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Iodixanol in femoral arteriography. A randomized, double-blind, phase III, parallel study with iodixanol 270 mg I/ml and iohexol 300 mg I/ml.

Two contrast media, iodixanol (Visipaque, Nycomed) 270 mg I/ml and iohexol (Omnipaque, Nycomed) 300 mg I/ml, were compared in femoral arteriography, in 147 patients. Both contrast media were diagnostically effective for use in femoral arteriography, without any significant difference. Pain was reported in connection with injection of iohexol by 36% of the patients, after injection of iodixanol none reported pain. Seventy-two percent of the patients in the iodixanol group reported a sensation of warmth in connection with contrast injection versus 90% in the iohexol group. The average intensity of the warmth was greater with iohexol than with iodixanol. Fourteen percent of patients in the iodixanol group and 1% in the iohexol group reported one or more subjective adverse events.

Aged↗

In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part III. Effects of mannitol and iohexol infusions after pretreatment with cyclosporin A.

In vivo fluorescence microscopy was used for experimental studies of the renal cortical microcirculation in normal mice and in mice pretreated with the nephrotoxic drug cyclosporin A. The cortical circulation was studied after i.v. infusions of a nonionic low osmolar contrast medium (iohexol) and after infusions of mannitol. All infusions produced marked effects on the distribution and velocity of cortical blood flow with no differences between iohexol and mannitol. The renal cortical blood flow was inhomogeneous regarding different capillaries and there was an initial rise in the number of capillaries with increased blood flow after infusions of both mannitol and iohexol. There was simultaneously an increased number of capillaries with decreased blood flow following all infusions. The decreased blood flow after infusion of iohexol was more pronounced when the animals had been pretreated with cyclosporin A. The difference was only significant (p < 0.05) during a short part of the observation period of 30 min, but it may indicate that kidneys previously exposed to cyclosporin A are more susceptible to infusions of iohexol.

Animals↗

Increased urinary excretion of iohexol after enteral administration in patients with ileal Crohn's disease. A new test for disease activity.

Iohexol is a water-soluble contrast medium that is partly absorbed/permeated through mucosa of the small bowel and excreted unchanged in the urine. Iohexol was administered orally to 12 patients with Crohn's disease of the ileum and to 10 healthy controls to measure its excretion in the urine. The location and activity of Crohn's disease were determined by barium double-contrast radiography in all patients and by ileoscopy and biopsy in 9 patients. Iohexol concentrations in serum and 24-hour urine were measured using reversed phase high-performance liquid chromatography. Urinary excretion of iohexol was significantly greater in patients with active Crohn's disease than in controls. We suggest this method as a new way of measuring Crohn's disease activity and mucosal damage in the small bowel. Bowel inflammation and mucosal cell damage are strongly indicated if the iohexol excreted in the urine is over 1% of the oral intake.

Administration, Oral↗

Hemodynamic effects of iodixanol and iohexol during ventriculography in patients with compromised left ventricular function.

A crossover study was performed to compare the hemodynamic effects of the iso-osmolar contrast agent iodixanol (Visipaque) 320 mg I/ml to those of the low-osmolar iohexol (Omnipaque) 350 mg I/ml. The main hypothesis was that iodixanol and iohexol would affect left ventricular end-diastolic pressure (LVEDP) to different degrees. In 48 patients with reduced cardiac function (mean ejection fraction 33. 4%), one ventricular injection was performed with each contrast medium. Ventricular, aortic and right atrial pressures and heart rate were measured continuously. Cardiac output (using Fick's principle) and systemic vascular resistance were calculated. LVEDP increased with both agents, but significantly less after iodixanol than after iohexol (P < 0.01), also in subgroups of patients in whom baseline LVEDP was severely increased and in whom 3-vessel disease was present. Immediate changes in variables reflecting vasodilatation were similar with both agents. In conclusion, both contrast agents influenced hemodynamics during ventriculography, but iodixanol had significantly less influence on LVEDP than did iohexol.

Adult↗

Absorption of iohexol from cerebrospinal fluid to blood: pharmacokinetics in humans.

The absorption of iohexol from the subarachnoid space was studied in 9 patients. Serum concentrations of iohexol were measured for a minimum of 24 hours after injection. Peak serum concentrations were observed after 2.2 (1.7-2.7) hours. The half-life of the subsequent decrease in serum concentrations was 3.4 (2.2-7.9) hours. Concentrations of iohexol in cerebrospinal fluid were 0.29-4.3 mg I/ml 24 hours after injection (7 patients). Serum and cerebrospinal fluid concentrations of iohexol are comparable to those found after intrathecal injection of metrizamide.

Adult↗

Side effects after diagnostic lumbar puncture and lumbar iohexol myelography.

A prospective, controlled study was performed to compare side effect incidences after lumbar iohexol myelography (n = 97) and diagnostic lumbar puncture (n = 85). No significant side effect incidence differences (iohexol vs. controls) were found regarding number of patients with any side effect (63 vs. 73%), headache (44 vs. 54%), nausea, dizziness, visual, auditory, or psychic symptoms. Early-onset headache occurred significantly more often in the iohexol group (17 vs 5%), while postural headache occurred most frequently after lumbar puncture (25 vs. 41%). These results suggest that apart from the slight early-onset headache, most side effects after lumbar iohexol myelography are related to the puncture per se, not to the contrast agent.

Adult↗

Complications in cerebral angiography. A comparison between the non-ionic contrast medium iohexol and meglumine metrizoate (Isopaque Cerebral).

Cerebral angiography was performed in 100 patients in order to study the frequency of adverse effects and complications with a new non-ionic contrast medium, iohexol, compared with an ionic medium, meglumine metrizoate. The study was performed as a double blind clinical trial. Iohexol was better tolerated than meglumine metrizoate, since more patients experienced the injections as painful and unpleasant with metrizoate than with iohexol. However, the subjective adverse effects were minor with both contrast media. There was no statistically significant difference in the frequency of more serious side effects. Transient hemiparesis was seen in two patients who prior to the angiography had suffered from numerous similar attacks per day and in one patient in whom a nearly occluded internal carotid artery was occluded during the examination. These complications occurred in the iohexol group, but are more likely to be due to thromboembolism than to contrast medium toxicity.

Adult↗

Is nonionic isotonic iohexol the contrast agent of choice for quantitative myocardial videodensitometry?

All currently used contrast media in coronary angiography induce a considerable hyperemic response interfering with the interpretation of circulation times derived from myocardial time-density curves. Aim of this study therefore, was to find a contrast agent with minimal hyperemic response. For this purpose 2, 4 and 6 ml of the nonionic isotonic low iodinated contrast agent iohexol (Omnipaque 140) and 6 ml of a similarly low iodinated but still hypertonic solution of the ionic diatrizoate (Urographin 30%) were administered into the left coronary artery of 8 anesthetized instrumented dogs. Heart rate was held constant by atrial pacing and left ventricular pressure, left ventricular dP/dt and mean and phasic coronary blood flow were recorded. To test the hypothesis that the hyperemic response to nonionic contrast media is partly due to an increase in inotropic state mediated by Ca++ion influx, all measurements were repeated 30 minutes after intracoronary administration of 0.5 mg verapamil. For iohexol the increase in coronary blood flow was small but significant: 12 +/- 7%, 25 +/- 11% and 38 +/- 16% for the 2, 4 and 6 ml administrations, respectively (mean +/- s.d.; p less than 0.01). For the diluted diatrizoate the increase in coronary blood flow was 65 +/- 23%. Increases for currently used contrast agents are on the order of 200-300%. After verapamil, the hyperemic response to iohexol decreased significantly to 9 +/- 5%, 20 +/- 8% and 29 +/- 12% for the 2, 4 and 6 ml administrations, respectively (p less than 0.01). The reaction to diatrizoate was not affected by verapamil. Moreover, there was a significant positive correlation between the increase in coronary blood flow and left ventricular dP/dt max under all conditions for all but one dog. We conclude that the isotonic, low iodinated nonionic contrast agent iohexol has only a moderate influence on coronary blood flow, which can be further attenuated by verapamil. By this approach, a more reliable assessment of circulation times from myocardial time-density curves obtained by digital subtraction angiography and videodensitometry becomes possible.

Angiography↗

Comparison of the nephrotoxicity between ioversol and iohexol.

To evaluate the renal toxicity of intravenous administration of ioversol and iohexol, the urinary N-acetyl-beta-glucosaminidase (NAG) to creatinine ratio was measured before and after drip infusion pyelography. Thirty patients received intravenous ioversol and 29 patients received iohexol. The urinary NAG to creatinine ratio tended to increase after respective contrast media: 5% increase in the ioversol-treated, and 8% in the iohexol-treated patients. There were no significant differences in these values; the nephrotoxicity of ioversol appeared to be just as insignificant as that of iohexol.

Contrast Media↗

Iopentol (Imagopaque 300 and 350) compared with iohexol (Omnipaque 300 and 350) in cerebral and aortic arch angiography. A clinical trial assessing adverse events and diagnostic information.

The safety of the non-ionic contrast medium iopentol (Imagopaque, Nycomed Imaging AS, Oslo, Norway) when used in cerebral angiography and aortic arch angiography, was the focus of this investigation. Overall quality of visualization and changes in heart rate and blood pressure were, however, also assessed. In total, 39 patients were injected with iopentol and 41 patients with the comparative contrast medium, iohexol (Omnipaque, Nycomed Imaging AS, Oslo, Norway). Two patients (5%) in each group reported contrast-related adverse events other than a sensation of heat, while three patients in the iopentol group and four in the iohexol group reported procedure-related adverse events. A sensation of heat was reported by 21 patients (54%) in the iopentol group, and by 20 patients (49%) in the iohexol group. There were no clinically relevant changes in heart rate or blood pressure. The diagnostic information obtained was of sufficient or excellent quality for all patients. Statistical analyses did not indicate any significant difference between the two contrast media. Iopentol was well suited for cerebral and aortic arch angiography, comparable to iohexol regarding safety and efficacy.

Aorta, Thoracic↗

A prospective survey of delayed adverse reactions to iohexol in urography and computed tomography.

We investigated 7505 inpatients who underwent intravenous urography or contrast-enhanced computed tomography to assess risk factors for delayed adverse drug reactions to iohexol, a non-ionic iodinated contrast medium. Focusing on delayed adverse reactions, all adverse events were prospectively investigated for 7 days after injection of iohexol. To explore the relevant risk factors, the relationship between occurrence of adverse reactions to iohexol and 17 different variables was evaluated by logistic regression analysis. To assess the influence of seasonal factors, adverse reactions were separately evaluated during two periods: February to April (the pollinosis period in Japan) and July to September (the non-pollinosis period). The prevalence of delayed adverse events and delayed adverse reactions was 3.5 and 2.8%, respectively, whereas the prevalence of adverse events and adverse reactions was 5.7 and 5.0%, respectively. Multivariate analysis showed that six parameters had a significant influence on delayed adverse reactions to iohexol, including (a) a history of allergy, (b) season, (c) radiographic procedure, (d) age, (e) concomitant surgery or other invasive procedures, and (f) concomitant medication. The prevalence of delayed reactions was lower than in previous large-scale studies. Significant risk factors included a history of allergy and performance of radiography during the pollinosis period, suggesting that allergy was involved in delayed adverse reactions. The type of radiographic procedure also had an influence.

Contrast Media↗

Alterations in fibrin detected in coronary sinus blood after heparin and coronary angiography with a nonionic contrast agent (iohexol).

Although heparin and some radiographic contrast agents inhibit coagulation, thrombi can still form in their presence. The chemical environment in which a thrombus forms affects fibrin structure that may alter the ability of the thrombus to be lysed. Therefore, we assessed changes in fibrin structure in 13 patients referred for coronary angiography. Blood was obtained from the femoral vein, femoral artery, ascending aorta, left main coronary artery (LMCA), and coronary sinus (CS) before, during, and after coronary angiography was performed with iohexol. The number of fibrin monomers per fiber cross section was determined by turbidity measurements of fibrin gels formed from plasma samples. At baseline there was no difference in the number of fibrin monomers per fiber cross section in plasma gels generated from the different sampling sites. After iohexol administration, there was a significant decrease in the number of fibrin monomers per fiber cross section at the sampling sites ranging from - 13% to -25% compared with the respective baseline values with the largest change in the LMCA CS (51+/-16 to 38+/-15, p <0.025). Transcardiac (LM - CS value) changes in the number of fibrin monomers per fiber cross section were dependent on the timing of the sample collection in the CS. In 7 patients, the CS sample was collected approximately 2 minutes after injection of contrast material and there was no transcardiac difference. When the CS sample was obtained during contrast injection (n=6) a large transcardiac change occurred (44+/-10 to 32+/-14, p=0.01). These data show transient changes in fibrin structure during coronary angiography with iohexol. The thinner fibers formed in the presence of iohexol were more resistant to fibrinolysis.

Anticoagulants↗

Glomerular filtration rate determination in diabetic patients using iohexol clearance--comparison of single and multiple plasma sampling methods.

Use of iohexol clearance has been described as the gold standard for the measurement of glomerular filtration rate (GFR). It is suggested that multiple plasma sampling following iohexol injection is required to accurately determine GFR by area under plasma clearance curve. The aim of this study was to determine whether single plasma sampling 4 h after injection of iohexol could accurately determine GFR in diabetic patients with mild to moderate renal failure, compared to multiple plasma sampling. A total of 120 GFR determinations in 36 patients with non-insulin dependent diabetic renal disease were done over 1 year. No acute deterioration was seen in renal function following injection of contrast in any patient. Strong correlation in GFR measurement was observed between the multiple plasma sampling method and the single plasma sampling method (r2 = 0.975). Single plasma sampling 4 h after bolus injection of iohexol is a safe and accurate method of determining GFR and change in GFR in diabetic subjects with mild to moderate renal impairment.

Diabetes Mellitus, Type 2↗

Capillary electrophoresis for the determination of glomerular filtration rate using nonradioactive iohexol.

High-performance liquid chromatography (HPLC) has been used as an alternative to the isotopic method to calculate glomerular filtration rate (GFR). With the HPLC method, serum iohexol or iothalamate levels are measured, and the plasma clearance rate of the compound is used as a surrogate for GFR. However, HPLC is a labor-intensive procedure, which limits its usefulness in the clinical setting. Capillary electrophoresis, a newer technique in which electrophoretic separations are performed in capillary tubes, is easier and faster than HPLC. We used capillary electrophoresis for the determination of serum iohexol levels and the calculation of GFR. Patients underwent a simultaneous 125I-iothalamate clearance test and a plasma iohexol clearance test to determine GFR. Mean GFR (+/-SD) was 70.9 +/- 29.9 mL/min (range, 14.5 to 131 mL/min) in 52 patients as determined by standard iothalamate clearance methods. For iohexol clearance, the correlation coefficient and standard error were 0.93 and 10.9 mL/min, respectively, using capillary electrophoresis compared with the iothalamate method. Capillary electrophoresis is a simple, rapid method that can be used to calculate GFR and provides results at least as accurate as those obtained by HPLC and x-ray fluorescence.

Adult↗

Sudden hearing loss following drip intravenous pyelography with iohexol: a case report.

A 37-year-old male developed severe sensorineural hearing loss (SNHL) following drip intravenous pyelography with iohexol. We suggest that this hearing disturbance might have been caused by a delayed allergic reaction to iohexol or to its toxicity, because hearing loss developed several hours after the infusion of iohexol. No improvement in hearing was achieved after various treatments. This is the first report of SNHL possibly attributable to the adverse effects of iohexol.

Adult↗

Long-residence-time nano-scale liposomal iohexol for X-ray-based blood pool imaging.

RATIONALE AND OBJECTIVES: Although soluble nonionic iodine compounds with low systemic toxic effects have been developed for use in computed tomography (CT), they have short residence times of a few minutes or mere seconds-insufficient time for blood pool imaging, even with high-speed multi-detector row spiral CT. Moreover, potential renal toxic effects preclude repeated administration of these contrast agents during imaging, as well as their use in patients with compromised renal function. The objective of this study was to develop and evaluate a CT contrast agent for blood pool imaging that remains in the blood for more than 3 hours and that is relatively nontoxic to the kidneys. MATERIALS AND METHODS: The authors assessed a liposomal iohexol formulation for its encapsulation efficiency in terms of milligrams of iodine per milliliter of lipid formulation and for its stability in phosphate buffer solution and in human plasma in vitro. Using a rabbit model, they also assessed the formulation's in vivo stability, residence time, and enhancement of contrast on images of various organ systems. RESULTS: The formulation, which contained 34.8 mg of iodine per milliliter of liposomal iohexol solution, remained stable in blood plasma both in vitro and in vivo, after injection into rabbit vasculature. An intravenous dose of 475 mg of iodine per kilogram of body weight produced contrast enhancement in the rabbit model of approximately 130 HU in the aorta and liver cortex and approximately 100 HU in the kidney cortex. Contrast enhancement was maintained for 3 hours after injection, and minimal clearance of the contrast agent via the kidneys was observed. CONCLUSION: The liposomal iohexol formulation tested in this study had a sufficient residence time for blood pool imaging in a rabbit model. Future experiments with long-residence-time iohexol formulations may lead eventually to applications in cardiac imaging and in early tumor detection.

Animals↗

A randomized trial of prophylactic acetylcysteine and theophylline compared with placebo for the prevention of renal tubular vacuolization in rats after iohexol administration.

RATIONALE AND OBJECTIVES: Renal tubular vacuolization (RTV), which has been shown to occur after the use of iodinated contrast material, may be one of the earliest signs of contrast medium-induced renal injury. In this study, the authors tested a method for preventing RTV with the administration of acetylcysteine, theophylline, or both, prior to contrast medium administration. MATERIALS AND METHODS: Eighty rats were randomly selected for inclusion in the study. The treatment group consisted of three subgroups, each of which received prophylactic acetylcysteine, theophylline, or both before injection of iohexol. The control group comprised five subgroups, each of which received acetylcysteine, theophylline, both, normal saline injection, or orally administered normal saline prior to iohexol injection. RESULTS: The occurrence of RTV in the treatment groups was compared with that in the control subgroup that received normal saline and iohexol. All of the rats in that control subgroup (n = 10) and 97% of the rats in the treatment group (n = 30) developed RTV. CONCLUSION: The administration of acetylcysteine, theophylline, or both prior to iohexol injection did not prevent RTV from occurring in rats.

Acetylcysteine↗

Hepatic imaging with iodinated nanoparticles: a comparison with iohexol in rabbits.

RATIONALE AND OBJECTIVES: We evaluated the efficacy of a particulate computed tomography (CT) contrast agent in an animal model of focal liver disease. METHODS: Ethyl ester of diatrizoic acid (EEDA) is an iodinated (89 mg I/ml) nanoparticulate (200 nm) contrast agent intended for intravenous use that is currently undergoing preclinical testing in our laboratory. Focal liver abscesses were created in 11 New Zealand White rabbits. Iohexol and EEDA were administered to each animal on different days. CT scanning was performed at intervals following contrast agent administration. Liver and abscess enhancement were measured and compared. Dynamic imaging experiments in normal animals were also performed using both agents. RESULTS: EEDA resulted in significantly greater enhancement of the liver and liver-to-abscess contrast than did iohexol at all time points beyond 5 min at approximately 25% of the total iodine load. During dynamic imaging, liver and aortic enhancement were greater with EEDA than with iohexol, except during a 20- to 40-sec period immediately following contrast agent administration. CONCLUSION: EEDA is superior to iohexol for imaging liver abscesses. Our results suggest that liver-directed agents such as EEDA may prove to be more efficacious than currently available extracellular agents designed for liver CT scanning.

Animals↗