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PubMed1999

Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR).

The purpose of this study was, using consensus methodology, to document current understanding of contrast media nephrotoxicity (CMN) and to identify areas where there is disagreement or confusion. To draw up guidelines for avoiding CMN based on the current understanding of the condition established by the survey. One hundred sixty-four statements were mailed to 148 members of the European Society of Urogenital Radiology (ESUR) and to 48 experts in the field of CMN. They were asked about the definition, clinical features, predisposing factors and pathophysiology of CMN and about prophylactic measures. The importance of the statements was rated on a scale from 1 to 10 (1 least important, 10 most important). Fifty-three members (38%) and 23 experts (48%) responded. Both groups considered that an increase in serum creatinine that peaks within 3-4 days and a decrease in creatinine clearance are the most important (rating > 7) features of CMN. Enzymuria was not considered important (rating < 6). Pre-existing renal insufficiency, diabetic nephropathy, dehydration, congestive heart failure, concurrent administration of nephrotoxic drugs and the dose and type of contrast media were considered to be risk factors. Reduction in renal perfusion and damage to tubular cells were considered the main factors in the pathophysiology of CMN (rating > 6). Hydration and the use of low osmolar contrast media were thought to minimize the incidence of CMN (rating > 6). The majority of the responders (84.6% of members and 95.5% of experts) believe that the incidence of CMN in patients with normal renal function is less than 5%. Of the members, 62.5%, and 35.3% of experts, believe that the incidence of CMN is 20-30% in the presence of risk factors. There was disagreement about the definition of CMN, the threshold dose of contrast media above which renal complications may develop, the safe period between repeat injections, the relevance of contrast media renal retention shown on CT and whether contrast media have long-term effects on renal function. The survey showed good understanding of CMN among those who answered the questionnaires, although areas of disagreement remain which require further research. Simple guidelines are proposed.

Contrast Media↗
PubMedDate not supplied

Effects on the ATP content of cultured cells after radiographic contrast media exposure. Evidence for accumulation of contrast media in cultured cells.

The ATP content of cultured cells after exposure to meglumine-calcium metrizoate, sodium metrizoate, iohexol, iopamidol and saline was studied. Initially, the ATP content diminished rapidly for a short period and thereafter slowly during the incubation. After incubation with contrast media or saline, the ATP content slowly increased to normal when the cells were reincubated with fresh nutrient medium. Different contrast media and saline with the same final osmolality produced a similar effect on the ATP content of the cultured cells. Cellular association of meglumine-sodium diatrizoate, sodium metrizoate, sodium-iothalamate, iohexol and iopamidol was also examined. The established cell line NHIK 3025 as well as primary cultures of human umbilical endothelium were found to accumulate contrast media in a time- and concentration-dependent manner. When the incubation was carried out at 4 degrees C, the cellular accumulation of contrast medium was less than 35 per cent of that seen at 37 degrees C. It therefore seems that energy-dependent processes are involved to some degree.

Adenosine Triphosphate↗
PubMed1992

[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.

Adult↗
PubMed1989

[Improved contrast enhancement with a positive pressure drip infusion method and 350 mg I/ml high concentration contrast media in routine contrast enhanced CT].

Sixty cases of routine contrast enhanced CT were analyzed about the utilities of positive pressure drip infusion method using high concentration contrast media 350 mgI/ml, 100 ml. They were divided into three groups and each twenty cases were received positive pressure drip infusion method using Iohexol 350 mg/ml, 100 ml (350PP), positive pressure drip infusion method using Iohexol 300 mgI/ml, 100 ml (300PP) or conventional drip infusion method using Iohexol 300 mgI/ml, 100 ml (300DI). Enhancement effects of the liver parenchyma, the aorta and the spleen at upper, middle and lower levels of the liver were evaluated with increased attenuation on pre- and postcontrast CT. And intrahepatic contrast was evaluated with attenuation difference between liver parenchyma and intrahepatic vessels on postcontrast CT. In result, 300PP kept better enhancement effects and obtained better intrahepatic contrast than 300DI at the each level of the liver, and 350PP was still better than 300PP. The analysis of relationship between intrahepatic contrast and body weight suggested that 300PP was the optimal choice for the cases with 40-50 kg body weight and 350PP was for the ones with 50-60 kg as the infusion method of routine contrast enhanced CT. And the dose of contrast media seemed to be more needed for the cases over 60 kg body weight. 350PP and 300PP were concluded as useful, safe and simple methods for routine contrast enhanced CT of the liver.

Body Weight↗
PubMed1990

Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media.

A large-scale (337,647 cases), nationwide comparative clinical study in Japan on adverse drug reactions (ADRs) to high-osmolar ionic contrast media and low-osmolar nonionic contrast media was performed prospectively. Ionic contrast media were administered in 169,284 cases (50.1%) and nonionic contrast media in 168,363 cases (49.9%). The overall prevalence of ADRs was 12.66% in the ionic contrast media group and 3.13% in the nonionic contrast media group. Severe ADRs occurred in 0.22% of the ionic and 0.04% of the nonionic contrast media examinations. One death occurred in each group, but a causal relationship to the contrast medium could not be established. It is concluded that nonionic contrast media significantly reduce the frequency of severe and potentially life-threatening ADRs to contrast media at all levels of risk and that use of these media represents the most effective means of increasing the safety of contrast media examinations.

Adolescent↗
PubMed1997

[Physiopathology, clinical aspects and prevention of renal insufficiency caused by contrast media].

Contrast-media associated nephropathy (CMAN) consists in a sudden impairment of glomerular filtration rate following exposure to radiographic contrast materials. Damage may be limited to an asymptomatic mild increase of blood creatinine, or reach the highest levels of nitrogen retention compatible with acute renal failure. Some preexisting clinical conditions or pathologies may lead to CMAN: not only renal insufficiency, diabetes mellitus, multiple myeloma, congestive heart failure and severe hypertension, but also simple dehydration and a growing series of immunologic diseases are recognized as predisposing condition. The exact mechanism responsible for renal injury is still doubtful but recently animal models have shown substantial ischemic changes that may be added to the traditional presumed pathogenesis of direct tubular toxicity and intra-tubular obstruction. As renal ischemia stimulates both endogenous vasoconstrictor and vasodilator substances, it is now supposed that CMAN acts similarly to non-steroidal anti-inflammatory agents, selectively inhibiting the vasodilatory prostaglandin phase and therefore causing a derangement of the physiologic vasoconstriction/vasodilatation balance of renal circulation. The role of oxygen free radicals to contribute to renal dysfunction is considered. Low osmolality non ionic contrast media when compared to conventional high osmolality ionic contrast media have reduced but not eliminated CMAN. Simple but effective lines of prevention include the previous selection of patients predisposed to CMAN for concomitant pathology, suspension of FANS or any other recognized nephrotoxic substance, the least amount of contrast media compatible with radiologic visualization of the patient's problem, careful hydration of the patient before contrast injection and sustained diuresis afterwards. The usefulness of pre-treatment with Ca-channel blockers or atrial natriuretic factors remains sub judice.

Acute Kidney Injury↗
PubMed2003

Nonionic contrast media are less nephrotoxic than ionic contrast media to rat renal cortical slices.

BACKGROUND: Nephrotoxicity induced by contrast media (CM) is well recognized. Nonionic CM with lower osmolality than that of conventional ionic CM have been developed in an effort to reduce toxicity. However, the nephrotoxic effects of nonionic CM have not been well evaluated. Although our previous experiments using rat renal cortical slices indicated that the direct cellular toxicity of nonionic CM is less than that of ionic CM, it was suggested that the less toxic effects of nonionic CM on the metabolic function of renal epithelial cells were in part attributable to the lower osmolality of nonionic CM. In the present experiment, the direct toxicity of nonionic CM on renal epithelial cells was compared with that of ionic CM under equiosmolar conditions, where the effects of osmotic pressure were excluded. METHODS: Rat renal cortical slices were incubated with several kinds of CM at 37 degrees C for 120 min. Diatrizoate and iothalamate were employed as ionic CM. Iopamidol and iohexol were employed as nonionic CM. The activities of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyltransferase (GGTP), and lactate dehydrogenase (LDH) released from the renal slices into the incubation buffer were determined in order to evaluate renal epithelial damage caused by CM. Gluconeogenesis, p-aminohippuric (PAH) acid accumulation and ATP content in rat renal slices were determined with a view to examine the inhibitory effects of CM on the metabolic function of renal epithelial cells. The toxic effects of nonionic CM were compared with those of ionic CM under equiosmolar conditions, where mannitol was added to the experimental groups containing nonionic CM in order to exclude the effects of osmotic pressure. RESULTS: A significant difference was generally not found with regard to enzyme release between ionic CM and nonionic CM plus mannitol. The inhibition of gluconeogenesis and PAH accumulation in rat renal slices by nonionic CM with mannitol was less than that by ionic CM. Although the ATP content was reduced by both ionic CM and nonionic CM plus mannitol, there was no significant difference between these two groups. CONCLUSIONS: The present experiments demonstrated that nonionic CM were less nephrotoxic than ionic CM with regard to the function of renal epithelial cells, including gluconeogenesis and PAH accumulation, under equiosmolar conditions. These differences in nephrotoxicity between ionic and nonionic CM cannot be fully attributable to differences in osmotic pressure.

Acetylglucosamine↗
PubMed1989

Reaction to contrast media in contrast-enhanced CT of the brain. A comparative investigation of non-ionic ultravist and ionic urografin-meglumin.

A comparison has been made of contrast medium reactions in contrast-enhanced CT of the cerebrum using Urografin-meglumin and a new non-ionic, low-osmolality radiologic contrast medium, Ultravist. The number of contrast medium reactions was significantly less with Ultravist, but many mild reactions were observed with both contrast media. Regardless of the contrast used, the incidence of contrast reactions was independent of the CT diagnoses.

Brain↗
PubMed1984

Contrast media reactions.

Contrast media reactions may be classified as anaphylactoid, vasomotor, severe or life threatening, and fatal. Anaphylactoid reactions mimic immunoglobulin E-mediated hypersensitivity in that signs may consist of urticaria, angioedema, wheezing, dyspnea, hypotension, or shock. These reactions occur in 2% to 8% of all contrast media infusions. Vasomotor reactions occur in 5% to 8% of patients and consist of nausea, vomiting, flushing, and warmth. Severe reactions during which there is a concern for life occur about once per 1000 procedures. Fatalities have occurred in from 1:3000 procedures for intravenous cholangiography to between 1:10,000 to 1:100,000 procedures for intravenous urography. The pathogenesis of contrast media reactions is unknown, and various mechanisms may be associated with different clinical features. Radiocontrast media infusions can cause rises in plasma histamine and complement activation by either classic or alternate pathways or nonsequentially, yet adverse reactions may or may not occur. Abnormalities in the complement system or an increased conversion of prekallikrein to kallikrein has been demonstrated in some patients who have had anaphylactoid reactions. It is unknown if these mechanisms can explain the pathogenesis of anaphylactoid contrast media reactions. When patients who have had definite anaphylactoid reactions require a repeat procedure, the incidence of reactions ranges from 35% to 60% for intravascular infusion. Pretreatment with prednisone and diphenhydramine has been demonstrated to reduce this reaction rate to 9% in 465 procedures. Prednisone-diphenhydramine and ephedrine have further reduced the reaction rate to 3.1% in 192 procedures. These results are statistically significant (X2 = 5.4996, p = 0.019). Emergency equipment should be available should a severe reaction occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗
PubMed1975

[The pharmaco-kinetics of angiographic contrast media with special reference to the extra-vascular spaces. Fundamental studies on dog for the characterisation of angiographic media. I The pharmaco-kinetics of various contrast media under conditions of constant infusion (balanced flow)].

The pharmaco-kinetics of angiographic contrast media in the extra-vascular space, which are largely unknown, were investigated experimentally in dogs. As part of a basic study, using radio-active contrast media, it was possible to determine the concentration and rate of elimination in practically all organs and tissues. Measurements were carried out first after prolonged infusion of the contrast under conditions of balanced flow, and secondly six hours after the end of the infusion. It was therefore possible to determine the inflow and loss of contrast medium in various organs, or organs systems. The most commonly used angiographic contrast media in Germany were investigated. Their kinetic behaviour is largely identical, their pattern of distribution and elimination depended principally on the organ or tissue. A comprehensive discussion of the results of all the experiments will be given in the third article.

Animals↗
PubMed1986

Advantages of the new low-osmolar radiographic contrast media.

Intravascular contrast media are important in the radiological diagnostic process. Their use is associated with significant side-effects, but new low-osmolar contrast agents have been developed in an attempt to decrease the severity and incidence of these. The molecular structure of contrast media and their relationship to side-effects is discussed. The advantages of, indications for and contraindications to the new low-osmolar contrast media are presented.

Chemical Phenomena↗
PubMed1987

[Complement activation after the intravascular administration of contrast media: a comparison between ionic and nonionic x-ray contrast media].

The effects of intravascular radiographic contrast media on the complement system were investigated in 46 patients. An ionic (sodium-/meglumine amidotrizoate, n = 22) or a non-ionic (iohexol, n = 24) contrast agent was applied for an i.v. urography. The levels of the complement-compounds C1q, C3, C5 and of the C1 inhibitor were determined at the end of the infusion and 20 minutes later. In both groups we obtained a significant (p less than 0.01) decrease of C3 during infusion for 10 to 15%. 20 minutes later these values were almost normalized again. Infusion of iohexol additionally caused a marked consumption of C5 and C1q (reduction to 85%), while the ionic contrast agent had no significant effect on these components. Both contrast media caused a decrease of the C1-inhibitor levels. Our results demonstrate an activation of the complement system by i.v. application of radiographic contrast media. The decrease of the C1q-level due to infusion of iohexol indicates an additional involvement of the classical activation pathway of the complement cascade.

Complement Activating Enzymes↗
PubMed1990

[Undesirable side effects of contrast media during i.v. DSA--a comparison of 2 nonionic contrast media].

For the first time a controlled double-blind study was performed to compare side effects and complications of i.v. DSA with central venous application of iopamidol and iopromide. 200 consecutive patients 15-85 years of age were studied. The randomisation brought up two homogeneously structured groups of 100 patients each. Using a given protocol, 66% of the patients were classified as high-risk patients. Side-effects and complications were registered by an extensive, standardised protocol. In 71 (35.5%) of 200 patients contrast-media related side effects and complications were noted. 37 reactions in 24 patients (9 iopamidol, 15 iopromide group) were classified as clinically relevant. In four patients (4%) of each group a drug therapy was initiated. Contrast-media related reactions occurred with delay in 5.5% of initially symptom-free patients. In no case intensive care or hospital admission became necessary. There were no significant differences between the two non-ionic contrast media in the incidence of side effects and complications. Both substances were well tolerated in i.v. DSA. In the total population patients with diseases known as auto-immune diseases and prior drug reactions demonstrated clinically relevant reactions significantly more often.

Adolescent↗
PubMed1996

[Can we know the frequency of true late adverse reactions to nonionic contrast media?: Late adverse reactions due to factors other than contrast media].

We investigated the frequency and causative factors of symptoms unrelated to contrast media (false late adverse reactions) among patients who were evaluated as having late adverse reactions to contrast media. The nature and frequency of complaints stated by each 200 of patients who underwent plain CT scans and enhanced CT scans were evaluated. In the plain CT group, three patients showed false late adverse reactions. The frequency was 2.6% among respondents and 1.5% in the population. These symptoms encompassed psychological effects and diseases that developed after CT scanning. It is difficult to detect only true late adverse reactions, because of survey bias.

Adult↗