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Excretory urography with iohexol: evaluation in children.

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.

Adolescent↗

Hemodialysis for elimination of the nonionic contrast medium iohexol after angiography in patients with impaired renal function.

We examined the kinetics of contrast agent elimination during hemodialysis in 7 patients with end-stage renal disease on regular hemodialysis treatment (group I) and in 13 patients with impaired renal function (serum creatinine 214-657 mumol/l; group II). The nonionic agent iohexol was administered at a dose of 0.4-4.5 g/kg, and a 6-hour hemodialysis was performed with 1-18 h delay. This procedure removed 60-90% (mean 77%) of the iohexol present in the circulation at the start of dialysis treatment. The mean extraction ratio across the dialysis membrane was 0.47 and was inversely related to blood flow. The total clearance of iohexol was 70.4 +/- 24.6 ml/min and was very close to dialyzer clearance, as estimated from blood flow and extraction ratio. The plasma iohexol level after dialysis was related to the dose administered, iohexol clearance, and the patients' body weight. During peritoneal dialysis (36-60 liters dialysis fluid), 43-72% of the iohexol dose was removed from the patients' circulation. In patients of group II no further impairment of the renal function (increase of serum creatinine) in conjunction with angiography was observed. We conclude that hemodialysis and peritoneal dialysis are effective methods for removal of iohexol. Our observations suggest also that accelerated elimination of contrast media by prophylactic dialysis can be beneficial in preventing further reduction in renal function after angiographic procedures in high-risk patients.

Adult↗

Image quality and safety after iodixanol in intravenous urography; a comparison with iohexol.

A double-blind, randomized phase III study compared intravenous urography in 100 adult patients receiving iodixanol 320 mgI ml-1 (Visipaque) with 99 patients receiving iohexol 350 mgI ml-1 (Omnipaque). The aim of the study was to investigate differences in image quality between a non-ionic dimeric contrast medium (CM) and a non-ionic monomer at 40 ml per patient and 60-100 ml per patient volume levels. There were no statistically significant differences between iodixanol and iohexol with respect to overall diagnostic information, which was found to be optimal in 86% and 79%, respectively. Immediately after the injection, the renal border was better delineated with iohexol than with iodixanol (p = 0.0001). Marked papillary blush occurred more often in the iodixanol group (16%) than in the iohexol group (0%), as did visualization of the collecting ducts (24% vs 5%) (p = 0.001). The incidence of adverse events was similar and low for both contrast media. In patients who received the higher doses of CM (60-100 ml), the frequency of discomfort was significantly lower after iodixanol than after iohexol (p = 0.006). We conclude that, in intravenous urography, iodixanol provides at least as good image quality as does iohexol. Iodixanol may cause less discomfort than iohexol, in particular when larger volumes of CM are injected.

Adult↗

Comparison of iohexol with barium in gastrointestinal studies of infants and children.

This study evaluates iohexol as a contrast agent in the gastrointestinal tract in children. In the first part of the study, iohexol in concentrations of 180 and 300 mg l/ml was compared in double-blind manner with barium. Sixty-four patients were studied. No significant difference in changes of blood pressure and pulse rate was found between the three groups of patients studied. Diarrhea was significantly more common in the children receiving iohexol than in children receiving barium. The diarrhea was not due to previously identified high-risk factors in the children, nor was it due to concurrent medication. When image quality was assessed in each anatomic region of the gastrointestinal tract, fewer nondiagnostic ratings occurred with barium than with iohexol. With barium, fewer ratings of poor mucosal coating and slightly fewer ratings of suboptimal contrast density occurred. The second part of the study was an open evaluation of iohexol 180 mg l/ml in 18 patients in whom barium was clinically contraindicated. Three of 53 assessments were nondiagnostic. Mucosal coating was poor in 6%, and contrast density was suboptimal in 8% of patients. The results of this study indicate that barium is the preferred contrast agent for routine evaluation of the gastrointestinal tract in children. Good-quality images can be obtained, however, with iohexol in concentrations of 180 or 300 mg l/ml, and iohexol is an excellent contrast agent for evaluation of the gastrointestinal tract in those patients in whom barium is relatively or absolutely contraindicated.

Adolescent↗

Elimination of the non-ionic X-ray contrast media iodixanol and iohexol in patients with severely impaired renal function.

Iodixanol (Visipaque) and iohexol (Omnipaque) are dimeric and monomeric, respectively, non-ionic X-ray contrast media (CM), with well-characterized pharmacokinetics in healthy volunteers. This study was undertaken to study the pharmacokinetics of the contrast media in patients with severely impaired renal function. A total of 16 patients referred for preoperative abdominal angiography were randomized to form two groups of eight patients, receiving either iodixanol 320 mgI ml-1 or iohexol 350 mgI ml-1. Urine and faeces were sampled before the examination and collected quantitatively for five days afterwards, and blood samples were drawn frequently. The concentrations of iodine and contrast medium in urine and in serum, and the amount of iodine in faeces were determined. Mean baseline creatinine clearance was 13.6 and 9.9 ml min-1 1.73 m-2 in the iodixanol and iohexol groups, respectively. Patients in the iodixanol group received on average 0.34 gI per kg bodyweight (bw) and those in the iohexol group 0.39 gI per kg bw. The semilogarithmic plots of serum concentration of CM vs. time indicated elimination according to a two-compartment model. The mean elimination half-life was 23.0 h for iodixanol and 27.2 h for iohexol, and the mean apparent volume of distribution was similar for the two CM, ranging from 0.20 to 0.30 1 per kg bw. Mean plasma clearance of iodixanol was 10.4 ml min-1 1.73 m-2 and 6.9 ml min-1 1.73 m-2 for iohexol, whereas the mean renal clearances were 8.7 and 6.1 ml min-1 1.73 m-2, respectively. Mean faecal recovery was 8.2% for iodixanol and 6.1% for iohexol, and the respective figures for that in urine were 76.1 and 74.8%. Renal clearance of radiolabelled iothalamate, a marker of glomerular filtration rate (GFR), measured simultaneously, indicated that both CM were eliminated by the kidneys by glomerular filtration only. Thus, both media are suitable as GFR markers.

Aged↗

Effects on renal hemodynamics and tubular function of the contrast medium iohexol in renal patients.

Renal function was assessed in 20 (11 female and 9 male, age 21-76 years, mean 53) renal patients with a creatinine clearance 25-145 ml/min, mean 95, to evaluate the effects of iohexol, a non-ionic low-osmolar contrast medium. Intravenous urography was performed in 16 patients and computed body tomography in 4, using a dose of iohexol ranged between 0.6-3.3 (mean 1.17) g/kg b.w. Different parameters of renal function were determined in the week preceding and 1, 3 and 5 days after the administration of iohexol. The principal renal effect of iohexol was an increase of urinary alanine aminopeptidase, gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatase and N-acetyl-beta-D-glucosaminidase. The maximum increase of enzymuria was observed on day 1 after the administration of iohexol. In most cases enzymes returned to base-line values within 3 days. No relevant variation of renal hemodynamics (glomerular filtration rate and effective renal plasma flow) was observed after iohexol. In conclusion, iohexol can increase of urinary enzymes, but the effect is rapidly reversible and is not accompanied by a clinically significant impairment of renal hemodynamics.

Acetylglucosaminidase↗

Anticoagulant effect of iohexol vs. ioxaglate during cardiac catheterization.

Contrast agent safety during cardiac catheterization (CC) may relate in part to anti- or procoagulant effect. We studied these effects in 177 patients who underwent standard CC (N=112) or percutaneous transluminal coronary angioplasty (PTCA) (N=65) and received either iohexol (N=111) or ioxaglate (N=66). Patients received either 0 or 2000u heparin for CC or 10,000u for PTCA. The groups were similar in regards to age, sex, amount of contrast used, and procedure time. Partial thromboplastin time (PTT) and activated clotting time (ACT) were both significantly increased (P less than .01) in patients who received 10,000u heparin irrespective of type of contrast agent although larger increases were seen in the iohexol group. With 2000u of heparin, ACT and PTT increased significantly (P less than .01) only in the iohexol group. PTT and ACT actually decreased to similar and significant (P less than .01) degrees after both iohexol and ioxaglate when heparin was not used. We conclude: 1) commonly used measures of anticoagulant (ACT and PTT) show greater prolongation after either 2000 or 10,000u of heparin with iohexol than ioxaglate, 2) ACT and PCT appear to shorten with both iohexol and ioxaglate if no heparin is used. This data would suggest that ioxaglate does not have an anticoagulant advantage over iohexol.

Aged↗

Iohexol: summary of North American and European clinical trials in adult lumbar, thoracic, and cervical myelography with a new nonionic contrast medium.

Iohexol, a new water-soluble nonionic contrast medium, was evaluated in clinical trials in Europe and North America for lumbar, thoracic, and cervical myelography using direct C1-2 or lumbar puncture. Iohexol was administered at 180, 240, or 300 mg I/ml to 677 adult patients for visualization of the lumbar subarachnoid space, and to 368 adult patients for evaluation of the cervical area. Compared with metrizamide, use of iohexol resulted in equivalent opacification but significantly reduced patient morbidity (headache, nausea, vomiting, dizziness). No epileptogenic activity was recorded in over 370 patients receiving iohexol. No mental or psycho-organic syndrome manifestations were observed in any of the 1,045 patients receiving iohexol. Adverse reactions occurring after iohexol injection were not related to the concentration or site used or to total dose administered. Iohexol has, thus far, proven superior to metrizamide for myelography.

Adult↗

Cardiac effects of adding electrolytes and oxygen to iohexol in a dog model of contrast media-induced ventricular fibrillation.

We investigated whether addition of a balanced electrolyte supplement and oxygen to the nonionic contrast medium iohexol reduces the risk of ventricular fibrillation (VF), and studied regional electrophysiology prior to the VF event. Twenty ml of each test solution were infused at a rate of 0.5 ml/s into the left anterior descending coronary artery (LAD) in 8 anesthetized dogs. LAD was externally occluded during infusion, to simulate a wedged catheter situation. ECG, hemodynamics, regional epicardial monophasic action potential duration (MAPD) and ventricular activation times (VAT) were calculated. All infusions with iohexol caused VF within 27 s. Five of 12 infusions with iohexol + 30 mmol NaCl, 3 of 11 infusions with iohexol+electrolytes (IPE) NaCl, KCl, CaCl2 and MgCl2) and 4 of 11 infusions with IPE with oxygen addition (IPE+O2) caused VF after 45 s. Iohexol did not change MAPD prior to the VF event. Iohexol + 30 mmol NaCl and the IPE solutions lengthened MAPD initially, but at the time of the VF event MAPD were normalized or shortened. We conclude that electrolyte supplement to iohexol may prevent VF, probably by lengthening MAPD.

Action Potentials↗

Experimental studies comparing iohexol and 51Cr-EDTA for glomerular filtration rate measurements.

The total plasma clearance as well as the renal clearance of iohexol were evaluated for determination of the glomerular filtration rate (GFR) in 16 anesthetized pigs. The iohexol levels in urine and plasma were measured by X-ray fluorescence. The total plasma clearance of 1 and 4 ml/kg b.w. of iohexol 300 mg I/ml was compared to the simultaneously as well as nonsimultaneously calculated total plasma clearance of 51Cr-EDTA. The total plasma clearance of 51Cr-EDTA and of iohexol turned out to be equal and independent of the injected dose of iohexol. The injected dose did not have any effect on the renal clearance of iohexol either. It is concluded that iohexol and 51Cr-EDTA are similar as marker substances for determination of the GFR.

Animals↗

Iodixanol in abdominal digital subtraction angiography. A randomized, double-blind, parallel trial with iodixanol and iohexol.

The safety, tolerability and efficacy of iodixanol 270 mg I/ml were compared to those of iohexol 300 mg I/ml in a double-blind, randomized, parallel abdominal intra-arterial DSA phase III trial. Fifty-nine patients were included in the trial; 39 patients received iodixanol and 20 received iohexol. The mean volume of iodixanol administered was 235.8 ml (0.93 g I/kg b.w.) while the mean volume of iohexol was 254.7 ml (1.10 g I/kg b.w.). No differences in diagnostic information and radiographic density were apparent in spite of the difference in the concentration of iodine. No serious adverse events occurred. Four patients (10%) in the iodixanol group and 2 (10%) in the iohexol group experienced adverse events. Eight percent of the injections of iodixanol promoted discomfort, compared to 12% of the injections of iohexol. An increase in S-urea and S-creatinine was seen with both agents the first day after injection, but appeared to be less pronounced with iodixanol than with iohexol. Other serum tests revealed no changes of clinical importance. Both iodixanol and iohexol were found to be effective, safe and well tolerated contrast media for abdominal intra-arterial DSA.

Abdomen↗

The toxicity of the non-ionic water-soluble contrast media iohexol and metrizamide (Amipaque) in selective vertebral angiography. An experimental study in rabbits.

Selective left vertebral angiography was carried out in 25 rabbits comparing the toxic effects of iohexol and metrizamide (Amipaque). The iodine concentration for iohexol was 280 and 350 mg/ml and for metrizamide 350 mg/ml. Short general convulsions were seen in many of the animals with iohexol in the concentration of 350 mg iodine/ml. Cardiovascular reactions were seen with both contrast media, but were more marked with iohexol than with metrizamide in the concentration of 350 mg iodine/ml. Both iohexol and metrizamide are far less toxic than the ionic contrast medium metrizoate, but metrizamide seems to be less toxic than iohexol in vertebral angiography.

Animals↗

Iohexol compared to metrizamide in cervical and thoracic myelography. A randomized double blind parallel study.

A randomized double blind study with iohexol (Omnipaque) and metrizamide (Amipaque) in cervical myelography was performed in 50 patients, 29 with iohexol and 21 with metrizamide. The myelographies were performed either with lumbar or with C1-C2 puncture in about equal groups, using 300 mg I/ml and 240 mg I/ml of the contrast media respectively. The image quality was equal with both contrast media, excellent in about 4/5 and good in 1/5 of the examinations. Subjective side effects were twice as frequent with metrizamide as with iohexol. The most frequent side effect was headache, occurring in 34% with iohexol and in 67% with metrizamide. Altogether 24% or the patients had EEG changes after iohexol as compared to 47% after metrizamide. All EEG changes were slight dysrythmia-except in three patients with spike activity after metrizamide. These were the only ones with mental reactions as well. It can be concluded that in this trial iohexol was better suited for cervical myelography than metrizamide.

Adult↗

Iopentol (Imagopaque 350) compared with iohexol (Omnipaque 350) in pediatric cardioangiography. A clinical trial assessing adverse events, ECG, blood pressure and diagnostic information.

A non-ionic, monomeric, low-osmolar contrast medium, iopentol (Imagopaque, Nycomed Imaging AS, Oslo, Norway) has been compared with iohexol (Omnipaque, Nycomed Imaging AS, Oslo, Norway) in a double-blind, randomized, parallel-group trial in children. The aims of the study were to compare the safety and radiographic efficacy of iopentol 350 mg I/ml versus those of iohexol 350 mg I/ ml in pediatric cardioangiography. Seventy-three children, of whom 35 received iopentol and 38 iohexol, were included in the evaluation. The quality of overall diagnostic information was excellent or adequate in all patients. There were no statistically significant differences between numbers of patients reporting adverse events nor number of patients reporting discomfort in the two groups. Three patients in the iopentol group and two patients in the iohexol group reported adverse events. Heat sensation was reported by 4 patients in the iopentol group and 5 patients in the iohexol group. Following injection of contrast medium, there were no differences between the groups regarding ECG, heart rate and systolic blood pressure at the site of injection. Iopentol was demonstrated to be as effective, safe and well tolerated as iohexol in pediatric cardioangiography.

Adolescent↗

A double-blind, prospective, randomized, multicenter group comparison study of iopromide 240 vs iohexol 240 in myelography.

The aim of this study was to evaluate the safety and efficacy of iopromide 240 mgI/ml in comparison with iohexol 240 mgI/ml in myelography. A total of 421 patients in seven centers and four countries received an average of 11.9 ml of either iopromide 240 (278 patients) or iohexol 240 (143 patients) for X-ray and/or CT myelography in a randomized (2:1), prospective, double-blind study. All patients were followed up 3-4 h after the procedure, and 327 patients remained hospitalized for 24 h. In 82 patients an EEG was recorded prior to as well as 3-4 h and 24 h after myelography. Physical examinations, including measurement of vital signs, were performed in all patients at these time points. The results were subject to statistical analysis with the primary variable being the incidence of adverse events. Both contrast media (CM) were equally effective in terms of opacification. The rating for opacity was "good" or "excellent" in 88 % for both CM. Four patients (iopromide group: n = 3; iohexol group: n = 1) had transient EEG changes but did not show clinical symptomatology. The overall rate of patients experiencing any adverse event (AE) was 16.9 % for iopromide 240 and 14.0 % for iohexol 240. Equivalence testing was inconclusive; however, the results indicated equivalence. The rate for AEs considered as study-drug related was slightly lower with iopromide 240 than with iohexol 240 (7.2 vs 7.7 %, respectively). Neither unknown nor unexpected AEs known for myelographic X-ray CM nor serious adverse events were observed. Iopromide 240 and iohexol 240 are equally safe and effective and can be recommended for myelography.

Adolescent↗

Hemodynamic and electrocardiographic effects in man of a new nonionic contrast agent (iohexol): advantages over standard ionic agents.

Iohexol is a new, nonionic contrast material that has been shown in animal studies to hold great promise as an agent for coronary arteriography and ventriculography with fewer adverse hemodynamic effects than standard ionic media. At present, it has not been studied systematically in man. Fifty patients referred for elective cardiac catheterization were randomized to receive either iohexol or meglumine sodium diatrizoate (Renografin-76). Both operator and patient were blinded as to which agent was being used. Hemodynamic variables measured were pulmonary artery wedge pressure and systemic blood pressure. In addition, the following electrocardiographic indexes were evaluated: S-T segment shifts, changes in Q-T interval, changes in T-wave amplitude, and changes in heart rate. These variables were measured after left ventriculography and after both left and right coronary arteriography. Both iohexol and sodium meglumine diatrizoate produced small transient elevations in pulmonary artery wedge pressure. Systemic hypotension occurred with both agents but was more profound and longer-lasting with sodium meglumine diatrizoate. Iohexol injection resulted in no electrocardiographic changes, whereas sodium meglumine diatrizoate produced marked Q-T prolongation, as well as changes in T-wave amplitude and heart rate. Iohexol was well tolerated by the patients, and radiographic opacification was good to excellent in all cases. Thus, iohexol produces fewer deleterious hemodynamic and electrocardiographic changes than sodium meglumine diatrizoate when studied in a typical adult population requiring diagnostic cardiac catheterization. This favorable preliminary experience in man has potential widespread importance because of the large number of patients undergoing angiographic procedures.

Aged↗

Iodixanol, a new isosmotic nonionic contrast agent compared with iohexol in cardiac angiography.

Iodixanol, a new ratio 6 nonionic iodinated contrast agent with an osmolality equal to serum, was compared with iohexol in a randomized, double-blind, parallel study. Two hundred patients undergoing elective diagnostic cardiac angiography were randomized to iodixanol (n = 101) or iohexol (n = 99). There were no differences noted between the 2 agents in the mean changes in systolic or diastolic blood pressure or heart rate during or immediately after any angiography. However, significantly more patients had a decrease in diastolic blood pressure of > 20 mm Hg during left coronary angiography with iodixanol. The only significant differences in any electrophysiologic parameter were slightly more PR prolongation during left coronary angiography with iodixanol and more ST-segment depression with iohexol during coronary angiography. Neither was clinically significant. Injection-associated discomfort occurred with both agents, but more patients experienced moderate to severe discomfort with iohexol (52%) than with iodixanol (17%) (p < 0.001). Only 1 potentially serious adverse event, ventricular fibrillation with iohexol, was considered related to contrast, and there were no differences noted between the agents. Overall, angiographic quality was equal with all angiograms being assessed as good or excellent in both groups (p = 0.885). In this low-risk population undergoing cardiac angiography, iodixanol is safe and effective without clinically important differences from iohexol. Additional studies in patients at high risk for complications should help further define the role of iodixanol in cardiac angiography.

Blood Pressure↗

Optimal contrast agents for vascular imaging on computed tomography: iodixanol versus iohexol.

RATIONALE AND OBJECTIVES: Dimeric nonionic iodinated contrast has a lower osmolality than monomeric nonionic iodinated contrast but is available at lower iodine concentrations. Less dilution of intravascular fluid by influx from the extravascular space is proposed to occur with decreasing osmolality. The purpose of this study was to determine if a dimeric nonionic iso-osmolar contrast agent (iodixanol) gives equal vascular enhancement compared with a monomeric nonionic hyperosmolar contrast agent (iohexol). MATERIALS AND METHODS: A dynamic single-level computed tomography (CT) scan was performed of the abdominal aorta of 12 sedated rabbits using a four-row multidetector CT scanner following injection of 1.5 mL contrast/kg body weight at 2 mL/sec. The rabbits were injected with the dimeric contrast agent iodixanol (Visipaque 320; Amersham Health) or the monomeric contrast agent iohexol (Omnipaque 350; Amersham Health). The order of the type of contrast media injected was randomized for each rabbit, and the interval between injections was 2 weeks. Using the 2.5-mm detectors, four contiguous 3-mm contrast-enhanced scans were obtained at a single level every 5 seconds for 120 seconds (total of 24 scans) with a kVp of 120, mA.s of 110, field of view of 106 mm, and soft tissue reconstruction algorithm. A single level was chosen to measure the attenuation of the abdominal aorta at 5-second intervals. The mean attenuation and standard deviation values were recorded for the whole aorta, for the central half of the vessel, and for the peripheral half of the vessel. A log-log transformation of the data was performed and regression analysis was done on the outcomes of interest (e.g., mean, standard deviation) on time for each region. RESULTS: There was no statistically significant difference in mean attenuation for the whole aorta for iodixanol and iohexol (P = .918) even though the iodine content was 9.3% less with the dimeric iodixanol. The time-attenuation curve of iodixanol paralleled that of iohexol for all time points. The mean attenuation values of the central half of the aorta (P = .354) and peripheral half of the aorta (P = .758) were also not statistically different for the two contrast agents. CONCLUSION: The vascular attenuation provided by a 9.3% lower iodine concentration of iso-osmolar iodixanol is equal to that given by hyperosmolar iohexol. This suggests that there is less intravascular dilution of iso-osmolar contrast. The enhancement across the cross section of the vessel is also similar for both contrast agents. This suggests the vascular studies with iodixanol and iohexol are of equal quality even when a lower dose of iodine is given with iodixanol. It is relevant for patients with borderline or diminished renal function in whom less volume of contrast may be administered.

Animals↗