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Addition of local anesthetics to contrast media. II. Increase of acute mortality in mice with intravenous contrast administration.

The acute intravenous toxicity (i.v. LD50) of solutions of the ratio 1.5 contrast media metrizoate or diatrizoate and the ratio 3.0 contrast medium metrizamide was determined in mice with and without the addition of local anesthetics to the solutions. The two local anesthetics mepivacaine or lidocaine were added to final concentrations up to 2.0 mg/ml of the contrast medium solutions. This corresponds to clinically used concentrations. All additions of local anesthetics to the solutions increased the mortalities caused by the contrast medium solutions. Addition of local anesthetics to a final concentration of 2 mg/ml approximately doubled the acute intravenous toxicity of the contrast media. The ratio 3 contrast media produce less hypertonic solutions than the ratio 1.5 contrast media and should be preferred for angiography because they cause less pain and do not require the addition of local anesthetics which increase the acute toxicity of the solutions.

Anesthetics, Local↗

Osmolality of intravascular radiological contrast media.

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.

Blood-Brain Barrier↗

Reactions to intravenous pyelography contrast media.

Reactions to contrast media used for intravenous pyelography are everyday possibilities in a radiology department, and statistics indicate that the incidence of fatalities has increased after a period of decline. The physiology of reactions and how to be prepared for them, as described here, are important parts of the technologist's knowledge.

Anaphylaxis↗

Vasodilatative and vasoconstrictive effects of angiography contrast media.

During angiography contrast media (CM) induces changes in vessel tone. The pathophysiological reasons for this are poorly understood. In this short review the anatomical structures and physiological factors involved in vessel tone are described, and previous and recent findings in vitro and in vivo concerning the effect of CM on vessel tone are discussed. Although multifactorial, the main effect seems to result from a direct action of the CM on the vessel wall. For a particular CM formulation, the effect is due to a combination of its osmolality, molecular properties as well as electrolyte content. In vitro experiments performed in iso-osmolar solutions of pure CM suggest the CM interfere with the cellular mechanisms controlling intracellular calcium. When injected intravascularly, CM may cause either vasodilatation and vasoconstriction. Vasodilatation is the most frequent effect when CM is injected into a vessel while vasoconstriction is relatively uncommon. Both vasodilatation and vasoconstriction can be caused by all types of CM.

Angiography↗

Tissue reaction follwing intratracheal application of roentgen contrast media in rats.

Contrast media (CM) given orally for roentgen examination of the upper gastrointestinal tract may inadvertently enter the lungs. The present paper describes the local effects on the lungs of rats after a single intratracheal instillation of the nonionic, iso-osmolar, dimer CM iodixanol and iotrolan, and the ionic hyperosmolar, monomeric CM diatrizoate. Hydrochloric acid (HCl) and saline were included as positive and negative controls, respectively. The test compounds were given by intratracheal instillation to anesthetized rats at low dose volumes of 0.5 ml/kg b.w. The animals were killed 6 hours, 24 hours or 7 days after dosing, and the trachea and lungs subjected to histopathological examination. Acute signs of dyspnea were observed in 7 out of 15 animals that received HCl. No clinical signs could be related to treatment with any of the CM. Histomorphological assessment of the respiratory tract did not reveal any CM-related adverse effects, whereas animals treated with HCl showed marked histopathological changes. The results indicate that accidental exposure of the respiratory system to iodixanol, iotrolan or diatrizoate is unlikely to cause any significant tissue damage or lead to respiratory complications.

Animals↗

Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application.

Radiographic contrast media (CM) can induce renal failure and this may serve as an experimental model of acute renal failure (ARF). One vasoactive factor likely to be involved in ARF is adenosine. In a double-blind, placebo-controlled study we investigated the effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM. Thirty-nine patients who received 100 ml of a non-ionic low osmolar CM (iopromide) were studied for changes in GFR and RPF by continuous inulin and PAH clearance before and until four hours after CM application. Forty-five minutes before the application of CM, patients were randomized and received either theophylline (5 mg/kg body wt) or the vehicle and placebo (saline) intravenously in a blinded manner. We additionally measured the creatinine clearance on the day before and two days after CM application. Sodium excretion, N-acetyl-beta-glucosaminidase (NAG) excretion, plasma renin activity (PRA) and aldosterone levels were also measured before and after CM application. Theophylline levels were within the therapeutic range in patients of the theophylline group during and four hours after CM application (59.0 +/- 10.6 mumol/liter and 40.1 +/- 10.9 mumol/liter). GFR, measured by inulin clearance significantly declined under CM application in patients without TP application (N = 19; 88 +/- 40 to 75 +/- 32 ml/min/1.72 m2; P < 0.01). In the group of patients receiving theophylline (N = 18) the GFR remained constant (75 +/- 26 vs. 78 +/- 33 ml/min/1.72 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Delayed reactions to urographic contrast media.

Reactions to urographic contrast media occurring after the patient had left the department were studied by giving patients a questionnaire to complete. 841 questionnaires were returned (about 80% of those issued). 70% of patients had no delayed reactions and 7% expressed a positive response to urography i.e., found the procedure interesting and not unpleasant; 13% had arm pain, 5% a rash and 14% had a variety of reactions, many of which were the same as those described in iodism. Women had significantly more rashes (7%) than men (4%) and those media containing the meglumine or iodamide ions caused more rashes than other media. Conray 420 caused more arm pain than Conray 280 or the non-ionic media, which would be expected from the known effects on vascular endothelium. Symptoms of iodism were equally common from the various contrast media.

Adolescent↗

The effect of sodium on the fibrillatory propensity of nonionic contrast media.

Removing sodium from standard ionic contrast media markedly increases the incidence of ventricular fibrillation in patients undergoing coronary angiography. Newer nonionic contrast media, iopamidol, iohexol, and ioversol contain only trace amounts of sodium. To determine whether sodium attenuates or potentiates ventricular fibrillation from nonionic contrast media, we measured the prolongation in QT interval and performed programmed electrical stimulation with one, two and three extra ventricular stimuli in 40 dogs during 4-mL intracoronary injections of iopamidol, iohexol, and ioversol. Solutions of each contrast medium with added NaCl at concentrations of 0.225%, 0.45%, and 0.9% were compared with standard contrast media. The addition of NaCl markedly increased the amount of QT interval prolongation produced by each contrast medium. With iopamidol, the amount of QT interval prolongation was 40 +/- 11 msec with standard iopamidol, but was 58 +/- 11 msec with 0.225% NaCl/iopamidol, 84 +/- 17 msec with 0.45% NaCl/iopamidol, and 132 +/- 42 msec with 0.9% NaCl/iopamidol (P less than .001). Similar results were seen with iohexol and ioversol. Ventricular fibrillation was difficult to induce with standard solutions of these agents (even with three extra stimuli), but became progressively easier to induce when NaCl was added. Three extra stimuli produced ventricular fibrillation in zero of 11 dogs with standard iopamidol, zero of 11 with 0.225% NaCl/iopamidol, three of 11 with 0.45% NaCl/iopamidol, and eight of 11 with 0.9% NaCl/iopamidol (P less than .001). Similar results were observed with iohexol and ioversol. The addition of choline chloride or dextrose did not increase ventricular fibrillation and QT interval prolongation. It is concluded that standard preparations of nonionic contrast media have a very low fibrillatory propensity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The potential risk of thrombosis during coronary angiography using nonionic contrast media.

The influence of contrast media on coagulation has an important association with thromboembolic complication during coronary angiography. In this study, whole blood was methodically mixed with nonionic contrast medium, Iohexol (IOH), conventional ionic contrast medium, Hypaque-76 (H76), and low osmolar ionic dimer Hexabrix (HB) in vitro. The thrombotic propensity of contrast agents can be evaluated by measuring the clot formation of the mixtures. The experiments were repeated with whole blood after systemic heparinization. In the in vitro study, 5 ml of canine (N = 10) and 3 ml of human (N = 11) whole blood was incubated for 30 min in glass tubes with equal volumes of IOH, H76, HB, and 0.9% NaCl before heparinization. Clot formation with IOH and 0.9% NaCl were seen both in dogs (4.0 +/- 0.7 gm and 5.6 +/- 0.8 gm) and in patients (1.4 +/- 0.9 gm and 2.9 +/- 1.3 gm), whereas no clot was seen with H76 or XB. Following heparinization, no clot was visualized in any mixture of whole blood with contrast media or 0.9% NaCl. Similar results were observed in the catheter-syringe system with canine blood (N = 11) mixed with the contrast agents. Blood clots found in 15 min and 30 min of IOH were 0.07 +/- 0.08 gm and 0.44 +/- 0.20 gm (P less than 0.01) and of NaCl were 0.29 +/- 0.37 gm and 0.69 +/- 0.38 gm (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Mental disorders after myelography with metrizamide and other water-soluble contrast media.

Water-soluble contrast media, which have been employed in the examination of the lumbar spinal canal for 30 years, can sometimes result in severe complications, such as arachnoiditis, epileptic seizures, and myoclonic spasm. These complications have been seen less frequently since the advent of metrizamide, a new non-ionic water-soluble contrast medium. However, a further neurological complication has now arisen--mental disorder, varying in kind and degree; for example, organic psychosis and perceptual disturbance. Some characteristic cases are described. A series of 75 patients, all of whom received varying amounts of metrizamide for the purpose of cervical, thoracic and lumbar myelography, has been studied. Seven patients were found to have a pronounced organic psychosis and three patients had visual illusions or hallucinations. It is suggested that there is some degree of correlation between the total amount of iodine received and patient age. By careful enquiry and examination, similar disturbances were also found some 4-8 h after myelography with other water-soluble contrast media.

Adult↗

Adverse reactions to intravascularly administered contrast media.

A hypothesis is formulated about the mechanisms causing adverse reactions to contrast media. Contrast media act in two ways. They stimulate the mast cells to release histamine and leukotrienes, and they inhibit the enzymes which otherwise degrade leukotrienes. Thus individuals, especially those with a history of allergy, are easily exposed to undue amounts of leukotrienes and these are responsible for the adverse reactions.

Arachidonic Acids↗

A survey of contrast media used in coronary angiography.

In recent years, various contrast media have been developed for use in coronary angiography. These contrast media may be divided into ionic contrast media of high osmolality, those of low osmolality, and nonionic contrast materials. We conducted our own clinical studies with 40 patients. In random succession a standard contrast medium (ionic, of high osmolality) and a new-generation contrast medium (either nonionic or ionic with low osmolality) were injected into the right and left coronary arteries. After each injection we measured the systolic and diastolic blood pressure using a liquid-filled coronary catheter. In addition, the change in the length of the cardiac cycle was registered in terms of the R-R interval (in ms) and at the same time, leads I, II, and III of the ECG were recorded. We studied the influence of the various contrast media on the activity of ATPase in in vitro experiments, using Lasser and Lang's [30]. When ionic contrast media of low osmolality and nonionic contrast media were utilized the heart rate showed no change. Disturbances of rhythm such as ventricular tachycardia or fibrillation were not observed. All of the contrast media used produced the same ECG changes. These changes can be ascribed to the inhibition of ATPase. The arterial blood pressure was lowered significantly only by ionic contrast media of high osmolality only.

Adenosine Triphosphatases↗

Adverse effects of contrast media: incidence, prevention and management.

Although contrast media are relatively well tolerated, a non-life-threatening, moderate reaction requiring some treatment occurs in 1 to 2% of patients receiving ionic high-osmolar contrast media and in 0.2 to 0.4% of patients receiving non-ionic low-osmolar contrast media. Severe, life-threatening reactions can be expected in about 0.2% of patients after injection of ionic high-osmolar and 0.04% after non-ionic low-osmolar contrast media. Prompt recognition and treatment are invaluable in blunting an adverse response of a patient to radiographic contrast material, and may prevent a reaction from becoming severe or even life-threatening. Some reactions can be prevented by pretreatment before administration of contrast media. Knowledge, training and preparation are crucial in guaranteeing appropriate and effective therapy in the event of an adverse contrast-related event. Radiologists and their staff should review treatment protocols regularly so that each can accomplish his or her role efficiently.

Contrast Media↗

[Varying results of different procedures for determining the FT4 concentration before and after the administration of contrast media].

After application of contrast media a rise in FT4 concentration was detected by use of the ultrafiltration method (Amicon) and the Dow-Lepetit method, especially after injection of Biliscopin, whereas the determination of FT4 concentration with the Amerlex method revealed a significant drop in FT4 concentration after contrast medium application. The results obtained with the Dow-Lepetit test have to be regarded as correct. The decrease detected by the Amerlex test is probably the result of a changed affinity of albumin to the labeled T4. Within 1 hr after application of contrast media blood for the determination of FT4 should not be collected.

Contrast Media↗

Coronary microvascular responses after exposure to iodinated contrast media.

RATIONALE AND OBJECTIVES: Iodinated contrast media can cause a number of well-described acute hemodynamic and vascular effects including vascular spasm, hypotension, and arrhythmias. Coronary microvessels were studied in vitro after high-dose exposure to an ionic, high-osmolar contrast agent diatrizoate meglumine in vivo. The aim of this study was to examine the endothelium-dependent and endothelium-independent vasodilator responses of the microvessels after previous contrast media administration in a clinically relevant setting. METHODS: Left coronary angiography was performed on six pigs using a cumulative dose of 60 mL (5 mL/injection) of diatrizoate meglumine. After 1 hour of reperfusion, epicardial coronary microvessels were studied in vitro in a pressurized, no-flow state with video microscopy. The vasodilators bradykinin, calcium ionophore A23187, and sodium nitroprusside were sequentially applied extraluminally after preconstriction. Serotonin and the thromboxane A2 analog U46619 were studied without preconstriction. RESULTS: Microvessels exposed to diatrizoate meglumine had normal relaxation responses to the endothelium-dependent vasodilators bradykinin and calcium ionophore A23187 when compared to control vessels. The vasoconstrictor responses to U46619 and serotonin were not significantly altered compared to control vessels. Responses to the endothelium-independent vasodilator sodium nitroprusside were not reduced or were slightly enhanced after exposure to contrast media. CONCLUSION: Coronary resistance vessels responses to the endothelium-dependent vasodilators bradykinin and calcium ionophore A23187 are not diminished after previous exposure to diatrizoate meglumine. The vasoconstrictor responses to U46619 and serotonin were similarly unaffected by previous exposure to contrast media. This suggests that, when used in clinically relevant amounts, diatrizoate meglumine does not cause functional endothelium or vascular smooth muscle impairment.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Adverse reactions to iodinated contrast media.

Adverse reactions to iodinated contrast media (ICM) are more likely to develop in patients with asthma, a history of allergy or contrast reaction and in those who are debilitated or medically unstable. These reactions can be divided into renal and general, and the latter are subdivided into acute and delayed. Acute general reactions can be minor, intermediate or severe. Fatal reactions are rare. The introduction of low-osmolality agents has caused an overall reduction in the number of non-fatal contrast reactions. Prompt recognition and treatment of acute adverse side effects to ICM is invaluable and may prevent a reaction from becoming severe. Familiarity with cardiopulmonary resuscitation is essential for successful management of life-threatening reactions. Contrast-media-induced renal impairment can be reduced with the use of low-osmolality contrast media and extracellular volume expansion. The use of ICM in diabetic patients receiving metformin should be carried out with care to avoid metformin-induced lactic acidosis. However, this problem is mainly observed in patients with diabetic nephropathy.

Acidosis, Lactic↗

Contrast media in double-contrast arthrography of the knee: a comparison of ioxaglate and iothalamate preparations.

Hexabrix (sodium and meglumine ioxaglate) is a satisfactory medium for use in double-contrast knee arthrography. It shows no advantage over the ionic medium, meglumine iothalamate, in the quality of the immediate films, but it produces significantly better coating of the meniscus in delayed films and better results in knees which have an effusion. These advantages are to some extent counteracted by the fact that Hexabrix causes more pain or discomfort after the examination than meglumine iothalamate.

Adolescent↗

Effect of molecular weight on the diffusion of contrast media into cartilage.

STUDY DESIGN: A comparison of contrast enhancement in the intervertebral disc from two magnetic resonance imaging contrast media in experimental animals. OBJECTIVES: To test the effect of molecular weight on the diffusion of ionic contrast media into the intervertebral disc. SUMMARY OF BACKGROUND DATA: Intravenously administered gadopentetate diffuses similarly into the fibrocartilage of intervertebral discs and herniated disc fragments. Differentiation between recurrent disc fragments and scar tissue via magnetic resonance imaging is optimized by using contrast media, which result in different contrast enhancement of these two tissues. Contrast media of higher molecular weight diffuse more slowly into cartilage; hypothetically, therefore, such media will produce better contrast between scar tissue and recurrent disc fragments. METHODS: Gadopentetate (molecular weight 546) or gadolinium-polylysine (molecular weight 40,000) was injected intravenously into rabbits. The signal intensities of intervertebral disc and muscle tissue were recorded by magnetic resonance imaging at baseline and at pre-determined intervals for 2 hours after injection of the contrast medium. Contrast enhancement in these tissues was calculated in each animal for each contrast medium, and differences in enhancement were tested for significance by a growth-curve model. RESULTS: Contrast enhancement in the intervertebral disc was significantly less with gadolinium-polylysine than with gadopentetate. In muscle, no significant difference between the two media was observed. CONCLUSIONS: Molecular weight affects the diffusion of paramagnetic contrast media into the intervertebral disc. Contrast media of a high molecular weight may produce better contrast between recurrent herniated disc fragments and scar tissue than contrast media of lower molecular weight. This possibility should be rested in further studies.

Animals↗