Biomedical subjects
Publications and source records attributed to R G Grainger.
Side-effects like pain or nausea are caused by contrast media of high osmolality. Therefore new compounds of low osmolality (1/3 of old Compounds) have been formulated. Clinical introduction has revealed better tolerance and very low rates of side-effects. Angiographies with Ioxaglate, Iopamidol or Metrizamide have become almost painless Procedures.
The intravascular contrast media in current use are solutions of salts of tri-iodinated substituted benzoic acids. Haemodynamic changes following injection of these contrast media are due mainly to their high osmolar concentration which is five to eight times physiological levels. In this study we compare the effect in dogs on femoral arterial flow following femoral arterial injection of three new low osmolality contrast media (Amipaque, Iopamidol and Hexabrix) compared to conventional contrast media (Coronary 280). Conventional salts such as Conray 280 cause a marked vasodilatation and increase in femoral blood flow to about twice pre-injection levels. The three new low osmolality contrast media cause much less vasodilation and increase in femoral blood flow (+32%). There was no significant difference between the effects of any of the three new media. The experiment suggests that any of three new low osmolality contrast media should be suitable for femoral arteriography as they cause much less vasodilatation (and therefore discomfort) than conventional contrast media. Our results do not indicate a preference for any of the three new contrast agents.
All current intravascular radiological contrast media are salts and produce solutions of very high osmolality--five to eight times that or tissue cells, plasma or tissue fluid (all of which have an osmolality of 300 mosmols per kg water). Erythrocytes and vascular endothelium are adversely affected by the high osmolality of intravascular contrast media, resulting in tissue anoxia and increased capillary permeability, the latter causing damage to the blood-brain barrier. Vasodilatation, systemic hypotension and osmotic hypervolaemia are generalized manifestations of the high osmolality of contrast media. New low osmolality contrast media have been synthesized, utilizing a non-ionizing radical (such as amide or amine) instead of the carboxyl group of a tri-iodinated substituted benzoic acid. Such examples are metrizamide (Amipaque) and Iopamidol (both non-ionic amides) and Hexabrix (salts of a mono-acid dimer). Early clinical evaluation suggests that these low osmolality solutions have major advantages in reducing pain, heat sensation and adverse reactions of angiography.
The discomfort of cerebral arteriography is due mainly to the osmolality of the contrast medium injection. A new low osmolality contrast medium--Hexabrix (32% iodine)--sodium and meglumine salts of ioxaglic acid was compared with Conray 280 (28% iodine)--meglumine iothalamate for carotid arteriography in 33 conscious patients. 30 patients preferred the ioxaglate solution which caused significantly less sensation of heat. Three patients could not distinguish between the two media. No patient preferred iothalamate. Ioxaglic acid is a newly synthesized mono-acid dimer. Its salts produce the same osmolality as non-ionics (e.g. metrizamide), and one third of the osmolality of currently used mono-valent salts (e.g. meglumine iothalamate) in solutions of the same iodine content. Low osmolality contrast media have significant clinical advantages and will probably become the media of choice for arteriography and venography.
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It is not possible to change from oily to aqueous contrast media for myelography without modifying the entire technique. The advantages of myelography with metrizamide (Amipaque) are so great in terms of improved diagnostic accuracy, no withdrawal of contrast medium and reduced incidence of arachnoiditis that it is firmly believed that this technique will soon replace oily myelography as standard practice, at least for the lumbar and thoracic regions.
In contradistinction to all currently available water-soluble contrast media, metrizamide (Amipaque) is not a salt, but a substituted amide and therefore does not dissociate in solution. This unique property results in solutions of high iodine content yet with low osmolality. Metrizamide probably has a lower neurotoxicity than any other known water-soluble contrast agent. A clinical trial of metrizamide lumbar myelography in 201 patients in three clinical centres represents the first clinical assessment of this new contrast medium in the United Kingdom. The technique of the radiological procedure and the adverse reactions encountered are presented and discussed. There were no serious adverse effects: no muscle spasm or epilepsy. Minor adverse reactions--headache, vomiting and nausea occur with approximately the same frequency as with meglumine iocarmate: 43 percent of patients complained of headache. In 118 patients, the lower dorsal subarachnoid space was also examined with no increase in toxic reactions. It is concluded that metrizamide is a safe contrast medium for lumbar and lower dorsal myelography. Water-soluble media will probably largely replace oil products for these investigations. Further clinical trials are being extended to include examination of the upper dorsal and cervical subarachnoid space.
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