmide (38%) and metrizoate (26%). Semiselective or selective nephroangiography with ioxaglate at an ordinary dose was in most patients sufficient to allow evaluation of renal vein involvement in disease, rendering high dose selective nephroangiography or selective nephrophlebography unnecessary. A slower diffusion rate of ioxaglate compared with metrizoate and metrizamide is considered to be the major explanation for the better demonstration of the renal veins.

Selective nephroangiography in the dog causing renal platelet aggregation and irregular nephrographic phase.

Selective renal artery injections of large single doses of the ionic contrast medium metrizoate produced an irregular nephrographic phase, 'patchy contrast medium retention', in 14 of 16 dogs. The irregular nephrographic phase was associated with a transient accumulation of platelets and fibrinogen in the kidney and with microscopically demonstrable transient thrombi in afferent arterioles and glomerular capillary tufts. These effects were followed by tubular damage, which was demonstrated in 4 of 6 dogs examined 48 hours after injection. Formation of thrombi was not demonstrated in 6 dogs given small single doses, which produced a homogeneous nephrographic phase. It is suggested that contrast medium induced endothelial damage is a pathogenetic mechanism in the development of thrombi and patchy contrast medium retention.

Factors that modify the flow response to intracoronary injections.

Coronary sinus flow (CSF) was measured in seven patients with normal coronary arteries (group A) during intracoronary injections of 6 ml arterial blood, 6 ml blood from the coronary sinus, 3 and 6 ml isotonic saline, 3 and 6 ml hypertonic glucose, and 6 ml of a contrast agent (sodium metrizoate). In 10 patients with coronary artery disease (group B), CSF was measured after administration of 6 ml isotonic saline, 6 ml sodium metrizoate, and 6 ml of another contrast medium (iohexol). In group A, arterial blood did not affect CSF, while coronary sinus blood induced a 33% increase. After 6 ml isotonic saline, there was a 35% increase in flow and after hypertonic glucose an increase of 70%. Metrizoate induced a rise in flow of 109%. In group B, the increase in CSF after intracoronary injection of saline, metrizoate, and iohexol was 30%, 83%, and 67%, respectively. Blood from the coronary sinus, in contrast to arterial blood, induced a marked rise in peak flow, suggesting a role for reactive hyperemia secondary to myocardial hypoxia in this response. A similar mechanism might have been operative after injection of isotonic saline, as well as after the hyperosmolar contrast agents. However, additional mechanisms mediated by the high osmotic pressure of these substances, such as induction of the Bezold-Jarisch reflex, which will induce coronary vasodilation, may have played a role. Finally, when hyperosmolar agents are used, the possibility of some direct vasodilating properties of the agents cannot be excluded.

High dose urography in patients with renal failure. A double blind investigation of iohexol and metrizoate.

The new non-ionic contrast medium iohexol 350 mg I/ml was compared with the ionic contrast medium metrizoate 350 mg I/ml in a double blind, two-group urographic study performed on 20 patients with stable, impaired renal function. A dose of contrast medium of 500 mg I/kg body weight was given to each patient. Iohexol resulted in significantly fewer subjective adverse reactions than metrizoate. A similar image quality was obtained with the two contrast media. No clinically significant difference existed between the two contrast media with respect to influence on blood pressure, pulse or clinical chemical parameters. A tendency to deterioration of renal function after urography was found in both groups, but no difference of statistical significance existed between the two contrast media with respect to possible nephrotoxicity. Inadequate hydration may have been partly responsible for the nephrotoxic effect of the urographic procedure.

Retrograde pulmonary arteriography.

We performed retrograde pulmonary arteriography by means of a pulmonary venous wedge injection in 10 patients with no demonstrable intrapericardial pulmonary arteries by "conventional" angiographic techniques. In all cases but one, the procedure demonstrated the feasibility of a further operation. No complications were observed. Retrograde pulmonary arteriography is an important additional method for determining the existence of surgically accessible pulmonary arteries when other techniques have failed.

Iohexol compared to meglumine-Ca-metrizoate in common carotid angiography. A randomized double blind cross-over study in man.

A randomized double blind cross-over study with iohexol (Omnipaque) and meglumine-Ca-metrizoate (Isopaque cerebral) was performed to answer questions concerning subjective side effects and tolerability that arose from a double blind parallel study with the same two media. The cross-over study design, with injection of the contrast media under identical conditions in the same artery, seems to be the most practical method of comparison of two well tolerated media. Iohexol showed significantly less side effects than meglumine-Ca-metrizoate. The routine premedication with atropine was neglected in this study to evaluate effects on heart rate due, for example, to the toxicity of the media. Small tachycardial and bradycardial reactions were equally divided between the media. However, a short asystolic period following the injection of meglumine-Ca-metrizoate in two different patients may indicate a higher toxicity of this medium.

Metrizamide, iothalamate, and metrizoate: effects of internal carotid arterial injections on the blood-brain barrier of the rabbit.

Experiments were conducted on anesthetized rabbits to determine the effect of internal carotid artery injection of various contrast media on permeability changes in the blood-brain barrier. Changes in respiratory pattern, neuromuscular effects, and trypan blue extravasation were recorded after 3-ml injections of ionic and nonionic contrast media. Metrizamide and iothalamate meglumine were compared at iodine doses of 300, 400, and 500 mg I/ml. Metrizoate at 280 and 440 mg I/ml and diatrizoate meglumine at 385 mg I/ml were also included for comparison. The results demonstrated that metrizamide at all three iodine concentrations used caused minimal disruption of the blood-brain barrier, the effect being no greater, statistically, than saline controls. Iothalamate was benign at the lowest iodine concentration, but caused significant barrier breakdown at the two higher concentrations. These results suggest that alterations in blood-brain barrier permeability following angiography are mediated by both hyperosmolality of the contrast medium and the chemotoxicity of the contrast molecule.

Blood inflow into vascular catheters following injection of saline solution and contrast medium. Model experiments.

Using an experimental model of the arterial system, inflow of blood into polyethylene catheters following injection of two contrast media, isotonic and hypertonic saline solutions was investigated. The experiments included an analysis of the influence of the density of the solutions and the orientation of the catheter as well as the effect of single fluid injection and continuous flushing of the catheter.