Ionic Contrast Media

Ionic contrast media are triiodobenzene derivatives carrying a negative electrical charge, water soluble only as sodium or meglumine (an organic cation similar to glucosamine) salts. 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

In various earlier surveys of conventional ionic contrast media, the incidence of minor reactions was one in 13-30 cases, the incidence of intermediate reactions one in 57-130 cases, and the incidence of severe reactions one in 1000-4000 cases. The figures for the non-ionic media are much more favorable. In 1990, the Japanese Committee on the Safety of Contrast Media surveyed 169 284 patients who had received ionic media and 168 363 who had received non-ionic contrast media (14). In patients with a previous history of reactions to contrast media, the incidence of severe reactions was 0.73% with ionic media and only 0.18% with non-ionic media. Among patients with asthma, severe and very severe reactions occurred in 1.88% with ionic media and 0.23% with non-ionic media. In a Canadian survey of 1992, the overall incidence of adverse effects to contrast media was 3.9% for ionic media and only 0.9% for non-ionic media, despite the fact that the proportion of patients with heart disease as a pre-existing susceptibility factor was much higher in the non-ionic group (SEDA-22, 500). 

According to a survey conducted by the Royal Australian College of Radiologists in 1986, the incidence of severe reactions with high-osmolar ionic contrast media was 0.36% in high-risk patients (patients with a strong history of allergy or bronchial asthma or a history... 

Rapid peripheral intravenous injection of concentrated ionic contrast media produces a brief rise in systemic arterial pressure followed by a prolonged fall the diastolic pressure decreases more than the systolic pressure and the heart slows the pulse contour changes, and the venous pressure rises the arterial hypotension is more marked if injection is rapid. The electrocardiogram can show flattening, splitting, or T-wave inversion tachycardia is probably compensatory, as are the concomitant increases in venous pressure and pulmonary arterial pressure. Hypotension associated with a vasovagal reaction probably explained four deaths from acute coronary insufficiency (two each with iodoalphionic acid and iopa-noic acid) in patients with ischemic heart disease. 

Intra-arterial injection of conventional ionic contrast media results in vasodilatation. This is due mainly to hypertonicity of the medium, but toxicity is also a factor. The vasodilatation may in addition be partly due to an anti-cholinesterase action, since it is partially blocked by atropine. In clinical practice, aortography and peripheral arteriography are usually associated with a slight fall in blood pressure, tachycardia and discomfort in the limbs, such as heat or pain. 

In spite of the safety of the non-ionic contrast media cardiac arrest can complicate the infusion of these agents. 

All ionic contrast media are neurotoxic and they should not be injected into the subarachnoid space or intra-thecally, and stern warnings against such use have been issued, for example by the American FDA (SEDA-18, 445). When they have accidentally been used, deaths have resulted (SEDA-18, 445) (78). Accidental misuse of dia-trizoate for myelography, with fatal consequences, has been a serious problem (SEDA-22, 500). Lavage of the subarachnoid space with saline in such cases has been effective in reducing toxicity (SEDA-15, 504). 

A single case of severe but reversible hypoplastic anemia has been attributed to sodium diatrizoate (125). Ionic contrast media have a disaggregating effect on erythrocytes, and hyperosmolar agents reduce their elasticity (SEDA-22, 501). When blood is diluted with 90% sodium diatrizoate in vitro, there is initially a reduction in... 

Acute pancreatitis is a well-recognized complication of ERCP, and contrast media have been incriminated in its pathogenesis. It has been suggested that the use of low-osmolar non-ionic contrast media may minimize the risk. However, this has not been proven conclusively. 

Fixed drug eruption caused by non-ionic contrast media is rare (SEDA-22, 502), but has been attributed to the nonionic contrast medium iomeprol (lomerone, Bracco) (201). 

This report shows that non-ionic contrast media can cause multiple fixed eruptions and that repeated administration of the causative agent can be associated with a more severe eruption. 

Intracutaneous and patch tests were performed in the first two patients (206) with a series of ionic and non-ionic contrast media in concentrations of 1% according to international guidelines. In the first patient there were late positive intracutaneous and patch tests after 24-48 hours only to some of the tested contrast agents. In the second patient intracutaneous and patch tests showed late reactions to... 

A 61-year-old man received ioversol dnring a CT examination and 1 day later developed a generalized macnlar rash, which lasted for 2 weeks. Prick, intradermal, and patch tests with different tjrpes of non-ionic contrast media showed a delayed hjrpersensitivity reaction to ioversol, which lasted for 7 days. 

Other rarities reported sporadically (but all in more than one case) include the Koebner phenomenon (210), fixed drug eruptions (for example with iotalamate (211)), and delayed reactions of various types. Reports of severe drug eruptions have become more frequent since the introduction of the non-ionic contrast media, but this may simply be due to the fact that in recent years there has been greater awareness of such reactions (SEDA-16, 538) (SEDA-19, 427) (SEDA-22, 502). 

The frequency of extravasation of ionic and non-ionic contrast media during rapid bolus injection in 5106 CT contrast-enhanced scans was 0.9% (31 patients had extravasation of ionic media and 17 patients had extravasation of non-ionic media) (273). There was no correlation between the injection rate and the frequency of extravasation. None of the patients who had extravasation had permanent damage. 

Extravasation of ionic and non-ionic contrast media after rapid bolus infusion has been stndied in 5106 CT studies in adults (276). The mean infusion rate was 2.8 ml/ second and extravasation occurred in 48 patients (0.9%). Injection rate did not correlate with the freqnency or amount of extravasation. Average age and nse of ionic versus non-ionic contrast medium were identical in patients with and without extravasation. There was no sex difference. There was extravasation of ionic contrast medium in 31 patients, nine of whom had extravasation of at least 50 ml. There was extravasation of non-ionic contrast medium in 17 patients, of whom seven had extravasation of at least 50 ml. Hyaluronidase infiltration was often used to treat more extensive extravasation in 10 patients each with extravasation of ionic or non-ionic media. No patient required surgical intervention and none had severe or long-term effects. 

Tolerance of non-ionic contrast media in myelography has been well documented (SEDA-22, 500). A report from India has documented the safety and diagnostic efficacy of the non-ionic monomer iohexol 7-10 ml (iodine 300 mg/ml) injected into the subarachnoid space in 25 patients (302). Only three patients developed minor adverse effects—headache and paresthesia in the legs. 

Ionic contrast media canse temporary prolongation of clotting time in patients treated with heparin this effect may last for 6 honrs and may interfere with laboratory assays (132). Non-ionic media do not have this anti-coagnlant effect, and if blood is allowed to mix with a non-ionic medinm in the sjringe or catheter, thrombus formation can occnr, which could be a potential cause of thromboembolism (SEDA-15, 502). 

Lesiak M, Grajek S, Pyda M, Skorupski W, Mitowski P, Cieslinski A. Percutaneous transluminal coronary angioplasty the influence of non-ionic and high osmolar ionic contrast media on the results and compheation of the procedure. Kardiol Pol 1999 50 311-21. 

Ono K, Haraguchi M, Kimura M, Fuji K, Matsuzaki M. A case of survival from severe non-cardiac pulmonary edema caused by non-ionic contrast media. Respir Circ 2000 48 193-7. 

Parvez Z, Moncada R, Messmore HL, Farced J. Ionic and non-ionic contrast media interaction with anticoagulant drugs. Acta Radiol Diagn (Stockh) 1982 23(4) 401. ... 

Hoffman JJML, Tielbeek AV, Krause W. Haemostatic effects of low osmolar non-ionic and ionic contrast media a double blind comparative study. Appl Radiol 2002 31(Suppl) 113-21. 

Willenbrock R, Berg KJ Nephrotoxicity in High-Risk Patients Study of Iso-Osmolar and Low-Osmolar Non-Ionic Contrast Media Study Investigators. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003 348(6) 491-9. 

Potential Radiopaques. A large number of organic iodine compounds synthesized in search of improved contrast agents are described in the patent literature limitation of space does not allow a full tabulation of these compounds. Because information concerning them may prove to be of value in the design and synthesis of new potential contrast agents, this chapter lists only the potential nonionic radiopaques, where the main current research effort is centered. Summaries of research on ionic contrast media may be found in early references (211,271). 

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