Contrast Media in Practice
Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong
Kong Barcelona Budapest
Dr. Peter Dawson Department of Radiology Hammersmith Hospital
Ducane Road, London W12 OHS United Kingdom
Dr. Wolfram ClauB Schering AG, Klinische Entwicklung Diagnostika
Miillerstr. 170 -178 13353 Berlin
ISBN-13: 978-3-540-57187-2 e-ISBN-13: 978-3-642-97530-1 DOl:
10.1007/978-3-642-97530-1
Library of Congress Cataloging-in-Publication Data
Contrast media in practice / P. Dawson. W. Clauss, (hrsg.) p.
cm.
1. Contrast media. I. Dawson, Peter H. II. Clauss, W. (Wolfram),
1940- RC78.7.C65C665 1993 616.0T54--dc20
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© Springer-Verlag Berlin Heidelberg 1993
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Contents
1 General Fundamentals
1.1 A Historical Overview of the Development of Contrast Media for
Diagnostic Imaging Procedures in Radiology H. J. Maurer and W.
Clauj3 . . . . . . . . . . . . . . . . . .. 1
1.2 Chemistry of X-Ray Contrast Media T. Gulbrandsen ..........
.
1.3 Structure - Toxicity Relationships and Molecule Design P.
Dawson ." ...................... .
1.4 Results of Toxicological Tests Assessing the Risk of Nonionic
Contrast Media in Humans
6
11
1.5 Physicochemical Properties of Contrast Media: Osmotic Pressure,
Viscosity, Solubility, Lipophilicity, Hydrophilicity, Electrical
Charge U. Speck . ...................... .
1.6 Pharmacokinetics of Contrast Media W. Krause and G.
Schuhmann-Gampieri
1.7 Clinical Documentation of the Tolerance, Safety and Efficacy of
X-Ray Contrast Media
20
26
E. Andrew, W. Clauj3, A. Alhassan and H. P. Bohn . . . .. 34
2 Pharmaceutical Quality and Stability of Contrast Media
2.1 What Are the Steps in the Production of Contrast Media? B.
Wolden . . . . . . . . . . . . . . . . . . . . . . . 39
2.2 Which Chemical Degradation Products Are Formed? D. Herrmann
39
VI Contents
2.3 What Additives Do Contrast Media Formulations Contain? B.
Wolden . . . . . . . . . . . . . . . . . . . . . . . . . 40
2.4 What Is the Importance of Additives in Contrast Medium
Formulations? P. Dawson. . . . . . . . . . . . . . . . . . . . . .
. . . 41
2.5 How Is the Sterility or Microbial Purity of Contrast Media
Checked? B. Wolden . . . . . . . . . . . . . . . . . . . . . . . .
. . 42
2.6 How Is the Chemical Stability of Contrast Media Checked? B.
Wolden . . . . . . . . . . . . . . . . . . . . . . . . . . 42
2.7 How Are Contrast Media Checked for Freedom from Pyrogens? B.
Wolden . . . . . . . . . . . . . . . . . . . . . . . . . . ..
43
2.8 To What Are Colour Changes of Contrast Media
Attributable?
2.9
D. Herrmann and B. Wolden .....
Does Particulate Contamination Occur, and How Important Is It? B.
Wolden .............. .
2.10 Which Factors Reduce the Stability of Contrast Media, and What
Are the Implications of Storage Recommendations? D. Herrmann
2.11 What Precautions Are Necessary in Drawing Up Contrast Media
into Syringes and in Administering Them Using Infusion Devices? D.
Herrmann
2.12 How Long Do Contrast Media Remain Usable After the Original
Container Has Been Opened? D. Herrmann
2.13 May Contrast Media Be Diluted or Mixed with Other Drugs? D.
Herrmann
2.14 Is the Resterilization and Reuse of Disposable Angiography
Catheters Justified?
43
44
44
47
48
49
Contents VII
2.15 Is There an Increased Risk of Coagulation when Catheters Are
Reused? P. Dawson . . . . . . . . . . . . . . . . . . . . . . . . .
. .. 51
3 3.1
Influence of Contrast Media on Organs and Vessels
What Are the Mechanisms of Toxicity Associated with Contrast Media?
P. Dawson . ................... .
3.2 Do Contrast Media Affect the Viscosity of Blood? N. H.
Strickland . . . . . . . . . . . . . . . . . .
3.3 Are There Any Differences Between Ionic and Nonionic Contrast
Media in Their Effect on Coagulation? P. Dawson .
.................... .
3.4 Do Contrast Media Affect Carciovascular Function? P. Dawson .
.................. .
3.5 Do Contrast Media Affect Pulmonary Function? P. Dawson .
................. .
3.6 Do Contrast Media Affect Hepatic Function? V. Taenzer
................. .
3.7 Do Contrast Media Affect Renal Function? 1. E. Scherb erich . .
. . . . . . . . . . . . .
3.8 Do Iodinated X-Ray Contrast Media Affect Thyroid
Function?
53
54
57
58
59
60
61
B. GlObel ........................... 63
3.9 What Is the Relationship Between Iodinated Contrast Media and
the Blood-Brain Barrier? P. Dawson . ...................... .
3.10 Do Contrast Media Affect the Central Nervous System? M.R. Sage
. .................. .
3.11 Do Contrast Media Affect Blood Vessel Walls? F. Laerum
................... .
64
64
67
VIII
Determination of Risk Factors Regarding the Administration of
Contrast Media
What Are the Known Risks of Contrast Media Use? W. Clauf3
....................... .
Does Known X-Ray Contrast Media Hypersensitivity and a History of
Allergies Mean Increased Risk in Examinations Using X-Ray Contrast
Media?
W. Clauf3 ......................... .
Does an Existing Iodine Allergy Mean Increased Risk in Examinations
Using X-Ray Contrast Media?
W. Clauf3 ......................... .
Why Does the Administration of Iodinated Contrast Media to Patients
with Manifest or Latent Hyperthyroidism Represent a Risk? B.
Globel
Why Does the Administration of Iodinated Contrast Media Represent a
Risk to Patients with Bland Nodular Goitre? B. Globel
....................... .
4.6 Does Underlying Cardiovascular Disease Constitute an Increased
Risk in Contrast Media Administration? P. Dawson .
.................. .
4.7 Why Is Pre-existing Lung Disease a Risk for the Administration
of Contrast Media?
4.8
4.9
P. Dawson . .................. .
Why Is Pre-existing Renal Impairment a Risk in the Administration
of Contrast Media? J. E. Scherberich . . . . . . . . . . . . . . .
. . . .
Why Is Pre-existing Diabetes Mellitus a Risk in the Administration
of Contrast-Media? J. E. Scherberich . . . . . . . . . . . . . . .
. . . .
4.10 Why Is Pre-existing Paraproteinaemia a Risk in the
Administration of Contrast Media?
J. E. Scherberich . . . . . . . . . . . . . . . . . . .
Contents IX
4.11 How Can the Risk of Provoking a Hypertensive Crisis in
Patients with Phaeochromocytoma Be Reduced? P. Dawson . . . . . . .
. . . . . . . . . . . . . . . . . . 78
4.12 Can Dehydration Before Contrast Media Administration Be
Recommended Today? 1. E. Scherberich . . . . . . . . . . . . . . .
. . . . . . . . 79
4.13 Are Patients with Autoimmune Disorders at Any Particular Risk
on Contrast Media Administration? P. Dawson . . . . . . . . . . . .
. . . . . . . . . . . . . 80
4.14 Does the Administration of Iodinated Contrast Media to
Patients with Sickle Cell Anaemia Result in Further Change in
Erythrocytic Shape? R. Dickerhoff . . . . . . . . . . . . . . . . .
. . . . . . . .. 81
4.15 Are Contrast Media-Induced Side Effects Dependent on Age? H.
Katayama . . . . . . . . . . . . . . . . . . . . . . . . . ..
82
4.16 Does Weather Influence the Rate of Undesirable Reactions to
Contrast Media Administration? D. Zuckert . . . . . . . . . . . . .
. . . . . . . . . . . . 83
4.17 Can Contrast Media Procedures Be Carried Out Despite Defined
Risks? P. Dawson . . . . . . . . . . . . . . . . . . . . . . . . .
84
4.18 What Interactions Are Known Between the Administration of
Contrast Media and Other Medications? P. Dawson . . . . . . . . . .
. . . . . . . . . . . . . . . 85
4.19 What Is the Role of X-Ray Contrast Media Administered During
Pregnancy or in Nursing Mothers?
5 5.1
Prophylactic Measures
What Is the Place of Fasting and Dehydration Before Contrast Media
Administration? w. Clauf3 . . . . . . . . . . . . . . . . . . . . .
. . . . . . .. 89
X Contents
5.2 Can Hypersensitivity Reactions to Contrast Media Be Predicted
Through Preliminary Testing?
W. ClaufJ and V. Taenzer .............. .
5.3 Is Sedation Indicated Before Administering Contrast Media? G.
Wisser
5.4 Does General Anaesthesia Prevent the Occurrence of Contrast
Media-Induced Side Effects? G. Wisser
5.5 Can the Rate of Contrast Media-Induced Side Effects Be Lowered
by Premedication with Antihistamines? R. Tauber
.................... .
5.6 Can the Adverse Reactions Rate/Be Reduced by Administration of
Corticosteroids?
W. ClauB
6 Informing the Patient Prior to Contrast Media
Administration
6.1 What Is the Patient's "Right to Know" Prior to an X-Ray
Examination Using Contrast Media?
91
91
92
93
94
H. 1. Maurer and W. Spann . . . . . . . . . . . . . . . . 97
6.2 What Special Information Should a Healthy Volunteer/Patient
Receive Who Is Participating in a Clinical Study of a New Drug? W.
ClaufJ and E. Andrew . . . . . . . . . . . . . . . . . 98
7 7.1
Administration of Contrast Media
Are Contrast Media Heated to Body Temperature Better Tolerated? P.
Dawson . ................... .
7.2 Are There Any Guidelines for Maximum Doses in Angiography? P.
Dawson . ................... .
101
102
Contents XI
7.3 Are There Any Guidelines for Maximum Doses in Myelography? l.
O. Skalpe ................... .
7.4 Are There Any Guidelines for Maximum Doses in
Cholegraphy?
102
7.5 Can "Maximum" Doses Be Exceeded? P. Dawson . ............. . .
........ 103
7.6 Does the Injection Rate Affect the Tolerance? P. Dawson .
................. . 104
7.7 What Fluids Can be Recommended for Flushing Catheters?
8
Adverse Reactions and Their Pathophysiology and Management
8.1 What Adverse Reactions Can be Expected After Administration of
Contrast Media?
.. 105
8.2 Do Late-Occurring Adverse Reactions to Contrast Media
Necessitate Longer Supervision of the Patient? P. Davies
8.3 Do Late Reactions Occur More Frequently After Administration of
Nonionic Contrast Media?
109
P. Davies . . .. 111
8.4 What Are the Mediators of Anaphylactoid Reactions to Iodinated
Contrast Media? P. Dawson . . . . . . . . . . . . . . . . . . . . .
. . . . . .. 112
8.5 What Adverse Reactions to Contrast Media Are Dose Independent
or Dependent? H. Katayama . . . . . . . . . . . . . . . . . . . . .
.
8.6 Are Antibodies to Radiographic Contrast Media Known?
... 113
XII Contents
8.7 Are There Allergies to Contrast Media? R. C. Brasch . . . . . .
. . . . . . . . . . . . . .. 115
8.8 Can Sensitization Due to Frequent Contrast Media Administration
Be Observed? R. C. Brasch . . . . . . . . . . . . . . . . . . . . .
.. 116
8.9 Can Epileptogenicity and Arachnoiditis Be Observed After
Myelography with Nonionic Contrast Media? l. O. Skalpe
........................... 116
8.10 Are Contrast Media Dialysable?
9
J. E. Scherb erich . . . . . . . . .
Clinical Use of Iodinated Contrast Media for the Visualization of
Vessels, Organs and Organ Systems
9.1 Carotid and Vertebral Arteries and Cerebral Vessels
117
9.3 Angiography of the Extremities H. J. Maurer . .................
128
9.4 Phlebography B. Hagen . .. . . .. 133
9.5 Direct Lymphography and Indirect Lymphangiography H. Weissleder
............. . .... 138
9.6 Angiography and Thoracic Aortography P. Romaniuk. . . . . . . .
. . . . . . .
9.7 Angiographic Procedures for the Liver, Spleen, Pancreas and
Portal Venous System
. 144
W. Rodl ............................. 161
9.8 Computed Tomography in the Liver, Pancreas and Spleen A. Adam .
............................ 169
Contents XIII
9.9 The Gastrointestinal Tract W. Dihlmann and L. Hering .......
176
9.10 Contrast Media in the Gallbladder and Bile Ducts v. Taenzer
...... . . ...... 190
9.11 Intravenous Urography P. Dawson . ..... .
9.12 Urethrography and Micturating Cystography, Cavernosogra phy,
and Seminal Vesiculography and Vasography
. 192
9.13 The Kidneys and Adrenal Glands G. P. Krestin . . . . . . . .
.. ................ 202
9.14 Contrast Media in Gynaecology H. 1. Maurer and 1. G. Heep
................. 208
9.15 Arthrography v. Papassotiriou ... 213
9.16 What Advantages Do Nonionic Contrast Media Have for Paediatric
Patients? H. 1. Kaufmann and C. Bassir. . . . . . . . . . . . . .
.
9.17 What Is the Role of Newer Contrast Media in Interventional
Radiology?
. 222
"'0' Contrast Media for Magnetic Resonance Imaging ~ and
Ultrasound
10.1 Contrast Media for Clinical Magnetic Resonance Imaging H. P.
Niendorf and 1. C. Dinger . . . . . . . . . . . . . . . ..
227
10.2 Ultrasonographic Contrast Media R. Schlief, R. Schiirmann, and
H. P. Niendorf . . . . . . . .. 234
Snbject Index ............................. 243
Contributors
Adam, A., Prof., Dept. of Radiology, Guy's Hospital, London Bridge,
London SE1 9 RT, UK
Alhassan, A., Dr., Schering AG, Arzneimittelsicherheit,
MiillerstraBe 170-178,13342 Berlin, Germany
Andrew, E., Dr., Nycomed AS Imaging, Slemdalsveien 37,0301 Oslo 3,
Norway
Bassir, c., Dr., Univ.-Klinikum RudolfVirchow, FUB, Padiatrische
Radiologie, KA VH, Heubnerweg 6, 12487 Berlin, Germany
Bohn, H. P., Dr., Nycomed AS Imaging, Slemdalsveien 37,0301 Oslo 3,
Norway
Brasch, Robert c., Prof., University of California, Department of
Radiology, Contrast Media Laboratory, Third and Parnassus Street,
San Francisco, CA 94143, USA.
Clauj3, Wolfram, Dr., Schering AG, Klinische Entwicklung
Diagnostika, MiillerstraBe 170-178, 13342 Berlin, Germany
Davies, Peter, Dr., F.R. C.R., Department of Radiology, City
Hospital, Nottingham, UK
Dawson, Peter, Dr., Dept. of Radiology, Univ. of London, Royal
Postgraduate Medical School, Hammersmith Hospital, Ducane Road,
London W12 OHS, UK
Dickerhoff, Roswitha, Dr., Kinderklinik, St. Augustin,
Arnold-lanssen-StraBe 29, 53757 St. Augustin, Germany
Dihlmann, W., Prof., Rontgeninstitut, Allgemeines Krankenhaus
Barmbek, Riibenkamp 148, 22307 Hamburg, Germany
Dinger, 1. c., Dr., Schering AG, GCP Methologie, MiillerstraBe
170-178,13353 Berlin, Germany
GlObel, B., Prof. Dr., Univ.-Kliniken des Saarlandes, Abteilung
Medizintechnik und Strahlenschutz, 66424 Homburg, Germany
XVI Contributors
Grainger, Ronald G., Prof., Royal Hallamshire Hospital, Department
of Radiology, Glossop Road, Sheffield SlO 2JF, UK
Giinzel, P., Dr., Schering AG, Experimentelle Toxikologie,
MiillerstraBe 170-178, 13342 Berlin, Germany
Gulbrandsen, Trygve, Dr., Nycomed AS Imaging, Slemdalsveien 37,
0301 Oslo 3, Norway
Hagen, Bernd, Dr., Martin-Luther-Krankenhaus, Rontgen- und
Strahlenabteilung, Caspar-Theyss-StraBe 27-31,14194 Berlin,
Germany
Heep, Josef, Prof., Josefskrankenhaus, Gynakologische Abteilung,
LandhausstraBe 25,69115 Heidelberg, Germany
Hering, L., Dr., Rontgeninstitut, Allgemeines Krankenhaus Barmbek,
Riibenkamp 148, 22307 Hamburg, Germany
Herrmann, Dirk, Dr., Schering AG, MiillerstraBe 170--178,13342
Berlin, Germany
Imhof, H., Prof., Zentrales Inst. fUr Radiodiagnostik, Allgemeines
Krankenhaus Wien, Lazarettgasse 14,1090 Wien, Austria
Katayama, Hitoshi, Prof., Department of Radiology, Juntendo
University, Hongo 3-1-3, Brunkyo-ku, Tokyo 113, Japan
Kaufmann, Herbert J., Prof., SchwerinstraBe 14, 10783 Berlin,
Germany
Krause, Werner, Dr., Schering AG, Forschung Rontgenkontrastmittel,
MiillerstraBe 170-178, 13342 Berlin, Germany
Krestin, G., Dr., Med. Einrichtungen d. Univ., Radiologische Inst.
und Poliklinik, Joseph-Stelzmann-StraBe 9,50931 KOln, Germany
Laerum, Frode, Prof., Section for Experimental Radiology,
Department of Diagnostic Radiology, Rikshospitalet, 0027 Oslo 1,
Norway
Maurer, H.-J., Prof., Obere FlurstraBe 11, 88131 Lindau-Bodolz,
Germany
Niendorf, Hans-Peter, Dr., Schering AG, Klinische Entwicklung
Diagnostika, MiillerstraBe 170--178,13342 Berlin, Germany
Papassotiriou, V., Dr., Wenckebach-Krankenhaus, Rontgenabteilung,
WenckebachstraBe 23,12099 Berlin, Germany
Contributors XVII
Romaniuk, Paul, Prof., Inst. flir KardiovaskuHire Diagnostik,
Charite Humboldt-Universitat, SchumannstraBe 20-21,10117 Berlin,
Germany
Sage, Michael R., Prof., Dept. of Radiology, The Flinders
University of South Australia, Flinders Medical Centre, Bedford
Park, South Australia 5042, Australia
Scherberich, 1. E., Dr., Klinikum der J.-W.-Goethe-Universitat,
Zentrum der Inneren Medizin, Theodor-Stem-Kai 7, 60596 Frankfurt,
Germany
Schlief, Reinhard, Dr., Schering AG, Klinische Entwicklung
Diagnostika, MiillerstraBe 170-178, 13342 Berlin, Germany
SchObel, Christel, Dr., Schering AG, Experimentelle Toxikologie,
MiillerstraBe 170-178,13342 Berlin, Germany
Schiirmann, R., Dr., Schering AG, Klinische Entwicklung
Diagnostika, MiillerstraBe 170-178, 13342 Berlin, Germany
Schuhmann-Gampieri, Gabriele, Dr., Schering AG, Forschung
Rontgenkontrastmittel, MiillerstraBe 170-178,13342 Berlin,
Germany
Skalpe, l. 0., Prof., Rikshospitalet, Rontgen-Radium-Avd.,
Pilestredet 32, 0027 Oslo 1, Norway
Spann, W., Prof., Ludwig-Maximilians-Univ., Fachbereich Medizin,
BavariastraBe 19, 80336 Miinchen, Germany
Speck, Ulrich, Prof., Schering AG, Diagnostika Forschung,
MiillerstraBe 170-178,13342 Berlin, Germany
Strickland, Nicola Hilary, Dr., Dept. of Radiology, Royal
Postgraduate Medical School, Hammersmith Hospital, Ducane Road,
London W12 OHS, UK
Taenzer, V., Prof., Krankenhaus Moabit, Rontgenabteilung,
TurmstraBe 21, 10559 Berlin, Germany
Tauber, R., Prof., Allgemeines Krankenhaus Barmbek, Urologische
Abteilung, Riibenkamp 148, 22307 Hamburg, Germany
XVIII Contributors
Thron, A., Prof., Neurologische Klinik der RWTH, Abteilung
Neuroradiologie, PauwellsstraBe, 52074 Aachen, Germany
Vergesslich, Klara, Dr., Universitatskinderklinik Wien, Wahringer
GurteI18-20, 1090 Wien, Austria
Weiss leder, H., Prof., Kreiskrankenhaus, Abt. fur
Rontgendiagnostik, GartenstraBe 40, 70312 Emmendingen,
Germany
Wisser, Gregor, Dr., Klinikum der Johannes-Gutenberg-Universitat,
Klinik fur Anasthesiologie, LangenbeckstraBe 1, 55131 Mainz,
Germany
Wolden, Brit, Dr., Nycomed AS Imaging, Sl~mdalsveien 37, 0301 Oslo
3, Norway
Zuckert, Dieter, Dr., Kissinger-StraBe 57,14199 Berlin,
Germany
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