Effect of low osmolar,ionic and nonionic,contrast media on the cytologic features of exfoliated urothelial cells

The effect of low osmolar, ionic and nonionic, contrast media on the cytologic features of exfoliated urothelial cells were measured in vitro and compared to those induced by standard, high osmolar radiographic contrast media. The low osmolar agents were found to induce no significant adverse effects on the cytologic features of the urothelial cells, whereas the ionic agents clearly distorted certain cytoplasmic and nuclear features. These findings may support the use of low osmolar nonionic agents for retrograde urography if posturographic cytologic studies are contemplated.     

Haemostatic effects of low osmolar non-ionic and ionic contrast media: a double-blind comparative study

In this prospective, double-blind, randomized study the effects of a non-ionic contrast medium (Iopromide) on the haemostatic system were compared with those of a low osmolar ionic medium (Ioxaglate). The aim was to investigate in vivo whether a non-ionic contrast agent is less anticoagulant or more pro-thrombotic than an ionic medium. A large number of haemostatic parameters, including activation markers, were measured. Either Iopromide (n = 16; median volume 102 ml; 95% confidence interval 90-108 ml) or Ioxaglate (n = 15; median 105 ml; 95% confidence interval 95-114 ml) was given to 31 patients scheduled for abdominal and femoral arteriography. Blood for laboratory investigations was collected before, and 5 and 30 min after, administering the contrast medium. Indications for activation of coagulation and platelets were already found in nearly 50% of the patients before any contrast medium was given. Both Iopromide and Ioxaglate caused further increases in thrombin-antithrombin complex, prothrombin fragments 1 + 2 and beta-thromboglobulin. The degree of activation was similar for both agents. Anticoagulant effects were not observed. The haemorheological effects were compatible with haemodilution by 5-8%, again without differences between the contrast agents. Contrary to the findings from in vitro studies, we found no significant differences between the effects of the non-ionic Iopromide and the ionic Ioxaglate on coagulation and platelets. Both agents activated these systems to a limited, but identical, degree. Our results support the notion that the catheterization procedure per se may represent a source of haemostatic activation and that the ionic contrast agent studied has insufficient anticoagulant effect to prevent clotting activation being induced by the contrast medium.     

The delayed adverse reactions of low osmolar contrast media

A computer scale survey to inspect the occurrence of delayed symptoms (adverse reactions) associated with the intravenous injection of low osmolar contrast medium (LOCM) was carried out. Of the recovered 1070 questionnaires, 290 had the delayed symptoms. Excluding 59 patients having the same symptoms in the past one year without contact with the contrast medium, the overall incidence of the delayed adverse reaction is 22.8% (231/1011). The delayed symptoms include arm pain (6.0%), headache (3.6%), itching (2.3%), rash (1.5%), general fatigue (1.4%), gastrointestinal symptoms, etc. Though the chi-square test had shown significance of the occurrence of the delayed symptoms for the group with a past history of drug allergy and nasal allergy (p less than 0.05), the delayed symptoms were mainly distributed in the middle-aged female to indicate that the sexuality is the cause of the foresaid significance. Furthermore, the incidence of the objective delayed symptoms such as rash in the group who had accepted more than two examinations is lower than the incidence in the group who accepted only one examination in the survey period. The disagreement to the fact that the repeated usage of the contrast medium is the risk factor to increase the incidence of the adverse reactions indicates the contrast medium may not be the only cause for the occurrence of the delayed symptoms, e.g. other factors such as sexual and psychological factors etc. may play a more important role than the contrast medium under this type of survey.     

Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro

PURPOSE: To compare the cytotoxic effects of dimeric and monomeric iodinated contrast media on renal tubular cells in vitro with regard to osmolality. MATERIALS AND METHODS: LLC-PK1 cells were incubated with ioxithalamate, ioversol, iomeprol-300, iomeprol-150, iodixanol, iotrolan, and hyperosmolar mannitol solutions for 1-24 hours at concentrations from 18.75 to 150 mg of iodine per milliliter. Cytotoxic effects were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Data were analyzed with one-way analysis of variance; post hoc tests were performed. RESULTS: At equal iodine concentrations, ioxithalamate showed stronger cytotoxic effects than did other contrast media (MTT conversion for ioxithalamate was 4% vs that for ioversol of 32%, that for iomeprol-300 of 34%, that for iodixanol of 40%, and that for iotrolan of 41% of undamaged control cells at 75 mg of iodine per milliliter, n = 61-90, P < .001); there was no significant difference between low-osmolar monomeric and iso-osmolar dimeric contrast media (P > .05). At equal molarity, dimeric contrast media induced significantly stronger cytotoxic effects than did low-osmolar monomeric contrast media (40% for iodixanol and 41% for iotrolan vs 64% for ioversol and 59% for iomeprol-300 at 98.5 mmol/L, n = 61-75, P < .001). At equimolar concentrations, both dimeric contrast media showed stronger cytotoxic effects than did iso-osmolar formulation of iomeprol-150 (51% for iodixanol and 50% for iotrolan vs 77% for iomeprol-150 at 98.5 mmol/L, n = 35-40, P < .001). Mannitol solutions induced weaker cytotoxic effects than did corresponding contrast media compounds (74% for mannitol-520 vs 34% for iomeprol-300 and 41% for mannitol-1860 vs 4% for ioxithalamate, P < .001). CONCLUSION: Besides hyperosmolality, direct cytotoxic effects of contrast media molecules contribute to their cytotoxic effects. Results of this study indicate that dimeric contrast media molecules have a greater potential for cytotoxic effects on proximal renal tubular cells in vitro than do monomeric contrast media molecules.     

离子型与非离子型对比剂的副反应处理

非离子型低渗对比剂虽然大大降低了对比剂的副反应的发生率，但仍有少数患者可发生严重反应。及时有一定的措施，也无可阻止副反应向严重甚至威胁生命的方向发展。因此做为放射医师及护理人员也建立必要的规章制度，以使放射科的每个人都能发挥有效的救护作用，及时处理对比剂副反应需要的知识与训练。     

Experience with low osmolar contrast media a clinical and experimental study

Low-osmolar contrast media were used in 546 patients: 371 with ioxaglate, 80 with iopamidol, 95 with iohexol. The image quality was good in all cases. Heat was observed in one patient (iopamidol) and pain was observed in 7 patients (ioxaglate: 4, iopamidol: 1, iohexol: 2). Blood pressure, heart rate as well as the parameters, BUN, SGOT and serum bilirubin showed no significant changes. Our experimental investigations were performed on 101 dog kidneys. Selective renal angiography was performed with 10 ml of contrast media metrizamide, ioxaglate, iopamidol, or iohexol. Comparative preparations were the high-osmolar contrast media iodamide and metrizoate. Untreated kidneys and kidneys given saline constituted baseline controls. Histological examination of tissues 3 and 24 hours after the injections showed moderate reversible changes (metrizamide 15/21, ioxaglate 5/17, iopamidol 2/18, iohexol 2/26). Electronmicroscopy (6 iohexol) showed no significant changes.     

Use of informed consent for ionic and nonionic contrast media.

The use of informed consent before intravenous administration of contrast material remains a controversial issue. It involves explaining the risks of intravenous contrast material and obtaining the patient's permission for its use. All physician groups who had billed Pennsylvania Blue Shield for at least three intravenous contrast material-enhanced procedures performed in 1989 were surveyed. Informed consent was obtained from at least some patients by about two-thirds of physician groups before using intravenous contrast material, regardless of whether it was ionic or nonionic. Nonradiologists were more likely to obtain informed consent before the use of ionic contrast material than radiologists. Regardless of specialty, practices associated with larger hospitals (greater than 250 beds), larger physician groups (greater than 10), or a university used informed consent less often than smaller physician groups or those associated with a smaller hospital or a private practice. Though results may be affected by regional variation or increased usage since previous surveys, the use of informed consent before the intravenous injection of contrast material is a common practice; it is obtained in the majority of patients.     

Plasma osmolality, iodine concentration and urographic images following high and low osmolar contrast media

Three contrast media (sodium iothalamate, iopamidol and sodium/methylglucamine ioxaglate) in a dose of 240 mg iodine per kilogram of body weight were compared in clinical urography. The ionic monomer sodium iothalamate was the only medium to significantly elevate the plasma osmolality though it returned to normal values within 4 min. All three media exhibited first order linear kinetics. When corrected for the effects of diuresis, sodium iothalamate was shown to give the highest urinary iodine concentrations. On visual scoring sodium iothalamate produced better nephrograms and overall urograms than either of the low osmolar agents.     

Anticoagulant effects of nonionic versus ionic contrast media in angiography syringes

To determine whether nonionic contrast media present a clotting hazard when plastic or glass injection syringes are contaminated with aspirated blood, we evaluated two nonionic (iohexol and iopamidol) and two ionic (ioxaglate and diatrizoate) contrast agents. We used a blood:contrast media ratio of 2 mL:5 mL and ten normal donors, each studied at 10, 20, 30, and 60 minutes, a parallel study of clotting and fibrinopeptide A (FPA) generation in plastic tubes, and life table analysis to estimate more accurately donor-based early clotting probabilities. While ionic contrast media are stronger anticoagulants, both nonionic and ionic media retard clotting in plastic tubes, and clotting in plastic and glass angiography syringes in comparison to saline controls. A clotting probability of 1% for nonionic agents in plastic syringes was not reached until a time (mean +/- SD) of 21.5 +/- 3.2 minutes. This contrasts with a time of 8.7 +/- 2.5 minutes for saline control. With plastic syringes, no clotting at all was observed at 10 and 20 minutes with either class of agents. Neither class of agents hastened the generation of FPA. We found no evidence, therefore, that nonionic agents either cause clots or are procoagulant.     

Arterial bolus dynamics of ionic and nonionic contrast media in intravenous administration

A more favourable intraarterial pattern of bolus dynamics can be expected in DSA on applying nonionic contrast media via the intravenous route, as can be concluded from the results of numerous experimental studies on the different effects of ionic and nonionic contrast media on cardiovascular function. However, bolus measurements of ionic and nonionic contrast media in intraindividual comparison of 28 patients via serio-CT did not yield any significant difference. The influences of various factors on measurement results--quantities of contrast media, time and method of measurement--are discussed as possible causes of this discrepancy.     

Effects of ionic and nonionic contrast media on the blood coagulation system, the fibrinolytic system and platelets

Effects of ionic and nonionic contrast media (CM) on blood coagulation, fibrinolytic system and platelet function were comparatively studied in vitro. By the gross observation of blood coagulation using mixture 2:8 of each contrast media and blood, its total coagulation time was clearly short with iopamidol and iohexol, and no complete coagulation was observed with ioxaglate and diatrizoate for 180 minutes. Anticoagulant effects of all CM were confirmed by the assays of APTT, PT, thrombin time, antithrombin III, FPA, TAT and anti-Xa activity. But, the ionic high osmolar CM (diatrizoate) and low osmolar CM (ioxaglate) showed a greater anticoagulant effect than nonionic CM. Anticoagulant effect of CM on coagulation system may be mainly caused by antithrombin effect. No effects of CM on the fibrinolytic system were observed by assays of the D-dimer, plasminogen and antiplasmin. And all the contrast media produced inhibitory effects of platelet aggregation induced by ADP. Ionic CM tended to have a little stronger inhibitory effect than non-ionic CM. In conclusion, it was suggested that a greater anticoagulant effect of ioxaglate ensures potential safety for thromboembolic complication during angiographic procedure.     

Quality of urography and renal clearance of ionic and nonionic contrast media.

The authors evaluated whether urographic quality correlated with patient hydration and the level of their renal function, depending on whether they received ionic or nonionic contrast media. One hundred patients with normal serum creatinine levels were randomly assigned to receive intravenous urography with either an ionic high-osmolar or a nonionic low-osmolar contrast medium. Patient hydration was evaluated by measuring urine osmolality in a sample voided just before the examination. The plasma concentration of iodine was determined in a single blood sample drawn approximately 3 hours later. From these determinations the plasma clearance of contrast medium was calculated. The urograms were assessed blindly with regard to nephrographic and pyelographic opacification, as well as overall diagnostic quality. The clearance varied between 42 and 115 mL x minutes-1 x 1.73 m-2. No systematic correlation of practical significance was found between the clearances and the urogram quality. A high urinary osmolality before the examination tended to improve quality with both media. It is not possible to assess glomerular filtration rate from nephrographic and pyelographic opacification, or from overall quality of routine urograms in patients with normal serum creatinine levels.     

The anticoagulant effects of ionic and nonionic low-osmolar contrast media in dogs.

RATIONALE AND OBJECTIVES. The anticoagulant effects of ionic and nonionic low-osmolar contrast media were evaluated in vivo. METHODS. The amount of clot deposited on guide wires placed in the femoral vessels of dogs was weighed 30 minutes after the injection of 2 mL/kg of different contrast media. Six dogs were examined after injection of ioxaglate (ioxaglate group), six after injection of iopamidol (iopamidol group), and five after injection of saline (saline group). RESULTS. The mean weights of clot deposited on the guide wires in dogs in the ioxaglate group, the iopamidol group, and saline group were 30.5, 63.1, and 74.2 mg, respectively. The mean weight of clot deposition on the guide wires in the ioxaglate group was significantly less than in the iopamidol and saline groups, whereas there was no statistical difference in the mean weight of clot deposition on the guide wires in the iopamidol and saline groups. CONCLUSIONS. Ioxaglate, a low-osmolar, ionic contrast medium, has a greater anticoagulant effect than a low-osmolar, nonionic contrast agent, such as iopamidol.     

Changes in the fibrinolytic system during angiography with ionic and with nonionic contrast media

RATIONALE AND OBJECTIVES: The purpose of the study was to evaluate and compare changes in some parameters of the fibrinolytic system caused by the use of ionic and nonionic contrast media during angiography in certain groups of patients. MATERIALS AND METHODS: Angiographic diagnostic procedures were performed in 126 patients (male and female) clinically suspected of having kidney cancer (38 patients), arteriosclerotic occlusive disease of lower extremities (44 patients), or dissection of cerebral artery (44 patients). The control group included 12 patients with clinical symptoms of the disease in whom angiographic examination excluded the presence of cerebral artery dissection or kidney cancer. Patients were randomly assigned to receive either an ionic (diatrizoate sodium) or a nonionic (iopromide) contrast medium. Immediately before and 30 minutes after administration, venous blood samples were obtained to determine select parameters of the hemostatic system. RESULTS: There were no significant differences in the fibrinolytic parameters within the control group after contrast medium administration. The nonionic contrast medium (iopromide) caused a decrease in fibrinolytic activity in the patients, unlike the controls, which was particularly pronounced among the patients undergoing renal angiography. CONCLUSION: The use of contrast media in some groups of patients led to transient changes in the fibrinolytic system. These results indicate that ionic contrast media should be used during angiographic procedures in patients at increased risk for thrombotic complications.     

Effects of contrast media under systemic heparinization on blood coagulation and fibrinolytic system during angiocardiography--comparison of ionic and nonionic contrast media]

Nonionic contrast media are suggested to cause increased thromboembolism (in vivo), because of less inhibitory action on blood coagulation and platelet aggregation (in vitro) as compared with ionic contrast media. Therefore, to prevent thrombotic complication, we examined whether differences in blood coagulation and fibrinolytic system between the two groups received nonionic (iopamidol) and ionic (ioxaglate) contrast media are seen in vivo when 2,500 unit heparin is administered during angiocardiography. 20 patients undergoing routine angiocardiography were randomized to two groups of 10 patients each. Blood heparin concentration, activated partial thromboplastin time, prothrombin time, thrombin-antithrombin III complex (TAT), antithrombin III, fibrinogen, alpha 2-plasmin inhibitor plasmin complex, fibrinogen and fibrin degradation product were measured at four stages during the procedure: before and 5 min after 2,500 unit bolus heparin administration, 5 min after left ventriculography, and at the end of procedure. Systemic heparinization inhibited clot formation in the presence of nonionic contrast media. TAT generations were elevated before heparinization, after heparinization, however these generations were remarkably inhibited in both groups. No remarkable differences were noted at 40 +/- 14 min duration of procedure when these parameters were compared between the two groups. Since nonionic contrast media did not activate blood coagulation and fibrinolytic system with 2,500 unit heparin administration as compared with ionic contrast media, systemic heparinization was demonstrated to be effective in the prevention of thrombotic complication.     

The aggravating effect of dehydration on pulmonary edema induced by ionic and nonionic contrast media

High intravenous doses of diatrizoate are known to induce a profound degree of pulmonary edema in the rat. In euhydrated rats, similar doses of iohexol do not induce significantly higher lung weights when compared with nontreated animals. However, for dehydrated rats, intravenous administration of equivalent doses of these agents results in significant pulmonary edema formation with iohexol, and enhanced edema with diatrizoate; the same magnitude of response is not seen in euhydrated rats. These results show that patients susceptible to severe contrast reactions should be well-hydrated and preferably given a nonionic agent when contrast material must be administered.