Low osmolar contrast agents

There are wide variations in the reported incidence of contrast nephrotoxicity because of differences in patient selection, the type of radiological procedure, and the definition of renal impairment. Contrast nephrotoxicity is relatively uncommon in people with normal renal function, in whom it is 0-10%. Pre-existing renal impairment increases the frequency, with a reported incidence of 12-27% in several prospective controlled studies. In some studies the incidence was as high as 50%, in spite of the use of low-osmolar contrast agents and adequate hydration. Dialysis may be required in some of these patients (SEDA-22, 502). 

Lipodystrophy syndrome - insulin resistance, hyperglycaemia, fat redistribution and raised lipid levels as adverse effect of antiretroviral therapy Lipolysis - break down of lipid LOCA - low osmolar contrast agent... 

Traditionally barium will be used as contrast agent. However, in a patient with suspected risk of aspiration (e.g. neurologically impaired children) or a neonate with a congenital proximal obstruction and suspicion of perforation (risk of barium peritonitis), non-ionic low-osmolar contrast agents will be used. The main advantages of the latter contrast agents are lack of large fluid shifts, absence of con-... 

There are four types of iodinated water-soluble contrast media, classified according to their physicochemical properties (Table 1). They are mainly used intravascularly but can also be injected into body cavities, particularly the low-osmolar contrast agents. Some are also used for oral or rectal administration, and the high-osmolar water-soluble contrast agent diatrizoate is suitable only for these purposes. Low-osmolar and iso-osmolar iodinated contrast media have almost completely replaced high-osmolar agents for intravascular use and administration into body cavities. 

Adverse reactions to intravascular iodinated agents are usually classified as minor, intermediate, or severe life-threatening. All types of reactions to low-osmolar contrast media are five times less common than reactions to high-osmolar contrast agents (SEDA-22, 489) (SEDA-23, 494) (SEDA-24, 519), and very severe adverse reactions to contrast media are rare, with a frequency of about 0.04% with high-osmolar agents and 0.004% with low-osmolar agents. However, there are no important differences in the safety profiles of the different low-osmolar non-ionic monomers (18). 

In another survey, the incidence of contrast media reactions after intravenous administration was evaluated over 14 years (25). The incidence of all reactions to contrast media was 6-8% with high-osmolar contrast media and only 0.2% with low-osmolar non-ionic agents. Most of the reactions (over 90%) were aUergic-like, and severe reactions were rare (0.05%). One death was reported after the use of a low-osmolar agent. These data are compatible with previous reports, which showed that low-osmolar contrast media have a much better safety profile than high-osmolar media and that there is no significant difference in the incidence of acute adverse reactions between non-ionic dimeric and monomeric contrast media. 

Hepatic cirrhosis is not a susceptibihty factor, according to the results of a study in 72 patients with hepatic cirrhosis and 72 controls, who received 100-150 ml of low-osmolar contrast media intravenously for abdominal or chest CT scans (174). Serum creatinine was measured before and 48-72 hours after the administration of the contrast agent. The incidence of contrast nephrotoxicity was comparable in the two groups (two patients in the cirrhosis group and one control). 

Acute reduction in renal perfusion is considered important in the pathophysiology of contrast agent-induced nephrotoxicity. Color-coded duplex sonography has been used in assessing intrarenal vascular resistance in 10 patients (mean age 51 years) after intravenous injection of 100 ml of the low-osmolar contrast medium iopamidol (iodine 300 mg/ml) (182). The resistive index was measured at 1-minute intervals over 10 minutes after injection in each patient. There was a statistically significant rise in resistive index at 2, 3, 4, and 5 minutes after injection, mean values 0.74, 0.75, 0.72, and 0.75... 

To protect residual renal function, use doses under 0.3 mmol/kg of gadolinium-based contrast agents Referto ESUR guidelines to avoid contrast medium-induced renal damage (hydration, use small doses of low-osmolar contrast media)... 

The incidence of CIN has fallen with the introduction of low-osmolar contrast media and the development of iso-osmolar agents. The difference in the incidence of contrast-induced nephropathy between low-osmolar and iso-osmolar agents has been studied, without definite conclusions. 

Low Osmolality Contrast Media. An ideal intravascular CM possesses several properties high opacity to x-rays, high water solubihty, chemical stabihty, low viscosity, low osmolahty, and high biological safety. Low cost and patentabihty are also important for commercial agents. The newer nonionic and low osmolar agents represent an advanced class of compounds in the development of x-ray contrast media. 

The analysis of X-ray contrast agents has not been described in too much detail in the hterature. Only scattered data for individual compounds can be found. In the following paragraphs, we will concentrate both on the determination of physicochemical characteristics, which allow for a classification of different contrast agents, e.g. into high and low-osmolar substances, and on the separation from by-products or biological material and on the determination of concentrations. Structural aspects of iodinated contrast agents have been described by Toennessen et al. [81]. 

Currently available contrast agents can be classified into three different groups, high-osmolar compounds with osmolalities in the order of 1500 mosm kg low-osmolar agents with 600 - 700 mosm kg and isotonic substances with osmolaH-ties similar to that of blood (300 mosm kg ). Data for individual contrast agents are summarized in Table 2. 

The development of low osmolar non-ionic X-ray contrast agents has resulted in a distinct reduction in the toxicity and the observed side-effects in patients. However, as already mentioned the osmotic activity of MRI contrast agents is less important in view of the smaller injection volumes which are used. All the formulations of extracellular gadolinium chelates are hypertonic when compared with blood. But the overall increase in osmolality after injection of even 0.3 mmol/kg body weight is insignificant. Osmololatiy-induced adverse reactions have been observed rarely not only because of the relatively small injection volumes but also because of the rapid dilution of the injected agent in the blood. 

The authors of the second report thought that these adverse effects were probably due to the low-osmolar non-ionic contrast agent. Disruption of the blood-brain barrier is a factor in the pathophysiology of this complication. 

The incidence of contrast-induced renal damage has been investigated in 100 consecutive trauma patients (mean age 37 years) who underwent angiographic embolization (mean dose of contrast agent non-ionic low osmolar 248 ml) for bleeding in the abdomen or pelvis (167). None had diabetes or renal impairment before the injury (mean baseline serum creatinine 88 gmol/l). The serum creatinine increased by more than 25% of baseline in five patients, and returned to baseline within 5 days. 

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