[Complications in administration of contrast media in the catheterization laboratory: a 5-year retrospective study]. / Komplikace podání kontrastních látek v katetrizacní laboratori: petiletá retrospektivní studie.

UNLABELLED: Iodine contrast substances (CS) are used since the twenties of the 20th century. From the chemical aspect benzoic acid derivatives are involved which are classified according to their osmolality (high-low- and isoosmolar) tendency of ionization (ionic and non-ionic) and according to the molecular structure monomers and dimers). Side-effects are due to their osmotic, ionic and chemical action on tissues. They include a number of systemic and organ symptoms (cardiovascular, immunological, haemocoagulation, neurological and renal), from the clinical aspect divided into mild, medium severe and severe. The relatively high incidence of undesirable reactions when ionic high-molecular CS are used led to the-development of non-ionic preparations with a lower osmolality, the more extensive use of which is limited by economic factors. Moreover so far convincing clinical data are lacking that the higher incidence of undesirable reactions after the use of CS has a clinical impact. OBJECTIVE: To summarize experience with administration of CS in the catheterization laboratory of the Cardiocentre of the General Faculty Hospital during diagnostic and intervention procedures within 5 years with regard to the occurrence of undesirable effects when comparing ionic and non-ionic CS. METHOD: Retrospective analysis of a group of patients examined in the catheterization laboratory to whom a CS was administered during the period between Jan. 1 1995 and Dec. 31 1999. RESULTS: In 1995-1999 (5 years) in the catheterization laboratory a total of 10,149 procedures where implemented where ionic (ioxitalam-Telebrix 350) and non-ionic (iopromide Ultravist 370, ioversol--Optiray 370 and iomeprol-Iomeron 350) contrast substances were administered. Ionic CS were administered in 4,668 (46%) and non-ionic CS in 5,481 (54%) instances. Undesirable effects were recorded in a total of 107 (1.1%) patients, incl. ventricular fibrillation in 76 (0.75%), cardiac arrest in 12 (0.12%) and in 19 (0.19%) there were other undesirable effects (weakness, nausea, hypotension, flush, urtica etc.). Ionic and non-ionic CS participated equally in complications: ionic CS in 53 (49.5%) cases and non-ionic CS in 54 (50.5%), whereby no difference was observed in the type of complications. No death in conjucntion with administration of CS was observed. CONCLUSION: The use of contemporary contrast substances in the catheterization laboratory for diagnostic and intervention procedures on the heart is relatively safe with a minimal risk of development of serious complications. No difference was observed between the use of ionic and non-ionic CS.

Effect of plasma binding of ortho- and para-I-benzoates on their distribution in blood and into lymph, biotransformation and excretion in rat urine.

Two positional iodine derivatives of benzoic acid, i.e. ortho- (OIB) and para- (PIB), were used alone and in combination with salicylic acid (SA) to study the effects of plasma binding on their pharmacokinetics. Their lymphatic bioavailability (central lymph), their biotransformation and urinary excretion in rats were also studied. Plasma binding of the two benzoates is different, about 95% of PIB and approximately 50% of OIB are bound. The competitive inhibition effect of SA was shown by an increase in the amount of free drug in plasma in both benzoates. Lymphatic binding is lower compared to plasma binding, an effect of SA of the free faction of drug in lymph was shown only with PIB. Kinetic parameters of benzoates are influenced by plasma binding; significant differences were found mainly in total clearance and areas under concentration curves. Lymphatic bioavailability (FL) differs only slightly with different plasma binding; a significant change in FL was, however, found in PIB after SA premedication. Significantly higher urinary excretion of OIB as compared with PIB corresponds to plasma binding of drugs, SA premedication decreases total excretion of both benzoates. SA also changes the proportion of the individual fractions of metabolites of benzoates in urine.

[Intraventricular contrast medium (non-ionic water soluble dimer) residue a month after injection; a case report].

We report a case with non-ionic water soluble dimer contrast media residue in the lateral ventricle a month after administration into the lateral ventricle. We believe that, in this subarachnoid hemorrhage patient, the intraventricularly instilled contrast media mixed with preexisting blood, aggregated and adhered to the ventricular wall.

Effect of sodium addition to non-ionic contrast media on cardiac contractile force. Perfusion of the isolated rabbit heart with iohexol and iopentol containing 0 to 154 mmol Na+/l added as NaCl.

Cardiac contractile force after adding NaCl to the non-ionic contrast media iohexol and iopentol was investigated in the isolated rabbit heart. Iodine concentrations of 150, 300 and 350 mg I/ml were used with sodium concentrations ranging from 0 to 154 mmol/l. From physiologic experiences of nutrient solutions it should follow that a sodium-free solution of a non-ionic contrast medium, which also has the lowest hypertonicity, should cause the smallest decrease in contractile force. However, a small amount of sodium added to the contrast medium solutions, in the range of 19.25 to 38.5 mmol/l, caused the least decrease in contractile force. The decrease in contractile force was significantly more pronounced when no sodium was added or when larger amounts of sodium were added. A small amount of sodium also decreases the risk of ventricular fibrillation. Thus there is a possibility that addition of sodium could reduce the adverse effects of cardioangiography.

Clinical summary of initial intravenous administration of ioversol.

Data from 23 double blind, controlled, parallel-group comparative studies evaluating the intravenous safety, efficacy, and patient tolerance of ioversol were collected. Nine open-label studies were evaluated, as well. A small number of side effects that would be considered serious were reported, but resulted in no clinically significant sequelae, (e.g., angina, bradycardia, vasovagal response, and hypoxia). There were no significant changes in vital signs related to the use of the drug. These studies indicate that ioversol 320 and 240 provide high diagnostic quality and are well tolerated by patients. The author concludes that ioversol is suitable for head and body computed tomography, intravenous urography, and venography.

[Determination of hematocrit and iodine concentrations following intravenous bolus administration of ionic and nonionic monomeric and dimeric contrast media--an animal experimental study]. / Hämatokrit- und Jodkonzentrationsbestimmungen nach intravenöser Bolusapplikation ionischer und nichtionischer monomerer und dimerer Kontrastmittel--Tierexperimentelle Studie.

A monomeric ionic (meglumine diatrizoate), a monomeric non-ionic (iopromide) and a dimeric non-ionic contrast medium were intravenously administered (V. jugularis) to 15 rabbits. Blood iodine concentration as well as haematocrit were determined from blood samples taken from the femoral artery immediately after injection until the 90th second p.i. The contrast media showed clear differences concerning the haematocrit, i.e. the isotonic non-ionic dimer induced its lowest decrease. The direct determination of the blood iodine concentration revealed no significant deviations between the contrast media studied. Only non-ionic dimers are iso-osmolar with plasma at the iodine concentrations employed in diagnostic radiology. Compared with monomeric compounds this study provides fundamental evidence that isotonic, non-ionic dimeric contrast media cause only slight effects on blood cells. This confirms experimentally the clinically reported good tolerance of dimeric contrast media in patients.

The optimal concentration of contrast medium for aortography and femoral arteriography: a comparison of Hexabrix 320 and Hexabrix 250.

A prospective double-blind randomised clinical trial of aortography and iliofemoral arteriography in 89 patients demonstrates that there is no difference in the diagnostic quality of the studies when Hexabrix 250 replaces Hexabrix 320. There is a minor reduction in patient subjective reaction, and the lower viscosity permits the use of smaller bore catheters. The major gain is that the cost of the contrast medium should be reduced by 22%.

Subarachnoid administration of iohexol in cynomolgus monkeys.

A non-ionic diagnostic medium, iohexol, was administered by subarachnoid injection to groups of six cynomolgus monkeys and compared with the vehicle, physiologically normal saline, and/or saline of equal osmolality to determine its potential for increasing total protein and leucocyte levels in cerebrospinal fluid. Also investigated was the effect of repeated spinal taps not subsequently followed by the intrathecal injection of test or control articles. In the monkey, unlike man, low-level leucocyte counts were consistently observed following initial withdrawal of spinal fluid. Elevated leucocyte and total protein levels were observed in the present investigations one day to a week after intrathecal injection of radiopaque, vehicle or saline solution. Total protein returned to normal levels earlier than did leucocyte counts. However, repeated needle puncture alone was found to be sufficient to cause an elevation of leucocytes 3 to 4 times the baseline level, while inflammatory effects were observed histologically only when autopsy was performed soon after the final spinal tap.

A comparative trial of the diagnostic quality of and tolerance for two concentrations of ioxaglate when used for phlebography.

We report a prospective, randomised, double blind study comparing the diagnostic quality of and tolerance for ascending phlebography in 100 patients using two different concentrations of ioxaglate, 320 mg/ml and 200 mg/ml. The immediate and delayed side effects were minimal in both groups and the difference between the two concentrations was not statistically significant. All the phlebograms were of diagnostic quality. We conclude that, with its lower osmolality, lower viscosity and lower cost, ioxaglate 200 mg/ml is a suitable medium for routine use in ascending phlebography of lower limbs.

Gallbladder visualisation following paediatric cardioangiography with Hexabrix.

Fifty children had an upper abdominal radiograph performed 24 hours after cardioangiography with Hexabrix (meglumine/sodium ioxaglate). The gallbladder was clearly visualised in 32 patients (64%) in the absence of clinical or radiographic evidence of renal impairment. Total contrast dose would appear to be the main determining factor. Hexabrix differs significantly in this respect from conventional uro-angiographic contrast media (diatrizoate and iothalamate) in which opacification of the gallbladder is unusual and strongly associated with renal impairment. Possible reasons for this difference are discussed.

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.

Intravascular studies with iohexol (Omnipaque). Results from the first 49 clinical trials.

In order to assess the vascular clinical trial program of iohexol (Omnipaque) in Europe, the results from the first 49 vascular trials are collectively reported. The included iohexol material comprises 1742 patients. In 40 comparative trials, other contrast media like metrizamide (Amipaque), ioxaglate (Hexabrix) and various monomeric ionic media were administered in 1292 patients included in this analysis. No severe or unexpected adverse reactions related to iohexol were encountered. No clinically significant differences in radiographic image quality between the media were documented. The overall tolerability of iohexol was superior to that of monomeric ionic media and seemed to be as good as that of metrizamide.

Clinical experience with ioxaglate (Hexabrix) in selective coronary arteriography.

This prospective nonrandomized study was performed to evaluate the safety and efficacy of, as well as patient tolerance for, a new low osmolality contrast medium, ioxaglate (Hexabrix), in 90 adult patients of both sexes who were referred to our cardiac catheterization laboratory for angiocardiography including selective coronary arteriography. Ioxaglate did not cause any major adverse effects; side effects were rare and mild. Hemodynamic changes were minimal, even in patients with severe coronary artery disease, and no arrhythmias were seen. The radiographic quality of angiograms was scored as good to excellent for each examination, and was equal to that of films performed using a conventional contrast medium. Ioxaglate may be the contrast medium of choice for angiocardiography, especially in patients at high risk, i.e., those with severe coronary artery disease or severe left ventricular dysfunction.

Optimal iodine concentration in digital subtraction arteriography.

The effects of two different concentrations of the contrast agent Hexabrix were evaluated in a total of 26 patients undergoing cerebral angiography and randomly assigned to two groups. Injection volume, rate, and iodine concentration were constant. Carotid digital exams using 8% and 12% Hexabrix in the same patient showed the higher concentration was preferred for vessels of all sizes. In comparing 12% and 16% concentrations of Hexabrix, there was again a preference for the higher concentration, although results were not statistically significant. Both 12% and 16% Hexabrix in carotid studies resulted in excellent quality exams. Vessel see-through ability was somewhat better with 12% Hexabrix. Subjective symptoms of all patients during the injection were minimal or absent. Hexabrix is theoretically more attractive than conventional agents in that optimal concentration for digital imaging is in a range which is iso-osmotic with serum.

Clinical testing of omnipaque and amipaque in external carotid and vertebral angiography: randomized double-blind crossover study.

Omnipaque, 300 mg l/ml, was compared with Amipaque, 300 mg l/ml, for cerebral angiography. Twelve patients were included in a randomized, double-blind, crossover study. Twenty comparisons were made in the external carotid and 21 in the vertebral artery, Both contrast media caused no or minor changes in blood pressure and heart rate. Good to excellent radiographic visualization of the cerebral arteries was obtained with both agents. The frequency of subjective reactions was almost equal, but the intensity of the reactions was less with Amipaque. No severe reactions were observed. Omnipaque is a more practical nonionic contrast medium than Amipaque because it is delivered in ready-to-use solutions.

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.