Elliott C. Lasser

Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material

The x-ray contrast mediums used over the past three decades have been salts of iodinated acids administered in highly hypertonic concentrations. We conducted a multiinstitutional randomized study of the protective effects of pretreatment with corticosteroids against reactions to intravenous contrast material. We gave 6763 patients two doses of oral corticosteroids (methylprednisolone, 32 mg) approximately 12 hours and 2 hours before challenge with contrast material, one dose of oral prednisolone approximately 2 hours before challenge, or placebo in the same dosages. The two-dose corticosteroid regimen, but not the one-dose regimen, significantly reduced the incidence of reactions of all types (P less than 0.05) except a category of reactions dominated by hives, for which the reduction approached significance (P = 0.055). In recent years, several relatively expensive monomeric nonionic iodinated compounds having approximately half the osmolality of the corresponding ionic compounds and a lower reaction rate have become available. With our two-dose corticosteroid regimen, the incidence of reactions necessitating therapy in patients receiving the ionic medium approximated that reported in an unblinded nonrandomized study of patients receiving a newer intravenous nonionic medium without corticosteroid pretreatment. We conclude that the much less expensive ionic medium, if administered with corticosteroid pretreatment, may serve as a reasonable alternative to intravenous nonionic medium, without loss of safety.

Activation of Serum Complement by Contrast Media

Evidence is presented for the activation of serum complement by contrast media, in vitro and in vivo. Activation as a function of concentration was measured and the increasing order of effectiveness was found to be metrizamide, iothalamate, diatrizoate, acetrizoate, iodipamide and iopanoate. This order is the same as for protein binding and enzyme inhibition. The activation mechanism for iodipamide, and by inference for the other compounds, does not involve gamma-globulin aggregation. Serial daily injections in normal dogs resulted in substantial declines in serum complement over several days. Guinea pigs which were depleted of serum complement with cobra venom factor were found to be no less sensitive to lethal doses of iodipamide than those with normal complement. Implications of these findings are discussed.

Histamine Release by Contrast Media

The blood draining organs with a high histamine content was sampled and elevation of plasma histamine was found to result from injections of certain contrast media. All methylglucamine contrast media tested to date (acetrizoate, diatrizoate, and iodipamide) produced such elevations. Methylglucamine chloride also caused elevation of plasma histamine. Some “allergic” reactions to contrast media may be explained on this basis.

An experimental basis for histamine release in contrast material reactions.

Perfusion of the canine liver or lung with methylglucamine contrast media or methylglucamine chloride alone will produce elevated histamine plasma levels in the effluent vascular channels from these organs. The sodium salts of the contrast media were less effective than the methylglucamine salts in producing histamine release. These studies suggest a threshold effect for contrast-media-induced histamine release as well as a potentiating effect for sequential injections. Using equal quantities of contrast media, injections over a 39-second period produced greater histamine release than 2-second injections.

Binding of roentgenographic contrast media to serum albumin.

As part of an investigation of the molecular basis of the phystologic properties of organic contrast media, the binding to serum albumin of diatrizoate, acetrizoate, iodipamide, iopanoate and-MP-231 was measured by the method of equilibrium dialysis. Binding to other serum proteins was not detected

Adverse Reactions to Intravascular Administration of Contrast Media

Adverse reactions to intravascular administration of contrast media, while low in incidence, merit serious consideration in view of increased utilization of these substances all over the world. Evidence for involvement of soluble mediators, antibody‐antigen reactions, psycho‐genie factors, and the acute activation systems, is reviewed. As a group, the pre‐contrast challenge plasmas of reactors are characterized by slightly diminished concentrations of C≲‐esterase inhibitor and total hemolytic complement, and by an accelerated rate of conversion of prekallikrein to kallikrein on exposure to contact activators. The role of intravenous pretesting and pretreatment is considered. A rationale for pretreatment with adrenocorticosteroids is presented.

Acute Systemic and Renal Hemodynamic Effects of Meglumine/sodium Diatrizoate 76% and Iopamidol in Euvolemic and Dehydrated Dogs

We examined the acute systemic and renal hemodynamic effects of intravenous meglumine/sodium diatrizoate-76% and iopamidol in euvolemic and dehydrated dogs. The physiologic responses were compared with acute changes in the level of an endogenous heparin-like material (EHM). One of eight dehydrated dogs receiving diatrizoate (2 ml/kg) had an immediate vomiting reflex associated with a very significant decline in all measured renal hemodynamic parameters; none of eight dehydrated dogs receiving iopamidol experienced a similar reaction. EHM levels did not correspond to the magnitude of the physiologic responses following either iopamidol or diatrizoate. Significant differences between iopamidol and diatrizoate were noted when comparing the magnitude of the decrease in systemic pressure (- delta 3.8 +/- 3.02, iopamidol, n = 8; vs. - delta 19.4 +/- 7.3 mm Hg, diatrizoate, n = 8; P less than .03), increased renal plasma flow (+ delta 6.2 +/- 4.9, iopamidol, n = 8; vs. + delta 33.7 +/- 8.0 ml/min, diatrizoate, n = 8; P less than .05), and decreased filtration fraction (- delta 0.09 +/- 0.01, iopamidol, n = 8; vs. - delta 0.14 +/- 0.02, diatrizoate, n = 8; P less than .03). There was no significant difference in the decrease in glomerular filtration rate (- delta 7.4 +/- 1.0, iopamidol, n = 8; vs. - delta 9.3 +/- 1.3, diatrizoate, n = 8; P greater than .05), since the marked drop in filtration fraction occurring with diatrizoate was counterbalanced by the marked increase in renal plasma flow. Acute systemic and renal hemodynamic effects are significantly lessened when comparing iopamidol with diatrizoate.

Experiments with radiopaque perfluorocarbon emulsions for selective opacification of organs and total body angiography.

Emulsions of radiopaque perfluorocarbon with small particle size were prepared by sonication and concentrated by centrifugation. The emulsions were well tolerated when given intravenously to rats in a dose up to 20 ml/kg. Whole-body angiograms were obtained for up to 6 hours after injection with visualization of vessels smaller then 1 mm. Hepatosplenograms were obtained after 2 hours and for several days after injections of radiopaque perfluorocarbon. Contrast enhancement was also seen in the myocardium, ovaries, adrenal glands, and intestines with brominated perfluorocarbon emulsions.

Altered Concepts of the Mechanism of Nonvisualization of the Gallbledder

Several observations made in the course of routine clinical cholecystography in recent months have rekindled an interest in our department in the basic mechanisms that determine whether or not visualization of the gallbladder will occur. The first such observation concerns the instance in which good opacification is apparent, but surgical extirpation reveals marked sclerosis of the gallbladder wall to an extent that suggests possible interference with the organs ability to concentrate contrast material. The second observation is the instance in which initial examination with contrast material fails to reveal a gallbladder shadow, and yet repeat examination with a similar dose on the following day demonstrates good opacification (Fig. 1). In Rosenbaums series of 450 consecutive patients examined by cholecystography (1), in 66 visualization was initially absent or inadequate without evidence of gallstones. Findings were normal in 10 per cent of those with initial nonvisualization and in 64 per cent of tho...

The Role of the Y and Z Hepatic Proteins in the Excretion of Radiographic Contrast Materials

The Y and Z proteins, found only in the liver and the mucosa of the small intestine, bind bilirubin, bromosulfophthalein, and certain other organic anions and may be responsible for the preferential hepatic uptake and biliary excretion of these compounds. Experiments show that two cholecystographic contrast media, iopanoic acid and iodipamide, bind to the Y and Z proteins, while iothalamate, a representative urographic contrast agent, does not, indicating that these proteins may be important in determining the pathway of excretion of contrast material.