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Comparison of nonionic contrast agents iohexol and iotrolan for cisternal myelography in dogs.

During this investigation, the use of iohexol was compared with iotrolan for canine cisternal myelography. Iohexol and iotrolan myelography was done in 6 dogs by cisternal puncture with a 6-week interval between both procedures; each dog served as its own control. Cerebrospinal fluid (CSF) was collected for baseline analysis from each dog immediately before the contrast agent was injected. Cerebrospinal fluid samples were obtained at 1, 3, 7, and 14 days after injection of each contrast medium for cytologic and chemical analysis. Total CSF leucocyte count and glucose concentration did not change significantly in comparison with baseline data in any of the samples. After the injection of iohexol, protein concentration increased significantly in the 24-hour sample, and lactate dehydrogenase activity increased significantly in the 3-day sample. Significant difference was not found between the different samples collected at 1, 3, 7, and 14 days, compared with both contrast media. None of the dogs had seizure activity during a 5-hour postmyelographic observation period. Pathologic changes were not found by gross or microscopic examination of the spinal cord. Although a degradation in time of radiographic quality of all myelograms took place, the average radiographic score decreased more rapidly with iohexol. The average score at 90 minutes with iotrolan was comparable with the score at 45 minutes with iohexol, and the average score at 150 minutes with iotrolan was better than the score at 90 minutes with iohexol. At 5 and 10 minutes after cisternal injection, no significant difference was observable between the myelograms, but from 45 minutes onward, myelograms with iotrolan were superior.

Animals↗

Gentamicin nephropathy and contrast media. A comparison between diatrizoate and iohexol in rats.

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol or saline in 30 rats, where a tubulo-interstitial nephropathy was induced by gentamicin given over a 14-day period. Another 10 rats who had an injection of saline served as controls. Iohexol increased the excretion of lactate dehydrogenase significantly more than both saline and diatrizoate for the first 3 days, whereas diatrizoate had no effect. Both media caused significantly increased excretion of L-gamma-glutamyltransferase compared with saline, but iohexol significantly more than diatrizoate. Compared with saline S-creatinine was significantly increased following iohexol at 24 h, 3 and 9 days, and following diatrizoate only at 9 days. Among rats having gentamicin light microscopy revealed more severe changes in kidneys exposed to iohexol than to either diatrizoate or saline 3 days after their injection. Six days later no obvious differences were found between the 3 groups. In conclusion, iohexol induced more renal dysfunction than diatrizoate in this animal model of gentamicin induced nephropathy.

Acetylglucosaminidase↗

[Clinical studies of a new non-ionic contrast medium--iohexol (Omnipaque)--in patients sensitive to ionic contrast medium].

Iohexol was used on 62 patients who had had side effects or adverse reactions to conventional ionic contrast medium. No side effects were observed. Iohexol provided better nephrographic and pyelographic effects, but in one case a diagnosis could not be made using 20 ml of Iohexol 300. Iohexol 350, 20 ml, was thought to be more suitable contrast medium than Iohexol 300, 20 ml, for ordinary intravenous pyelography. Iohexol could be used safely in patients with previous adverse reactions to ionic contrast media.

Adolescent↗

Nephropathy induced by intramuscularly administered glycerol and contrast media in rats. A comparison between diatrizoate, iohexol and ioxilan.

Urine profiles (albumin, glucose, NAG, LDH, GGT, sodium, and phosphate) were followed for 14 days after intravenous injection of either diatrizoate, iohexol, ioxilan, or saline in 24 Wistar rats with a glomerular and tubular dysfunction induced by intramuscularly (i.m.) administered glycerol. Another 6 rats exposed to neither glycerol nor contrast media served as controls. The effect of ioxilan and saline on the albumin excretion was similar, whereas diatrizoate and iohexol increased it significantly. The contrast media had no further inhibitory effect on the reabsorption of glucose. Iohexol caused significantly increased excretion of all three enzymes, ioxilan of NAG and LDH, whereas diatrizoate only increased the excretion of LDH. The sodium excretion was further increased by ioxilan and diatrizoate, whereas none of the contrast media affected the phosphaturia. Both ioxilan and iohexol caused a round cell response around the tubules shown by light microscopy whereas diatrizoate caused no further changes. It is concluded that diatrizoate and iohexol increase glomerular dysfunction induced by glycerol i.m.; all three contrast media cause some further increase in the tubular dysfunction. Neither diatrizoate, iohexol nor ioxilan prolong nephropathy induced by glycerol i.m. determined by the chemical analyses. The histologic finding indicates a direct toxic effect of non-ionic low osmolar contrast media in this animal model of nephropathy.

Animals↗

Intravenous injection of ioxilan, iohexol and diatrizoate. Effects on urine profiles in the rat.

Effects of intravenous ioxilan, a new third generation non-ionic contrast medium, diatrizoate, iohexol and saline on urine profiles were compared. Albumin, glucose, sodium, phosphate, and the enzymes NAG, LDH and GGT were followed in 24 normal rats over 7 days. Diatrizoate significantly affected all profile components during the first two hours. Albuminuria was significantly greater after diatrizoate than after iohexol or ioxilan, and excretion of glucose, LDH and GGT was significantly higher than after ioxilan. Both iohexol and ioxilan increased the excretion of albumin, LDH and GGT, while iohexol also significantly increased excretion of glucose and sodium. There was a greater excretion of glucose and GGT after iohexol than after ioxilan. Saline did not induce any changes. At day 7, serum sodium, urea, creatinine, and albumin were normal for all test substances, and kidney histology revealed no difference between the groups of animals. It is thus concluded that both high osmolar ionic and low osmolar non-ionic contrast media may cause temporary glomerular and tubular dysfunction in rats. In this model, the kidney is affected most by diatrizoate, less by iohexol, and least by ioxilan.

Animals↗

Summary of U.S. and European intravascular experience with iohexol based on the clinical trial program.

The nonionic contrast medium, iohexol, was released by Nyegaard, Oslo, in 1980 for clinical testing. Results of a three-phase clinical trial program carried out in Europe and the U.S. through December 1983 are summarized. Evaluation of phase I studies of human tolerance and excretion--and phase II studies of effects on pharmacologic and physiologic parameters--indicated that iohexol was well tolerated and effective. Phase III consisted mainly of controlled parallel and crossover studies comparing iohexol with conventional ionic media and with other nonionic agents in a variety of radiographic studies. Image quality was as good or better with iohexol than with ionic media. Iohexol was tolerated significantly better than ionic agents. Patients consistently reported fewer and less intense pain and heat sensations. Iohexol had less effect on blood pressure, blood flow, heart rate, and electrophysiologic parameters, and caused fewer adverse reactions than ionic media for all types of reactions observed.

Clinical Trials as Topic↗

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.

Adult↗

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.

Adult↗

Clinical trial of Iohexol vs. Conray 60 for cerebral angiography.

Iohexol, a new nonionic contrast agent, and Conray 60 were compared in a double-blind clinical trial of 60 patients for safety, imaging effectiveness, and patient discomfort in cerebral angiography. There was no significant difference between the two agents in physiologic changes, film quality, or incidence of adverse effects in the 60 patients. One patient in the iohexol group suffered a cardiac arrest, which was clinically due to septic shock and was probably the result of inadvertent contamination of the iohexol used for test injections in this case. Bacterial growth can be supported in iohexol under certain circumstances, due to the lack of preservatives in this contrast material. The patients in the iohexol group experienced significantly less discomfort than the Conray 60 group. Iohexol is a safe, effective contrast agent when handled properly and causes less discomfort to patients than Conray 60.

Adult↗

The use of iohexol clearance to determine GFR in patients with severe chronic renal failure--a comparison between different clearance techniques.

UNLABELLED: The nonionic low-osmolar contrast medium iohexol was used as marker of glomerular filtration rate (GFR) in 53 patients with stable renal function (group I: n = 32, group II: n = 21). All the patients had clearance values < or = 30 ml.min-1.1.73 m-2 body surface; 40 patients < 20 ml.min-1.1.73 m-2 body surface. Simultaneous determinations of renal clearance and plasma clearance, both as slope clearance and single sample clearance, were performed after intravenous injection of 10 ml iohexol 300 mg iodine/ml. In groups I and II plasma was sampled early (around 3 hours) and late (up to 24 hours) after the injection. In group I urine was collected during four 40-minute periods and in group II during one 3-hour period and in group II the residual urine was estimated by ultrasound. Plasma and urine iodine concentrations were analyzed with X-ray fluorescence technique (Reanalyzer PRX90, Provalid AB, Sweden). In group II S-creatinine and tubular function test were followed to detect any signs of nephrotoxicity. In 6 anuric patients (group III) 10 ml iohexol 300 mg I/ml was injected to assess its extrarenal clearance. In groups I and II the slope clearance correlated excellently with the single sample clearance (r = 0.99) when a late plasma sample was used in both techniques. In group II, where residual urine was estimated by ultrasound, renal clearance correlated better with slope clearance than in group I (r = 0.94 vs r = 0.89). There were no signs of nephrotoxicity in the parameters noted. In group III, extrarenal plasma clearance of iohexol did not exceed 2 ml.min-1.1.73 m-2. CONCLUSION: GFR < 20 ml/min can accurately and safely be determined as renal clearance or plasma clearance of iohexol after an intravenous dose of 10 ml 300 mg I/ml. Plasma clearance techniques, which have the practical clinical advantage of no urine sampling, do at low GFR require a late plasma sample taken, for instance, 24 hours after injection of iohexol, irrespective of whether slope technique or single sample technique or one-compartment or poly-compartment models are used.

Adult↗

CNS-effects from subarachnoid injections of iohexol and the non-ionic dimers iodixanol and iotrolan in the rabbit.

The neural tolerance of the new non-ionic dimer iodixanol was compared with that of the clinically used monomer iohexol and the dimer iotrolan. Behaviour of non-anaesthetised rabbits was monitored for 3 hours after intracisternal injection, at a dose-volume of 1 ml/kg of iodixanol 150 mg I/ml, iodixanol 320 mg I/ml, iohexol 350 mg I/ml, or iotrolan 300 mg I/ml (10 rabbits in each group). Iotrolan induced generalized seizures in 5 rabbits, iodixanol 320 mg I/ml in 2 rabbits, and iodixanol 150 mg I/ml in one rabbit. No excitative changes were observed in rabbits, iodixanol 320 mg I/ml in 2 rabbits, and iodixanol 150 mg I/ml in one rabbit. No excitative changes were observed in rabbits injected with iohexol, but compared with the dimeric contrast media the difference was not significant. Iohexol produced significantly more severe depressive changes than iodixanol 150 mg I/ml (p < 0.01), iodixanol 320 mg I/ml (p < 0.05), and iotrolan 300 mg I/ml (p < 0.05). The results indicate that the excitative neurotoxic potential of the dimer iodixanol is likely to be lower than that of the clinically used dimer iotrolan, but slightly higher than that of iohexol. It may be expected that both dimers will produce a lower frequency of minor neurological adverse reactions than iohexol.

Akathisia, Drug-Induced↗

Comparison of meglumine sodium diatrizoate, iopamidol, and iohexol for coronary angiography and ventriculography.

Meglumine sodium diatrizoate (Urografin), iopamidol, and iohexol were compared in a double-blind, randomized study of 287 patients undergoing elective cardiac angiography. Ninety-six patients received Urografin, 98 received iopamidol, and 92 received iohexol. The groups were similar in all respects. Variables measured before and after contrast injection were left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), systolic arterial pressure (SAP), RR, PR, and QTc intervals, QRS duration, ST segment change greater than 2 mm, arrhythmias, and symptoms. The adequacy of coronary and ventricular opacification was assessed by two experienced observers. Following left ventriculography, small rises in LVEDP occurred with iopamidol and iohexol (mean +/- SD: 18 +/- 7 to 21 +/- 7 mmHg) and a moderate fall in LVSP with Urografin (150 +/- 32 to 133 +/- 32 mmHg). Following coronary angiography there was a progressive fall in SAP (130 +/- 26 to 117 +/- 30 mmHg) and prolongation of RR intervals (900 +/- 138 to 1,266 +/- 692 msec) and QTc (440 +/- 61 to 471 +/- 73 msec) and QRS duration (87 +/- 25 to 100 +/- 27 msec) with Urografin. There was a small fall in SAP with iopamidol (138 +/- 25 to 128 +/- 27 mmHg) and prolongation of QRS duration with iohexol (85 +/- 29 to 90 +/- 24 msec). Other parameters were not significantly affected. Frequent bradyarrhythmias (sinus pause 14.5%, asystole 6%) and ST segment depression occurred following Urografin. Urografin was less well tolerated, with 10% of patients experiencing severe nausea or vomiting and 30% of patients experiencing extreme heat sensation. Differences between iohexol and iopamidol were minor.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Comparison of iohexol 300 mg I/ml and Hexabrix 320 mg I/ml in central angiography. A double-blind trial.

Iohexol 300 mg I/ml and Hexabrix 320 mg I/ml have been compared in a randomized, double blind, parallel study, to evaluate hemodynamic parameters, diagnostic information and adverse reactions. A total of 55 patients entered the study, one of them was later excluded, because both contrast media were given by mistake. In the included material, 21 patients were given iohexol 300 mg I/ml in 55 selective injections, and 23 patients Hexabrix 320 mg I/ml in 65 selective injections. The median total dose was 52 (12-88) ml in the iohexol group and 51 (13-118) ml in the Hexabrix group. No changes in heart rate were seen. Angiograms of good or excellent quality were obtained, and no difference between the two media was shown. No serious adverse reaction occurred, and no statistical significant difference was found between the two media with respect to subjective patient reactions. The results indicate that the non-ionic, low-osmotic contrast medium iohexol is well tolerated in cerebral angiography with respect to the parameters tested. No statistical significant difference was found in any of these parameters between iohexol and Hexabrix.

Adult↗

Iodixanol in intra-arterial cerebral digital subtraction angiography: a comparison with iohexol.

We randomised 86 patients undergoing intra-arterial cerebral digital subtraction angiography (IADSA) to receive iodixanol (Visipaque; Nycomed, Oslo, Norway) 150 mgI/ml or iohexol (Omnipaque; Nycomed) 140 mgI/ml. The efficacy and safety of these two contrast media were compared: efficacy by evaluating the diagnostic information and radiographic density yielded by the angiograms, safety by recording all discomfort connected with the injections, and all adverse events up to 24 h after the investigation. Diagnostic information was optimal in all patients and the overall radiographic density optimal in all but one (iohexol) (P = 0.49). A feeling of warmth, the only discomfort reported, was experienced by 43% and 54% of patients receiving iodixanol and iohexol, respectively (P = 0.26). Two patients in the iodixanol group and five in the iohexol group reported one adverse event (nausea, dizziness, visual disturbance or paraesthesiae) (P = 0.30); all were of mild severity except for one moderate adverse event in each group. Iodixanol 150 mgI/ml and iohexol 140 mgI/ml were demonstrated to be suitable for IADSA, with no clinically or statistically significant differences in efficacy, discomfort or adverse events.

Adult↗

Iodixanol in cerebral computed tomography: a randomized, double-blind, phase-III, parallel study with iodixanol and iohexol.

Iodixanol is a new nonionic dimer, isotonic with blood at all clinically relevant concentrations. Iodixanol (270 mg I/ml) was compared in a double-blind, randomized, parallel-group, phase-III study to the monomeric nonionic iohexol (300 mg I/ml) for evaluation of safety, tolerability and radiographic efficacy during cerebral CT. One hundred adult patients scheduled to undergo contrast-enhanced cerebral CT were randomly allocated to receive either iodixanol or iohexol. All completed the trial. Safety was evaluated by recording discomfort and other adverse events, tolerance by assessing intensity and incidence of discomfort. Radiographic efficacy was assessed from the diagnostic information and the radiographic density. No serious adverse events occurred. One patient (2 %) in the iodixanol group and one patient (2 %) in the iohexol group experienced a transient reddening at the neck and lower neck-line, respectively. Both contrast agents were well tolerated. One patient (2 %) in the iodixanol group and two patients (4 %) in the iohexol group experienced a sensation of warmth (discomfort) in connection with the injection. No difference between the two contrast media were noted radiographically. This comparison between iodixanol and iohexol showed both contrast media to be safe, well-tolerated and efficacious for use in cerebral CT.

Adult↗

Multicenter trial of ionic versus nonionic contrast media for cardiac angiography. The Iohexol Cooperative Study.

Contrast agents used for cardiac angiography are different in regard to ionicity, osmolality and physiologic effects. The nonionic contrast media have been shown to have less toxic effects and a better safety profile than do higher osmolar agents. To better assess this risk, clinically stable patients undergoing cardiac angiography were stratified according to the presence of diabetes mellitus, and level of serum creatinine, and then randomized to receive either iohexol (Omnipaque 350) or sodium meglumine diatrizoate (Renografin 76). All adverse events that occurred during and immediately after angiography were tabulated. A multivariate model was used to identify patients at increased risk for adverse outcome. The 1,390 patients were randomized to iohexol (n = 696) or diatrizoate (n = 694). Significant differences were found in the number of patients with contrast media-related adverse (iohexol vs diatrizoate: 10.2 vs 31.6%; p < 0.001) and cardiac adverse (7.2 vs 24.5%; p < 0.001) events. Severe reactions and the need for treatment were more frequent with diatrizoate than with iohexol, but there was no difference in the incidence of death. The presence of New York Heart Association classification 3 or 4 and serum creatinine > or = 1.5 mg/dl predicted a higher incidence of adverse events as a result of contrast media alone. Use of iohexol is associated with a lower incidence of all types of adverse events during cardiac angiography than is diatrizoate.

Adult↗

Iohexol vs. ioxaglate in lower extremity angiography: a comparative randomized double-blind study in 80 patients.

The aim of this study was to detect clinically relevant differences between iohexol 300 mgI/ml and ioxaglate 320 mgI/ml in lower extremity arteriography. In this randomized double-blind study, 40 patients were examined with iohexol and 40 patients with ioxaglate. Adverse events were evaluated by recording the time of onset and the duration of possible adverse events: during or immediately following the contrast medium injections, after 6 h, and after 24 h following these injections. Heat and pain were scored on visual analog scales. The amount of contrast medium and possible thromboembolic complications were noted. Image quality was evaluated. There were no significant differences in the total amounts of contrast agent administered (ioxaglate mean 121.5 ml vs. iohexol 125.1 ml), scores for heat (ioxaglate mean 6.1 vs. iohexol 6.1) and pain (both agents mean 2.35). Nausea/vomiting was noticed significantly more frequently with ioxaglate (ioxaglate seven patients vs. iohexol one patient (chi 2, P < 0.05)). Thromboembolic complications were not detected. Opacification of vessels was optimal in all patients. No clues were found indicating that one of the agents was better tolerated 6-24 h after the procedure than the other. Nausea/vomiting occurred significantly more frequent with ioxaglate; no further clinically relevant differences were detected.

Adult↗

Differential effects of the iodinated contrast agents Ioxaglate, Iohexol and Iodixanol on thrombus formation and fibrinolysis.

INTRODUCTION: Contrast media (CM) possess both pro-thrombotic and anticoagulant properties. Here we investigate the effect of three classes of CM; Iohexol, Iodixanol and Ioxaglate, on thrombus formation and fibrinolysis in vitro and evaluated the contribution of platelets to this process. MATERIALS AND METHODS: Non-anticoagulated blood was mixed with CM or saline (50% or 20% (v/v)) for 1 min then citrated. Thrombi were produced in vitro under flow in a Chandler loop. Thrombus structure was visualized by immunohistochemistry using FITC-fibrin/ogen antibodies, and propidium iodide to identify nucleated blood cells. To measure fibrino/thrombolysis release of FITC-labeled fibrinogen, added prior to thrombus formation, was measured over 24 h. Platelet degranulation was analyzed by whole blood flow-cytometry. RESULTS: No thrombi formed from blood incubated with Ioxaglate. Thrombi formed with Iohexol or Iodixanol weighed > OR = 10x more than saline controls (116+/-52 and 230+/-128 mg vs. 11+/-3 mg, respectively; p<0.0005), and were more resistant to thrombolysis as evidenced by the release of FITC over 24 h (19.1+/-8.9 and 31.9+/-17.2 U vs. 65.1+/-19.1 U, respectively; p<0.02). Thrombi formed with Iodixanol and Iohexol had larger, more diffuse platelet-rich head areas and tail regions composed of a more open fibrinogen/fibrin meshwork enclosing denser RBC rich areas compared to controls. Iodixanol and Ioxaglate did not increase platelet degranulation, but Iohexol caused a significant increase compared to the saline control (percentage of platelets expressing P-selectin 68.9+/-23.43% vs. 4.93+/-1.44%, respectively; p=0.001). CONCLUSION: Thus thrombi formed with Iodixanol or Iohexol will be larger and more resistant to thrombolysis, whereas Ioxaglate may reduce the risk of thrombus formation.

Blood Platelets↗