N-acetylcysteine attenuates iodine contrast agent-induced nephropathy in 5/6-nephrectomized rats.

AIMS: In the present study we tested the efficacy of N-acetylcysteine (NAC) to minimize nephrotoxic effects of iodine contrast agents in intact rats as well as in 5/6-nephrectomized (5/6-Nx) rats. METHODS: Rats were allocated to a group of intact rats (n = 42) and a group of 5/6-Nx rats (n = 42). After 1 month of recovery from surgery, 5/6-Nx rats and intact (sham-operated) animals received either 6 ml/kg body weight (b.w.) meglumine ioxithalamate (Telebrix 350) or 6 ml/kg b.w. iohexol (Omnipaque 350) intravenously with or without pretreatment with 100 mg/kg b.w. NAC. Plasma and urinary concentrations of creatinine, sodium and protein in 24-hour urine collections were determined prior to and on days 1, 3 and 7 after drug administration. RESULTS: In intact animals, contrast agents caused no significant changes in kidney function throughout the duration of the experiment. In contrast, significant increases in plasma creatinine levels and decreases in creatinine clearance were induced by both contrast agents in 5/6-Nx rats. These changes were significantly attenuated by NAC pretreatment. CONCLUSION: The results of the present study demonstrate that iodine contrast agent-induced nephropathy in 5/6-Nx rats is significantly attenuated by intravenous pretreatment with NAC.

Severe transient leukopenia following hysterosalpingography.

Severe anaphylaxis to contrast media used in hysterosalpingography is very rare. Leukopenia may sometimes be seen in severe anaphylaxis associated with shock. This case report is about an atypical presentation of anaphylaxis following the injection of Conray 280 for hysterosalpingography. The patient had severe leukopenia without other associated features of anaphylaxis that resolved spontaneously after 48 h. This type of reaction to Conray 280 has not been reported before.

Prospective evaluation of adverse reactions to iodine-containing contrast media after ERCP.

BACKGROUND: The incidence of contrast media reactions administered at the time of ERCP is unknown. Despite the lack of formal recommendations, numerous types of prophylactic regimens are routinely used in patients with a history of prior reactions to intravascular contrast media. OBJECTIVE: Our purpose was to document the incidence of contrast media reactions at the time of ERCP and to determine whether various perceived risk factors are predictive of adverse reactions. DESIGN: Prospective study. SETTING: Tertiary academic center. PATIENTS: A total of 601 patients undergoing ERCP as clinically indicated. INTERVENTIONS: ERCP done with full-strength high osmolality contrast media. No prophylactic medications were given to any patient. MAIN OUTCOME MEASUREMENTS: Adverse reactions to contrast media. RESULTS: Six hundred one patients were enrolled. Eighty patients had prior documented reactions to intravascular contrast media (39 mild, 21 moderate, 20 severe). Of the 80 patients, 15 additionally reported shellfish allergy, and 46 reported allergic diathesis. Of the 521 patients with no prior reaction to intravascular contrast, 215 reported other history of allergic reaction. Forty-nine were allergic to shellfish, and 166 had underlying allergic diathesis. At ERCP, 277 patients had cholangiograms, 48 pancreatograms, and 276 both. The average volume of contrast per ERCP was 22 mL. No adverse reactions associated with the administration of contrast media at the time of ERCP were observed in any of the patients. CONCLUSIONS: The incidence of adverse reaction to iodine-containing contrast media administered at the time of ERCP even in patients considered to be at high risk is exceedingly low. The use of prophylactic regimens before ERCP appears to be unnecessary.

Sweet's syndrome-like neutrophilic dermatosis resulting from exposure to a radiocontrast agent.

Radiocontrast agents are known to be the cause of many cutaneous manifestations. The present report describes a unique case of a Sweet's syndrome-like neutrophilic dermatosis that recurred three times over 5 years following administration of a radiocontrast agent administered during the course of an intravenous pyelography.

Severe reaction to intravenous administration of an ionic iodinated contrast agent in two anesthetized dogs.

CASE DESCRIPTION: Acute severe systemic reactions developed during i.v. administration of an ionic iodinated contrast agent (iothalamate meglumine) in 2 dogs undergoing contrast-enhanced computed tomography. CLINICAL FINDINGS: Both dogs developed marked changes in heart rate and systolic arterial blood pressure during or immediately after i.v. administration of the contrast agent. The first dog became profoundly hypertensive and bradycardic with poor oxygenation, apparent bronchospasm, and prolonged diarrhea. The second dog became hypotensive and tachycardic with erythema on the ventral aspect of the abdomen and pelvic limbs, periocular edema, and diarrhea. TREATMENT AND OUTCOME: Both dogs were treated for shock by means of i.v. fluid administration, and anesthesia was discontinued. The first dog was placed on a ventilator to improve oxygenation but was hypertensive and unresponsive for 6.5 hours following contrast agent administration. Bloody diarrhea persisted once consciousness was regained. The dog was discharged 3 days after contrast agent administration, and diarrhea resolved 15 days later. The second dog responded to phenylephrine administration, but urine output appeared low immediately following recovery from anesthesia. Urine output was normal the following day, and the dog was released 36 hours after contrast administration with no residual adverse effects. CLINICAL RELEVANCE: Findings highlighted the potential risk for severe reactions associated with i.v. administration of ionic iodinated contrast agents in dogs. Both hypertensive and hypotensive responses were seen. Supportive care for systemic manifestations was effective in these 2 dogs, and extended hospitalization was not necessary.

Accidental Intrathecal Injection of Ionic Contrast: Case Report and Review of the Literature.

BACKGROUND: Ionic contrast, if accidentally injected into the intrathecal space during routine imaging studies or interventional procedures, may significantly interfere with neuronal activity, potentially causing ascending tonic-clonic seizure syndrome and even death. As a result, ionic contrast is strictly contraindicated for intrathecal use. Rapid recognition of the condition followed by prompt management, typically involving aggressive cerebrospinal fluid (CSF) drainage, is critical to improving patient outcome. Lumbar drain has previously been well described as a management strategy. CASE DESCRIPTION: We present a case of accidental intrathecal injection of an ionic contrast agent, iothalamate meglumine, in a patient undergoing cervical epidural steroid injection. This patient was managed successfully with drainage of CSF using an external ventricular drain alone. CONCLUSION: Our literature review and analysis of the previously published cases demonstrate that aggressive CSF drainage is essential to improve outcomes, and in some cases an external ventricular drain alone may be effectively used.

Acute renal failure after percutaneous cholangiography.

A patient had acute renal insufficiency following repeated injections of water-soluble radiologic contrast material for transhepatic cholangiography .

Contrast-induced seizure associated with thrombotic thrombocytopenic purpura. Case report.

A patient with thrombotic thrombocytopenic purpura had a seizure as the result of a contrast media injection given during computed tomographic examination. To our knowledge, ours is the first such case reported.

Cortical blindness due to osmotic disruption of the blood-brain barrier by angiographic contrast material: CT and MRI studies.

Numerous experimental studies have demonstrated disruption of the blood-brain barrier by the hyperosmolar, iodinated contrast agents in common use for intravascular injection during radiologic studies. We report 4 cases in which cortical blindness occurred after cerebral angiography. The patients underwent x-ray CT within 1 hour. CT showed abnormal contrast enhancement in the occipital regions in all 4 instances. Two patients underwent MRI; 1 of these manifested abnormal high-signal intensity in the occipital lobes on T2-weighted images. Only 2 previous cases documenting immediate contrast enhancement within the brain substance on CT following angiography are in the literature.

Comparative neurotoxicity of angiographic contrast media.

The neurotoxic effects in cerebral angiography of three iodinated ionic contrast media, nonionic iopamidol, 25% mannitol, and saline controls were compared in 25 rabbits. Diatrizoate sodium meglumine was the most toxic agent, followed by diatrizoate and meglumine, iothalamate meglumine, and mannitol in terms of blood-brain barrier (BBB) disruption and coupled perfusion decline. HIPDm distribution was more sensitive than trypan blue extravasation for monitoring brain dysfunction. Iopamidol and saline controls exhibited no visual BBB breakdown or alteration in regional uptake of I-125 HIPDm, confirming the safety of nonionic iopamidol as compared with presently used ionic contrast media.

Elevation of serum creatine kinase B-subunit levels by radiographic contrast agents in patients with neurologic disorders.

The effect of radiographic contrast agents on the central nervous system was evaluated by measurement of serum creatine kinase B-subunit (CKB) levels with use of radioimmunoassay in 58 patients who underwent computed tomographic (CT) scanning and 46 patients who underwent cerebral angiography for evaluation of cerebrovascular diseases, brain tumors, and other neurologic disorders. In 11 patients (10.6%), the CKB increased to abnormally high levels within 4 hours after the radiographic procedures, and the median value after 30 minutes was significantly higher than the corresponding precontrast value (P less than 0.01). Eight of the 11 patients had recent ischemic cerebrovascular diseases, and 7 of the 11 had undergone CT scanning. On the basis of the information available in the literature, elevation of the serum CKB levels may be interpreted as reflecting breakdown of the blood-brain barrier and neural damage. Intravascularly administered radiographic media are generally safe, but the results of the current investigation suggested the potential for detrimental effects, particularly in patients with recent cerebrovascular diseases.

Comparison of iothalamate meglumine, metrizamide and iodophendylate in cerebral ventriculography. A clinical, radiological and histopathological study in the rat.

Clinical, radiological and histopathological findings following cerebral ventriculography in the rat using the water-soluble contrast media iothalamate meglumine and metrizamide, and the oil-soluble iodophendylate are reported. Clinically, iothalamate meglumine caused convulsions, while there were no adverse reactions to the other media. Radiologically there was good visualizaiton of the ventricles with all media. Iodophendylate was retained in the ventricles for the duration of the experiment (up to 60 days), while the water-soluble media had disappeared within 20 minutes. Histologically there were no pathological changes attributable to the water-soluble media. Iodophendyalte led to enlargement of the ventricles, and macrophages containing oil were seen on the ependymal lining.

Clinical experience with ioversol for angiography.

Ioversol, the new nonionic, low-osmolality contrast agent, has been well characterized chemically and in terms of basic toxicity testing. Ioversol has a formula similar to that of other nonionic agents, and has been used in a variety of clinical studies. These have been reviewed in detail in other papers. This article reviews the worldwide experience to date with the intra-arterial use of this contrast agent. Ioversol has been given to more than 500 patients for studies including intra-arterial digital subtraction angiography, and cerebral, visceral, peripheral, and cardiac angiography. In 23 carefully monitored studies, ioversol was shown to be safe and diagnostically efficacious, as compared with several high- and low-osmolality agents. To date, there have been no deaths or other severe reactions with this new nonionic formulation. Ioversol is likely to provide a useful addition to the current formulary of low-osmolality agents.

Iohexol in patients with previous adverse reactions to contrast media.

Iohexol (Omnipaque) was used for enhancement of brain CT in 17 patients with previous adverse reactions to contrast media. Two of these patients also had cerebral angiography using iohexol. No premedication was given. The only adverse reaction was a skin reaction 24 hours after the iohexol injection, which might have been induced by the contrast medium or treatment with antibiotics. Five of the patients had repeated iohexol injections at different occasions without adverse reactions.

Arrhythmogenic and cardiodepressive effects of contrast media on isolated rat atria.

The cardiotoxicity of four radiopaque contrast media were studied on spontaneously beating isolated rat atria in order to compare the low-osmolar non-ionic medium, metrizamide, with three other contrast media having different cation compositions. The addition of the ionic contrast media to concentrations of 28 and 84 mg I/ml induced atrial arrhythmias in the following order of potency: meglumine iothalamate greater than meglumine--Na--Ca metrizoate greater than meglumine--Na diatrizoate. No arrhythmias were observed after the addition of metrizamide. Metrizamide had only slight effects on the rate and amplitude of the atrial contractions, and hence the work index was almost unaffected. The highest concentration of the three ionic contrast media had very significant cardiodepressive effects. Meglumine iothalamate had the most severe influence on the spontaneous rate of the contractions, while meglumine--Na diatrizoate induced the greatest initial reduction in the amplitude of the contractions and the work index. The present study indicates that the low-osmolar non-ionic medium, metrizamide, is better tolerated by the myocardium than the ionic contrast media.

Pain and aortofemoral arteriography: the importance of chemical structure and osmolality of contrast agents.

A total of 216 aortofemoral angiograms were performed on 72 patients being triple-injected with different contrast media. The characteristics of the contrast media being studied with relation to injection pain included the anionic component, the cationic component, and osmolality. A double-blind study was carried out with neither the examiner nor the patient being aware of the specific contrast medium being injected. The patients were then questioned as to which contrast agent was most painful. There was a significantly lower incidence of severe injection pain with pure meglumines and contrast media with low osmolality. Variation of the anionic component did not improve injection pain.

Iohexol cerebral angiography. Multicenter clinical trial.

Ionic contrast media currently used in cerebral angiography frequently cause discomfort due to hyperosmolality. This double-blind, multicenter trial compared two ionic media, meglumine iothalamate and meglumine-Na diatrizoate, with the new nonionic agent, iohexol, in 277 patients undergoing cerebral angiography. Vital signs, cardiovascular changes, and neurologic status were evaluated before, during, and after injection. Patients were observed for adverse reactions for up to 24 hours following studies. Patient discomfort and image quality were evaluated. Visualization was good or excellent with all media studied. No significant physiological differences were observed between the ionic and iohexol groups, but fewer iohexol patients experienced large increases (greater than 20 mmHg) in systolic blood pressure. Iohexol patients experienced significantly less discomfort; ionic patients reported severe discomfort 21/2 times more often. This finding was attributed to iohexol's low osmolality. Iohexol may be indicated particularly for use in selective angiograms where discomfort is a factor and for patients suspected of having blood-brain barrier disruption.

Effects of radiographic contrast material on cultured myocardial cells.

Radiographic contrast material in doses commonly used in clinical practice produces major alterations in cardiac rhythm. In order to separate the direct cellular effect of the constituents of contrast material from the indirect actions of neural and hormonal mediators, a tissue culture technique was developed using newborn rat heart cells. The rate of contraction of both individual cells and of a syncytium of cells decreased and became briefly asystolic after contrast material was added to the media, then recovered with varying degrees of arrhythmia. Cells in culture less than one week showed significantly fewer arrhythmias and less recurrent asystole after contract material than older cells (P less than 0.05). Cells pretreated with pharmacologic amounts of atropine (0.08 microgram/ml), ouabain (0.02 microgram/ml), lidocaine (16 microgram/ml), and quinidine (20 microgram/ml) continued to demonstrate the initial asystole, although quinidine and lidocaine diminished the frequency of arrhythmias in the recovery stage. Hyperosmolar dextrose produced asystole, as did Renografin-60, Hypaque-50, and Conray only at concentrations greater than 1000 mOsm, suggesting that an osmolarity threshold may exist for the production of asystole. Less fibrillation occurred when the sodium and calcium ionic concentrations of contrast material were adjusted to that of plasma, although the arrhythmias could not be eliminated. Renografin-60, containing the greatest amount of calcium-chelating agents, produced a significantly greater degree of terminal asystole (P less than 0.05), which was reversible upon addition of CaCl2. Thus, contrast material produces a decrease in the rate of contraction in cultured cardiac cells in the absence of neural and hormonal mediators. The evoked arrhythmias are dependent upon the osmolality and ionic sodium and calcium concentrations.

Cardiovascular effects of ionic monomeric, ionic dimeric and non-ionic contrast media. Effects in animals on myocardial contractile force, pulmonary and aortic blood pressure and aortic endothelium.

Three different types of contrast media, monomeric ionic, dimeric ionic and monomeric non-ionic, were tested and compared concerning their toxicity on three experimental models: I. Pulmonary artery and aortic pressure after contrast medium injection into the right atrium in rabbits: II. Ventricular contractile force and heart rate after perfusion of the coronary arteries on the isolated rabbit heart: III. Aortic endothelium of rats. Non-ionic contrast medium was, in all three experiments, less toxic than monomeric ionic; thus it caused less rise in pulmonary artery pressure (I) and caused less reduction in ventricular contractile force and heart rate (II) and caused less damage on aortic endothelium of rats (III). The non-ionic contrast medium also gave less toxic reaction in two (I and II) of the three models compared to the dimericionic contrast medium. In experimental model III there was no difference between these two agents. Also, the dimeric ionic contrast medium caused less toxic reactions in all three models than the monomeric ionic contrast medium.

Reactions to contrast material during retrograde pyelography.

Reactions to contrast material during retrograde pyelography are rare. Two cases are reported, and the literature is reviewed.