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C. Miscellaneous

C. MISCELLANEOUS

C.1. Contrast medium extravasation

C.2. Pulmonary effects of iodine-based contrast media

C.3. Effects of contrast media on blood and endothelium

C.3.1. Thrombosis

C.3.1.1. Iodine-based contrast media

C.3.2. Sickle cell disease

C.3.2.1. Iodine-based contrast media

C.3.2.2. Gadolinium-based contrast agents

C.4. Contrast agents and catecholamine producing tumors (pheochromocytoma and paraganglioma)

C.5. Pregnancy and lactation

C.6. Interaction with other drugs and clinical tests

C.7. Gadolinium issues

C.7.1. Gadolinium retention in the brain

C.7.1.1. Detection

C.7.1.2. Characteristics

C.7.1.3. Relation to gadolinium-based agents

C.7.2. Gadolinium retention in bone, liver and skin

C.7.2.1. Detection

C.7.2.2. Characteristics

C.7.3. Gadolinium contamination of the environment

C.8. Safety of ultrasound contrast agents

C.9. Safety of barium contrast media

C.10. Pediatric use of contrast agents

C.11. Off-label use of contrast agents


C. MISCELLANEOUS

C.1. CONTRAST MEDIUM EXTRAVASATION

Type of injuries

  • Most injuries are minor.
  • Severe injuries include skin ulceration, soft-tissue necrosis, and compartment syndrome.

RISK FACTORS

Technique-related

  • Use of a power injector.
  • Less optimal injection sites including lower limb and small distal veins.
  • Large volume of contrast medium.
  • High-osmolar contrast media.
  • High-viscosity contrast media.

Patient-related

  • Inability to communicate.
  • Fragile or damaged veins.
  • Arterial insufficiency.
  • Compromised lymphatic and/or venous drainage.
  • Obesity.

To reduce the risk

  • Intravenous technique should always be meticulous using an appropriate sized plastic cannula placed in a suitable vein to handle the flow rate used during the injection.
  • Consider use of cannulas with sideholes.
  • Test injection with normal saline.
  • Use non-ionic iodine-based contrast medium.

Management

  • Documenting the extravasation with a plain radiograph, CT scan or MR scan of the affected region may be helpful.
  • Conservative management is adequate in most cases.
    • Limb elevation
    • Ice packs
    • Careful monitoring.
  • If a serious injury is suspected, seek the advice of a surgeon.

C.2. PULMONARY EFFECTS OF IODINE-BASED CONTRAST MEDIA

Pulmonary adverse effects

  • Bronchospasm.
  • Increased pulmonary vascular resistance.
  • Pulmonary edema.

Patients at high risk

  • History of asthma.
  • History of pulmonary hypertension.
  • Incipient cardiac failure.

To reduce the risk of pulmonary adverse effects

  • Use low- or iso-osmolar contrast media.
  • Avoid large doses of contrast media.

C.3. EFFECTS OF CONTRAST MEDIA ON BLOOD AND ENDOTHELIUM

C.3.1. Thrombosis

C.3.1.1. Iodine-based contrast media

The clinically important adverse effect of iodine-based contrast media on blood and endothelium is thrombosis.

It is recognized that:

  • All contrast media have anticoagulant properties, especially ionic agents.
  • High-osmolar ionic contrast media may induce thrombosis due to endothelial damage, particularly in phlebographic procedures.
  • Drugs and interventional devices that decrease the risk of thromboembolic complications during interventional procedures minimize the importance of the effects of contrast media.

Guidelines

  • Meticulous angiographic technique is mandatory and is the most important factor in reducing thromboembolic complications.
  • Low- or iso-osmolar contrast media should be used for diagnostic and interventional angiographic procedures including phlebography.

C.3.2. Sickle Cell Disease

C.3.2.1. Iodine-based contrast media

  • In patients with sickle cell disease, high-osmolar iodine-based contrast media may cause red cell sickling, leading to hemolysis and small vessel occlusion.
  • Low- or iso-osmolar iodine-based contrast media produce no more adverse events in patients with sickle cell disease than in the normal population.

Guidelines

  • Use low- or iso-osmolar iodine-based contrast media.
  • Hydrate patients before contrast medium administration.

C.3.2.2. Gadolinium-based contrast media

  • The smaller doses of gadolinium-based contrast agents compared to iodine-based contrast media reduce the osmolar load, so contrast agent osmolality is unlikely to be a significant problem.
  • No adverse events suggestive of red blood cell sickling have been reported after gadolinium-based contrast agents.

Guidelines

  • Use any gadolinium-based contrast agent.
  • No special preparation is necessary.

C.4. CONTRAST AGENTS AND CATECHOLAMINE PRODUCING TUMORS (PHEOCHROMOCYTOMA AND PARAGANGLIOMA)

Preparation

a) Before intravenous iodine- or gadolinium-based contrast agent: no special preparation is required.

b) Before intra-arterial iodine-based contrast medium: α and β-adrenergic blockade with orally administered drugs under the supervision of the referring physician is recommended.

Type of contrast agent which should be used

Iodine-based: non-ionic agent.

Gadolinium-based: any agent.

C.5. PREGNANCY AND LACTATION

Iodine-based contrast media

Gadolinium-based contrast agents

Pregnancy

a)In exceptional circumstances, when radiographic examination is essential, iodine-based contrast media may be given to the pregnant female.

b) Following administration of iodine-based contrast media to the mother during pregnancy, thyroid function should be checked in the neonate during the first week.

a) When there is a very strong indication for enhanced MR, the smallest possible dose of a macrocyclic gadolinium contrast agent (see A.3.2. Agents with lowest risk of NSF) may be given to the pregnant female.

b) Following administration of gadolinium-based agents to the mother during pregnancy, no neonatal tests are necessary.

Lactation

Breast feeding may be continued normally when iodine-based contrast media is given to the mother.

Breast feeding may be continued normally when macrocyclic gadolinium-based contrast agents are given to the mother.

Pregnant or lactating mother with renal impairment

See renal adverse reactions (B.2.). No additional precautions are necessary for the fetus or neonate.

Do not administer gadolinium-based contrast agents.

C.6. INTERACTION WITH OTHER DRUGS AND CLINICAL TESTS

General recommendation

  • Be aware of the patient’s drug history.
  • Keep a proper record of the contrast agent injection (time, dose, name).
  • Do not mix contrast agents with other drugs in tubes and syringes.

Drugs needing special attention

Metformin

Refer to renal adverse reactions section (B.4.).

Nephrotoxic drugs

Cyclosporine

Cisplatin

Aminoglycosides

Non steroid anti-inflammatory drugs

Stopping nephrotoxic drugs before administering contrast agents is not generally recommended.

ß-blocker

ß-blockers may impair the management of bronchospasm and the response to adrenaline.

Interleukin-2

Refer to late adverse reactions section (A.2.).

Non-emergency biochemical assays

Recommendation

  • Preferably collect urine and blood before administration of a contrast agent.
  • In patients with normal renal function, blood can be collected 4 hours after contrast agent administration if necessary.
  • In patients with reduced renal function (eGFR < 45 ml/min/1.73 m2), blood collection should be delayed for as long as possible after contrast agent administration.
  • Urine collection should not be done within 24 hours of administration of a contrast agent.
  • The effects of the contrast agents on the analyses may differ dependent on which analytic method is used.

Isotope studies and/or treatment

Thyroid

  • Patients undergoing therapy with radioactive iodine should not have received iodine-based contrast medium for at least 2 months before treatment.
  • Isotope imaging of the thyroid should be avoided for 2 months after iodine-based contrast medium injection.

Bone, red blood cell labelling

  • Avoid iodine-based contrast medium injection for at least 24 hours before the isotope study.

C.7. GADOLINIUM ISSUES

C.7.1. Gadolinium retention in the brain

C.7.1.1. Detection

  • Seen as regions of increased signal intensity in the deep brain nuclei on unenhanced T1-weighed MR-images.
  • The association between these appearances and gadolinium-based contrast agents was first noted in 2014.

C.7.1.2. Characteristics

  • The signal intensity changes are not specific and may occur after manganese, iron, calcium etc.
  • MR is less sensitive for detecting gadolinium in the brain than tissue analysis after biopsy.
  • It is not known whether the deposited gadolinium is chelated.
  • No neurological symptoms have yet been reported.
  • The clinical significance of these changes is not yet known.
  • All studies have been retrospective.
  • Occurs independent of renal function.

C.7.1.3. Relation to gadolinium-based agents

  • High signal intensity in the deep brain nuclei on MRI has been reported after all linear gadolinium-based agents, but not after macrocyclic agents.
  • Analysis of brain tissue has detected gadolinium after all gadolinium-based agents with the highest levels of gadolinium in patients who had linear chelates and the lowest levels in those who had macrocyclic agents.
  • The greater the previous cumulative dose of the gadolinium-based agent, the more widespread are the areas of increased signal intensity.
  • Only occurs after multiple doses.

C.7.2. Gadolinium retention in bone, liver and skin

C.7.2.1. Detection

  • Requires biopsy and tissue analysis.

C.7.2.2. Characteristics

  • Occurs independent of renal function.
  • May occur after any agent but greater amounts are retained after non-ionic linear agents.
  • Cannot be detected by MRI.
  • The amounts deposited are small but greater than in the brain.
  • Bone and liver retention do not produce clinical symptoms.
  • Skin deposition causes red skin plaques similar to those seen in NSF.
  • Apart from NSF, the clinical consequences of bone, liver and skin deposition are unknown.

C.7.3. Gadolinium contamination of the environment

  • Use of gadolinium-based contrast agents for MRI has led to gadolinium reaching the environment in waste water.
  • At present the amounts of gadolinium in surface and tap water are very low but they are likely to increase with increasing use of gadolinium-based contrast agents.
  • The risks of this gadolinium in the environment are not yet known but there is concern that it might contribute to gadolinium deposition in human tissues.
  • Monitoring of gadolinium level in the water and better water purification using reverse osmosis membranes are needed to reduce the potential for harm (see Acta Radiol 2017, 58: 259-263).

C.8. SAFETY OF ULTRASOUND CONTRAST AGENTS

Statements

  • Ultrasound contrast agents are generally safe.
  • Clinical evidence of ultrasound contrast agent related events in critically ill patients and patients with acute coronary disease is limited.

Contraindication

  • Avoid ultrasound contrast agents in the 24 hours before extracorporeal shock wave treatment.

Type and severity of reactions

  • The majority of reactions are minor (e.g. headache, nausea, sensation of heat, altered taste) and self-resolving.
  • More severe acute reactions are rare and are similar to those after iodine- and gadolinium-based agents (see A.1.).

To reduce the risk

  • Check for intolerance to any of the components of the contrast agent.
  • Use the lowest level of acoustic output and shortest scanning time to allow a diagnostic examination.

Treatment

  • If a serious event occurs – see General adverse reaction section A.1.2.

C.9. SAFETY OF BARIUM CONTRAST MEDIA

Statements

Recommended action

Contraindications

Integrity of gut wall compromised

  • Use iodine-based water-soluble contrast media.
  • In neonates and patients at risk of leakage into mediastinum and/or lungs use low- or iso-osmolar contrast media.

Previous allergic reactions to barium products

Use iodine-based 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.

C.10. PEDIATRIC USE OF CONTRAST AGENTS

  • Safety considerations when using contrast media in neonates, infants and children are similar to, but not the same as, in adults.
  • Contrast agent dose must be adjusted for patient age and weight.
  • Age-specific normal values of serum creatinine etc. must be used.
  • The revised Schwartz equation is recommended to measure eGFR (see B.1.).
  • For iodine-based contrast media, non-ionic agents should be used.
  • For gadolinium-based contrast agents, high-risk agents should be avoided.
  • The Summary of Product Characteristics for the contrast agent should be consulted, because not all contrast agents are approved for use in children.
  • If no suitable contrast agent approved for use in children is available, informed consent for off-label use must be obtained from the parents. However, if use of a specific contrast agent in children is absolutely contra-indicated, it may not be used, even with informed consent.

C.11. OFF-LABEL USE OF CONTRAST AGENTS

  • Off-label use of diagnostic and therapeutic medication is common.
  • The Summary of Product Characteristics (SPC) or label should be checked to see if the proposed contrast agent use is approved for the particular patient and indication.
  • Choose a contrast agent which is approved for the particular patient and indication whenever possible.
  • If there is no suitable approved contrast medium, the prescriber must tell the patient about the risks and benefits of off-label contrast agent use, and must obtain the patient’s informed consent to off-label contrast agent administration.

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