Appendix
21 ESUR Guidelines on Contrast Media
Henrik S. Thomsen, Sameh K. Morcos, Torsten Almén, Peter Aspelin,
Marie-France Bellin, Hugo Flaten, Jean-Marc Idée, Jarl Å. Jakobsen, Andrea Löwe, Raymond Oyen, Alberto Spinazzi, Fulvio Stacul, Aart J. van der Molen, and
Judith A. W. Webb
The Contrast Media Safety Committee of the European Society of Urogenital Radiology c/o Henrik S. Thomsen, MD, Professor, Department of Diagnostic Radiology, Copenhagen University Hospital at Herlev, 2730 Herlev, Denmark
CONTENTS
21.1 Renal Adverse Reactions 146
21.1.1 To Avoid Contrast Medium-Induced Nephrotoxicity 146 21.1.2 Determination of Serum Creatinine 147
21.1.3 Dialysis and Contrast Media Administration 148
21.1.4 Administration of Contrast Media to Diabetics Taking Metformin 148
21.1.5 The Use of Gadolinium-Based Contrast Media for Radiographic Examinations 149
21.2 Non-renal Adverse Reactions 150
21.2.1 Prevention of Generalized Contrast Medium Reactions 150 21.2.2 Management of Acute Adverse Reactions to Contrast Media 150 21.2.2.1 Drugs/Instruments 150
21.2.2.2 First Line Treatment of Acute Reactions to Contrast Media 151 21.2.3 Late Adverse Reactions to Intravascular Iodinated Contrast Media 152
21.3 Other Adverse Effects of Contrast Media 153
21.3.1 Prevention and Management of Extravasation of Contrast Media 153 21.3.2 Effect of Iodinated Contrast Media on Thyroid Function in Adults 154 21.3.3 Pulmonary Effects of Contrast Media 154
21.3.4 Contrast Media and Catecholamine-Producing Tumours (Phaeochromocytoma and Paraganglioma) 155
21.3.5 The Use of Iodinated and Gadolinium Contrast Media During Pregnancy and Lactation 155
21.3.6 Avoiding Interaction Between Contrast Media and Other Drugs 156 21.3.7 Safety of Ultrasound Contrast Media 156
21.3.8 Safety of MR Extracellular Contrast Media 157 21.3.9 Safety of Liver Specific MR Contrast Media 157 21.3.10 Safety of Barium Contrast Media 158
21.3.11 Effects of Iodinated Contrast Media on Blood and Endothelium 158
21.4 Publications from the Contrast Media Safety Committee of the European Society of
Urogenital Radiology 159
Definition Contrast medium nephrotoxicity is a condition in which an impairment in renal function [an increase in serum creatinine by more than 25% or 44 Pmol/l (0.5 mg/dl)] occurs within 3 days following the intravascular administration of a contrast medium (CM) in the absence of an alterna- tive etiology
Risk factors Look for: x Raised S-creatinine levels, particularly secondary to diabetic
nephropathy x Dehydration
x Congestive heart failure x Age over 70 years old
x Concurrent administration of nephrotoxic drugs, e.g. non-steroid
anti-inflammatory drugs In patients
with risk factor(s)
Do: x Make sure that the patient is well hydrated; give at least 100 ml oral
(e.g. soft drinks) or intravenous (normal saline) fluids, depending on
the clinical situation, per hour starting 4 h before to 24 h after contrast
administration – in warm areas increase the fluid volume x Use low- or iso-osmolar contrast media
x Stop administration of nephrotoxic drugs for at least 24 h
x Consider alternative imaging techniques, which do not require the
administration of iodinated contrast media Do not: x Give high osmolar contrast media
x Administer large doses of contrast media
x Administer mannitol and diuretics, particularly loop-diuretics
x Perform multiple studies with contrast media within a short period of
time
21.1 Renal Adverse Reactions
ESUR Guidelines
21.1.1 To Avoid Contrast Medium-Induced Nephrotoxicity
21.1.2 Determination of Serum Creatinine
At time of referral for a contrast enhanced imag- ing examination identify patients with increased probability of abnormal S-creatinine levels
The referring clinician should ask the patient for a history of:
x Renal disease x Renal surgery x Proteinuria x Diabetes mellitus x Hypertension x Gout
x Recent nephrotoxic drugs
The answers should be provided to the department of Radiology with the imaging request
Serum creatinine not older than 6 months should be provided with the imaging request, if available
Non-emergency examinations
Look for: x Positive answer to one or more of the above questions x Known abnormal S-creatinine level at time of referral
x Procedures requiring intraarterial contrast medium administration Action: x S-creatinine level must be measured within 7 days of the examination x The Department of Radiology must be informed if the S-creatinine level is increased at least 24 h before the scheduled examination time in order to make the necessary arrangements
Emergency examinations
1. In emergency situations S-creatinine measurement can be waived 2. If the procedure can be deferred without harm to the patient, S-creatinine should be measured
In patients with abnormal S-creatinine levels
xConsider alternative imaging techniques, which do not require the administration of iodinated contrast media
xStop administration of nephrotoxic drugs for at least 24 h xMake sure that the patient is well hydrated
xUse low- or iso-osmolar contrast media
21.1.3 Dialysis and Contrast Media Administration
Patients Recommendations
On hemodialysis
(all contrast media can be removed by hemodialysis)
x Avoid osmotic and fluid overload
x Correlation of the time of contrast medium injection with the hemodialysis session is unnecessary
x Extra hemodialysis session for removal of contrast medium is unnecessary
With severely reduced renal function
x Please refer to ESUR guidelines to avoid contrast medium-induced nephrotoxicity (hydration, use small doses of low osmolar contrast media)
x Hemodialysis is unnecessary
x In MRI examinations avoid doses more than 0.3 mmol/kg BW of gadolinium-based contrast agents
On continuous ambula- tory peritoneal dialysis (CAPD)
[all contrast media can be removed by peritoneal dialysis]
Examinations using iodinated agents:
x To protect residual renal function please refer to ESUR guidelines to avoid contrast medium-induced nephrotoxicity
x Hydration should be considered only after careful evaluation of fluid balance state of the patient
x Hemodialysis is not recommended
Examinations using gadolinium agents:
x To protect residual renal function use doses up to 0.3 mmol/kg BW of gadolinium-based contrast agents
x Hemodialysis is not recommended
21.1.4 Administration of Contrast Media to Diabetics Taking Metformin
S-creatinine level should be measured in every diabetic patient treated with biguanides prior to intra- vascular administration of contrast media. Low-osmolar contrast media should always be used in these patients.
Elective studies
a) If the serum creatinine is normal, the radiological examination should be performed and intake of metformin stopped from the time of the study. The use of metformin should not be resumed for 48 h and should only be restarted if renal function/serum creatinine remains within the normal range.
b) If renal function is abnormal, the metformin should be stopped and the contrast study should be delayed
for 48 h. Metformin should only be restarted 48 h after contrast medium, if renal function/serum creati-
nine is unchanged.
Emergency cases
a) If the serum creatinine is normal, the study may proceed as suggested for elective patients.
b) If the renal function is abnormal (or unknown), the physician should weigh the risks and benefits of contrast administration. Alternative imaging techniques should be considered. If contrast media admin- istration is deemed necessary and the following precautions should be implemented:
x Metformin therapy should be stopped.
x The patient should be hydrated (e.g. at least 100 ml per hour of soft drinks or intravenous saline up to 24 h after contrast medium administration – in warm areas more fl uid should be given).
x Monitor renal function (S-creatinine), serum lactic acid and pH of blood.
x Look for symptoms of lactic acidosis (vomiting, somnolence, nausea, epigastric pain, anorexia, hyper- pnea, lethargy, diarrhea and thirst). Blood test results indicative of lactic acidosis: pH < 7.25 and lactic acid > 5 mmol.
ESUR Position Statement
21.1.5 The Use of Gadolinium-Based Contrast Media for Radiographic Examinations
Legal position Gadolinium-based contrast media are not approved for X-ray examinations
Uses of gadolinium-based contrast media for X-ray examinations reported in the literature
x Significant renal impairment
x Prior severe generalized adverse reaction to iodinated contrast
media
x Imminent thyroid treatment with radioactive iodine
ESUR position 1. The use of gadolinium-based contrast media for radiographic examinations is not recommended to avoid nephrotoxicity in
patients with renal impairment since they are more nephrotoxic
than iodinated contrast media in equivalent X-ray attenuating doses
2. The use of gadolinium-based contrast medium in approved intra-
venous doses up to 0.3 mmol/kg BW will not give diagnostic
radiographic information in most cases
21.2 Non-renal Adverse Reactions
ESUR Guidelines
21.2.1 Prevention of Generalized Contrast Medium Reactions A. Risk Factors for Reactions
x Previous generalized contrast medium reaction, either moderate (e.g. urticaria, bronchospasm, moderate hypotension) or severe (e.g. convulsions, severe bronchospasm, pulmonary edema, cardio- vascular collapse).
x Asthma.
x Allergy requiring medical treatment.
B. To Reduce the Risk of Generalized Contrast Medium Reactions x Use nonionic agents.
C. Premedication is Recommended in High Risk Patients (Defined in A) x When ionic agents are used.
x When nonionic agents are used, opinion is divided about the value of premedication.
D. Recommended Premedication x Corticosteroids
Prednisolone 30 mg orally or methylprednisolone 32 mg orally 12 and 2 h before contrast medium.
Corticosteroids are not effective if given less than 6 h before contrast medium.
x Antihistamines H1 and H2 may be used in addition to corticosteroids, but opinion is divided.
E. Remember for All Patients
x Have a trolley with resuscitation drugs in the examination room.
x Observe patients for 20–30 min after contrast medium injection.
F. Extravascular Administration
x When absorption or leakage into the circulation is possible, take the same precautions as for intra- vascular administration.
21.2.2 Management of Acute Adverse Reactions to Contrast Media 21.2.2.1 Drugs/Instruments
x Oxygen
x Adrenaline 1:1,000
x Antihistamine H1 – suitable for injection x Atropine
x β2-agonist metered dose inhaler
x IV Fluids – normal saline or Ringers solution x Anti-convulsive drugs (diazepam)
x Sphygmomanometer
x One-way mouth “breather” apparatus
First line emergency drugs and instruments should be in the examination room
21.2.2.2 First Line Treatment of Acute Reactions to Contrast Media Nausea/Vomiting
Transient: Supportive treatment.
Severe, protracted: Appropriate antiemetic drugs should be considered.
Urticaria
Scattered, transient: Supportive treatment including observation.
Scattered, protracted: Appropriate H1-antihistamine intramuscularly or intravenously should be consid- ered. Drowsiness and/or hypotension may occur.
Profound: Consider adrenaline 1:1,000, 0.1–0.3 ml (0.1–0.3 mg) intramuscularly in adults, 0.01 mg/kg intra- muscularly up to 0.3 maximum in children. Repeat as needed.
Bronchospasm
1. Oxygen by mask (6–10 l/min)
2. β-2-agonist metered dose inhaler (2–3 deep inhalations) 3. Adrenaline
a) Normal blood pressure
Intramuscular: 1:1,000, 0.1–0.3 ml (0.1–0.3 mg) [use smaller dose in a patient with coronary artery disease or elderly patient]
In pediatric patients: 0.01 mg/kg up to 0.3 mg maximum b) Decreased blood pressure
Intramuscular: 1:1,000, 0.5 ml (0.5 mg), (in pediatric patients: 0.01 mg/kg intramuscularly) Laryngeal Edema
1. Oxygen by mask (6–10 l/min)
2. Intramuscular adrenaline (1:1,000), 0.5 ml (0.5 mg) for adults, repeat as needed.
Hypotension
Isolated hypotension 1. Elevate patient’s legs
2. Oxygen by mask (6–10 l/min)
3. Intravenous fl uid: rapidly, normal saline or lactated Ringer’s solution
4. If unresponsive: adrenaline (1:1,000), 0.5 ml (0.5 mg) intramuscularly, repeat as needed Vagal reaction (hypotension and bradycardia)
1. Elevate patient’s legs
2. Oxygen by mask (6–10 l/min)
3. Atropine 0.6–1.0 mg intravenously, repeat if necessary after 3–5 min, to 3 mg total (0.04 mg/kg) in adults.
In pediatric patients give 0.02 mg/kg intravenously (maximum 0.6 mg per dose) repeat if necessary to 2 mg total
4. Intravenous fl uids: rapidly, normal saline or lactated Ringer’s solution Generalized anaphylactoid reaction
1. Call for resuscitation team 2. Suction airway as needed
3. Elevate patient’s legs if hypotensive 4. Oxygen by mask (6–10 l/min)
5. Intramuscular adrenaline (1:1,000), 0.5 ml (0.5 mg) in adults. Repeat as needed. In pediatric patients 0.01 mg/kg to 0.3 mg (maximum dose)
6. Intravenous fl uids (e.g. normal saline, lactated Ringer’s)
7. H1-blocker e.g. diphenhydramine 25–50 mg intravenously
21.2.3 Late Adverse Reactions to Intravascular Iodinated Contrast Media
Definition: A late adverse reaction to intravascular iodinated contrast medium is defined as a reaction which occurs between 1 h and 1 week after contrast medium injection
Reactions: A variety of late symptoms (e.g. nausea, vomiting, headache, musculoskeletal pains, fever) have been described following contrast medium, but many are not related to contrast medium
Skin reactions of similar type to other drug eruptions are true late adverse reac- tions. They are usually mild to moderate and self-limiting
Risk factors for skin reactions:
x Previous contrast medium reaction x Interleukin-2 treatment
Management: Symptomatic and similar to the management of other drug-induced skin reactions
Prophylaxis: x Generally not recommended
x Patients who have had a previous serious late adverse reaction, can be given oral steroids (see ESUR guidelines on prevention of generalized adverse reactions)
Recommenda- tions:
Tell patients who have had a previous contrast medium reaction or who are on
interleukin-2 treatment that a late skin reaction is possible and that they should
contact a doctor if they have a problem
21.3 Other Adverse Effects of Contrast Media
ESUR Guidelines
21.3.1 Prevention and Management of Extravasation of Contrast Media
Risk factors relate to: The technique:
x Use of a power injector
x Less optimal injection sites including lower limb and small distal veins x Large volume of contrast medium
x High osmolar contrast medium
The patient:
x Unable to communicate x With fragile or damaged veins x With arterial insufficiency
x With compromised lymphatic and/or venous drainage
To reduce the risk: x Intravenous technique should always be careful, preferably using plastic catheters for power injection
x Use low osmolar contrast medium
Type of injuries x Most injuries are minor
x Severe injuries include skin ulceration, soft tissue necrosis,
and compartment syndrome
Treatment x Conservative management is adequate in most cases:
o Limb elevation o Apply ice packs o Careful monitoring
x If a serious injury is suspected, seek the advice of a surgeon
21.3.2 Effect of Iodinated Contrast Media on Thyroid Function in Adults
Absolute contraindication
x Iodinated contrast media should not be given to patients with manifest hyper-
thyroidism
Development of thyrotoxicosis after iodinated contrast media
No risk x Patients with normal thyroid function
At risk x Patients with Graves’ disease
x Patients with multinodular goiter and thyroid autonomy, especially if they are elderly and/or live in areas of dietary iodine deficiency
Recommendations x Prophylaxis is generally not necessary
x Patients at risk should be closely monitored by endocrinologists after iodinated contrast medium injection
x In selected high-risk patients, prophylactic treatment may be given by an endocrinologist; this is more relevant in areas of dietary iodine deficiency x Intravenous cholangiographic contrast media should not be given to patients at risk
Radioactive iodine treatment
Recommendation x Patients undergoing therapy with radioactive iodine should not have received iodinated contrast media for at least 2 months before treatment
Isotope imaging of the thyroid
Recommendation x Isotope imaging of the thyroid should be avoided for 2 months after iodinated contrast medium injection
21.3.3 Pulmonary Effects of Contrast Media
High risk patients Action
History of pulmonary hypertension History of bronchial asthma Incipient cardiac failure
x Use low or iso-osmolar contrast media
x Avoid large doses of contrast media
21.3.4 Contrast Media and Catecholamine-Producing Tumours (Phaeochromocytoma and Paraganglioma)
Tumour localisation when catecholamine-producing tumour detected biochemically
Characterisa- tion of inciden- tally detected adrenal mass Preparation
(a) Before intravenous con- trast medium (iodinated or gadolinium)
D and E-Adrenergic blockade with orally adminis- tered drugs under the supervision of the referring physician is advised. Further D-blockade with intra- venous phenoxy-benzamine is not necessary
No special prep- aration
(b) Before intra-arterial iodinated contrast medium
D and E-Adrenergic blockade with orally admin- istered drugs and D-blockade with intravenous phenoxybenzamine under the supervision of the referring physician are recommended
Type of contrast medium which should be used
Iodinated agent Nonionic agent Nonionic agent
Gadolinium agent Any agent (ionic or nonionic) Any agent (ionic
or nonionic)
21.3.5 The Use of Iodinated and Gadolinium Contrast Media During Pregnancy and Lactation
Iodinated agents Gadolinium agents
Pregnancy a) In exceptional circumstances, when radiographic examination is essential, iodinated contrast media may be given to the pregnant female
a) When MR examination is necessary, gadolinium media may be given to the pregnant female
b) Following administration of iodin- ated agents to the mother during pregnancy, thyroid function should be checked in the neonate during the first week
b) Following administration of gado- linium agents to the mother during preg- nancy, no neonatal tests are necessary
Lactation Breast feeding may be continued nor- mally when iodinated agents are given to the mother
Breast feeding may be continued nor- mally when gadolinium agents are given to the mother
Pregnant or lactating mother with renal impairment
No additional precautions are necessary for the fetus or neonate. Follow ESUR guidelines for contrast media adminis- tration when renal function is impaired
No additional precautions are necessary
for the fetus or neonate. Follow ESUR
guidelines for contrast media adminis-
tration when renal function is impaired
21.3.6 Avoiding Interaction Between Contrast Media and Other Drugs
Do Be aware of the patient’s drug history
Keep proper records of the contrast medium injection (time, dose, name)
Drugs needing special atten- tion
Metformin Refer to ESUR guidelines on Metformin
Cyclosporine Cisplatin
Aminoglycosides
Non-steroid anti-inflammatory drugs
Refer to ESUR guidelines on nephrotoxicity
β−blocker Refer to ESUR guidelines on prevention and management of adverse reactions
Interleukin-2 Refer to ESUR guidelines on delayed reactions Hydralazine Avoid contrast medium injection if possible Do not Mix contrast media with other drugs in tubes or syringes
Make non emergency biochemical analysis on blood or urine collected within 24 h of contrast medium injection
Isotope studies Thyroid Refer to ESUR guidelines on thyroid func- tion in adults
Bone, red blood cell labeling Avoid contrast medium injection for at least 24 h before the isotope study
21.3.7 Safety of Ultrasound Contrast Media
Statement: x Ultrasound contrast media are generally safe Type and severity
of reactions:
x The majority of reactions are minor (e.g. headache, nausea, sensation of heat, altered taste) and self-resolving
x Allergy-like reactions occur rarely
To reduce the risk: x Check for intolerance of any of the components of the contrast agent x Use the lowest level of acoustic output and shortest scanning time to allow a diagnostic examination
Treatment: x If a serious event occurs – refer to ESUR guidelines on management
of adverse reactions to contrast media
21.3.8 Safety of MR Extracellular Contrast Media
Safety Generally safe; low incidence of adverse event
Adverse events Similar type to those seen after iodinated contrast media Management See ESUR guidelines on management
Prophylaxis If there has been a previous hypersensitivity-like reaction to gadolinium based compounds, consider an alternative modality or premedication (see ESUR guidelines on prophylaxis)
Contrast medium- induced nephropathy
May occur – see ESUR guidelines on nephrotoxicity
Dialysis See ESUR guidelines on dialysis
S-creatinine Hydration No special precautions are recommended Pregnancy and Lactation See ESUR guidelines on pregnancy and lactation Interaction See ESUR guidelines on interaction
Radiography Not approved for this use
21.3.9 Safety of Liver Specific MR Contrast Media Types of adverse
reactions
Similar to reactions observed with other types of contrast media such as nausea, vomiting, urticaria, rash, generalized anaphylactoid reactions. Back pain may also occur with superparamagnetic iron oxides. Serious life threatening reactions are rare
Patients < 18 years old
Safety has not yet been established
Contraindications Iron oxides
– Known allergy or hypersensitivity to parenteral iron or dextran Manganese based contrast media
– Known allergy to the preparation – Pregnancy
– Lactation
– Severe liver impairment, Gadolinium based contrast media – Known allergy to the preparation Cautions Iron oxides
– In patients with hemosiderosis or hemochromatosis: iron-overload may be aggravated
Manganese based contrast media – Liver impairment and heart failure Gadolinium based contrast media
x Agent with high hepatocyte uptake: liver and renal failure
x Agent with low hepatocyte uptake: renal failure
21.3.10 Safety of Barium Contrast Media
Recommended action
Contraindications Integrity of gut wall compromised
Use iodinated water-soluble contrast media
In neonates and patients at risk of leakage into medi- astinum and/or lungs use low- or isoosmolar contrast media
Previous allergic reac- tions to barium prod- ucts
Use iodinated water-soluble contrast media and be prepared to treat a reaction
Cautions Bowel strictures Use only small amounts Extensive colitis Avoid barium enemas
Complications Reduced bowel motility Encourage fluid intake
Venous intravasation Early identification and careful observation Antibiotics and intravenous fluids
Emergency treatment may be needed Aspiration Bronchoscopic removal for large amounts
Chest physiotherapy Antibiotics
ESUR Statement
21.3.11 Effects of Iodinated Contrast Media on Blood and Endothelium
The clinically important adverse effect of iodinated contrast media on blood and endothelium is throm- bosis. It is recognized that:
x All contrast media have anticoagulant properties, especially ionic agents.
x High osmolar ionic contrast media may induce thrombosis due to endothelial damage, particularly in phlebographic procedures.
x Drugs and interventional devices that decrease the risk of thromboembolic complications during inter- ventional procedures minimize the importance of the effects of contrast media.
Guidelines
x Meticulous angiographic technique is mandatory and is the most important factor in reducing throm- boembolic complications.
x Low or iso-osmolar contrast media should be used for diagnostic and interventional angiographic pro-
cedures including phlebography.
21.4 Publications from the Contrast Media Safety Committee of the European Society of Urogenital Radiology
Bellin M-F, Jakobsen JÅ, Tomassin I, Thomsen HS, Morcos SK, Members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology (2002) Contrast medium extravasation injury: guidelines for prevention and management. Eur Radiol 12:2807–2812
Bellin M-F, Webb JAW, Molen AJvd, Thomsen HS, Morcos SK, Members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR) (2005) Safety of MR liver specific contrast media. Eur Radiol 15:1607–1614 Jakobsen JÅ, Oyen R, Thomsen HS, Morcos SK, Members of
Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR) (2005) Safety of ultrasound contrast agents. Eur Radiol 15:941–945
Molen AJvd, Thomsen HS, Morcos SK, Members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR) (2004) Effect of iodinated contrast media on thyroid function in adults. Eur Radiol 14:902–906 Morcos SK, Thomsen HS, Exley CM, Members of Contrast
Media Safety Committee of European Society of Urogeni- tal Radiology (ESUR) (2005) Contrast media: interaction with other drugs and clinical tests. Eur Radiol 15:1463–
1468)
Morcos SK, Thomsen HS, Webb JAW and members of con- trast media safety committee of the European Society of Urogenital Radiology (ESUR) (1999) Contrast media induced nephrotoxicity: a consensus report. Eur Radiol 9:1602–1613
Morcos SK, Thomsen HS, Webb JAW and members of con- trast media safety committee of the European Society of Urogenital Radiology (ESUR) (2001) Prevention of gener- alized reactions to contrast media: a consensus report and guidelines. Eur Radiol 11:1720–1728
Morcos SK, Thomsen HS, Webb JAW, Members of the Contrast
Media Safety Committee of European Society of Urogenital Radiology (2002) Dialysis and contrast media. Eur Radiol 12:3026–1629
Thomsen HS, Almén T, Morcos SK, Members of Contrast Media Safety Committee of European Society of Uro- genital Radiology (2002) Gadolinium-containing contrast media for radiographic examinations: a position paper. Eur Radiol 12:2600–2605
Thomsen HS, Morcos SK and members of contrast media safety committee of the European Society of Urogenital Radiology (ESUR) (1999) Contrast media and metformin.
Guidelines to diminish the risk of lactic acidosis in non- insulin dependent diabetics after administration of con- trast media. Eur Radiol 9:738–740
Thomsen HS, Morcos SK, Members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR) (2004) Management of acute adverse reactions to contrast media. Eur Radiol 14:476–481
Thomsen HS, Morcos SK, Members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR) (2005) In which patients should serum-creatinine be measured before contrast medium administration? Eur Radiol 15:749–754
Webb JAW, Stacul F, Thomsen HS, Morcos SK, Members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) (2003) Late adverse reac- tions to intravascular iodinated contrast media. Eur Radiol 13:181–184
Webb JAW, Thomsen HS, Morcos SK, Members of Contrast
Media Safety Committee of European Society of Urogenital
Radiology (ESUR) (2005) The use of iodinated and gado-
linium contrast media during pregnancy and lactation. Eur
Radiol 15:1234–1240
Subject Index
A
abdominal – discomfort 140 – pain 133, 139 abnormal – smell 133 – taste 125, 133 acetazolamide 94 acetylcysteine 40–42
activated partial thromboplastin time 69 acute
– adverse reaction 20
– idiosyncratic systemic reaction 11 – – prevention 13
– infl ammation 100 – reaction 11
– renal failure, see also contrast medium nephropathy 35, 47
adenosine 41, 67 adherence 66
adrenaline 21, 23, 89, 150
adverse effect/reaction 15, 109, 123, 133, 139 – moderate 19
– severe 19
affi nity to proteins 20 albuterol 22 allergic reaction 133 allergy
– history 12, 29
– requiring medical treatment 14, 150 allergy-like reaction 156
alpha blocker 95
alpha-adrenergic blockade 155 alpha-receptor blocker 94 altered taste 108, 132, 156 aminoglycoside 37, 156 amniotic fl uid 60 analeptics 96
anaphylactoid reaction 15, 19, 23, 108, 132 anaphylaxis-like reaction 94
angioedema 23, 27, 140 angiography 1 – device 70
– diagnostic procedure 69, 158 – digital 115
– – subtraction 117
– interventional procedure 158 – meticulous technique 158 anorexia 133
anticoagulant activity 69
antihistamine 27, 96, 150 – H1 receptor antagonist 84 antipsychotics 96
anuria 119 apnea 83 apoptosis 67 appendicitis 140 arm pain 20, 27 arterial insuffi ciency 99 asthma 12, 14, 19, 150 atherosclerosis 99 atrial
– fi brillation 133 – natriuretic peptide 41 atropine 22, 150
B
back pain 123, 133 balloon 69 barium – agent 1
– contrast media 158 – leakage 140 – preparation – – adverse effects 140 – pulmonary emboli 140 – sulphate 2, 139 – – aspiration 140 baroliths 139
baseline cyclic AMP increments 22 basophils 86
benzene ring 2
beta blocker 12, 22, 95, 156
beta-2-adrenergic agonist 22, 84, 150 – inhaler 24
beta-adrenergic blockade 19, 155 beta-thromboglobulin 68 biguanides 53
bilirubin determination 97 biochemical assay 97 bleeding time 95 blood 65, 158 – cell rouleaux 66 bone imaging 96 bowel obstruction 140 bradykinin 83 breastfeeding 62
bronchospasm 11, 15, 20, 23, 83, 86, 140, 151 buformin 53
butyrophenone 96
C
calcium 97 – antagonist 19, 95 – channel – – antagonist 50 – – blocker 41, 96 – measurement 97
calcium-binding properties 20 cardiac
– arrest 11, 20 – disease 29 – dysrhythmia 20 – failure 40 cardiovascular – collapse 20 – effect 124 catecholamine 89 – release 90
catecholamine-producing tumour 90, 155 catheter 69
cavitation 132
chemical pneumonia 140 chemotaxis 66
chemotherapy 99 chemotoxic-type effect 20 chest pain 132, 133 chills 132
cholinesterase inhibition 83 chromosomal damage 59 chronic infl ammation 100 cisplatin 156
Clinical Trials Directive 5 clot formation 69 clotting
– test 97 – time 95
coagulant property 67 coagulation 67, 95
– disseminated intravascular 140 – extrinsic 95
– intrinsic 95
Cockroft-Gault equation 38 colon
– perforation 140 – toxic dilatation 140 colonic obstruction 139
colorimetric assay for angiotensin-converting enzyme 97 compartmental syndrome 101
compromised venous drainage 99 computed tomography (CT) 1, 115, 117 – contrast media enhanced 28 – unenhanced 28
congenital long QT syndrome 108 congestive cardiac failure 37, 146 connective tissue disease 99 constipation 139, 140 contact allergy 29
contrast agent, see contrast media contrast media
– acute adverse reaction 19 – – management 19
– adverse reaction/effect 109, 123, 133, 139
– – moderate 19 – – severe 19 – – treatment 108
– anaphylactoid reaction 19, 23, 108, 132 – anaphylaxis-like reaction 94
– avoiding interaction with other drugs 156 – barium 1
– biliary 76, 79
– cardiovascular effects 124
– catecholamine-producing tumour 155 – chromosomal damage 59
– delayed reactions 94 – elimination 47 – extracellular 157 – extravasated 100 – fatal reactions 20
– gadolinium 11, 43, 54, 59, 61, 90 – – in milk 61
– gadolinium-based 111, 119, 121, 149, 157 – – nephrotoxic potential 111
– general adverse reactions 116
– generalised anaphylactoid reaction 151, 157 – hemodialysis 48
– – patient factor 48 – high-osmolar 2, 37, 40, 66
– iodinated 11, 43, 54, 59, 60, 65, 117, 155 – – half-life 47
– – in milk 61 – – water-soluble 60 – iodine 1
– ionic 2, 13, 19 – iso-osmolar 2 – late adverse reaction 27 – – true frequency 28 – liver specifi c 121, 126, 157 – – MR 157
– low-osmolar 2, 37, 40 – magnetic resonance (MR) 100 – manganese based 157 – mutagenic effects 59 – negative 1
– nephropathy 35, 36, 41–43, 49, 119, 146 – nonionic 2, 19
– paramagnetic 2, 3 – – hepatobiliary 126
– physiological characteristics 20 – positive 1
– prevention of reactions 15 – previous generalised reaction 150 – previous reaction 12, 152 – pseudo-allergic reaction 20 – pulmonary adverse effect 83 – pulmonary effect 154 – radiographic 1, 35, 115 – removal 48
– risk factors 19
– serious allergic reaction 133 – severe life-threatening reaction 20 – side effects 49
– superparamagnetic 3
– teratogenic effect 59
– ultrasound 3, 131, 156
– vagal reaction 23, 151
conventional radiography 1 convulsion 11, 20
copper 97
corticosteroid 22, 150 – prophylaxis 84 cramps 133
CT, see computed tomography cutaneous vasculitis 94 cyclosporine 94, 156 cytotoxicity 100
D
degranulation 66 dehydration 37 delayed reactions 94 dense adhesion 140 dessicocyte formation 66 diabetes 38
– mellitus 29, 37, 99, 147 – non-insulin dependent 53
diabetic nephropathy 41, 47, 54, 94, 146 diabetics taking metformin 148 diagnostic scintigraphy 79, 96 dialysis 47, 48, 119
– peritoneal 49 diarrhea 95, 133
digital angiography 115, 117 dimer 2
– nonionic iso-osmolar 40, 41 disaggregation 66
diuretic 39
dizziness 27, 132, 133 dopamine 41 double dosage 108 drug
– allergy 20, 29 – anti-convulsive 150 – fi rst line 21 – idiosyncrasy 20 – interaction 93 – – classifi cation 93 – intolerance 20 – nephrotoxic 37, 40, 147
– non-steroid antiinfl ammatory 40 dry mouth 133
dyspepsia 133 dyspnea 83, 132, 133
E
echinocyte formation 66 edema
– facial 11
– laryngeal 11, 20, 23, 151 – pulmonary 20, 67
encapsulated gas microbubble 4
endogenous biomechanical disturbance 36 endoscopic retrograde
cholangiopancreatography 80
endothelial – cell 67
– vasoactive substance 67 endothelin 41, 67, 83, 84 endothelium 65, 85, 158 ephedrine 13, 22 erythema 27, 95 erythrocythes 65, 66, 85 European
– Commission 5 – medicine legislation 5 – Medicines Agency 6 – regulatory system 6 extracellular
– gadolinium chelates 126 – volume expansion 39, 43 extravasation 153 – detection 101 – – accessory (EDA) 101 – high volume 100 – injury 99 – management 101
F
fatal reactions 20 fenoldopam 41 fever 27, 95, 132 fi brinolysis 67, 70, 96 fi brosis 140
fl u-like syndrome 29, 95 fl ushing 20, 95, 123–125, 132 foetal thyroid 60
Food and Drug Administration 6 foodstuff 12
free iodide 75, 76 free manganese 3 free thyroxine 76 furosemide 40, 94
G
gadobenate dimeglumine 3 gadobutrol 3
gadodiamide 3
gadolinium (Gd) 3, 39, 90, 155, 157 – BOPTA 3
– contrast media 11, 43, 49, 54, 61, 121 – – adverse events 15
– – anaphylactoid reaction 15 – – bronchospasm 15 – – in milk 61
– – previous reaction 15 – – rash 15
– – urticaria 15 – EOBDTPA 3
– extracellular chelates 126 – hepatobiliary chelates 125 – molecules 116
gadoxetate 3 – meglumine 3
gall bladder opacifi cation 36
gas microbubble – encapsulated 4 – nonencapsulated 4 gastrointestinal – disturbance 27 – uptake 123
generalised anaphylactoid reaction 151 gentamicin 40, 94
geriatric patient 77 glomerular fi ltration rate 37 – decreased 80
goiter 75, 78 – multinodular 77 gout 38, 147 GpIIb/IIIa blocker 70
granulomatous infl ammatory reaction 140 Graves‘ disease 75, 77
guidewire 69
H
H1 antihistamine 13 H2
– antagonist 13 – antihistamine 22 – receptor 22
headache 20, 27, 108, 125, 132, 133, 156 heart failure 157
heat sensation 156 hemochromatosis 123, 157 hemodialysis 39, 47, 50 – prophylactic 49 – regular 48 hemofi ltration 39 hemolysis 132 hemosiderosis 123, 157 hepatic excretion 48 hepatobiliary – excretion 121
– gadolinium chelates 125 high-osmolality ionic agent 2, 67 – rate of reaction 11
high-osmolar – agent 2, 40
– contrast media 39, 66 histamine 20, 83 – release 84
– – from basophils 86 – – from lung mast cells 86 hives 108
hydralazine 29, 156 – treatment 94 hydration 43
hydrophilicity 20, 21, 48 5-hydroxytryptamine 83 hypersensitivity 94, 141
– to the latex balloon catheter 141 hypertension 37, 38, 133, 147 hyperthyroidism 75–77 – iodine-induced 77, 79 – manifest 79
hyperuricemia 37
hypokalemia 108
hypotension 20, 23, 140, 151 – isolated 151
hypotensive shock 11 hypothyroidism 76
I
idiosyncratic systemic reaction 11 infant 99
– blood 62 infl ammation – acute 100 – chronic 100
injection site reaction 125 – hypersensitivity 133
interleukin-2 12, 19, 29, 94, 95, 152, 156 intravascular fl uid administration 21 intravenous cholangiographic media 81 iodide 75, 76
– excess 77
iodinated contrast media 11, 43, 54, 59, 65, 117, 155 – half-life 47
– in milk 61 – molecules 116
– previous generalised reaction 14 – previous reaction 13
– water-soluble 60 iodine 12, 75 – agent 1 – atoms 116 – defi ciency 75, 76 – defi cient area 78
– topical skin preparation 12 iodine-defi cient area 75 iodine-induced – hyperthyroidism 77 – thyrotoxicosis 75
ionic contrast media/agent 2, 13, 19 – late reaction 28
ionising radiation 59 iron 97
– oxyde 157
iso-osmolar agent 2, 40
isotope imaging of the thyroid 154 itching 11, 27
K
kidney surgery 28
L
lactation 61, 155 – renal impairment 155 lactic acidosis 54, 149 laryngeal edema 20, 23, 151
leucocyte adhesion to endothelium 85
life-threatening reactions 20
liver – disease 29 – enhancement 124 – failure 157 – impairment 157
liver-specifi c contrast agent 121, 126 low osmolality nonionic agent 2, 12, 40 – rate of reaction 12
lung mast cells 86 lymphatic drainage 99
M
macular exanthema 27 maculopapular rash 27 magnesium 97
magnetic resonance (MR) 107 – contrast media 2, 35, 100 – gadolinium-based 115 mangafodipir trisodium 3 manganese-based – contrast media 157 – preparation 121 Mannitol 38, 40
Marketing Authorisation 5 mechanical compression 100 medicine
– European legislation 5 – unlicensed 5, 7, 8 metal needle 100 metallic taste 124 metaproterenol 22 metformin 53, 156 microparticle – emulsion 4 – suspension 4 molecular mass 48 monomer 2 – nonionic 28, 41 – – low osmolar 40 musculoskeletal system 133 mutagenic effects 59
N
nausea 11, 20, 22, 27, 95, 108, 125, 133, 151, 156, 157 negative contrast media 1
neonate 61 nephrogram 36 nephropathy 35, 54 – diabetic 36, 37, 41, 94 nephrotoxic drug 37, 40 nephrotoxicity 50
– of the gadolinium-based contrast agent 119 nitric oxide 42, 67
noncardioselective beta-blocking medication 23 nonencapsulated gas microbubble 4
nonionic
– contrast media 2, 19 – – late reaction 28 – dimer 28
– low osmolality agent 13
non-selective adenosine receptor antagonist 41
non-steroid antiinfl ammatory drug (NSAID) 37, 40, 94, 146, 156
noradrenaline 89
O
off-label use 5–8 old age 146
one-way mouth breather apparatus 150 osmolality 2, 20, 65, 100
– of gadolimium agents 108 osmotic load 108
osmotoxicity 20 oxygen 21, 150
oxygen-free radicals 37, 40, 42
P
Paediatric Regulation 7 pain 133
palpitation 133 paraganglioma 155 paramagnetic – contrast agent 2,3
– hepatobiliary contrast media 126 paresthesia 101, 133
percutaneous coronary intervention 70 perforation
– extraperitoneal 140 – of the colon 140 peritoneal dialysis 49 – continuous ambulatory 49 peritonitis 140
persistent pain 101
phaeochromocytoma 89, 155 phagocytosis 66
pharmacokinetics 47, 94, 116
pharmacological manipulation 39, 41, 43 phenformin 53
phenothiazine 96
phenoxybenzamine alpha-blockade 89 phlebitis 101
phlebography 158 phosphate 97 placenta 59 plasma protein 48 plastic cannulae 100 platelet 68
– activation 68, 95 – adhesion 68 – aggregation 68, 132 – degranulation 68, 95 – function 67
positive contrast media 1 power injection 100 predisposing factor 28 prednisolone 84
pregnancy 22, 24, 59–61, 155
– renal impairment 60, 155
premedication regime 13
prescriber 7, 8 pretesting 14
prophylactic thyrostatic therapy 81 prophylaxis 29
prostacyclin 67
protein assay technique 97 proteinuria 37, 38, 147 prothrombin time 69 protstaglandin 83 pruritus 20, 23, 29, 95, 133 pseudo-allergic reaction 20 pulmonary
– adverse effects 83 – arterial hypertension 81 – artery pressure 84, 85 – collapse 20
– edema 20, 67, 83, 85, 86 – hypertension 132
– vascular resistance 66, 67, 84, 85 – – increase 86
Q
questionnaire 39
R
radioactive iodine treatment 154 radiographic
– contrast media 1, 35, 115 – examination 117 radiography 1
radioiodine treatment 79, 80, 96 rash 15, 95, 133, 157
recalcifi cation clotting time 69
recombinant tissue-type plasminogen activator (rt-PA) 70, 96 red blood cells 65
– aggregation 85 – morphology 66 red cell rigidity 66 renal
– disease 29, 147 – – history 38
– – modifi cation of diet 38 – excretion 48
– failure 157 – – acute 111, 119 – – chronic 49 – function 37, 55 – – impaired 80, 111 – – pre-existing reduced 94 – impairment 49
– – chronic 59
– – pre-existing 36, 37, 47 – insuffi ciency 54, 117 – perfusion, reduction 36 – surgery 147
reptilase time 69 respiratory – arrest 11 – failure 140
resuscitation – drug 150 – equipment 14 – team 20
risk stratifi cation 39 route of administration 37
S
salivary gland swelling 47 scattered hive 23 scintigraphy 79, 96
selective dopamine-1 receptor agonist 41 septicaemia 140
serotonin 68
serum creatinine 37, 42, 55, 117, 146 – levels 147
– measurement 38 skin
– blistering 101 – eruption 27 – late reaction 28 – rash 27, 29 – reaction 27 – testing 28 small children 99 sodium 20 – bicarbonate 39 – chlorid hydration 40 sphygmomanometer 150 spironolactone 94 stent 69
steroid 14, 27 – prophylaxis 29 stomatocyte 66 streptokinase 70, 96
Summary of Product Characteristics (SPC) 6 superparamagnetic
– contrast agent 3 – iron oxide (SPIO) 3, 121 – – particles 121 sweating 133
systemic lupus erythematosus 29
T
T2 relaxation agent 121 tachycardia 133 teratogenic effects 59 terbutaline 22 theophylline 42 thioxanthene 96 thrombolysis 70
thrombosis 71, 99, 101, 158 thrombotic
– complication 69
– property 67
thromboxane 83
thyroid 156
– autonomy 75
– function 81, 154 – scintigraphy 79
thyroid-stimulating hormone 60, 75 thyrotoxicosis 75, 78
– contrast-medium-induced 77, 78 – – prevalence 77
– iodine-induced 75, 78 – – prevention 78 thyroxine 60, 77 tissue perfusion 101 topical emollient 27 total iron binding 97 toxicity 36
transmetallation 112 tricyclic antidepressant 96 tri-iodothyronine 60, 77 triple dosage 108, 111 TSH 76
tubular cell 36 – toxicity 37
U
ultra small superparamagnetic iron oxide (USPIO) 3 ultrasound contrast media 3, 131, 133, 156
unconsciousness 20 unlicensed medicine 5, 7, 8 urokinase 70, 96
urticaria 11, 15, 20, 23, 27, 140, 157
V vagal
– reaction 23, 151 – refl ex 83 vascular tone 67 vasculitis 47 – cutaneous 94 vasodilatation 133 vasodilator 41 vasovagal reaction 11 viscosity 20, 65, 85
vomiting 11, 20, 22, 95, 108, 132, 151, 157
W
warm sensation 132 warmth 124 weakness 133 white blood cells 66 – infl ammatory response 67
X
X-ray examination 149 Z
zinc 97
List of Contributors
CMYK
Peter Aspelin , MD
Professor, Department of Radiology Karolinska University Hospital 14186 Stockholm
Sweden
Marie-France Bellin, MD Professor, Department of Radiology University Paris-Sud 11
Paul Brousse Hospital, AP-HP 12-14 avenue Paul Vaillant Couturier 94804 Villejuif Cedex
France
Remy W. F. Geenen, MD Department of Radiology
Erasmus MC – University Medical Center Rotterdam Dr. Molewaterplein 40
3015 GD Rotterdam The Netherlands
Jarl Å. Jakobsen , MD
Professor, Department of Diagnostic Radiology Rikshospitalet
0017 Oslo Norway
Gabriel P. Krestin , MD
Professor, Department of Radiology
Erasmus MC – University Medical Center Rotterdam Dr. Molewaterplein 40
3015 GD Rotterdam The Netherlands
Sameh K. Morcos , FRCS, FFRRCSI, FRCR Department of Diagnostic Imaging Northern General Hospital
Sheffi eld Teaching Hospitals NHS Trust Herries Road
Sheffi eld S5 7AU UK
Raymond Oyen , MD, PhD Professor, Adjunct Clinic Head Department of Radiology Catholic University of Leuven Herestraat 49
3000 Leuven Belgium
June M. Raine, MD Medicines Control Agency Market Towers
1 Nine Elms Lane London, SW8 5NQ UK
Fulvio Stacul, MD Institute of Radiology Ospedale di Cattinara 34149 Trieste
Italy
Henrik S. Thomsen , MD Professor, Department of Diagnostic Radiology 54E2
Copenhagen University Hospital at Herlev Herlev Ringvej 75
2730 Herlev Denmark
Aart J. van der Molen , MD Department of Radiology – C2-S Leiden University Medical Center P.O. Box 9600
2300 RC Leiden The Netherlands Judith A.W. Webb , MD
Department of Diagnostic Imaging St. Bartholomew’s Hospital
West Smithfi eld
London EC1 A 7BE
UK
CMYK
