- Email: [email protected]
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47
Radiological contrast media
Barium sulfate (SED-12, 1165; SEDA-17, 535;
SED-12, 1165) Allergic reactions Hypersensitivity reactions to barium sulfate previously regarded as rare, are now being recognized with increasing frequency (SEDA-4, 33; SEDA-6, 804; SEDA-10, 422; SEDA-12, 394; SEDA-14, 421; SEDA-15, 498; SEDA-16, 529). The majority of reactions have occurred following double contrast barium enemas; hypersensitivity to the latex balloon catheter appears to be the most frequent cause, but a reaction to glucagon was also postulated in some cases. Less commonly, reactions have been attributed to additives in the barium sulfate suspension and a recent report describes hypersensitivity reactions to E-Z-PAQUE following single contrast barium meals in two children. A severe reaction with angioedema, dyspnea, tachycardia and hypotension occurred in an 11-year-old boy with eczema, asthma and multiple food allergies. He responded to resuscitation and a subsequent biopsy showed eosinophilic gastroenteropathy. Two previous barium meals with E-Z-PAQUE had been symptomless, but may possibly have been a cause of sensitization. The other reaction occurred in a 7-year-old girl with a mild allergy to penicillin. She developed generalized urticaria, but had no cardiac or respiratory symptoms. Attention is drawn to the risk of reactions in atopic patients and particularly in those with food allergies. Immediate facilities for resuscitation should be available (lCR).
WATER-SOLUBLE CONTRAST M E D I A (SED-12, 1166) Where iohexol is administered orally, absorption is increased if there is mucosal damage in the bowel. In patients with ileal Crohn's 9 1995 Elsevier Science B.V. All rights reserved.
Side Effects of Drugs Annual 18 J.K. Aronson and C.J. van Boxtel, eds.
disease a 24-h urinary excretion exceeding 1% of the dose correlates strongly with mucosal damage and active disease. Patients and controis had diarrhea during the first day, but there were no adverse reactions (2cR)
ORAL C H O L E C Y S T O G R A P H Y (SED-12,
1166) A 66-year-old man with a known history of sensitivity to parabens developed a pruritic rash after oral cholecystography with Biloptin (sodium ipodate). Patch tests showed positive reaction to methyl, ethyl, propyl and butylparaben. Administration of a Biloptin capsule which contains methyl and propyl paraben as additives caused focal flare up as did 5 mg methylparaben, whereas the capsule contents (ipodate) or a gelatine capsule had caused no reaction (3CR).
INTRAVASCULAR CONTRAST M E D I A (SEDA-17, 535; SED-12, 1167) There has been increasing use of low osmolar media for intravascular purposes. These media are now used exclusively in Sweden, Norway, Finland and Japan. On the basis of 1990 and 1991 data the lowest estimated use appeared to be in the Netherlands and France (20 30%) with intermediate use in other countries: Denmark, U.K., Spain (51-65%); Germany, Austria, Italy (75-80%) (4CR). In the United States, during the first 6 months of 1992, low osmolar media were used in 66% of approximately 8,850,000 procedures (approximately 17,700,000 procedures annually) (5R). Idiosyncratic reactions (SEDA-17, 536) The incidence of adverse reactions found in the iohexol preregistration trials was 2-10 times the incidence of subsequent reports in postmarketing surveillance data. The relative risk for all reactions was 3-6 times higher for ionic 441
442 media vs non-ionic media and this ratio was similar in both pre- and postregistration studies (6CR). Another recent review of the literature indicates that although all iodinated contrast media have excellent safety records, nonionic media are safer than ionic media (7R). In children, even minor reactions, particularly vomiting and extravasation, may upset the child emotionally and physically and this may justify the routine use of non-ionic media (8R). Costs of treatment of adverse reactions to contrast media vary, depending on various factors and the type and severity. In cardiac angiography, a history of unstable angina or renal insufficiency, multiple reactions and thromboembolism were major factors contributing to the cost of such treatment (9OR). It is perhaps thought provoking that 3 cases of thromboembolism resulted in the highest treatment costs, since use of non-ionic media might be associated with a somewhat greater risk of thromboembolism (SEDA-17; 537). Anxiety has previously been considered a risk factor for contrast media reactions and it has been suggested that seeking informed consent may increase the risk. A study involving 1251 patients indicated that the majority of patients attending an X-ray department already have an increased 'anxiety score': explaining the possible risks of contrast media did not increase the score. It is therefore concluded that failure to obtain informed consent cannot be justified on this basis (10CR). In higher risk patients with a history of previous reactions to contrast media, a prophylactic premedication regime of prednisolone, diphenhydramine combined with the use of non-ionic medium, has recently been advocated (SEDA-16, 531) (7 R, llR). Steroid premedication has also been advocated in asthmatic patients. A booster dose of steroids may be appropriate if there is any possibility of adrenal suppression from long-term corticosteroid therapy (12 R, 13c). A recent editorial (14 R) criticizes earlier studies which supported prophylactic steroids and concludes that steroid premedication may reasonably be abandoned when non-ionic media are used. This editorial has itself been criticized in subsequent correspondence (15 R, 16R). Moreover, a carefully controlled study in 1155 patients showed that corticosteroid premedication significantly reduced the incidence of all reactions and grade
Chapter 47
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I (mild) reactions in patients given non-ionic media. The incidence of grade II (moderate) and grade III (severe) reactions were also reduced, but because of the small numbers involved, these did not reach statistical significance (17oR). Providing that there is no clinical contraindication to the use of corticosteroids, it is recommended that high-risk patients should receive both corticosteroid prophylaxis and non-ionic media (18CR). In an unusual case of anaphylactic collapse, marked bilateral parotid enlargement with overlying erythema occurred approximately 1 h after commencing an infusion of 100 ml ioxaglate followed by 60 ml of ioxithalamate. Ten minutes later the patient developed dysphagia, dyspnea and hypotensive collapse which responded rapidly to intravenous fluids and adrenaline. There was no evidence of renal failure. There was no history of allergy and a previous cerebral arteriogram with ioxithalamate had not caused any reaction. The patient had received 8 mg dexamethasone intravenously immediately prior to the present examination, but steroid prophylaxis at this time is likely to be ineffective. The authors tabulate 27 other reported cases of parotid enlargement following iodinated contrast media (19CR). The majority of contrast media reactions do not appear to have a true immunological basis, but this may be a possibility in a few cases. A patient who had suffered anaphylactic shock and cardiac arrest on two previous occasions using ioxithalamate and diatrizoate, respectively, had a positive intradermal reaction to diatrizoate and ioxithalamate and a positive basophil degranulation test (HBTD) to diatrizoate and ioxithalamate. The basophil degranulation test to iothalamate was negative using preheated serum suggesting IgE involvement. HBDT and skin tests were negative to ioxaglate and iopamidol. Two subsequent arteriograms using iopamidol caused no reaction (20 oR) (see also SEDA-16, 531). Cutaneous vasculitis There have been two previous reports of fatal Stevens-Johnson syndrome following non-ionic media in patients with systemic lupus erythematosus or receiving hydralazine (SEDA-11, 411; SEDA-14, 422). An additional case of severe cutaneous vasculitis following iopamidol has now been reported in a patient receiving hydralazine. Contrast
Radiological contrast media Chapter 47 examination should be avoided in such patients if possible (21CR).
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reported in 0.11%, myocardial infarction in 0.06%, neurologic complications in 0.05%, arrhythmias in 0.31%, vascular complications in lnterleukin-2 0.44%, contrast media reactions in 0.25%, and others in 0.48%. For percutaneous coronary Toxic recall reactions may occur when con- angioplasty (PTC), non-ionic media were used trast media are administered to patients who in 77%, ioxaglate in 13%, and ionic monomers have previously received interleukin-2 (IL-2) in 10%. Major complications occurred in 5% (SEDA-15, 499; SEDA-16, 532; SEDA-17, of patients. Death occurred in 0.3%, myo537). Reactions occur 1-4 h after contrast cardial infarction in 0.5%, and emergency administration and include fever, chills, vomit- by-pass surgery was required in 1.4% of cases ing, diarrhea, rash, wheezing, hypotension, (24cr). The American College of Cardiology, edema and oliguria. In 70 patients receiving Cardiovascular Imaging Committee has issued high-dose interleukin-2, reactions appeared to a position statement on the use of low osmolar be more common with contrast administration media in cardiovascular procedures (25R). 2 weeks after therapy (11%) compared with 6 Iohexol was compared with sodium meglumine weeks (1.7%), but this did not reach statistical diatrizoate in a multicenter randomized trial significance. Seven patients required hospitali- involving 1390 patients undergoing cardiac zation with 4 requiring intensive care. The angiography. The incidence of contrast media incidence of reactions following non-ionic related adverse effects was 10.2% for iohexol media was approximately one half that follow- vs 31.6% for diatrizoate P <0.001 and for ing ionic media, but this also did not reach cardiac adverse events 7.2 vs 24.5% P < 0.001. statistical significance. It has previously been It should be noted that the diatrizoate used in claimed that premedication with steroids and this study (Renografin 76 TM) causes calcium antihistamines prevented such reactions binding and this may have caused a somewhat (SEDA-I 5,499), but a severe reaction occurred higher incidence o f cardiac adverse events with a repeat contrast examination at 4 weeks (SEDA-16, 533). The presence of New York despite such premedication. Five other patients Heart Association classification 3 or 4 and had no reaction at 4 weeks. The authors advise serum creatinine -> 1.5 mg/dl predicted a higher against routine steroid premedication since this incidence of contrast media related adverse may block the IL-2 effector mechanism (22CR). events (26CR). The higher cost of using non-ionic media for Thyroid function In 28 neonates requiring diagnostic angiography is partially offset by parenteral nutrition, opacification of the cathe- lower management costs of adverse drug reacter using 0.5 ml of ioxaglate (diluted) caused tions. The extent of such offset may vary from transitory hypothyroidism in 3 patients (10.7%); 33 to 75%, depending on the criteria used smaller doses of contrast media in 26 further (27cR). neonates caused only 1 case of hypothyroidism Iodixanol 320 is a new non-ionic dimer (3.8%) (not statistically significant) (23~r). which is virtually isosmolar. A double-blind randomized comparison with iohexol was performed in 72 patients undergoing cardioangiC A R D I A C A N G I O G R A P H Y (SEDA-17, ography. There were few side effects and these 536; SED-12, 1175) appeared to be milder in the iodixanol group (28CR). The Society for Cardiac Angiography and Transient cortical blindness occurred shortly Interventions has introduced a personal com- after a difficult coronary angiography with puter-based registry. Data relating to 92,157 iohexol in a 62-year-old patient with arterioprocedures performed in 72 hospitals during sclerosis who had previously had a coronary 1991 have been analyzed. In diagnostic cath- by-pass. Computerized tomography (CT) eterization non-ionic media were used in 72% showed considerable contrast enhancement of of procedures, ioxaglate in 5%, and ionic the occipital lobes 2 h after the angiogram and monomers in 17%. The overall number of repeat CT at 3 days showed complete clearing major complications was 1.5%. Death was of contrast with no evidence of infarction. This
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Chapter 47 G. Ansell
suggested disruption of the blood-brain barrier with leakage of contrast medium. It was thought possible that a large amount of contrast may have entered the left vertebral artery. The supine position of the patient may also be relevant (29cr). Another paper reports 3 cases of transient cortical blindness after PTCA. Subsequently, repeat coronary angiography was required. Left ventriculography was omitted to decrease the volume of contrast medium and there was no recurrence of cortical blindness in the 3 patients (contrast medium was not specified) (30CR). One patient developed transient global amnesia and cortical blindness following cardiac angiography with iodixanol in a clinical trial (3lC).
the catheter or contrast medium may cause platelet aggregation, adhesion and deposition with peripheral thrombus formation. In this respect non-ionic media may cause less damage. However, it is essential to ensure meticulous syringe and catheter techniques with adequate heparinization (34 R, 35R). A recent study suggests an additional possible mechanism for thrombotic events involving non-ionic media. Iohexol and other non-ionic substances produced profound degranulation of platelets in vitro. This was not related to thrombin generation and was not blocked by pretreatment with heparin or aspirin. Diatrizoate caused considerably less degranulation whilst ioxaglate produced virtually no platelet degranulation (36R).
CEREBRAL A N G I O G R A P H Y (SED-12, 1178)
Interactions A previous report suggested that injection of papaverine with iopamidol may cause intra-arterial thrombosis (SEDA-17, 537). Subsequent correspondence indicates that heparin precipitates papaverine and that this may have been the major factor (37r).
Latchaw reviews the literature on the use of non-ionic media in neuroangiography. Although animal studies show less blood-brain barrier damage with non-ionic media in comparison with ionic media, clinical studies have generally not shown a lower incidence of neurological side effects with non-ionic media. While previously advocating the routine use of non-ionic media for cerebral angiography, Latchaw now believes that this is no longer justified for routine cases, and he now restricts the use of non-ionic media in cerebral angiography to cases where there is probably a blood-brain barrier break; for spinal angiography or for neurointerventional procedures (32cR). Two cases of transient global amnesia have been reported after cerebral angiography with iohexol. This appeared to be due to vascular insufficiency affecting the median temporal lobe and hippocampus following vertebral artery injection (33CR). Thromboembolism There is continuing controversy concerning the possibility that nonionic media may increase the incidence of thromboembolism (SEDA-10, 424; SEDA-12, 395; SEDA-14, 423; SEDA-15, 502; SEDA-16, 534, SEDA-t7, 537). Two reviews suggest that these risks have been exaggerated, clots forming in the syringe and catheter are only one aspect. Injury to the vascular endothelium by
Nephrotoxicity Previous studies suggested that low osmolar media generally have lower nephrotoxicity (SEDA-15, 501; SEDA-16, 534; SEDA-17, 537). A meta-analysis of 25 clinical trials containing adequate data provides further evidence that low osmolar media are less nephrotoxic than higher osmolar media in patients with underlying renal failure, but they do not appear to have any advantage in patients with normal renal function (38CR). It has been suggested that calcium channel blockers may be of value in decreasing the nephrotoxicity of contrast media (39 cR, 40R), but another study suggested that they may even have a deleterious effect, particularly in patients receiving high osmolar media or with diabetes (41c). A small clinical trial in patients with normal renal function suggested that a new non-ionic dimer iodixanol may possibly be less nephrotoxic than iohexol, but this requires further evaluation in higher risk patients (28CR). TWO further reviews are of interest (42 R, 43R). If an increase of serum creatinine of 1 mg/dl occurs, it is likely to increase treatment costs and this could provide an economic argument for preferring low osmolar media in high-risk patients (42R).
Radiological contrast media Chapter 47
Polyarthropathy Two unusual cases of severe acute polyarthropathy occurred 6 and 16 h after venography with iopamidol in patients with end-stage renal failure. There were severe constitutional changes with nausea and vomiting, one patient was pyrexial. The other patient who had amyloidosis involving the adrenals became profoundly hypotensive despite fluid overload. Intravenous injection of 200 mg of hydrocortisone promptly restored the blood pressure to normal. Both patients responded to treatment with NSAIDS (13CR).
RETROGRADE AND ANTEGRADE UROGRAPHY Absorption of contrast medium during retrograde urography may very rarely lead to systemic reactions (SED-12, 1174). Two such reactions occurred during voiding cystourethrography with megumine iothalamate. In one case without ureteric reflux, the patient developed urticaria. In the second patient, there was bilateral ureteric reflux and the patient developed tachycardia, hypotension and syncopal collapse, but this responded to simple posture and epinephrine was not required (44~ Severe and prolonged hypotensive collapse occurred following antegrade pyelography through a nephrostomy tube under general anesthesia. The patient had a previous history of a reaction to IVU and was, therefore, given diphenhydramine i.v. before the injection of non-ionic medium into the ureter (45CR).
M Y E L O G R A P H Y (SEDA-17, 538; SED-12, 1179) Two recent reports from contrast media manufacturers record a total of 17 cases, in which ionic media were mistaken for non-ionic media and inadvertently used for myelography resulting in 8 deaths. Intrathecal injection of ionic media causes myoclonic spasms, convulsions and other neurological complications. Convulsions may be temporarily controlled by intravenous diazepam, but general anesthesia with neuromuscular agents may be required. Other complications include rhabdomyolysis, fractures, hyperthermia and acidosis (46 oR, 47CR). It is important that the contrast medium
445 used should subsequently be identified by analysis in all doubtful cases. Lavage of the subarachnoid space with isotonic saline may be life-saving (SED-8, 1046; SEDA-15, 504). The U.S. Food and Drugs Administration (FDA) has received 19 reports of mistaken intrathecal administration of ionic media in the 3 years up to 1993. The F D A has instructed manufacturers to place a boxed label on ionic media warning against intrathecal use (48CR). Convulsions are rare after iohexol myelography (SEDA-16, 536). A case of prolonged status epilepticus is reported, commencing 30 min after myetography with 15 ml iohexol 300. General anesthesia was required for 41 h and recovery occurred after a period of 2 weeks (49cR). In another patient, an acute encephalopathy was reported 4 h after myelography with iohexol leading to coma. This was treated with dexamethasone: recovery commenced at 24 h and was complete within 1 week (50 cR) (see also SEDA-17, 538). It is curious that both of these cases were reported from Turkey in early 1992. It is not clear if the contrast medium was checked. An additional case of aseptic meningoencephalitis has been reported after iopamidol (51 cr) (see also SED-12, 1182; SEDA-11, 415; SEDA-16, 536). In a series of 225 patients undergoing iohexol myelography, postmyelogram headache was more common in patients with a previous history of headache, and in patients with normal myelograms. The data showed rather more cases after early ambulation, but this was concluded to be not statistically significant (52CR). This conclusion is at variance with a previous study (SEDA-15, 503).
Pyelosinus extravasation A 53-year-old man became acutely distressed after injection of 100 ml iohexol for abdominal CT. Initially, a contrast reaction was suspected. Abdominal radiography revealed dilation of the upper urinary tract with pyelosinus extravasation into the perirenal space. It was presumed that obstruction of the lower ureters was due to earlier radiotherapy (53cr).
OILY CONTRAST M E D I A A patient with a previous history of reactions to i.v. contrast media and sea foods
Chapter 47 G. Ansell
446 collapsed 3 h after lymphangiography with 7 ml ethiodol and became profoundly hypotensive. She recovered after intravenous administration of 2 liters of saline. This reaction occurred despite premedication with 2 doses of methylprednisolone and diphenhydramine. Methylene blue had also been used to avoid the idiosyncrasy risk of patent blue violet (54cr). Lipiodol mixed with iopamidol and doxorubicin may be injected into the hepatic artery to treat hepatocellular carcinoma. Transitory thickening of the gallbladder wall was detected by ultrasound in 17 out of 37 cases and 6 patients had a positive Murphy's sign (55CR). Pulmonary oil embolism with hypoxemia occurred in 6 out of 336 patients receiving hepatic oily chemoembolism and one of these 6 patients died. There appears to be a particular risk with administration of more than 20 ml of oil (56CR).
reaction, but it subsequently transpired that he was an athlete and that this may have accounted for the slow pulse. Seven less severe reactions also occurred in approximately 80 patients (59CR).
RADIOPHARMACEUTICALS
(SED-12, 1187; SEDA-14, 424; SEDA-15, 506; SEDA-16, 537; SEDA-17, 539) A recent review provides a detailed discussion of adverse reactions to radiopharmaceuticals and a wide range of drug interactions which may affect the diagnostic accuracy of investigation by radiopharmaceuticals. It is not possible to summarize this paper which should be read in the original by those interested (60R). Thorotrast (SED-12, 1188; SEDA-15, 506;
M A G N E T I C RESONANCE I M A G I N G (MRI) (SED-12, 1187)
Gadopentate dimeglumine (Gd-DTPA) A number of severe anaphylactoid reactions have been reported following injection of GdDTPA (SEDA-17, 538; SEDA-16, 537; SEDA15, 505). An additional case report stresses the importance of monitoring and provision for resuscitation during MRI (57"). Another patient developed a transitory polyarthralgia affecting her wrists, elbows and knees, several hours after Gd-DTPA (58c').
Gadoteridol This is a new non-ionic MRI agent. A patient with known allergies to codeine and acetarninophen had a moderately severe anaphylactoid reaction to this new agent with resulting hypotension and cyanosis. He also had a pulse of 50 per minute, suggesting a vagal
SEDA-16, 537) A follow-up of mortality patterns in 999 Danish patients who had undergone carotid angiography with thorotrast between 1935 and 1947 showed an excess mortality which could only partially be explained by neurological disease and by diseases known to be induced by thorotrast such as cirrhosis and cancer of the liver, leukemia 'and other hematological diseases. It is suggested that non-specific effects induced by the or-radiation of thorotrast may have contributed to this excess mortality (61OR). A case report of thorotrastosis and cholangiocarcinoma suggests that M R I is more useful than ultrasound and CT for detecting thorotrast-induced liver tumors, but that CT is more useful for detecting thorotrast deposits (62CR). Deposits of radio-opaque thorotrast in the bones may cause a spurious increase in bone density as measured by dual-energy X-ray absorptiometry (DXA) (63CR).
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34, 237-241. 3. Kuwano A, Sugai T, Mochida K (1993) Systemic contact dermatitis induced by oral contrast medium for the gallbladder. Skin Res., 35 (Suppl. 16), 114-120. 4. Thomsen HS, Dorph S (1993) Review article. High osmolar and low osmolar contrast media. An update on frequency of adverse drug reactions. Acta RadioL, 34, 205 209. 5. Morris TW (1993) X-ray contrast media: Where are we now and where are we going? Radiology, 188, 11-16. 6. Andrew E, Haider T (1993) Incidence of Roentgen contrast media reactions after intravenous injection in pre-registration and post marketing surveillances. Acta RadioL, 34, 210-213. 7. Siegle RL (1993) Rates of idiosyncratic reactions. Ionic versus nonionic media. Invest. Radiol., 28 (Suppl. 5), 595-598. 8. Cohen MD (1993) A review of the toxicity of nonionic contrast agents in children. Invest. Radiol., 28, (Suppl. 5), 587-593. 9. Powe NR, Moore RD, Steinberg EP (1993) Adverse reactions to contrast media: factors that determine the cost of treatment. Am. J. Roentgenol., 161, 1089 1095. 10. Hopper KD, Houts PS, TenHave TR, Mathews YL, Colon E, Haseman DB, Hartzel J (1994) The effect of informed consent on the level of anxiety in patients given 1.V. contrast material. Am. J. Roentgenol., 162, 531-535. 11. Bush WH, McClennan BL, Swanson DP (1993) Contrast media reactions: prediction, prevention and treatment. Postgrad Radiol., 13, 137-147. 12. Ansell G (1993) Adverse reactions profile: 8. Intravascular iodinated radiocontrast media. Prescr. J., 33, 82 88. 13. Donnelly PK, Williams B, Watkin EM (1993) Polyarthropathy - a delayed reaction to low osmolarity angiographic contrast medium in patients with end stage renal disease. Ear. ,s Radiol., 17, 130~132. 14. Dawson P, Sidhu PS (1993) Review. Is there a role for corticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents? Clin. Radiol., 48, 225 226. 15. Ansell G e t al. (1994) (correspondence) Corticosteroid prophylaxis for contrast media reactions. Clin. Radiol., 49, 507-510. 16. Lasser EC, Berry CC et al. (1994) (correspondence) Corticosteroid prophylaxis in patients at increased risk of adverse reactions to isovascular contrast agents. Clin. Radiol., 49, 582-584. 17. Lasser EC, Berry CC, Mishkin MM, Williamson B, Zheutlin N, Silverman JM (1994) Pretreatmerit with corticosteroids to prevent adverse reactions to nonionic contrast media. Am. J. RoentgenoL, 162, 523 526. 18. Dunnick NR, Cohan RH (1994) Cost, corticosteroids and contrast media. Am. J. RoentgenoL,
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448 31. Anderson PE, Bolstad B, Berg KJ, Justesen P, Thayssen P, Kloster YF (1993) Iodixanol and ioxaglate in cardioangiography: a double blinded randomized phase IIl study. Clin. Radiol., 48, 268-272. 32. Latchaw RE (1993) The use of nonionic contrast agents in neuroangiography. A review of the literature and recommendations for clinical use. Invest. Radiol., 28 (Suppl. 5), 555-561. 33. Brady AP, Hough DM, Lo R, Gill G (1993) Transient global amnesia after cerebral angiography with iohexol. Can. Assoc. Radiol. J., 44, 450-452. 34. Dawson P, Cousins C, Bradshaw A (1993) The clotting issue: etiologic factors in thromboembolism. II: clinical considerations. Invest. Radiol., 28 (Suppl. 5), 531-538. 35. Grabowski EF, Head C, Michelson AD (1993) Nonionic contrast media. Procoagulants or clotting innocents. Invest. Radiol., 28 (Suppl. 5), 521-524. 36. Chronos NAF, Goodall AH, Wilson D J, Sigwart U, Buller NP (1993) Profound platelet degranulation is an important side effect of some types of contrast media used in interventional cardiology. Circulation, 88, 2035 2044. 37. Finelli DA (1993) Was heparin the culprit? Radiolog); 189, 624-625. 38. Barrett BJ, Carlisle EJ (1993) Metaanalysis of the relative nephrotoxicity of high and low osmolarity iodinated contrast media. Radiology, 188, 171-178. 39. Neumayer HH, Gellert J, Luft FC (1993) Calcium antagonists and renal protection. Renal Fail., 15, 353 358. 40. Epstein E (1993) Calcium antagonists and the kidney. Implications for renal protection. Am. J. Hypertens., 6, 2515-2595. 41. Moore RD, Steinberg EP, Powe NR, Brinker JA, Fishman EK, Graziano SL et al. (1993) Comparative frequency of and risk factors for nephrotoxicity in patients receiving high versus low osmolarity contrast media. Radiology, RSNA annual meeting. Abstract 1119. 42. Goldfarb S, Spinier S, Berns JS, Rudnick MR (1993) Low osmolarity contrast media and the risk of contrast-associated nephrotoxicity. Invest. Radiol., 28 (Suppl. 5), $7 S10. 43. Porter GA (1993) Contrast medium-associated nephropathy. Recognition and management. Invest. Radiol., 28 (Suppl. 4), 511 518. 44. Weese DL, Greenberg HM, Zimmern PE (1993) Contrast media reactions during voiding cystourethrography or retrograde pyelography. Urology, 41, 81 84. 45. Gaiser RR, Chua E (1993) Anaphylactic/anaphylactoid reaction to contrast dye administration in the ureter. J. Clin. Anesth., 5, 510-512. 46. Rosati G, Leto Di Priolo S, Tirone P (1992) Serious fatal complications after inadvertent administration of ionic water-soluble contrast media in myelography. Eur J. Radiol., 15, 95-100.
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G. Ansell
47. Bohan HP, Reich L, Sultaga-Petchel K (1992) Inadvertent intrathecal use of ionic contrast media for myelography. Am. J. Neuroradiol., 13, 1515-1519. 48. McClennan BL (1993) Contrast media warning. Am. J. Neuroradiol.. 161, 1028. 49. Tahta K, I~zgent T, Berker M, Ciger A (1993) Status epilepticus following iohexol myelography. Neuroradiology, 35, 322-323. 50. Ceylan S, Bakal S, Kuzeyli K, Aktiirk F, Komsuoglu S (1993) A case of acute encephalopathy after iohexol lumbar myelography. ClinNeurol. Neurosurg., 95, 4547. 51. Berod T, Knebelmann O, Marjoo F (1993) Aseptic meningoencephalitis after iopamidol myeIography. Ann. Pharmacother., 27, 1140. 52. Hallam DM, Sonne NM, Jensen GS, Ahlgren P (1993) Headache after lumbar iohexol myelography: the influence of a history of headaches and early ambulation. Neuroradiology, 35, 319 321. 53. Collins CD, King DM, Gleeson JA (1993) Bilateral pyelosinus extravasation secondary to probable radiation induced nreteric fibrosis. B~ J. Urol., 72, 385-386. 54. Lossef SV, Barth KH (1993) Severe delayed hypotensive reaction after ethiodol lymphangiography despite premedication. Am. J. Roentgenol., 161, 417M18. 55. Yoshino I, Matsumata T, Adachi E, Sakaguchi M, Kanematsu T, Sugimachi K (1993) Morphologic changes of the gallbladder following lipiodolization for hepatic tumours: an ultrasonographic study. Reg. Cancer Treat., 6, 40~13. 56. Chung JW, Park JH, Im JG, Han JK, Han MC (1993) Pulmonary oil embolism after transcatheter oily chemoembolization of hepatocellular carcinoma. Radiology, 187, 689-693. 57. Takebayashi S, Sugiyama M, Nagase M, Matsubara S (1993) Severe adverse reaction to I.V. gadopentate dimeglumine. Radiology, 160, 659. 58. Wexler DM, Spencer JD (1993) Case report: generalised arthralgia following Gd-DTPA administration. Clin. Radiol., 48, 68. 59. ShelIock FG, Hahn HP, Mink JH, Itskovich E (1993) Adverse reaction to intravenous gadoteridol. Radiology, 189, 151-152. 60. Sampson CB (1993) Adverse drug reactions and drug interactions with radiopharmaceuticals. Drug SaX, 8, 280-294. 61. Andersson M, Juel K, Storm HH (1993) Pattern of mortality among Danish Thorotast patients. J. Clin. Epidemiol., 46, 637-644. 62. Hayasaka K, Amoh K, Kakiska A, Mito M (1993) MRI appearances of thorotrast-induced cholangiocarcinoma in a case of thorotrastosis. Radiol. Med., 11, 60 62. 63. Stern D, Zamenhof R, Dawson-Hughes B (1993) Spurious dual energy x-ray absorptiometry images in a patient exposed to the contrast agent thorotrast. Osteoporosis Int., 3, 283 285.
47
Radiological contrast media
Barium sulfate (SED-12, 1165; SEDA-17, 535;
SED-12, 1165) Allergic reactions Hypersensitivity reactions to barium sulfate previously regarded as rare, are now being recognized with increasing frequency (SEDA-4, 33; SEDA-6, 804; SEDA-10, 422; SEDA-12, 394; SEDA-14, 421; SEDA-15, 498; SEDA-16, 529). The majority of reactions have occurred following double contrast barium enemas; hypersensitivity to the latex balloon catheter appears to be the most frequent cause, but a reaction to glucagon was also postulated in some cases. Less commonly, reactions have been attributed to additives in the barium sulfate suspension and a recent report describes hypersensitivity reactions to E-Z-PAQUE following single contrast barium meals in two children. A severe reaction with angioedema, dyspnea, tachycardia and hypotension occurred in an 11-year-old boy with eczema, asthma and multiple food allergies. He responded to resuscitation and a subsequent biopsy showed eosinophilic gastroenteropathy. Two previous barium meals with E-Z-PAQUE had been symptomless, but may possibly have been a cause of sensitization. The other reaction occurred in a 7-year-old girl with a mild allergy to penicillin. She developed generalized urticaria, but had no cardiac or respiratory symptoms. Attention is drawn to the risk of reactions in atopic patients and particularly in those with food allergies. Immediate facilities for resuscitation should be available (lCR).
WATER-SOLUBLE CONTRAST M E D I A (SED-12, 1166) Where iohexol is administered orally, absorption is increased if there is mucosal damage in the bowel. In patients with ileal Crohn's 9 1995 Elsevier Science B.V. All rights reserved.
Side Effects of Drugs Annual 18 J.K. Aronson and C.J. van Boxtel, eds.
disease a 24-h urinary excretion exceeding 1% of the dose correlates strongly with mucosal damage and active disease. Patients and controis had diarrhea during the first day, but there were no adverse reactions (2cR)
ORAL C H O L E C Y S T O G R A P H Y (SED-12,
1166) A 66-year-old man with a known history of sensitivity to parabens developed a pruritic rash after oral cholecystography with Biloptin (sodium ipodate). Patch tests showed positive reaction to methyl, ethyl, propyl and butylparaben. Administration of a Biloptin capsule which contains methyl and propyl paraben as additives caused focal flare up as did 5 mg methylparaben, whereas the capsule contents (ipodate) or a gelatine capsule had caused no reaction (3CR).
INTRAVASCULAR CONTRAST M E D I A (SEDA-17, 535; SED-12, 1167) There has been increasing use of low osmolar media for intravascular purposes. These media are now used exclusively in Sweden, Norway, Finland and Japan. On the basis of 1990 and 1991 data the lowest estimated use appeared to be in the Netherlands and France (20 30%) with intermediate use in other countries: Denmark, U.K., Spain (51-65%); Germany, Austria, Italy (75-80%) (4CR). In the United States, during the first 6 months of 1992, low osmolar media were used in 66% of approximately 8,850,000 procedures (approximately 17,700,000 procedures annually) (5R). Idiosyncratic reactions (SEDA-17, 536) The incidence of adverse reactions found in the iohexol preregistration trials was 2-10 times the incidence of subsequent reports in postmarketing surveillance data. The relative risk for all reactions was 3-6 times higher for ionic 441
442 media vs non-ionic media and this ratio was similar in both pre- and postregistration studies (6CR). Another recent review of the literature indicates that although all iodinated contrast media have excellent safety records, nonionic media are safer than ionic media (7R). In children, even minor reactions, particularly vomiting and extravasation, may upset the child emotionally and physically and this may justify the routine use of non-ionic media (8R). Costs of treatment of adverse reactions to contrast media vary, depending on various factors and the type and severity. In cardiac angiography, a history of unstable angina or renal insufficiency, multiple reactions and thromboembolism were major factors contributing to the cost of such treatment (9OR). It is perhaps thought provoking that 3 cases of thromboembolism resulted in the highest treatment costs, since use of non-ionic media might be associated with a somewhat greater risk of thromboembolism (SEDA-17; 537). Anxiety has previously been considered a risk factor for contrast media reactions and it has been suggested that seeking informed consent may increase the risk. A study involving 1251 patients indicated that the majority of patients attending an X-ray department already have an increased 'anxiety score': explaining the possible risks of contrast media did not increase the score. It is therefore concluded that failure to obtain informed consent cannot be justified on this basis (10CR). In higher risk patients with a history of previous reactions to contrast media, a prophylactic premedication regime of prednisolone, diphenhydramine combined with the use of non-ionic medium, has recently been advocated (SEDA-16, 531) (7 R, llR). Steroid premedication has also been advocated in asthmatic patients. A booster dose of steroids may be appropriate if there is any possibility of adrenal suppression from long-term corticosteroid therapy (12 R, 13c). A recent editorial (14 R) criticizes earlier studies which supported prophylactic steroids and concludes that steroid premedication may reasonably be abandoned when non-ionic media are used. This editorial has itself been criticized in subsequent correspondence (15 R, 16R). Moreover, a carefully controlled study in 1155 patients showed that corticosteroid premedication significantly reduced the incidence of all reactions and grade
Chapter 47
G. Ansell
I (mild) reactions in patients given non-ionic media. The incidence of grade II (moderate) and grade III (severe) reactions were also reduced, but because of the small numbers involved, these did not reach statistical significance (17oR). Providing that there is no clinical contraindication to the use of corticosteroids, it is recommended that high-risk patients should receive both corticosteroid prophylaxis and non-ionic media (18CR). In an unusual case of anaphylactic collapse, marked bilateral parotid enlargement with overlying erythema occurred approximately 1 h after commencing an infusion of 100 ml ioxaglate followed by 60 ml of ioxithalamate. Ten minutes later the patient developed dysphagia, dyspnea and hypotensive collapse which responded rapidly to intravenous fluids and adrenaline. There was no evidence of renal failure. There was no history of allergy and a previous cerebral arteriogram with ioxithalamate had not caused any reaction. The patient had received 8 mg dexamethasone intravenously immediately prior to the present examination, but steroid prophylaxis at this time is likely to be ineffective. The authors tabulate 27 other reported cases of parotid enlargement following iodinated contrast media (19CR). The majority of contrast media reactions do not appear to have a true immunological basis, but this may be a possibility in a few cases. A patient who had suffered anaphylactic shock and cardiac arrest on two previous occasions using ioxithalamate and diatrizoate, respectively, had a positive intradermal reaction to diatrizoate and ioxithalamate and a positive basophil degranulation test (HBTD) to diatrizoate and ioxithalamate. The basophil degranulation test to iothalamate was negative using preheated serum suggesting IgE involvement. HBDT and skin tests were negative to ioxaglate and iopamidol. Two subsequent arteriograms using iopamidol caused no reaction (20 oR) (see also SEDA-16, 531). Cutaneous vasculitis There have been two previous reports of fatal Stevens-Johnson syndrome following non-ionic media in patients with systemic lupus erythematosus or receiving hydralazine (SEDA-11, 411; SEDA-14, 422). An additional case of severe cutaneous vasculitis following iopamidol has now been reported in a patient receiving hydralazine. Contrast
Radiological contrast media Chapter 47 examination should be avoided in such patients if possible (21CR).
443
reported in 0.11%, myocardial infarction in 0.06%, neurologic complications in 0.05%, arrhythmias in 0.31%, vascular complications in lnterleukin-2 0.44%, contrast media reactions in 0.25%, and others in 0.48%. For percutaneous coronary Toxic recall reactions may occur when con- angioplasty (PTC), non-ionic media were used trast media are administered to patients who in 77%, ioxaglate in 13%, and ionic monomers have previously received interleukin-2 (IL-2) in 10%. Major complications occurred in 5% (SEDA-15, 499; SEDA-16, 532; SEDA-17, of patients. Death occurred in 0.3%, myo537). Reactions occur 1-4 h after contrast cardial infarction in 0.5%, and emergency administration and include fever, chills, vomit- by-pass surgery was required in 1.4% of cases ing, diarrhea, rash, wheezing, hypotension, (24cr). The American College of Cardiology, edema and oliguria. In 70 patients receiving Cardiovascular Imaging Committee has issued high-dose interleukin-2, reactions appeared to a position statement on the use of low osmolar be more common with contrast administration media in cardiovascular procedures (25R). 2 weeks after therapy (11%) compared with 6 Iohexol was compared with sodium meglumine weeks (1.7%), but this did not reach statistical diatrizoate in a multicenter randomized trial significance. Seven patients required hospitali- involving 1390 patients undergoing cardiac zation with 4 requiring intensive care. The angiography. The incidence of contrast media incidence of reactions following non-ionic related adverse effects was 10.2% for iohexol media was approximately one half that follow- vs 31.6% for diatrizoate P <0.001 and for ing ionic media, but this also did not reach cardiac adverse events 7.2 vs 24.5% P < 0.001. statistical significance. It has previously been It should be noted that the diatrizoate used in claimed that premedication with steroids and this study (Renografin 76 TM) causes calcium antihistamines prevented such reactions binding and this may have caused a somewhat (SEDA-I 5,499), but a severe reaction occurred higher incidence o f cardiac adverse events with a repeat contrast examination at 4 weeks (SEDA-16, 533). The presence of New York despite such premedication. Five other patients Heart Association classification 3 or 4 and had no reaction at 4 weeks. The authors advise serum creatinine -> 1.5 mg/dl predicted a higher against routine steroid premedication since this incidence of contrast media related adverse may block the IL-2 effector mechanism (22CR). events (26CR). The higher cost of using non-ionic media for Thyroid function In 28 neonates requiring diagnostic angiography is partially offset by parenteral nutrition, opacification of the cathe- lower management costs of adverse drug reacter using 0.5 ml of ioxaglate (diluted) caused tions. The extent of such offset may vary from transitory hypothyroidism in 3 patients (10.7%); 33 to 75%, depending on the criteria used smaller doses of contrast media in 26 further (27cR). neonates caused only 1 case of hypothyroidism Iodixanol 320 is a new non-ionic dimer (3.8%) (not statistically significant) (23~r). which is virtually isosmolar. A double-blind randomized comparison with iohexol was performed in 72 patients undergoing cardioangiC A R D I A C A N G I O G R A P H Y (SEDA-17, ography. There were few side effects and these 536; SED-12, 1175) appeared to be milder in the iodixanol group (28CR). The Society for Cardiac Angiography and Transient cortical blindness occurred shortly Interventions has introduced a personal com- after a difficult coronary angiography with puter-based registry. Data relating to 92,157 iohexol in a 62-year-old patient with arterioprocedures performed in 72 hospitals during sclerosis who had previously had a coronary 1991 have been analyzed. In diagnostic cath- by-pass. Computerized tomography (CT) eterization non-ionic media were used in 72% showed considerable contrast enhancement of of procedures, ioxaglate in 5%, and ionic the occipital lobes 2 h after the angiogram and monomers in 17%. The overall number of repeat CT at 3 days showed complete clearing major complications was 1.5%. Death was of contrast with no evidence of infarction. This
444
Chapter 47 G. Ansell
suggested disruption of the blood-brain barrier with leakage of contrast medium. It was thought possible that a large amount of contrast may have entered the left vertebral artery. The supine position of the patient may also be relevant (29cr). Another paper reports 3 cases of transient cortical blindness after PTCA. Subsequently, repeat coronary angiography was required. Left ventriculography was omitted to decrease the volume of contrast medium and there was no recurrence of cortical blindness in the 3 patients (contrast medium was not specified) (30CR). One patient developed transient global amnesia and cortical blindness following cardiac angiography with iodixanol in a clinical trial (3lC).
the catheter or contrast medium may cause platelet aggregation, adhesion and deposition with peripheral thrombus formation. In this respect non-ionic media may cause less damage. However, it is essential to ensure meticulous syringe and catheter techniques with adequate heparinization (34 R, 35R). A recent study suggests an additional possible mechanism for thrombotic events involving non-ionic media. Iohexol and other non-ionic substances produced profound degranulation of platelets in vitro. This was not related to thrombin generation and was not blocked by pretreatment with heparin or aspirin. Diatrizoate caused considerably less degranulation whilst ioxaglate produced virtually no platelet degranulation (36R).
CEREBRAL A N G I O G R A P H Y (SED-12, 1178)
Interactions A previous report suggested that injection of papaverine with iopamidol may cause intra-arterial thrombosis (SEDA-17, 537). Subsequent correspondence indicates that heparin precipitates papaverine and that this may have been the major factor (37r).
Latchaw reviews the literature on the use of non-ionic media in neuroangiography. Although animal studies show less blood-brain barrier damage with non-ionic media in comparison with ionic media, clinical studies have generally not shown a lower incidence of neurological side effects with non-ionic media. While previously advocating the routine use of non-ionic media for cerebral angiography, Latchaw now believes that this is no longer justified for routine cases, and he now restricts the use of non-ionic media in cerebral angiography to cases where there is probably a blood-brain barrier break; for spinal angiography or for neurointerventional procedures (32cR). Two cases of transient global amnesia have been reported after cerebral angiography with iohexol. This appeared to be due to vascular insufficiency affecting the median temporal lobe and hippocampus following vertebral artery injection (33CR). Thromboembolism There is continuing controversy concerning the possibility that nonionic media may increase the incidence of thromboembolism (SEDA-10, 424; SEDA-12, 395; SEDA-14, 423; SEDA-15, 502; SEDA-16, 534, SEDA-t7, 537). Two reviews suggest that these risks have been exaggerated, clots forming in the syringe and catheter are only one aspect. Injury to the vascular endothelium by
Nephrotoxicity Previous studies suggested that low osmolar media generally have lower nephrotoxicity (SEDA-15, 501; SEDA-16, 534; SEDA-17, 537). A meta-analysis of 25 clinical trials containing adequate data provides further evidence that low osmolar media are less nephrotoxic than higher osmolar media in patients with underlying renal failure, but they do not appear to have any advantage in patients with normal renal function (38CR). It has been suggested that calcium channel blockers may be of value in decreasing the nephrotoxicity of contrast media (39 cR, 40R), but another study suggested that they may even have a deleterious effect, particularly in patients receiving high osmolar media or with diabetes (41c). A small clinical trial in patients with normal renal function suggested that a new non-ionic dimer iodixanol may possibly be less nephrotoxic than iohexol, but this requires further evaluation in higher risk patients (28CR). TWO further reviews are of interest (42 R, 43R). If an increase of serum creatinine of 1 mg/dl occurs, it is likely to increase treatment costs and this could provide an economic argument for preferring low osmolar media in high-risk patients (42R).
Radiological contrast media Chapter 47
Polyarthropathy Two unusual cases of severe acute polyarthropathy occurred 6 and 16 h after venography with iopamidol in patients with end-stage renal failure. There were severe constitutional changes with nausea and vomiting, one patient was pyrexial. The other patient who had amyloidosis involving the adrenals became profoundly hypotensive despite fluid overload. Intravenous injection of 200 mg of hydrocortisone promptly restored the blood pressure to normal. Both patients responded to treatment with NSAIDS (13CR).
RETROGRADE AND ANTEGRADE UROGRAPHY Absorption of contrast medium during retrograde urography may very rarely lead to systemic reactions (SED-12, 1174). Two such reactions occurred during voiding cystourethrography with megumine iothalamate. In one case without ureteric reflux, the patient developed urticaria. In the second patient, there was bilateral ureteric reflux and the patient developed tachycardia, hypotension and syncopal collapse, but this responded to simple posture and epinephrine was not required (44~ Severe and prolonged hypotensive collapse occurred following antegrade pyelography through a nephrostomy tube under general anesthesia. The patient had a previous history of a reaction to IVU and was, therefore, given diphenhydramine i.v. before the injection of non-ionic medium into the ureter (45CR).
M Y E L O G R A P H Y (SEDA-17, 538; SED-12, 1179) Two recent reports from contrast media manufacturers record a total of 17 cases, in which ionic media were mistaken for non-ionic media and inadvertently used for myelography resulting in 8 deaths. Intrathecal injection of ionic media causes myoclonic spasms, convulsions and other neurological complications. Convulsions may be temporarily controlled by intravenous diazepam, but general anesthesia with neuromuscular agents may be required. Other complications include rhabdomyolysis, fractures, hyperthermia and acidosis (46 oR, 47CR). It is important that the contrast medium
445 used should subsequently be identified by analysis in all doubtful cases. Lavage of the subarachnoid space with isotonic saline may be life-saving (SED-8, 1046; SEDA-15, 504). The U.S. Food and Drugs Administration (FDA) has received 19 reports of mistaken intrathecal administration of ionic media in the 3 years up to 1993. The F D A has instructed manufacturers to place a boxed label on ionic media warning against intrathecal use (48CR). Convulsions are rare after iohexol myelography (SEDA-16, 536). A case of prolonged status epilepticus is reported, commencing 30 min after myetography with 15 ml iohexol 300. General anesthesia was required for 41 h and recovery occurred after a period of 2 weeks (49cR). In another patient, an acute encephalopathy was reported 4 h after myelography with iohexol leading to coma. This was treated with dexamethasone: recovery commenced at 24 h and was complete within 1 week (50 cR) (see also SEDA-17, 538). It is curious that both of these cases were reported from Turkey in early 1992. It is not clear if the contrast medium was checked. An additional case of aseptic meningoencephalitis has been reported after iopamidol (51 cr) (see also SED-12, 1182; SEDA-11, 415; SEDA-16, 536). In a series of 225 patients undergoing iohexol myelography, postmyelogram headache was more common in patients with a previous history of headache, and in patients with normal myelograms. The data showed rather more cases after early ambulation, but this was concluded to be not statistically significant (52CR). This conclusion is at variance with a previous study (SEDA-15, 503).
Pyelosinus extravasation A 53-year-old man became acutely distressed after injection of 100 ml iohexol for abdominal CT. Initially, a contrast reaction was suspected. Abdominal radiography revealed dilation of the upper urinary tract with pyelosinus extravasation into the perirenal space. It was presumed that obstruction of the lower ureters was due to earlier radiotherapy (53cr).
OILY CONTRAST M E D I A A patient with a previous history of reactions to i.v. contrast media and sea foods
Chapter 47 G. Ansell
446 collapsed 3 h after lymphangiography with 7 ml ethiodol and became profoundly hypotensive. She recovered after intravenous administration of 2 liters of saline. This reaction occurred despite premedication with 2 doses of methylprednisolone and diphenhydramine. Methylene blue had also been used to avoid the idiosyncrasy risk of patent blue violet (54cr). Lipiodol mixed with iopamidol and doxorubicin may be injected into the hepatic artery to treat hepatocellular carcinoma. Transitory thickening of the gallbladder wall was detected by ultrasound in 17 out of 37 cases and 6 patients had a positive Murphy's sign (55CR). Pulmonary oil embolism with hypoxemia occurred in 6 out of 336 patients receiving hepatic oily chemoembolism and one of these 6 patients died. There appears to be a particular risk with administration of more than 20 ml of oil (56CR).
reaction, but it subsequently transpired that he was an athlete and that this may have accounted for the slow pulse. Seven less severe reactions also occurred in approximately 80 patients (59CR).
RADIOPHARMACEUTICALS
(SED-12, 1187; SEDA-14, 424; SEDA-15, 506; SEDA-16, 537; SEDA-17, 539) A recent review provides a detailed discussion of adverse reactions to radiopharmaceuticals and a wide range of drug interactions which may affect the diagnostic accuracy of investigation by radiopharmaceuticals. It is not possible to summarize this paper which should be read in the original by those interested (60R). Thorotrast (SED-12, 1188; SEDA-15, 506;
M A G N E T I C RESONANCE I M A G I N G (MRI) (SED-12, 1187)
Gadopentate dimeglumine (Gd-DTPA) A number of severe anaphylactoid reactions have been reported following injection of GdDTPA (SEDA-17, 538; SEDA-16, 537; SEDA15, 505). An additional case report stresses the importance of monitoring and provision for resuscitation during MRI (57"). Another patient developed a transitory polyarthralgia affecting her wrists, elbows and knees, several hours after Gd-DTPA (58c').
Gadoteridol This is a new non-ionic MRI agent. A patient with known allergies to codeine and acetarninophen had a moderately severe anaphylactoid reaction to this new agent with resulting hypotension and cyanosis. He also had a pulse of 50 per minute, suggesting a vagal
SEDA-16, 537) A follow-up of mortality patterns in 999 Danish patients who had undergone carotid angiography with thorotrast between 1935 and 1947 showed an excess mortality which could only partially be explained by neurological disease and by diseases known to be induced by thorotrast such as cirrhosis and cancer of the liver, leukemia 'and other hematological diseases. It is suggested that non-specific effects induced by the or-radiation of thorotrast may have contributed to this excess mortality (61OR). A case report of thorotrastosis and cholangiocarcinoma suggests that M R I is more useful than ultrasound and CT for detecting thorotrast-induced liver tumors, but that CT is more useful for detecting thorotrast deposits (62CR). Deposits of radio-opaque thorotrast in the bones may cause a spurious increase in bone density as measured by dual-energy X-ray absorptiometry (DXA) (63CR).
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Radiological contrast media
Chapter 47
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448 31. Anderson PE, Bolstad B, Berg KJ, Justesen P, Thayssen P, Kloster YF (1993) Iodixanol and ioxaglate in cardioangiography: a double blinded randomized phase IIl study. Clin. Radiol., 48, 268-272. 32. Latchaw RE (1993) The use of nonionic contrast agents in neuroangiography. A review of the literature and recommendations for clinical use. Invest. Radiol., 28 (Suppl. 5), 555-561. 33. Brady AP, Hough DM, Lo R, Gill G (1993) Transient global amnesia after cerebral angiography with iohexol. Can. Assoc. Radiol. J., 44, 450-452. 34. Dawson P, Cousins C, Bradshaw A (1993) The clotting issue: etiologic factors in thromboembolism. II: clinical considerations. Invest. Radiol., 28 (Suppl. 5), 531-538. 35. Grabowski EF, Head C, Michelson AD (1993) Nonionic contrast media. Procoagulants or clotting innocents. Invest. Radiol., 28 (Suppl. 5), 521-524. 36. Chronos NAF, Goodall AH, Wilson D J, Sigwart U, Buller NP (1993) Profound platelet degranulation is an important side effect of some types of contrast media used in interventional cardiology. Circulation, 88, 2035 2044. 37. Finelli DA (1993) Was heparin the culprit? Radiolog); 189, 624-625. 38. Barrett BJ, Carlisle EJ (1993) Metaanalysis of the relative nephrotoxicity of high and low osmolarity iodinated contrast media. Radiology, 188, 171-178. 39. Neumayer HH, Gellert J, Luft FC (1993) Calcium antagonists and renal protection. Renal Fail., 15, 353 358. 40. Epstein E (1993) Calcium antagonists and the kidney. Implications for renal protection. Am. J. Hypertens., 6, 2515-2595. 41. Moore RD, Steinberg EP, Powe NR, Brinker JA, Fishman EK, Graziano SL et al. (1993) Comparative frequency of and risk factors for nephrotoxicity in patients receiving high versus low osmolarity contrast media. Radiology, RSNA annual meeting. Abstract 1119. 42. Goldfarb S, Spinier S, Berns JS, Rudnick MR (1993) Low osmolarity contrast media and the risk of contrast-associated nephrotoxicity. Invest. Radiol., 28 (Suppl. 5), $7 S10. 43. Porter GA (1993) Contrast medium-associated nephropathy. Recognition and management. Invest. Radiol., 28 (Suppl. 4), 511 518. 44. Weese DL, Greenberg HM, Zimmern PE (1993) Contrast media reactions during voiding cystourethrography or retrograde pyelography. Urology, 41, 81 84. 45. Gaiser RR, Chua E (1993) Anaphylactic/anaphylactoid reaction to contrast dye administration in the ureter. J. Clin. Anesth., 5, 510-512. 46. Rosati G, Leto Di Priolo S, Tirone P (1992) Serious fatal complications after inadvertent administration of ionic water-soluble contrast media in myelography. Eur J. Radiol., 15, 95-100.
Chapter 47
G. Ansell
47. Bohan HP, Reich L, Sultaga-Petchel K (1992) Inadvertent intrathecal use of ionic contrast media for myelography. Am. J. Neuroradiol., 13, 1515-1519. 48. McClennan BL (1993) Contrast media warning. Am. J. Neuroradiol.. 161, 1028. 49. Tahta K, I~zgent T, Berker M, Ciger A (1993) Status epilepticus following iohexol myelography. Neuroradiology, 35, 322-323. 50. Ceylan S, Bakal S, Kuzeyli K, Aktiirk F, Komsuoglu S (1993) A case of acute encephalopathy after iohexol lumbar myelography. ClinNeurol. Neurosurg., 95, 4547. 51. Berod T, Knebelmann O, Marjoo F (1993) Aseptic meningoencephalitis after iopamidol myeIography. Ann. Pharmacother., 27, 1140. 52. Hallam DM, Sonne NM, Jensen GS, Ahlgren P (1993) Headache after lumbar iohexol myelography: the influence of a history of headaches and early ambulation. Neuroradiology, 35, 319 321. 53. Collins CD, King DM, Gleeson JA (1993) Bilateral pyelosinus extravasation secondary to probable radiation induced nreteric fibrosis. B~ J. Urol., 72, 385-386. 54. Lossef SV, Barth KH (1993) Severe delayed hypotensive reaction after ethiodol lymphangiography despite premedication. Am. J. Roentgenol., 161, 417M18. 55. Yoshino I, Matsumata T, Adachi E, Sakaguchi M, Kanematsu T, Sugimachi K (1993) Morphologic changes of the gallbladder following lipiodolization for hepatic tumours: an ultrasonographic study. Reg. Cancer Treat., 6, 40~13. 56. Chung JW, Park JH, Im JG, Han JK, Han MC (1993) Pulmonary oil embolism after transcatheter oily chemoembolization of hepatocellular carcinoma. Radiology, 187, 689-693. 57. Takebayashi S, Sugiyama M, Nagase M, Matsubara S (1993) Severe adverse reaction to I.V. gadopentate dimeglumine. Radiology, 160, 659. 58. Wexler DM, Spencer JD (1993) Case report: generalised arthralgia following Gd-DTPA administration. Clin. Radiol., 48, 68. 59. ShelIock FG, Hahn HP, Mink JH, Itskovich E (1993) Adverse reaction to intravenous gadoteridol. Radiology, 189, 151-152. 60. Sampson CB (1993) Adverse drug reactions and drug interactions with radiopharmaceuticals. Drug SaX, 8, 280-294. 61. Andersson M, Juel K, Storm HH (1993) Pattern of mortality among Danish Thorotast patients. J. Clin. Epidemiol., 46, 637-644. 62. Hayasaka K, Amoh K, Kakiska A, Mito M (1993) MRI appearances of thorotrast-induced cholangiocarcinoma in a case of thorotrastosis. Radiol. Med., 11, 60 62. 63. Stern D, Zamenhof R, Dawson-Hughes B (1993) Spurious dual energy x-ray absorptiometry images in a patient exposed to the contrast agent thorotrast. Osteoporosis Int., 3, 283 285.