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Radiological contrast media
G. Ansell
48
Radiological contrast media
ALIMENTARY TRACT Barium sulfate (SED-I O, 850; SEDA-8, 426) A fatal case of aspiration pneumonia occurred in an 81-year-old female who inhaled approximately 1 5 - 2 0 ml of barium sulfate suspension into the left lower lobe. Pyrexia developed after 45 minutes, the patient became comatose, developed circulatory collapse and death occurred at 32 hours ( 1 c ~ ) . This is a rare complication, but a fatal case has been reported previously after blockage of the trachea b y barium paste (SEDA-2,373). In another unusual complication reported recently, oral barium impacted in the small bowel for several days in an infant with cystic fibrosis. The obstruction was relieved by an enema of 30% Hypaque (2Cr). It has been suggested that barium encephalopathy may result after prolonged stasis o f barium in the bowel (SEDA-6,404). Another possible case has now been reported after intraperitoneal rupture o f a barium enema. Myoclonic changes and mental deterioration occurred after 16 days and the patient died 8 weeks after the perforation. Two samples of cerebrospinal fluid obtained by lumbar puncture shortly before death contained 180 and 160 #g/1 of barium respectively. Although contamination could not be entirely excluded, this was thought to be unlikely (3Cr). It will be recalled that in SEDA-8 (p. 426) other instances o f perforation were discussed and one of mental changes in a neonate with barium peritonitis. Accidental venous intravasation of barium during a barium enema usually has a high immediate mortality due to barium embol-
Side Effects of Drugs Annual 9 M.N.G. Dukes, editor 9 Elsevier Science Publishers B.V., 1985 ISBN 0 444 90394 1 $0.85 per article per page (transactional system) $0.20 per article per page (licensing system)
ism in the lungs, but occasionally it causes few symptoms (SEDA-1, 352). In a recent case, however, there was hypotension and evidence of disseminated intravascular coagulation with prolonged bleeding from puncture sites. The patient recovered after intensive treatment but developed a barium granuloma in the rectovaginal septum (see SED-10, 850). In-vitro coagulation studies showed that barium sulfate mixed with plasma caused a decrease in coagulation factors, particularly Factor XII. There was also substantial generation of bradykinin. Culture of samples of the barium sulfate used also showed contamination by endotoxin-producing organisms. Endotoxins may have been a significant factor in causing hypotension and disseminated intravascular coagulation (4 c R). Diatrizoate (SED-I O, 851,853; SEDA-8,
426) In a series of 1118 endoscopic retrograde cholangiopancreatographic (ERCP) examinations performed with methylglucamine diatrizoate, acute pancreatitis was an occasional complication; the incidence increased from 0.7% during 1978 and 1979 to 3% in 1980. Analysis showed that the increased incidence was associated with difficulty in opacifying the common bile duct and with multiple injections which opacified the pancreatic duct. Reduction in the number o f injections and use of minimal quantities of contrast medium reduced the incidence of pancreatitis to acceptable levels (5Cr). Significant quantities o f contrast medium may be absorbed after ERCP and even after duodenal instillation o f diatrizoate. Endoscopists must therefore be prepared to treat contrast medium reactions (6).
Inflammatory changes in the colonic mucosa occurred following .prolonged retention of a Hypaque (diatrizoate) enema over a period o f 17 days. Histological examination showed mucosal and submucosal edema, dilated blood vessels and macrophages containing a brown-staining pigment (7 CR) (see also SEDA-3,377).
408 Oral cholecystography (SED-I O, 851) Thrombocytopenic purpura has previously been described following sodium ipodate and iopanoic acid. A further case of severe thrombocytopenia with recovery has now occurred with iocetamic acid (8CR). EXCRETION UROGRAPHY (SED-IO, 854; SEDA-8, 427) Idiosyncratic reactions The blood pressure and pulse rate were monitored in 97 patients undergoing excretion urography with 1.5 ml/kg 60% methylglucamine iothalamate. 51 Patients (53%) had an initial decrease in mean blood pressure. Six of these patients became significantly hypotensive (mean blood pressure < 60 mmHg) but showed no abnormal clinical manifestations other than slowing of the pulse in 2 cases. All 6 patients recovered spontaneously without sequelae and radiographs did not show evidence of 'shock kidneys'. Fifteen patients (15%) showed an initial increase in blood pressure and there was a significantly higher incidence of nausea and vomiting in this group. Some patients showed a byphasic blood pressure response. Thirty-one patients (32%) showed no change in mean blood pressure (9 C R). In 3200 intravenous urograms performed in children using Urografin 76%, the incidence of adverse reactions in 111 'trauma' patients was 13.51%, whereas in the 3089 patients without a history of trauma, the incidence o f reactions was only 4.24% (10cr), indicating that prior trauma should be added to the list of risk situations discussed in SED-10 (pp. 856,857). Agardh et al (11 c R ) describe a program of desensitization used in 12 patients with a previous history of reactions to contrast media. Commencing with an intravenous injection o f 1 ml of 1:100 dilution of contrast medium, 12 injections with gradually increasing doses were administered spaced over a period of 3 days. This appeared to be effective if repeat contrast examination was performed within 5 days, but significant reactions occurred in 2 of 5 patients who had examinations repeated after 5 days. It was suggested that the desensitization program caused successive consumption of complement proteins so that the available level of complement was temporarily too low for a reaction to occur.
Chapter 48
G. Ansell
Aggregation o f granulocytes was found in the pulmonary arterioles in a patient who had a fatal reaction to contrast medium. It is suggested that this leukostasis was due to complement activation (12 c R). In 200 patients undergoing intravenous urography with 100 ml Renografin 60 (methylglucamine diatrizoate) measurements showed raised urinary histamine excretion as compared with controls. Patients with reactions had raised urinary histamine levels similar to those occurring in mild anaphylactic reactions (13CR). In 750 patients undergoing excretion urography with iodamide, urinary excretion of Nt-methylhistamine (a metabolite of histamine) showed an even more significant relationship to contrast media reactions (14Cr). These findings suggest that histamine is produced during contrast medium reactions. The possible value of combined use o f HI- and H2-recept o t antagonists in contrast medium reactions is suggested b y a case-report of a patient with a known previous history o f contrast medium sensitivity who subsequently developed a further reaction to Renografin 76 despite premedication with steroids and diphenhydramine over a period o f 3 days. There was no response to further intravenous steroids and diphenhydramine, but the reaction subsided rapidly after the infusion of 300 mg of cimetidine (15CR). Large doses of contrast media may cause pulmonary edema in patients with incipient cardiac failure (SED-10, 855). In rats, very large intravenous doses of methylglucamine diatrizoate produced transient pulmonary edema, the degree of edema formation being related to the rate of injection and the dose. The effect appeared to represent a chemotoxic action rather than hypertonicity and may be due to increased vascular permeability (16R). Transient increase of extravascular lung water also occurred in dogs following right atrial injection of methylglucamine diatrizoate but did not occur after injection of similar amounts o f the non-ionic-medium iohexol ( 17 R ). Effects o n renal function ISED-IO, 856; SEDA-8, 427) Data continue to accumulate on the effect of contrast medium on renal function, and some recent data throw light on the incidence of such problems and on risk factors. In a retrospective analysis of 400 patients undergoing angiography with large doses of contrast medium (in the region o f 200 ml or more), the overall
Radiological contrast media Chapter48 incidence o f acute renal dysfunction (ARD) was 11.3%. In patients who already had pre-existing renal disease, the incidence was 41.7%, whereas in patients with previously normal renal function ARD occurred in only 8.2% of cases. Several patients in both groups required permanent dialysis. The incidence was higher with abdominal aortography. Other risk factors included congestive heart disease treated with digoxin, contrast medium dose and patient's age. Intravenous hydration did not prevent the onset of ARD (18Cr). In another series of 266 patients undergoing renal angiography, the overall incidence of acute renal dysfunction was 16.9%. Various risk factors were analyzed. The ' o d d s ratio' (increased risk factor) in patients with underlying renal disease was 6.6. Other significant odds ratios were age (1.9), male sex (3.21), contrast medium dose (2.0), multiple examinations (1.9), proteinuria (3.2), hypertension (2.2), vascular disease (2.2). The odds ratio for the use of sodium and methylglucamine containing Renografin 76, in comparison with the pure methylglutamine salt Renografin M76, was also significant, showing an increased risk factor of 2.5 for Renografin 76. Some o f the risk factors were interrelated, but the risk of ARD increased with the number of factors present. Logistic regression was used to construct a clinical model which predicted the probability of developing acute renal dysfunction. Although diabetes has generally been regarded as a risk factor (SED-10, 856), the odds ratio for diabetes (3.0) did not here reach statistical significance, although the number of cases involved was small (19CR). Serial radionuclide studies showed that contrast media affected tubular function more than gomerular function. There was also a relationship with dose and probably with site of injection close to the renal arteries (20 cR). The technique used may also determine the degree of risk. Whereas conventional renal angiography with diatrizoate caused a significant increase in serum creatinine levels and a transient proteinuria, these changes were not noted with digital vascular imaging of the renal arteries using a similar dose of diatrizoate intravenously or when iopamidol was used for conventional angiography (2 lCR). Similarly, renal angiography with metrizoate caused transitory elevation
409 of serum creatinine levels and albuminuria, but this did not occur with iohexol (22CR). Enzymuria following renal angiography was also decreased by iopamidol in comparison with iodamide (23 c R). It therefore appears that the new non-ionic media are likely to be less nephrotoxic than the conventional ionic media. It was formally believed, in the light of work by Berdon and co-workers dating from 1969 (see SED-10, 856), that some cases of contrast medium n e p h r o p a t h y might be explained by precipitation o f Tamm-Horsfall protein in the urine. Recent work has failed to confirm that urographic contrast media precipitate Tamm-Horsfall protein. The cholegraphic medium, ioglycamidr showed some precipitation but only in high concentrations. This mechanism therefore now seems unlikely to play a significant role in contrast media nephrotoxicity (24). Ihle and co-workers described 2 successive episodes of renal failure in an elderly patient following repeated contrast examinations involving sodium ipodate and meglumine iotalamate. Renal biopsy showed an interstitial nephritis and there were eosinophils in the urine but no systemic allergic reaction (25CR). Two cases of acute nephritis and necrotizing vasculitis causing generalized purpuric rashes occurred 1 2 - 2 2 hours after contrast media in patients with malignant disease (26 c R). Hematological complications Symptomless eosinophilia may occur as an incidental finding 48 hours after contrast media examinations and last for approximately 6 days. It is of no clinical significance and should not be confused with other causes of eosinophilia (27 c R) (see also SEDA-2, 374).
ANGIOGRAPHY {SED-1 O, 858; SEDA-8,
428.) Cardioangiography As might have been anticipated from earlier observations (SEDA-8, 428, 430), the low-osmolar contrast medium, ioxaglate, causes fewer subjective symptoms than Renografin 76 or Conray 420 during left ventriculography and also appears to cause fewer hemodynamic changes (28 c R , 29Cr).
410 In animal experiments the hemodynamic effects and prolongation of the PR interval produced by both Renografin 76 and verapamil were additive. The non-ionic medium, iohexol, did not cause these changes and may be preferable for coronary angiography in patients receiving verapamil and other calcium antagonists (30) (see also SEDA-8,429). Injections of contrast medium into the pulmonary artery cause an increase in pulmonary artery pressure. It has generally been assumed (SED-10, 858) that this is due to an increase in pulmonary vascular resistance. It has now been shown in animal experiments that the pulmonary vascular resistance actually falls and that the increased pulmonary artery pressure is due to increased cardiac output, associated with a fall in aortic pressure and peripheral vascular resistance in the systemic circulation, due to peripheral vasodilatation. Iohexol caused fewer hemodynamic changes than conventional contrast media (31). The relevance of these findings to examinations in patients with pre-existing pulmonary hypertension is at present uncertain. Severe hypotensive reactions without electrocardiographic changes occurred following coronary angiography in 2 patients; both had previous histories of reactions requiring cardiopulmonary resuscitation following intravenous urography. The hypotensive reactions responded to 0.4 mg of adrenaline intravenously (32 c R).
Thyroid
function Transient increase in thyrotrophic hormone occurred in infants undergoing cardioangiography, suggesting liberation of free iodine, producing a WolfChalkoff effect on the thyroid gland with resultant transient hypothyroidism. The effect was more marked with ioxaglate (31.4%) than with iopamidol (19.4%) (33CR).
Chapter 48
G. Ansell
toxicity (34CR). Three elderly patients being evaluated for cerebrovascular disease developed confusional states following cerebral arteriography and 2 of these patients became stuporose. There were no localizing neurological signs and recovery ensued (35CR). Since there is no mention of hypotensive changes in these patients, one has to regard this as an increased toxic effect of contrast medium.
Peripheral arteriography In a double-blind trial, iohexol was compared with Conray 60 (methylglucamine iotalamate) in 61 adults undergoing abdominal femoral arteriography. There was considerably less pain in the iohexol group (36CR).
COMPUTED TOMOGRAPHY (SED-I O, 858;
SEDA-8, 429) Hypertonic mannitol has been infused into the carotid or vertebral arteries to open temporarily the b l o o d - b r a i n barrier in cases of cerebral tumor, immediately prior to intra-arterial infusion of methotrexate. This has resulted in significant regression of some cerebral tumors and particularly of lymphomata. The procedure also involves the use of computed tomographic (CT) examinations with intravenous methylglucamine iotalamate to document the degree and extent of b l o o d - b r a i n barrier disruption. The contrast medium used for CT resulted in seizures in 8 of 19 patients. When radionuclide scans were used to document b l o o d - b r a i n barrier disruption, seizures occurred only in 2 of 19 patients, but the radionuclide scans were less sensitive than the contrast CT examinations (37CR).
Cerebral angiography (SED-1 O, 861;
VENOGRAPHY
SEDA-8, 429)
430)
In a double-blind comparison in 100 patients using iohexol and Isopaque cerebral (meglumine metrizoate) there were fewer subjective symptoms of pain in the iohexol group. Three cases of transient neurological change occurred in the iohexol group, but these were thought to be due to thromboembolism rather than to contrast medium
In a series of double-blind studies, the incidence of postphlebographic deep-vein thrombosis was lower with ioxaglate as compared with Urografen 60 (sodium methylglucamine diatrizoate) (38 c R ) and also lower with iopamidol than with meglumine iothalamate (39CR). In a large series, comparing 4 different media, the incidence of
(SED-IO,
862; SEDA-8,
Radiological contrast media Chapter48 pain was lowest with iopamidol (3%), followed by ioxaglate (10%), ioglicinate (23%) and ioxitalamate (37%). The incidence of anaphylactoid reactions was lowest with iopamidol (1%) and highest with ioxagiate (17%). Ioglicinate (7%) and ioxitalamate (10%) gave intermediate results (40 c R). MYELOGRAPHY
Water-soluble media The side effects of metrizamide have been discussed in detail in previous volumes (SEDA-4,335; S E D A - 5 , 4 2 2 ; S E D A - 6 , 4 0 7 ; SEDA-7, 453; SEDA-8, 431). Recent individual case-reports of metrizamide encephalopathy include transient triphasic electroencephalographic discharges (41 cr) and transient cortical blindness due to accidental accumulation of metrizamide in the occipital region during a cervical myelogram (42CR). A more severe recent case involved an accumulation of a concentration of metrizamide in the left temporoparietal and occipital regions. The patient developed a fight-sided Jacksonian seizure 1 hour after the examination with a right hemiplegia and aphasia. There was gradual improvement of the hemiplegia, but there was still slight residual aphasia 6 months later (43cr). A patient with systemic lupus erythematosus (SLE) suffered a transitory exacerbation following metrizamide myelography. Some 12 hours after the myelogram, he developed acute delirium with meningeal irritation and pyrexia. The cerebrospinal fluid was opalecent and xanthochromic with raised protein levels and pleocytosis. There was also exacerbation of the arthralgia and a slight rash. He was treated with antibiotics and prednisolone. The mental state was normal at 48 hours and the arthralgia and rash improved over a period of 3 weeks (44Cr). This case suggests that SLE should perhaps be added to the risk factors in metrizamide myelography. The whole question of risk factors in myelography has been discussed in a recent review of 358 patients undergoing metrizamide myelography. Patients who had no objective clinical signs of neurological involvement and who were subsequently shown to have normal myelograms, suffered more than twice the incidence of side el-
411 fects than patients who had positive clinical findings and positive myelograms. There was also more prolonged hospitalization in the former group. As a general rule, it is clear that myelography should be confined to patients with objective physical findings. Two patients with alcoholism had seizures; alcoholism is regarded as a contraindication to metrizamide myelography (45CR). A series of 120 patients undergoing cervical myelography by direct puncture at the C 1 - 2 level were randomly aUocated to a regime of bed rest for 24 hours or they were fuUy ambulant following the examination. There was no significant difference in the incidence of side effects in the 2 groups (46cr); this suggests that in the average case there is no need for such a long rest period. Very large doses of metrizamide can produce arachnoiditis experimentally in monkeys. No arachnoiditis occurred in animals receiving equivalent doses of iohexol (47); the condition never seems to have been described in m a n with metrizamide (SED-10, 866). The new non-ionic water-soluble media iopamidol (Niopam) and iohexol (Omnipaque) are cheaper than metrizamide and more convenient to use. Several small trials have shown that they are satisfactory myelographic media and there is a general impression that they may have a lower neurotoxicity. In a comparison between iopamidol and metrizamide in 179 patients, the incidence of side effects was lower with iopamidol, but patients who developed symptoms with iopamidol appeared to have a more prolonged course (48Cr). Kendall et al (49 c R ) report a trial of iohexol for myelography in 80 patients and, on the basis of personal observation, they conclude that the incidence and severity of reactions were less than was the case with their experience using metrizamide. There were no electroencephalographic changes with iohexol. Until larger numbers of examinations have been performed in patients with the newer media, it is still too early to assess their lack of neurotoxicity.
Lipiodol A case of eosinophilic meningitis has been reported following myelography with lipiodol. There was a favorable response to cor-
Chapter 48
412 ticosteroid therapy (50Or). It is somewhat surprising to find that lipiodol is still being used for myelography. HYSTEROSALPINGOGRAPHY (SED-I O, 868; SEDA-8, 433J
Contrast media reactions are u n c o m m o n after hysterosalpingography, although hypersensitivity reactions can occur (SED-10, 868). A severe reaction occurred approximately 10 minutes after injection of methylglucamine oxytalamate with polyvidone (Telebrix Hystero). Initially there was giant urticaria; approximately 5 minutes later there was profound cardiovascular collapse with hypotensive shock. Intensive treatment resulted in recovery 24 hours later ~5.1Cr). A randomized comparison using Amipaque (metrizimide, 215 mg I/ml) or Urografin 45 (methylglucamine diatrizoate, 219 mg I/ml) for hysterosalpinography showed no significant difference in the incidence of side effects between the 2 media (52Cr). THOROTRAST
(SED-IO,
869;
SEDA-8,
433j k patient with thorotrastosis identified during a nationwide survey in Japan was
G. Ansell
advised to have 6 monthly follow-up examinations. In December, 1980, the 7-GTP level was elevated, but liver scintigraphy and computed tomography (CT) were negative; 6 months later the 7-GTP level became further elevated. At this time CT showed a low-density, rounded tumor in the liver. The tumor was also shown by scintigraphy and ultrasound. The right lobe of the liver was resected and contained a cholangiocarcinoma. The patient was well 8 months later. This case indicates the potential value of regular screening in patients with thorostratosis to detect the early onset of a tumor (53Cr). In a review of 62 patients with renal tumor following retrograde pyelography with thorotrast, the mean latent period for transitional cell carcinoma was 35.8 years (range 2 5 - 4 7 years). This was significantly longer than the mean latent period for renal carcinoma (27.6 years, range 1 4 - 4 5 years). It has concluded that additional cases of transitional cell carcinoma may be expected to develop (54Cr). A cauda equina lesion occurred 11 years after thorotrast was used to outline a cerebral abscess. A thorotrast residue was visible in the sacral theca. The thorotrast had presumably escaped from the cerebral abscess and sedimented to the sacral region where it caused late fibrosis (5 5Cr).
REFERENCES 1. Von Schneider V, Maxener H (1983) T6dliche Kontrastmittelaspiration bei R6ntgenuntersuchung der oberen Speisewege. Beitr. Gerichtl. Med., XL/, 81. 2. Fischer WW, Nice CM (1984) Barium impaction as a cause of small bowel obstruction in an infant with cystic fibrosis. Pediatr. Radiol., 14, 230. 3. Deixonne B, Baumel H, Mauras Y et al (1983) Un cas de baryto-p~ritoine avec atteinte neurologique: int~r~t du dosage du barium dans les liquides biologiques. J. Chir. (ParisJ, 120, 611. 4. Blom H, Nauta EH, Van Rosevelt RF, Ten Cate JW (1983) Disseminated intravascular coagulation and hypotension after intravasation of barium.Arch. Intern. Med., 143, 1253. 5. Hamilton I, Lintott DJ, Rothwel/ J, Axon ATR (1983) Acute pancreatitis following endoscopic retrograde cholangiopancreatography. Clin. Radiol., 34, 543. 6. Sable RA, Rosenthal WS, Seigle Jet al (1983) Absorption of contrast medium during ERCP.
Dig. Dis. Sci., 28, 801; Radiology, 1984, 151, 819 (Abstract). 7. Creteur V, Douglas D, Galante M, Margulis AR (1983) Inflammatory colonic changes produced by contrast material. Radiology, 147, 77. 8. Insauti CLG, Lechin F, Van der Digs B (1983) Severe thrombocytopenia following oral cholecystography with iocetamic acid. Am J. Hematol., 14, 285. 9. Fischer HW, Katzberg RW, Morris TW, Spataro RF (1984) Systemic response to excretory urography. Radiology, 151, 31. 10. Brinkmann H, Gtinther M (1984) Geh~iuftes Auftreten yon Kontrastmittel-Reaktionen bei Urogrammen nach Unf~llen im Kindesalter. Klin. Pgdiatr., 196, 100. 11. Agardh C-D, Arner B, Ekholm S, Boijsen E (1983) Desensitization as a means of preventing untoward reactions to ionic contrast media. Acta Radiol. DiagrL, 24, 235. 12. Schneiderman H, Hammerschmidt DE, McCall
Radiological contrast media
Chapter 48
AR, Jacob HS (1983) Fatal complement-induced leukostasis after diatrizoate injection: principles of clinicopathologic diagnosis. J. Am. Med. Assoc., 250, 2340. 13. Kaliner M, Dyer J, Merlin S e t al (1984) Increased urine histamine and contrast media reactions, lnvest. Radiol., 19, 116. 14. Keyzer JJ, Uddin~ H, De Vries K (1984) Measurement of Nt-methylhistamine concentrations in urine as a parameter for histamine release by radiographic contrast media. Diagn. Imag. Clin. Med., 53, 67. 15. Myers GE, Bloom FL (1981) Cimetidine (Tagamet) combined with steroids and HI antihistamines for the prevention of serious radiographic contrast material reactions. Catheter. Cardiovasc. Diagn., 7, 65. 16. Mare K, Violante M (1983) Pulmonary edema induced by high intravenous doses of diatrizoate in the rat. Acta Radiol. Diagn., 24, 419. 17. Slutsky RA, Hackney DB, Peck WW, Higgins CB (1983) Extravascular lung water: effects of ionic and nonionic contrast media. Radiology, 149, 375. 18. Martin-Paredero V, Dixon SM, Baker JD et al (1983) Risk of renal failure after major angiography. Arch. Surg., 118, 1417. 19. Cochran ST, Wong WS, Roe DJ (1983) Predicting angiography induced acute renal function impairment: clinical risk model. Am. J. RoentgenoL, 141, 1027. 20. Gates GF, Green GS (1983) Transient reduction in renal function following arteriography: a radionuclide study. J. Urol., 129, 1107. 21. Khoury GA, Hopper JC, Varghese Z et al (1983) Nephrotoxicity of ionic and non-ionic contrast material in digital vascular imaging and selective renal arteriography. Br. J. Radiol., 56, 631. 22. Tornquist C, Holt~is S (1984) Renal angiography with iohexol and metrizoate. Radiology, 150, 331. 23. Mannella P, Tartaranni G, Benea G et al (1983) L'indagine contrastografica renale nel paziente iperteso: confronto della nefrotossicita tra mezzi di contrasto ionici e non ionici. Radiol. Med., 69, 422. 24. Dawson P, Freedman DB, Howell MJ, Hine AL (1984) Contrast medium induced acute renal failure and Tamm-Horsfall proteinuria. Br. J. Radiol., 57, 577. 25. Ihle BU, Byrnes CA, Simenhoff ML (1982) Acute renal failure due to interstitial nephritis from radio contrast agents. Aust. NZ Med., 12, 630. 26. Kerdel FA, Fraker DL, Haynes HA (1984) Necrotising vasculitis from radiographic contrast media. J. Am. Acad. Derrnatol., 10, 25. 27. Pla~si6 B, Zumani6 D, Rotvi6 I (1983) Eosinophilia caused by iodinated radiographic media. Clin. RadioL, 34, 639. 28. Theler A, Baur HR (1983) Haemodynamic
413 changes after angiocardiography with a new low-osmolar contrast medium (sodium-meglumine-ioxaglate) Catheter. Cardiovasc. Diagn., 9, 577. 29. Lyons J, Brooks N, Cattell M et al (1984) Comparison of Hexabrix 320 and Conray 420 for left ventriculography in patients with coronary artery disease. Br. J. RadioL, 57, 209. 30. Higgins CB, Kuber M, Slutsky RA (1983) Interaction between verapamil and contrast media in coronary arteriography: comparison of standard ionic and non-ionic media. Circulation, 68, 628. 31. Peck WW, Slutsky RA, Hackney DB et al (1983) Effects of contrast media on pulmonary hemodynamics: comparison of ionic and nonionic agents. Radiology, 149, 371. 32. Slack JD, Slack LA, Orr C (1982) Recurrent severe reaction to iodinated contrast medium during cardiac catheterisation. Heart Lung, 11, 348. 33. Von Rohner G, Rautenburg HW, H6pfner B (1983) Transiente Hypothyreose bei S,~uglingen nach RiSntgenkontrastmitteln. R6ntgenpraxis, 36, 301. 34. Skalpe IO, Anke IM (1983) Complications in cerebral angiography: a comparison between the non-ionic contrast medium iohexol and meglumine metrizoate (Isopaque cerebral). Neuroradiology, 25, 157. 35. Haley EC (1984) Encephalopathy following arteriography: a possible toxic effect of contrast agents. Ann. Neurol., 15,100. 36. Gordon 13, Skoblar RS, Chicatelli PO, Leon J (1984) A comparison of iohexol and Conray60 in peripheral angiography. Am. J. Roentgenol., 142, 563. 37. Neuwelt EA, Specht HD, Howieson J et al (1983) Osmotic blood-brain barrier modification: clinical documentation by enhanced CT scanning and/or radionuclide brain scannning. Am. J. Roentgenol., 141,829. 38. Eliasen B, H~rup A, Reimer Jensen A (1983) Thrombosis following phlebography with highosmolar and low-osmolar contrast media. Eur. J. Radiol., 3, 97. 39. Lea Thomas M, Keeling FP, Piaggio RB, Treweeke PS (1984) Contrast agent induced thrombophlebitis following leg phlebography: iopamidol versus meglumine iothalamate. Br. J. Radiol., 57, 205. 40. Hagen B (1984) Systemische und lokale Reaktionen bei der Beinphlebographie unter besonderer Beriicksichtigung postphlebographischer Komplikationen: randomisierte, prospektive, intraindividuelle Doppelblindstudie mit jodhaltigen Kontrastmitteln unterschiedlicher Osmolit~t unter Jodkonzentration. t. Mitteilung. Radiologe, 24, 46. 41. Drake M, Erwin CW (1984) Triphasic EEG discharges in metrizamide encephalopathy. J. Neurol. Neurosurg. Psychiatr.. 4 7, 324. 42. Smirniotopoulos JG, Murphy FM, Schellinger
414 D et al (1984) Cortical blindness after metrizamide myelography: report of a case and proposed pathophysiologic mechanism. Arch. Neut.
ol., 41,224. 43. Angiari P, Crisi G, Merci G (1984) Aphasia and right hemiplegia after cervical myelography with metrizamide. Neuroradiology, 26, 6 I. 44. Gelmers HJ (1984) Exacerbation of sytemic lupus erythematosus, aseptic meningitis and acute mental symptoms following metrizamide myelography. Neuroradiology, 26, 65. 45. Herkowitz HN, Romeyn RL, Rothman RH (1983) The indications for metrizamide myelography: relationship with complications after myelography. J. Bone Jt Surg., 65A, 1144. 46. Teasdale E, Macpherson P (1983) Incidence of side effects following direct puncture cervical myelography: bed rest versus mobility. Neuroradiology, 25, 85. 47. Haughton VM, Ho KC, Lipman BT (1982) Experimental study of arachnoiditis from iohexol, an investigational nonionic contrast medium. Am. J. Neuroradiol., 3, 375. 48. Stoddart PGP, Watt I (1983) The symptomatic complications of iopamidol (Niopam) and
Chapter 48
G. Ansell
metrizamide (Amipaque) following lumbar radiculography. Br. J. Radiol., 57, 349. 49. Kendall B, Schneidan A, Stevens J, Harrison M (1983) Clinical trial of iohexol for lumbar myelography. Br. J. RadioL, 56, 534. 50. Marte-Masso JF, Y Carrera N, Zabalda R (1983) Meningitis eosinofilica por mielografia con lipiodol. Med. Clin. (Barcelona), 81,440. 51. Capdeville R, R6my J (1983) Un accident major d'hysterosalpingographie. J. Radiol., 64, 561. 52. Cold AS, Hansen KF, Pederson PR, Peterson J (1983) Biviskiner af urografin og amipaque red hysterosalpingographie: en randomiseret prospective undersogelse. Ugeskr. Laeg.; 145, 1304. 53. Kiyosawa K, Akahane Y, Sato K et al (1983) Resection of thorotrast-induced cholangiocarcinoma. Am. Z Gastroenterol., 78, 429. 54. Christensen P, Madsen MR, Jensen OM (1983) Latency of thorotrast-induced renal tumours: survey of literature and case report. Scand. J. Urol. Nephrol., 17, 127. 55. Freilich D (1983) Cauda equina lesion due to thorotrast. Aust. NZ Med., 13, 283.
48
Radiological contrast media
ALIMENTARY TRACT Barium sulfate (SED-I O, 850; SEDA-8, 426) A fatal case of aspiration pneumonia occurred in an 81-year-old female who inhaled approximately 1 5 - 2 0 ml of barium sulfate suspension into the left lower lobe. Pyrexia developed after 45 minutes, the patient became comatose, developed circulatory collapse and death occurred at 32 hours ( 1 c ~ ) . This is a rare complication, but a fatal case has been reported previously after blockage of the trachea b y barium paste (SEDA-2,373). In another unusual complication reported recently, oral barium impacted in the small bowel for several days in an infant with cystic fibrosis. The obstruction was relieved by an enema of 30% Hypaque (2Cr). It has been suggested that barium encephalopathy may result after prolonged stasis o f barium in the bowel (SEDA-6,404). Another possible case has now been reported after intraperitoneal rupture o f a barium enema. Myoclonic changes and mental deterioration occurred after 16 days and the patient died 8 weeks after the perforation. Two samples of cerebrospinal fluid obtained by lumbar puncture shortly before death contained 180 and 160 #g/1 of barium respectively. Although contamination could not be entirely excluded, this was thought to be unlikely (3Cr). It will be recalled that in SEDA-8 (p. 426) other instances o f perforation were discussed and one of mental changes in a neonate with barium peritonitis. Accidental venous intravasation of barium during a barium enema usually has a high immediate mortality due to barium embol-
Side Effects of Drugs Annual 9 M.N.G. Dukes, editor 9 Elsevier Science Publishers B.V., 1985 ISBN 0 444 90394 1 $0.85 per article per page (transactional system) $0.20 per article per page (licensing system)
ism in the lungs, but occasionally it causes few symptoms (SEDA-1, 352). In a recent case, however, there was hypotension and evidence of disseminated intravascular coagulation with prolonged bleeding from puncture sites. The patient recovered after intensive treatment but developed a barium granuloma in the rectovaginal septum (see SED-10, 850). In-vitro coagulation studies showed that barium sulfate mixed with plasma caused a decrease in coagulation factors, particularly Factor XII. There was also substantial generation of bradykinin. Culture of samples of the barium sulfate used also showed contamination by endotoxin-producing organisms. Endotoxins may have been a significant factor in causing hypotension and disseminated intravascular coagulation (4 c R). Diatrizoate (SED-I O, 851,853; SEDA-8,
426) In a series of 1118 endoscopic retrograde cholangiopancreatographic (ERCP) examinations performed with methylglucamine diatrizoate, acute pancreatitis was an occasional complication; the incidence increased from 0.7% during 1978 and 1979 to 3% in 1980. Analysis showed that the increased incidence was associated with difficulty in opacifying the common bile duct and with multiple injections which opacified the pancreatic duct. Reduction in the number o f injections and use of minimal quantities of contrast medium reduced the incidence of pancreatitis to acceptable levels (5Cr). Significant quantities o f contrast medium may be absorbed after ERCP and even after duodenal instillation o f diatrizoate. Endoscopists must therefore be prepared to treat contrast medium reactions (6).
Inflammatory changes in the colonic mucosa occurred following .prolonged retention of a Hypaque (diatrizoate) enema over a period o f 17 days. Histological examination showed mucosal and submucosal edema, dilated blood vessels and macrophages containing a brown-staining pigment (7 CR) (see also SEDA-3,377).
408 Oral cholecystography (SED-I O, 851) Thrombocytopenic purpura has previously been described following sodium ipodate and iopanoic acid. A further case of severe thrombocytopenia with recovery has now occurred with iocetamic acid (8CR). EXCRETION UROGRAPHY (SED-IO, 854; SEDA-8, 427) Idiosyncratic reactions The blood pressure and pulse rate were monitored in 97 patients undergoing excretion urography with 1.5 ml/kg 60% methylglucamine iothalamate. 51 Patients (53%) had an initial decrease in mean blood pressure. Six of these patients became significantly hypotensive (mean blood pressure < 60 mmHg) but showed no abnormal clinical manifestations other than slowing of the pulse in 2 cases. All 6 patients recovered spontaneously without sequelae and radiographs did not show evidence of 'shock kidneys'. Fifteen patients (15%) showed an initial increase in blood pressure and there was a significantly higher incidence of nausea and vomiting in this group. Some patients showed a byphasic blood pressure response. Thirty-one patients (32%) showed no change in mean blood pressure (9 C R). In 3200 intravenous urograms performed in children using Urografin 76%, the incidence of adverse reactions in 111 'trauma' patients was 13.51%, whereas in the 3089 patients without a history of trauma, the incidence o f reactions was only 4.24% (10cr), indicating that prior trauma should be added to the list of risk situations discussed in SED-10 (pp. 856,857). Agardh et al (11 c R ) describe a program of desensitization used in 12 patients with a previous history of reactions to contrast media. Commencing with an intravenous injection o f 1 ml of 1:100 dilution of contrast medium, 12 injections with gradually increasing doses were administered spaced over a period of 3 days. This appeared to be effective if repeat contrast examination was performed within 5 days, but significant reactions occurred in 2 of 5 patients who had examinations repeated after 5 days. It was suggested that the desensitization program caused successive consumption of complement proteins so that the available level of complement was temporarily too low for a reaction to occur.
Chapter 48
G. Ansell
Aggregation o f granulocytes was found in the pulmonary arterioles in a patient who had a fatal reaction to contrast medium. It is suggested that this leukostasis was due to complement activation (12 c R). In 200 patients undergoing intravenous urography with 100 ml Renografin 60 (methylglucamine diatrizoate) measurements showed raised urinary histamine excretion as compared with controls. Patients with reactions had raised urinary histamine levels similar to those occurring in mild anaphylactic reactions (13CR). In 750 patients undergoing excretion urography with iodamide, urinary excretion of Nt-methylhistamine (a metabolite of histamine) showed an even more significant relationship to contrast media reactions (14Cr). These findings suggest that histamine is produced during contrast medium reactions. The possible value of combined use o f HI- and H2-recept o t antagonists in contrast medium reactions is suggested b y a case-report of a patient with a known previous history o f contrast medium sensitivity who subsequently developed a further reaction to Renografin 76 despite premedication with steroids and diphenhydramine over a period o f 3 days. There was no response to further intravenous steroids and diphenhydramine, but the reaction subsided rapidly after the infusion of 300 mg of cimetidine (15CR). Large doses of contrast media may cause pulmonary edema in patients with incipient cardiac failure (SED-10, 855). In rats, very large intravenous doses of methylglucamine diatrizoate produced transient pulmonary edema, the degree of edema formation being related to the rate of injection and the dose. The effect appeared to represent a chemotoxic action rather than hypertonicity and may be due to increased vascular permeability (16R). Transient increase of extravascular lung water also occurred in dogs following right atrial injection of methylglucamine diatrizoate but did not occur after injection of similar amounts o f the non-ionic-medium iohexol ( 17 R ). Effects o n renal function ISED-IO, 856; SEDA-8, 427) Data continue to accumulate on the effect of contrast medium on renal function, and some recent data throw light on the incidence of such problems and on risk factors. In a retrospective analysis of 400 patients undergoing angiography with large doses of contrast medium (in the region o f 200 ml or more), the overall
Radiological contrast media Chapter48 incidence o f acute renal dysfunction (ARD) was 11.3%. In patients who already had pre-existing renal disease, the incidence was 41.7%, whereas in patients with previously normal renal function ARD occurred in only 8.2% of cases. Several patients in both groups required permanent dialysis. The incidence was higher with abdominal aortography. Other risk factors included congestive heart disease treated with digoxin, contrast medium dose and patient's age. Intravenous hydration did not prevent the onset of ARD (18Cr). In another series of 266 patients undergoing renal angiography, the overall incidence of acute renal dysfunction was 16.9%. Various risk factors were analyzed. The ' o d d s ratio' (increased risk factor) in patients with underlying renal disease was 6.6. Other significant odds ratios were age (1.9), male sex (3.21), contrast medium dose (2.0), multiple examinations (1.9), proteinuria (3.2), hypertension (2.2), vascular disease (2.2). The odds ratio for the use of sodium and methylglucamine containing Renografin 76, in comparison with the pure methylglutamine salt Renografin M76, was also significant, showing an increased risk factor of 2.5 for Renografin 76. Some o f the risk factors were interrelated, but the risk of ARD increased with the number of factors present. Logistic regression was used to construct a clinical model which predicted the probability of developing acute renal dysfunction. Although diabetes has generally been regarded as a risk factor (SED-10, 856), the odds ratio for diabetes (3.0) did not here reach statistical significance, although the number of cases involved was small (19CR). Serial radionuclide studies showed that contrast media affected tubular function more than gomerular function. There was also a relationship with dose and probably with site of injection close to the renal arteries (20 cR). The technique used may also determine the degree of risk. Whereas conventional renal angiography with diatrizoate caused a significant increase in serum creatinine levels and a transient proteinuria, these changes were not noted with digital vascular imaging of the renal arteries using a similar dose of diatrizoate intravenously or when iopamidol was used for conventional angiography (2 lCR). Similarly, renal angiography with metrizoate caused transitory elevation
409 of serum creatinine levels and albuminuria, but this did not occur with iohexol (22CR). Enzymuria following renal angiography was also decreased by iopamidol in comparison with iodamide (23 c R). It therefore appears that the new non-ionic media are likely to be less nephrotoxic than the conventional ionic media. It was formally believed, in the light of work by Berdon and co-workers dating from 1969 (see SED-10, 856), that some cases of contrast medium n e p h r o p a t h y might be explained by precipitation o f Tamm-Horsfall protein in the urine. Recent work has failed to confirm that urographic contrast media precipitate Tamm-Horsfall protein. The cholegraphic medium, ioglycamidr showed some precipitation but only in high concentrations. This mechanism therefore now seems unlikely to play a significant role in contrast media nephrotoxicity (24). Ihle and co-workers described 2 successive episodes of renal failure in an elderly patient following repeated contrast examinations involving sodium ipodate and meglumine iotalamate. Renal biopsy showed an interstitial nephritis and there were eosinophils in the urine but no systemic allergic reaction (25CR). Two cases of acute nephritis and necrotizing vasculitis causing generalized purpuric rashes occurred 1 2 - 2 2 hours after contrast media in patients with malignant disease (26 c R). Hematological complications Symptomless eosinophilia may occur as an incidental finding 48 hours after contrast media examinations and last for approximately 6 days. It is of no clinical significance and should not be confused with other causes of eosinophilia (27 c R) (see also SEDA-2, 374).
ANGIOGRAPHY {SED-1 O, 858; SEDA-8,
428.) Cardioangiography As might have been anticipated from earlier observations (SEDA-8, 428, 430), the low-osmolar contrast medium, ioxaglate, causes fewer subjective symptoms than Renografin 76 or Conray 420 during left ventriculography and also appears to cause fewer hemodynamic changes (28 c R , 29Cr).
410 In animal experiments the hemodynamic effects and prolongation of the PR interval produced by both Renografin 76 and verapamil were additive. The non-ionic medium, iohexol, did not cause these changes and may be preferable for coronary angiography in patients receiving verapamil and other calcium antagonists (30) (see also SEDA-8,429). Injections of contrast medium into the pulmonary artery cause an increase in pulmonary artery pressure. It has generally been assumed (SED-10, 858) that this is due to an increase in pulmonary vascular resistance. It has now been shown in animal experiments that the pulmonary vascular resistance actually falls and that the increased pulmonary artery pressure is due to increased cardiac output, associated with a fall in aortic pressure and peripheral vascular resistance in the systemic circulation, due to peripheral vasodilatation. Iohexol caused fewer hemodynamic changes than conventional contrast media (31). The relevance of these findings to examinations in patients with pre-existing pulmonary hypertension is at present uncertain. Severe hypotensive reactions without electrocardiographic changes occurred following coronary angiography in 2 patients; both had previous histories of reactions requiring cardiopulmonary resuscitation following intravenous urography. The hypotensive reactions responded to 0.4 mg of adrenaline intravenously (32 c R).
Thyroid
function Transient increase in thyrotrophic hormone occurred in infants undergoing cardioangiography, suggesting liberation of free iodine, producing a WolfChalkoff effect on the thyroid gland with resultant transient hypothyroidism. The effect was more marked with ioxaglate (31.4%) than with iopamidol (19.4%) (33CR).
Chapter 48
G. Ansell
toxicity (34CR). Three elderly patients being evaluated for cerebrovascular disease developed confusional states following cerebral arteriography and 2 of these patients became stuporose. There were no localizing neurological signs and recovery ensued (35CR). Since there is no mention of hypotensive changes in these patients, one has to regard this as an increased toxic effect of contrast medium.
Peripheral arteriography In a double-blind trial, iohexol was compared with Conray 60 (methylglucamine iotalamate) in 61 adults undergoing abdominal femoral arteriography. There was considerably less pain in the iohexol group (36CR).
COMPUTED TOMOGRAPHY (SED-I O, 858;
SEDA-8, 429) Hypertonic mannitol has been infused into the carotid or vertebral arteries to open temporarily the b l o o d - b r a i n barrier in cases of cerebral tumor, immediately prior to intra-arterial infusion of methotrexate. This has resulted in significant regression of some cerebral tumors and particularly of lymphomata. The procedure also involves the use of computed tomographic (CT) examinations with intravenous methylglucamine iotalamate to document the degree and extent of b l o o d - b r a i n barrier disruption. The contrast medium used for CT resulted in seizures in 8 of 19 patients. When radionuclide scans were used to document b l o o d - b r a i n barrier disruption, seizures occurred only in 2 of 19 patients, but the radionuclide scans were less sensitive than the contrast CT examinations (37CR).
Cerebral angiography (SED-1 O, 861;
VENOGRAPHY
SEDA-8, 429)
430)
In a double-blind comparison in 100 patients using iohexol and Isopaque cerebral (meglumine metrizoate) there were fewer subjective symptoms of pain in the iohexol group. Three cases of transient neurological change occurred in the iohexol group, but these were thought to be due to thromboembolism rather than to contrast medium
In a series of double-blind studies, the incidence of postphlebographic deep-vein thrombosis was lower with ioxaglate as compared with Urografen 60 (sodium methylglucamine diatrizoate) (38 c R ) and also lower with iopamidol than with meglumine iothalamate (39CR). In a large series, comparing 4 different media, the incidence of
(SED-IO,
862; SEDA-8,
Radiological contrast media Chapter48 pain was lowest with iopamidol (3%), followed by ioxaglate (10%), ioglicinate (23%) and ioxitalamate (37%). The incidence of anaphylactoid reactions was lowest with iopamidol (1%) and highest with ioxagiate (17%). Ioglicinate (7%) and ioxitalamate (10%) gave intermediate results (40 c R). MYELOGRAPHY
Water-soluble media The side effects of metrizamide have been discussed in detail in previous volumes (SEDA-4,335; S E D A - 5 , 4 2 2 ; S E D A - 6 , 4 0 7 ; SEDA-7, 453; SEDA-8, 431). Recent individual case-reports of metrizamide encephalopathy include transient triphasic electroencephalographic discharges (41 cr) and transient cortical blindness due to accidental accumulation of metrizamide in the occipital region during a cervical myelogram (42CR). A more severe recent case involved an accumulation of a concentration of metrizamide in the left temporoparietal and occipital regions. The patient developed a fight-sided Jacksonian seizure 1 hour after the examination with a right hemiplegia and aphasia. There was gradual improvement of the hemiplegia, but there was still slight residual aphasia 6 months later (43cr). A patient with systemic lupus erythematosus (SLE) suffered a transitory exacerbation following metrizamide myelography. Some 12 hours after the myelogram, he developed acute delirium with meningeal irritation and pyrexia. The cerebrospinal fluid was opalecent and xanthochromic with raised protein levels and pleocytosis. There was also exacerbation of the arthralgia and a slight rash. He was treated with antibiotics and prednisolone. The mental state was normal at 48 hours and the arthralgia and rash improved over a period of 3 weeks (44Cr). This case suggests that SLE should perhaps be added to the risk factors in metrizamide myelography. The whole question of risk factors in myelography has been discussed in a recent review of 358 patients undergoing metrizamide myelography. Patients who had no objective clinical signs of neurological involvement and who were subsequently shown to have normal myelograms, suffered more than twice the incidence of side el-
411 fects than patients who had positive clinical findings and positive myelograms. There was also more prolonged hospitalization in the former group. As a general rule, it is clear that myelography should be confined to patients with objective physical findings. Two patients with alcoholism had seizures; alcoholism is regarded as a contraindication to metrizamide myelography (45CR). A series of 120 patients undergoing cervical myelography by direct puncture at the C 1 - 2 level were randomly aUocated to a regime of bed rest for 24 hours or they were fuUy ambulant following the examination. There was no significant difference in the incidence of side effects in the 2 groups (46cr); this suggests that in the average case there is no need for such a long rest period. Very large doses of metrizamide can produce arachnoiditis experimentally in monkeys. No arachnoiditis occurred in animals receiving equivalent doses of iohexol (47); the condition never seems to have been described in m a n with metrizamide (SED-10, 866). The new non-ionic water-soluble media iopamidol (Niopam) and iohexol (Omnipaque) are cheaper than metrizamide and more convenient to use. Several small trials have shown that they are satisfactory myelographic media and there is a general impression that they may have a lower neurotoxicity. In a comparison between iopamidol and metrizamide in 179 patients, the incidence of side effects was lower with iopamidol, but patients who developed symptoms with iopamidol appeared to have a more prolonged course (48Cr). Kendall et al (49 c R ) report a trial of iohexol for myelography in 80 patients and, on the basis of personal observation, they conclude that the incidence and severity of reactions were less than was the case with their experience using metrizamide. There were no electroencephalographic changes with iohexol. Until larger numbers of examinations have been performed in patients with the newer media, it is still too early to assess their lack of neurotoxicity.
Lipiodol A case of eosinophilic meningitis has been reported following myelography with lipiodol. There was a favorable response to cor-
Chapter 48
412 ticosteroid therapy (50Or). It is somewhat surprising to find that lipiodol is still being used for myelography. HYSTEROSALPINGOGRAPHY (SED-I O, 868; SEDA-8, 433J
Contrast media reactions are u n c o m m o n after hysterosalpingography, although hypersensitivity reactions can occur (SED-10, 868). A severe reaction occurred approximately 10 minutes after injection of methylglucamine oxytalamate with polyvidone (Telebrix Hystero). Initially there was giant urticaria; approximately 5 minutes later there was profound cardiovascular collapse with hypotensive shock. Intensive treatment resulted in recovery 24 hours later ~5.1Cr). A randomized comparison using Amipaque (metrizimide, 215 mg I/ml) or Urografin 45 (methylglucamine diatrizoate, 219 mg I/ml) for hysterosalpinography showed no significant difference in the incidence of side effects between the 2 media (52Cr). THOROTRAST
(SED-IO,
869;
SEDA-8,
433j k patient with thorotrastosis identified during a nationwide survey in Japan was
G. Ansell
advised to have 6 monthly follow-up examinations. In December, 1980, the 7-GTP level was elevated, but liver scintigraphy and computed tomography (CT) were negative; 6 months later the 7-GTP level became further elevated. At this time CT showed a low-density, rounded tumor in the liver. The tumor was also shown by scintigraphy and ultrasound. The right lobe of the liver was resected and contained a cholangiocarcinoma. The patient was well 8 months later. This case indicates the potential value of regular screening in patients with thorostratosis to detect the early onset of a tumor (53Cr). In a review of 62 patients with renal tumor following retrograde pyelography with thorotrast, the mean latent period for transitional cell carcinoma was 35.8 years (range 2 5 - 4 7 years). This was significantly longer than the mean latent period for renal carcinoma (27.6 years, range 1 4 - 4 5 years). It has concluded that additional cases of transitional cell carcinoma may be expected to develop (54Cr). A cauda equina lesion occurred 11 years after thorotrast was used to outline a cerebral abscess. A thorotrast residue was visible in the sacral theca. The thorotrast had presumably escaped from the cerebral abscess and sedimented to the sacral region where it caused late fibrosis (5 5Cr).
REFERENCES 1. Von Schneider V, Maxener H (1983) T6dliche Kontrastmittelaspiration bei R6ntgenuntersuchung der oberen Speisewege. Beitr. Gerichtl. Med., XL/, 81. 2. Fischer WW, Nice CM (1984) Barium impaction as a cause of small bowel obstruction in an infant with cystic fibrosis. Pediatr. Radiol., 14, 230. 3. Deixonne B, Baumel H, Mauras Y et al (1983) Un cas de baryto-p~ritoine avec atteinte neurologique: int~r~t du dosage du barium dans les liquides biologiques. J. Chir. (ParisJ, 120, 611. 4. Blom H, Nauta EH, Van Rosevelt RF, Ten Cate JW (1983) Disseminated intravascular coagulation and hypotension after intravasation of barium.Arch. Intern. Med., 143, 1253. 5. Hamilton I, Lintott DJ, Rothwel/ J, Axon ATR (1983) Acute pancreatitis following endoscopic retrograde cholangiopancreatography. Clin. Radiol., 34, 543. 6. Sable RA, Rosenthal WS, Seigle Jet al (1983) Absorption of contrast medium during ERCP.
Dig. Dis. Sci., 28, 801; Radiology, 1984, 151, 819 (Abstract). 7. Creteur V, Douglas D, Galante M, Margulis AR (1983) Inflammatory colonic changes produced by contrast material. Radiology, 147, 77. 8. Insauti CLG, Lechin F, Van der Digs B (1983) Severe thrombocytopenia following oral cholecystography with iocetamic acid. Am J. Hematol., 14, 285. 9. Fischer HW, Katzberg RW, Morris TW, Spataro RF (1984) Systemic response to excretory urography. Radiology, 151, 31. 10. Brinkmann H, Gtinther M (1984) Geh~iuftes Auftreten yon Kontrastmittel-Reaktionen bei Urogrammen nach Unf~llen im Kindesalter. Klin. Pgdiatr., 196, 100. 11. Agardh C-D, Arner B, Ekholm S, Boijsen E (1983) Desensitization as a means of preventing untoward reactions to ionic contrast media. Acta Radiol. DiagrL, 24, 235. 12. Schneiderman H, Hammerschmidt DE, McCall
Radiological contrast media
Chapter 48
AR, Jacob HS (1983) Fatal complement-induced leukostasis after diatrizoate injection: principles of clinicopathologic diagnosis. J. Am. Med. Assoc., 250, 2340. 13. Kaliner M, Dyer J, Merlin S e t al (1984) Increased urine histamine and contrast media reactions, lnvest. Radiol., 19, 116. 14. Keyzer JJ, Uddin~ H, De Vries K (1984) Measurement of Nt-methylhistamine concentrations in urine as a parameter for histamine release by radiographic contrast media. Diagn. Imag. Clin. Med., 53, 67. 15. Myers GE, Bloom FL (1981) Cimetidine (Tagamet) combined with steroids and HI antihistamines for the prevention of serious radiographic contrast material reactions. Catheter. Cardiovasc. Diagn., 7, 65. 16. Mare K, Violante M (1983) Pulmonary edema induced by high intravenous doses of diatrizoate in the rat. Acta Radiol. Diagn., 24, 419. 17. Slutsky RA, Hackney DB, Peck WW, Higgins CB (1983) Extravascular lung water: effects of ionic and nonionic contrast media. Radiology, 149, 375. 18. Martin-Paredero V, Dixon SM, Baker JD et al (1983) Risk of renal failure after major angiography. Arch. Surg., 118, 1417. 19. Cochran ST, Wong WS, Roe DJ (1983) Predicting angiography induced acute renal function impairment: clinical risk model. Am. J. RoentgenoL, 141, 1027. 20. Gates GF, Green GS (1983) Transient reduction in renal function following arteriography: a radionuclide study. J. Urol., 129, 1107. 21. Khoury GA, Hopper JC, Varghese Z et al (1983) Nephrotoxicity of ionic and non-ionic contrast material in digital vascular imaging and selective renal arteriography. Br. J. Radiol., 56, 631. 22. Tornquist C, Holt~is S (1984) Renal angiography with iohexol and metrizoate. Radiology, 150, 331. 23. Mannella P, Tartaranni G, Benea G et al (1983) L'indagine contrastografica renale nel paziente iperteso: confronto della nefrotossicita tra mezzi di contrasto ionici e non ionici. Radiol. Med., 69, 422. 24. Dawson P, Freedman DB, Howell MJ, Hine AL (1984) Contrast medium induced acute renal failure and Tamm-Horsfall proteinuria. Br. J. Radiol., 57, 577. 25. Ihle BU, Byrnes CA, Simenhoff ML (1982) Acute renal failure due to interstitial nephritis from radio contrast agents. Aust. NZ Med., 12, 630. 26. Kerdel FA, Fraker DL, Haynes HA (1984) Necrotising vasculitis from radiographic contrast media. J. Am. Acad. Derrnatol., 10, 25. 27. Pla~si6 B, Zumani6 D, Rotvi6 I (1983) Eosinophilia caused by iodinated radiographic media. Clin. RadioL, 34, 639. 28. Theler A, Baur HR (1983) Haemodynamic
413 changes after angiocardiography with a new low-osmolar contrast medium (sodium-meglumine-ioxaglate) Catheter. Cardiovasc. Diagn., 9, 577. 29. Lyons J, Brooks N, Cattell M et al (1984) Comparison of Hexabrix 320 and Conray 420 for left ventriculography in patients with coronary artery disease. Br. J. RadioL, 57, 209. 30. Higgins CB, Kuber M, Slutsky RA (1983) Interaction between verapamil and contrast media in coronary arteriography: comparison of standard ionic and non-ionic media. Circulation, 68, 628. 31. Peck WW, Slutsky RA, Hackney DB et al (1983) Effects of contrast media on pulmonary hemodynamics: comparison of ionic and nonionic agents. Radiology, 149, 371. 32. Slack JD, Slack LA, Orr C (1982) Recurrent severe reaction to iodinated contrast medium during cardiac catheterisation. Heart Lung, 11, 348. 33. Von Rohner G, Rautenburg HW, H6pfner B (1983) Transiente Hypothyreose bei S,~uglingen nach RiSntgenkontrastmitteln. R6ntgenpraxis, 36, 301. 34. Skalpe IO, Anke IM (1983) Complications in cerebral angiography: a comparison between the non-ionic contrast medium iohexol and meglumine metrizoate (Isopaque cerebral). Neuroradiology, 25, 157. 35. Haley EC (1984) Encephalopathy following arteriography: a possible toxic effect of contrast agents. Ann. Neurol., 15,100. 36. Gordon 13, Skoblar RS, Chicatelli PO, Leon J (1984) A comparison of iohexol and Conray60 in peripheral angiography. Am. J. Roentgenol., 142, 563. 37. Neuwelt EA, Specht HD, Howieson J et al (1983) Osmotic blood-brain barrier modification: clinical documentation by enhanced CT scanning and/or radionuclide brain scannning. Am. J. Roentgenol., 141,829. 38. Eliasen B, H~rup A, Reimer Jensen A (1983) Thrombosis following phlebography with highosmolar and low-osmolar contrast media. Eur. J. Radiol., 3, 97. 39. Lea Thomas M, Keeling FP, Piaggio RB, Treweeke PS (1984) Contrast agent induced thrombophlebitis following leg phlebography: iopamidol versus meglumine iothalamate. Br. J. Radiol., 57, 205. 40. Hagen B (1984) Systemische und lokale Reaktionen bei der Beinphlebographie unter besonderer Beriicksichtigung postphlebographischer Komplikationen: randomisierte, prospektive, intraindividuelle Doppelblindstudie mit jodhaltigen Kontrastmitteln unterschiedlicher Osmolit~t unter Jodkonzentration. t. Mitteilung. Radiologe, 24, 46. 41. Drake M, Erwin CW (1984) Triphasic EEG discharges in metrizamide encephalopathy. J. Neurol. Neurosurg. Psychiatr.. 4 7, 324. 42. Smirniotopoulos JG, Murphy FM, Schellinger
414 D et al (1984) Cortical blindness after metrizamide myelography: report of a case and proposed pathophysiologic mechanism. Arch. Neut.
ol., 41,224. 43. Angiari P, Crisi G, Merci G (1984) Aphasia and right hemiplegia after cervical myelography with metrizamide. Neuroradiology, 26, 6 I. 44. Gelmers HJ (1984) Exacerbation of sytemic lupus erythematosus, aseptic meningitis and acute mental symptoms following metrizamide myelography. Neuroradiology, 26, 65. 45. Herkowitz HN, Romeyn RL, Rothman RH (1983) The indications for metrizamide myelography: relationship with complications after myelography. J. Bone Jt Surg., 65A, 1144. 46. Teasdale E, Macpherson P (1983) Incidence of side effects following direct puncture cervical myelography: bed rest versus mobility. Neuroradiology, 25, 85. 47. Haughton VM, Ho KC, Lipman BT (1982) Experimental study of arachnoiditis from iohexol, an investigational nonionic contrast medium. Am. J. Neuroradiol., 3, 375. 48. Stoddart PGP, Watt I (1983) The symptomatic complications of iopamidol (Niopam) and
Chapter 48
G. Ansell
metrizamide (Amipaque) following lumbar radiculography. Br. J. Radiol., 57, 349. 49. Kendall B, Schneidan A, Stevens J, Harrison M (1983) Clinical trial of iohexol for lumbar myelography. Br. J. RadioL, 56, 534. 50. Marte-Masso JF, Y Carrera N, Zabalda R (1983) Meningitis eosinofilica por mielografia con lipiodol. Med. Clin. (Barcelona), 81,440. 51. Capdeville R, R6my J (1983) Un accident major d'hysterosalpingographie. J. Radiol., 64, 561. 52. Cold AS, Hansen KF, Pederson PR, Peterson J (1983) Biviskiner af urografin og amipaque red hysterosalpingographie: en randomiseret prospective undersogelse. Ugeskr. Laeg.; 145, 1304. 53. Kiyosawa K, Akahane Y, Sato K et al (1983) Resection of thorotrast-induced cholangiocarcinoma. Am. Z Gastroenterol., 78, 429. 54. Christensen P, Madsen MR, Jensen OM (1983) Latency of thorotrast-induced renal tumours: survey of literature and case report. Scand. J. Urol. Nephrol., 17, 127. 55. Freilich D (1983) Cauda equina lesion due to thorotrast. Aust. NZ Med., 13, 283.