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{{Short description|Substance which enhances visibility in X-ray-based imaging}}
'''Radiocontrast agents''' are substances used to enhance the visibility of internal structures in [[X-ray]]-based imaging techniques such as [[computed tomography]] (CT), radiography, and [[fluoroscopy]]. Radiocontrast agents are typically iodine, barium-sulphate or gadolinium based compounds.
'''Radiocontrast agents''' are substances used to enhance the visibility of internal structures in [[X-ray]]-based imaging techniques such as [[computed tomography]] ([[contrast CT]]), [[projectional radiography]], and [[fluoroscopy]]. Radiocontrast agents are typically iodine, or more rarely [[barium sulfate]]. The [[contrast agent]]s absorb external X-rays, resulting in decreased exposure on the [[X-ray detector]]. This is different from [[radiopharmaceutical]]s used in [[nuclear medicine]] which emit radiation.


[[Magnetic resonance imaging]] (MRI) functions through different principles and thus utilizes [[MRI contrast agent|different contrast agents]]. These compounds work by altering the magnetic properties of nearby hydrogen nuclei.
[[Magnetic resonance imaging]] (MRI) functions through different principles and thus [[MRI contrast agent]]s have a different mode of action. These compounds work by altering the magnetic properties of nearby hydrogen nuclei.


==Types and uses==
==Types and uses==
Radiocontrast agents used in [[X-ray]] examinations can be grouped based on its use.
Radiocontrast agents used in [[X-ray]] examinations can be grouped in positive (iodinated agents, barium sulfate), and negative agents (air, carbon dioxide, methylcellulose).<ref>{{cite book|first1=Yuxy C|last1=Dong|first2=David P.|last2=Cormode|title=Metal Ions in Bio-Imaging Techniques|publisher=Springer|year=2021
|pages=457–484|chapter=Chapter 17. Heavy Elements for X-Ray Contrast|doi=10.1515/9783110685701-023|s2cid=233676619}}</ref>


===Iodinated (intravascular)===
===Iodine (circulatory system)===
[[File:Cerebral Angiogram Lateral.jpg|thumb|200px|Example of iodine based contrast in [[cerebral angiography]]]]
[[File:Cerebral Angiogram Lateral.jpg|thumb|200px|Example of iodine based contrast in [[cerebral angiography]]]]
{{Main|Iodinated contrast}}
Iodine-based contrast media are usually classified as ionic or non-ionic. Both types are used most commonly in radiology due to their relatively harmless interaction with the body and its solubility. Contrast media are primarily used to visualize vessels and changes in tissues on radiography and CT. Contrast media can also be used for tests of the urinary tract, uterus and fallopian tubes. It may cause the patient to feel as if they have had urinary incontinence. It also puts a metallic taste in the mouth of the patient.
[[Iodinated contrast]] contains [[iodine]]. It is the main type of radiocontrast used for [[intravenous administration]]. Iodine has a particular advantage as a contrast agent for radiography because its innermost electron ("k-shell") binding energy is 33.2 keV, similar to the average energy of x-rays used in diagnostic radiography. When the incident x-ray energy is closer to the k-edge of the atom it encounters, photoelectric absorption is more likely to occur. Its uses include:

* [[Contrast CT]]s
Modern intravenous contrast agents are typically based on iodine. This may be bound either in an organic (non-ionic) compound or an ionic compound. Ionic agents were developed first and are still in widespread use depending on the requirements, but may result in additional complications. Organic agents which [[covalent]]ly bind the iodine have fewer side effects as they do not dissociate into component molecules. Many of the side effects are due to the hyperosmolar solution being injected. i.e. they deliver more iodine atoms per molecule. The more iodine, the more "dense" the X-ray effect.
* [[Angiography]] (''arterial investigations'')
* [[Venography]] (''venous investigations'')
* VCUG (''[[Voiding cystourethrogram|voiding cystourethrography]]'')
* HSG (''[[hysterosalpingogram]]'')
* IVU (''intravenous [[urography]]'')


Organic iodine molecules used for contrast include [[iohexol]], [[iodixanol]] and [[ioversol]].
Organic iodine molecules used for contrast include [[iohexol]], [[iodixanol]] and [[ioversol]].
Iodine-based contrast media are water-soluble. These contrast agents are sold as clear, colorless water solutions, with the concentration usually expressed as mg I/ml. Modern iodinated contrast agents can be used almost anywhere in the body. Most often they are used [[intravenously]], but for various purposes they can also be used intraarterially, intrathecally (as in diskography of the spine) and intraabdominally – just about any body cavity or potential space.

Iodine contrast agents are used for the following:
*[[CT scan#Contrast|Contrast-enhanced CT scans]]
*[[Angiography]] (''arterial investigations'')
*[[Venography]] (''venous investigations'')
*VCUG (''[[Voiding cystourethrogram|voiding cystourethrography]]'')
*HSG (''[[hysterosalpingogram]]'')
*IVU (''intravenous [[urography]]'')

====Ionic ====
Ionic contrast media typically, but not always, have higher osmolality and more side-effects.{{Citation needed|date=January 2012}}

{| class="wikitable sortable" border="1" cellpadding="5" cellspacing="0" align="center"
|+'''Commonly used iodinated contrast agents'''
|-
! style="background:#ffdead;" | Compound
! style="background:#ffdead;" | Name
! style="background:#ffdead;" | Type
! style="background:#ffdead;" | Iodine content
! style="background:#ffdead;" colspan="2" | Osmolality
|-
| Ionic
| [[diatrizoate]] (Hypaque 50/ Gastrografin)
| Monomer
| 300 mgI/ml
| 1550
| High
|-
| Ionic
| [[metrizoate]] (Isopaque 370)
| Monomer
| 370 mgI/ml
| 2100
| High
|-
| Ionic
| [[iothalamate]] (Conray)
|
|
| 600-2400
| High
|-
| Ionic
| [[ioxaglate]] (Hexabrix)
| Dimer
| 320 mgI/ml
| 580
| Low
|}

====Non-ionic====
Non-ionic contrast media have lower osmolality and tend to have fewer side-effects.{{Citation needed|date=January 2012}}

{| class="wikitable sortable" border="1" cellpadding="5" cellspacing="0" align="center"
|+'''Commonly used non-ionic contrast agents'''
|-
! style="background:#ffdead;" | Compound
! style="background:#ffdead;" | Name
! style="background:#ffdead;" | Type
! style="background:#ffdead;" | Iodine content
! style="background:#ffdead;" colspan="2" | Osmolality
|-
| Non-ionic
| [[iopamidol]] (Isovue 370)
| Monomer
| 370 mgI/ml
| 796
| Low
|-
| Non-ionic
| [[iohexol]] (Omnipaque 350)
| Monomer
| 350 mgI/ml
| 884
| Low
|-
| Non-ionic
| [[ioxilan]] (Oxilan 350)
| Monomer
| 350 mgI/ml
| 695
| Low
|-
| Non-ionic
| [[iopromide]] (Ultravist 370)
| Monomer
| 370 mgI/ml
| 774
| Low
|-
| Non-ionic
| [[iodixanol]] (Visipaque 320)
| Dimer
| 320 mgI/ml
| 290
| Low
|-
| Non-ionic
| [[ioversol]]
|
|
|
|
|}


===Barium (gastro-intestinal)===
===Barium sulfate (digestive system)===
{{main article|Upper gastrointestinal series}}
[[File:Human intestinal tract, as imaged via double-contrast barium enema.jpg|thumb|200px|Example of a DCBE]]
[[File:Human intestinal tract, as imaged via double-contrast barium enema.jpg|thumb|200px|Example of a DCBE]]
[[Barium sulfate]] is mainly used in the imaging of the digestive system. The substance exists as a water-insoluble white powder that is made into a slurry with water and administered directly into the [[gastrointestinal tract]].
[[Barium sulfate]] is mainly used in the imaging of the digestive system. The substance exists as a water-insoluble white powder that is made into a slurry with water and administered directly into the [[gastrointestinal tract]].{{cn|date=April 2022}}
*[[Lower gastrointestinal series|Barium enema]] (''large bowel investigation'') and DCBE (''double contrast barium enema'')
* [[Upper gastrointestinal series]]
* [[Lower gastrointestinal series|Barium enema]] (''large bowel investigation'') and DCBE (''double contrast barium enema'').
*Barium swallow (''oesophageal investigation'')
* Barium swallow (''oesophageal investigation'')
*Barium meal (''stomach investigation'') and double contrast barium meal
* Barium meal (''stomach investigation'') and double contrast barium meal
*Barium follow through (''stomach and small bowel investigation'')
* Barium follow through (''stomach and small bowel investigation'')
*CT pneumocolon / virtual colonoscopy
* CT pneumocolon / virtual colonoscopy


Barium sulfate, an insoluble white powder is typically used for enhancing contrast in the GI tract. Depending on how it is to be administered the compound is mixed with water, thickeners, de-clumping agents, and flavourings to make the contrast agent. As the barium sulfate doesn't dissolve, this type of contrast agent is an opaque white mixture. It is only used in the digestive tract; it is usually swallowed or administered as an enema. After the examination, it leaves the body with the [[feces]].
Barium sulfate, an insoluble white powder, is typically used for enhancing contrast in the GI tract. Depending on how it is to be administered the compound is mixed with water, thickeners, de-clumping agents, and flavourings to make the contrast agent. As the barium sulfate doesn't dissolve, this type of contrast agent is an opaque white mixture. It is only used in the digestive tract; it is usually swallowed as a [[barium sulfate suspension]] or administered as an enema. After the examination, it leaves the body with the [[feces]].


===Air===
===Air===
Line 137: Line 39:


===Carbon dioxide===
===Carbon dioxide===
{{main|Carbon-dioxide angiography}}
Carbon dioxide also has a role in angiography. It is low-risk as it is a natural product with no risk of allergic potential. However, it can be used only below the diaphragm as there is a risk of embolism in neurovascular procedures. It must be used carefully to avoid contamination with room air when injected. It is a negative contrast agent in that it displaces blood when injected intravascularly.

Carbon dioxide also has a role in angioplasty. It is low-risk as it is a natural product with no risk of allergic potential. However, it can be used only below the diaphragm as there is a risk of embolism in neurovascular procedures. It must be used carefully to avoid contamination with room air when injected. It is a negative contrast agent in that it displaces blood when injected intravascularly.


===Discontinued agents===
===Discontinued agents===
====Thorotrast====
====Thorotrast====
[[Thorotrast]] was a contrast agent based on [[thorium dioxide]], which is [[radioactive]]. It was first introduced in 1929. While it provided good image enhancement, its use was abandoned in the late 1950s since it turned out to be [[carcinogenic]]. Given that the substance remained in the bodies of those to whom it was administered, it gave a continuous radiation exposure and was associated with a risk cancers of the liver, bile ducts and bones, as well higher rates of [[hematological malignancy]] (leukemia and lymphoma).<ref>{{cite journal|last1=Grosche|first1=B.|last2=Birschwilks|first2=M.|last3=Wesch|first3=H.|last4=Kaul|first4=A.|last5=van Kaick|first5=G.|title=The German Thorotrast Cohort Study: a review and how to get access to the data|journal=Radiation and Environmental Biophysics|date=6 May 2016|volume=55|issue=3|pages=281–289|doi=10.1007/s00411-016-0651-8|pmid=27154786}}</ref> Thorotrast may have been administered to millions of patients prior to being disused.{{citation needed|date=October 2017}}
[[Thorotrast]] was a contrast agent based on [[thorium dioxide]], which is [[radioactive]]. It was first introduced in 1929. While it provided good image enhancement, its use was abandoned in the late 1950s since it turned out to be [[carcinogenic]]. Given that the substance remained in the bodies of those to whom it was administered, it gave a continuous radiation exposure and was associated with a risk of cancers of the liver, bile ducts and bones, as well as higher rates of [[hematological malignancy]] (leukemia and lymphoma).<ref>{{cite journal|last1=Grosche|first1=B.|last2=Birschwilks|first2=M.|last3=Wesch|first3=H.|last4=Kaul|first4=A.|last5=van Kaick|first5=G.|title=The German Thorotrast Cohort Study: a review and how to get access to the data|journal=Radiation and Environmental Biophysics|date=6 May 2016|volume=55|issue=3|pages=281–289|doi=10.1007/s00411-016-0651-8|pmid=27154786|s2cid=45053720}}</ref> Thorotrast may have been administered to millions of patients prior to being disused.{{citation needed|date=October 2017}}


====Nonsoluble substances====
====Nonsoluble substances====
In the past, some non water-soluble contrast agents were used. One such substance was [[iofendylate]] (trade names: Pantopaque, Myodil) which was an iodinated oil-based substance that was commonly used in [[myelography]]. Due to it being oil-based, it was recommended that the physician remove it from the patient at the end of the procedure. This was a painful and difficult step and because complete removal could not always be achieved, iofendylate's persistence in the body might sometimes lead to [[arachnoiditis]], a potentially painful and debilitating lifelong disorder of the spine.<ref>{{cite news|last1=Dunlevy|first1=Sue|title=Australians crippled and in chronic pain from dye used in toxic X-rays|url=http://www.dailytelegraph.com.au/lifestyle/health/australians-crippled-and-in-chronic-pain-from-dye-used-in-toxic-xrays/news-story/e35f258d50c2508c214809896673da88|accessdate=27 October 2017|work=[[The Daily Telegraph (Sydney)]]|date=10 December 2016}}</ref><ref>{{cite book|author1=William P. Dillon|author2=Christopher F. Dowd|title=Aminoff's Neurology and General Medicine|pages=1089–1105|edition=5th|accessdate=27 October 2017|chapter=Chapter 53 – Neurologic Complications of Imaging Procedures|date=2014}}</ref> Iofendylate's use ceased when water-soluble agents (such as [[metrizamide]]) became available in the late 1970s. Also, with the advent of [[magnetic resonance imaging|MRI]], myelography became much less-commonly performed.
In the past, some non water-soluble contrast agents were used. One such substance was [[iofendylate]] (trade names: Pantopaque, Myodil) which was an iodinated oil-based substance that was commonly used in [[myelography]]. Due to it being oil-based, it was recommended that the physician remove it from the patient at the end of the procedure. This was a painful and difficult step and because complete removal could not always be achieved, iofendylate's persistence in the body might sometimes lead to [[arachnoiditis]], a potentially painful and debilitating lifelong disorder of the spine.<ref>{{cite news|last1=Dunlevy|first1=Sue|title=Australians crippled and in chronic pain from dye used in toxic X-rays|url=http://www.dailytelegraph.com.au/lifestyle/health/australians-crippled-and-in-chronic-pain-from-dye-used-in-toxic-xrays/news-story/e35f258d50c2508c214809896673da88|access-date=27 October 2017|work=[[The Daily Telegraph (Sydney)]]|date=10 December 2016}}</ref><ref>{{cite book|author1=William P. Dillon|author2=Christopher F. Dowd|title=Aminoff's Neurology and General Medicine|pages=1089–1105|edition=5th|chapter=Chapter 53 – Neurologic Complications of Imaging Procedures|date=2014}}</ref> Iofendylate's use ceased when water-soluble agents (such as [[metrizamide]]) became available in the late 1970s. Also, with the advent of [[magnetic resonance imaging|MRI]], myelography became much less-commonly performed.


==Adverse effects==
==Adverse effects==
{{Further|Iodinated contrast}}
Modern iodinated contrast agents - especially non-ionic compounds - are generally well tolerated.<ref name="AustriaCodex">{{cite book|title=Austria-Codex|editor=Haberfeld, H|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2009|edition=2009/2010|isbn=3-85200-196-X|language=German}}</ref> The adverse effects of radiocontrast can be subdivided into type A reactions (e.g. thyreotoxicosis), and type B reactions (hypersensitivity reactions: allergy and non-allergy reactions [formerly called 'anaphylactoid reactions']).<ref name="pmid28085538">{{cite journal |vauthors=Boehm I, Morelli J, Nairz K, Silva Hasembank Keller P, Heverhagen JT |title=Myths and misconceptions concerning contrast media induced anaphylaxis: a narrative review |journal=Postgrad Med |volume= 129|issue= 2 |pages= 259–266|year=2017 |pmid=28085538 |doi=10.1080/00325481.2017.1282296
Modern iodinated contrast agents – especially non-ionic compounds – are generally well tolerated.<ref name="AustriaCodex">{{cite book|title=Austria-Codex|editor=Haberfeld, H|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2009|edition=2009/2010|isbn=978-3-85200-196-8|language=de}}</ref> The adverse effects of radiocontrast can be subdivided into type A reactions (e.g. thyrotoxicosis), and type B reactions (hypersensitivity reactions: allergy and non-allergy reactions [formerly called anaphylactoid reactions]).<ref name="pmid28085538">{{cite journal |vauthors=Boehm I, Morelli J, Nairz K, Silva Hasembank Keller P, Heverhagen JT |title=Myths and misconceptions concerning contrast media induced anaphylaxis: a narrative review |journal=Postgrad Med |volume= 129|issue= 2 |pages= 259–266|year=2017 |pmid=28085538 |doi=10.1080/00325481.2017.1282296
}}</ref>
|s2cid=205452727 }}</ref>

===Hypersensitivity reactions===
[[Anaphylactoid reactions]] occur rarely,<ref>{{cite journal |vauthors=Karnegis JN, Heinz J | title=The risk of diagnostic cardiovascular catheterization | journal=Am Heart J | year=1979 | pages=291–7 | volume=97 | issue=3 | pmid=420067 | doi=10.1016/0002-8703(79)90427-7}}</ref><ref>{{cite journal | doi=10.1056/NEJM198710013171401 |vauthors=Lasser EC, Berry CC, Talner LB, Santini LC, Lang EK, Gerber FH, Stolberg HO | title=Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material | journal=N Engl J Med | year=1987 | pages=845–9 | volume=317 | issue=14 | pmid=3627208}}</ref><ref>{{cite journal |vauthors=Greenberger PA, Patterson R, Tapio CM | title=Prophylaxis against repeated radiocontrast media reactions in 857 cases. Adverse experience with cimetidine and safety of beta-adrenergic antagonists | journal=Arch Intern Med | year=1985 | pages=2197–200 | volume=145 | issue=12 | pmid=2866755 | doi=10.1001/archinte.145.12.2197}}</ref> but can occur in response to injected as well as oral and rectal contrast and even retrograde [[pyelography]].
They are similar in presentation to [[anaphylaxis|anaphylactic reactions]], but are not caused by an IgE-mediated immune response. Patients with a history of contrast reactions, however, are at increased risk of anaphylactoid reactions.<ref>{{cite journal |vauthors=Greenberger PA, Patterson R | title=Adverse reactions to radiocontrast media | journal=Prog Cardiovasc Dis | year=1988 | pages=239–48 | volume=31 | issue=3 | pmid=3055068 | doi=10.1016/0033-0620(88)90017-5}}</ref><ref>{{cite journal |vauthors=Lang DM, Alpern MB, Visintainer PF, Smith ST | title=Elevated risk of anaphylactoid reaction from radiographic contrast media is associated with both beta-blocker exposure and cardiovascular disorders | journal=Arch Intern Med | year=1993 | pages=2033–40 | volume=153 | issue=17 | pmid=8102844 | doi=10.1001/archinte.153.17.2033}}</ref>
Pretreatment with corticosteroids has been shown to decrease the incidence of adverse reactions.<ref>{{cite journal |vauthors=Lasser EC, Berry CC, Talner LB, Santini LC, Lang EK, Gerber FH, Stolberg HO | title=Protective effects of corticosteroids in contrast material anaphylaxis | journal=Invest Radiol | year=1988 | pages=S193–4 | volume=23 Suppl 1 | pmid=3058630 | doi=10.1097/00004424-198809001-00035}}</ref><ref>{{cite journal |vauthors=Wittbrodt ET, Spinler SA | title=Prevention of anaphylactoid reactions in high-risk patients receiving radiographic contrast media | journal=Ann Pharmacother | year=1994 | pages=236–41 | volume=28 | issue=2 | pmid=8173143 | doi = 10.1177/106002809402800215 }}</ref>

Anaphylactoid reactions range from [[urticaria]] and itching, to [[bronchospasm]] and facial and laryngeal [[edema]]. For simple cases of urticaria and itching, an oral or intravenous antihistamine such as [[diphenhydramine]] is appropriate. For more severe reactions, including bronchospasm and facial or neck edema, albuterol inhaler, or subcutaneous or IV epinephrine, plus diphenhydramine may be needed. If respiration is compromised, an airway must be established prior to medical management.

Anaphylaxis to ionic (high osmolar) contrast agent injections occurred in two clusters of reactions on two occasions (1983 and 1987) in a single radiology clinic in London, Ontario. On each occasion, these anaphylactic reactions were associated with contamination of the injection by natural rubber components (disposable plastic syringes in the first case and rubber ampoule seals in the second case). The allergenic-toxic rubber leachate was MBT (mercaptobenzothiazole). This is a known allergen that becomes bound to plasma proteins, creating a hapten-protein complex – a signature mechanism in true IgE drug allergy and true anaphylactic reactions (not "anaphylactoid" reactions).
A Japanese syringe manufacturer, Terumo, implicated in syringe-related toxic laboratory cell culture effects in Australia in 1981, was instrumental in pro-actively making Japanese disposable syringes and ampoule seals free of natural rubber. Katayama's 1990 article in ''[[Radiology (journal)|Radiology]]'' showed that a new type of nonionic (low osmolar) contrast agent was associated with significantly fewer severe life-threatening reactions than the older ionic (high osmolar) contrast agents.<ref>{{cite journal |author1=Katayama H |author2=Yamaguchi K. |author3=Kozuka T. | year = 1990 | title = , "Adverse Reactions to Ionic and Nonionic Contrast Media. A Report from the Japanese Committee on the Safety of Contrast Media | url = | journal = Radiology | volume = 175 | issue = | pages = 621–28 | doi=10.1148/radiology.175.3.2343107|display-authors=etal}}</ref> By merchandizing the Katayama series reprints, manufacturers persuaded users worldwide to switch to the almost exclusive use of the expensive nonionic agents.

What was unknown to the Katayama researchers was that the ampoule seals of the "safer" nonionic contrast agents were made from artificial rubber, whereas the ionic agents were sealed with natural rubber. In 1987, it was the leaching of allergenic MBT from the rubber seals of ionic ampoules that caused a series of allergic reactions (including anaphylaxis) in a radiology office in Canada.<ref>{{cite journal | author = Hamilton Gavin | year = 1990 | title = Medical Rubber Anaphylaxis | doi = 10.1016/0140-6736(90)93165-l | journal = Lancet | volume = 336 | issue = | pages = 1453–1454 }}</ref> The worldwide hazard of MBT contamination of injections was unknown then and, as the World Health Organization reported it remains as an unknown hazard still – after three decades.<ref>Book review "The Nurses are Innocent," Lethal, odd and ‘new’ in pharmacovigilance. Uppsala Reports 61 - April 2013: Page 10–11.</ref>

The most significant study, proving that injections of ionic (high osmolar) agents are at least as safe as the newer, very expensive nonionics was published in ''Radiology'' in 1997.<ref>{{cite journal |author1=Lasser E.C. |author2=Lyon G.L. |author3=Berry C.C. | year = 1997 | title = Reports on Contrast Media Reactions: Analysis of Data from Reports to the U.S. Food and Drug Administration | url = | journal = Radiology | volume = 203 | issue = | pages = 605–10 | doi=10.1148/radiology.203.3.9169676 | pmid=9169676}}</ref> Lasser did not comment that the marked drop in the incidence of severe reactions with ionic agents was related to the removal of natural rubber contamination from ionic ampoule seals.

====Contribution of seafood and other allergies====
The term "iodine allergy" should be omitted because this kind of allergy does not exist.<ref>https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0042-110102</ref> Seafood "allergy" is no contraindication for the use of iodinated contrast materials, because in seafood allergy the immune system is directed against the muscle protein tropomyosin. While iodine levels in seafood are higher than in non-seafood items, the consumption of the latter exceeds that of the former by far and there is no evidence that the iodine content of seafood is related to reactions to seafood.<ref name="pmid9308442">{{cite journal |vauthors=Coakley F, Panicek D |title=Iodine allergy: an oyster without a pearl? |journal=AJR Am J Roentgenol |volume=169 |issue=4 |pages=951–2 |year=1997 |pmid=9308442 |doi=10.2214/ajr.169.4.9308442}}</ref> Available data suggest that seafood allergy increases the risk of a contrast-mediated reaction by approximately the same amount as allergies to fruits or those with asthma.<ref name="pmid1170768">{{cite journal |author=Shehadi W |title=Adverse reactions to intravascularly administered contrast media. A comprehensive study based on a prospective survey |journal=Am J Roentgenol Radium Ther Nucl Med |volume=124 |issue=1 |pages=145–52 |year=1975 |pmid=1170768 |doi=10.2214/ajr.124.1.145}}</ref> In other words, over 85% of patients with seafood allergies will not have an adverse reaction to iodinated contrast.<ref name="pmid9308442"/> Finally, there is no evidence that adverse skin reactions to iodine-containing topical antiseptics (e.g., [[povidone-iodine]]) are of any specific relevance to administration of I.V. contrast material.<ref name="pmid9308442"/><ref name="pmid2302848">{{cite journal |vauthors=van Ketel W, van den Berg W |title=Sensitization to povidone-iodine |journal=Dermatol Clin |volume=8 |issue=1 |pages=107–9 |year=1990 |pmid=2302848}}</ref>

===Contrast-induced nephropathy===
{{main article|Contrast-induced nephropathy}}
Contrast-induced [[nephropathy]] is defined as either a greater than 25% increase of serum creatinine or an absolute increase in serum creatinine of 0.5&nbsp;mg/dL.<ref name="pmid16436769">{{cite journal |vauthors=Barrett BJ, Parfrey PS |title=Clinical practice. Preventing nephropathy induced by contrast medium |journal=N. Engl. J. Med. |volume=354 |issue=4 |pages=379–86 |year=2006 |pmid=16436769 |doi=10.1056/NEJMcp050801}}</ref>


Patients receiving contrast via IV typically experience a hot feeling around the throat, and this hot sensation gradually moves down to the pelvic area.
===Effects on thyroid function===
A 2012 paper in the Journal of the American Medical Association reports that "Iodinated contrast media exposure is associated with subsequent development of incident [[hyperthyroidism]] and incident overt [[hypothyroidism]]."<ref>[http://archinte.jamanetwork.com/article.aspx?articleid=1108674]</ref><ref>[http://well.blogs.nytimes.com/2012/01/23/iodide-heart-scans-linked-to-thyroid-disease/]</ref>


The documentation of adverse drug reactions to contrast media should be documented precisely so that the patient receives adequate prophylaxis if contrast medium is administered again. <ref name=”pmid32142634”>{{cite journal |vauthors= Böhm IB, van der Molen AJ |title=Recommendations for Standardized Documentation of Contrast Medium-Induced Hypersensitivity |journal=J Am Coll Radiol |volume= 17|issue= 8|pages=1027-1028|year=2020 |pmid=32142634 |doi=10.1016/j.jacr.2020.02.007|hdl=1887/3184447 |hdl-access=free }}</ref>
===Drug interactions===
It has been recommended that [[metformin]], an oral antidiabetic agent, be stopped for 48 hours following the [[intravascular]] administration of contrast media and that the use of metformin not be resumed until renal function has been shown to be normal. The reasoning is that if the contrast medium causes kidney failure (as happens rarely) and the person continues to take metformin (which is normally excreted by the kidneys), there may be a toxic accumulation of metformin, increasing the risk of [[lactic acidosis]], a dangerous complication.<ref name="pmid9640281">{{cite journal |vauthors=Rasuli P, Hammond DI |title=Metformin and contrast media: where is the conflict? |journal=Can Assoc Radiol J |volume=49 |issue=3 |pages=161–6 |year=1998 |pmid=9640281 }}</ref>


===Contrast induced nephropathy===
However, guidelines published by the American College of Radiologists suggest this is not as important for patients who have [[creatinine|normal renal function]] and no evidence of acute kidney injury. If renal impairment is found before administration of the contrast, metformin should be withheld for 48 hours following the procedure and until renal function has returned to normal.<ref>{{Cite web|url=https://www.acr.org/~/media/37D84428BF1D4E1B9A3A2918DA9E27A3.pdf|title=ACR Manual on Contrast Media|last=American College of Radiology|first=|date=2016|website=|publisher=|page=46|access-date=6 January 2017 }}</ref>
{{Main|Contrast-induced nephropathy}}
Iodinated contrast may be [[nephrotoxicity|toxic to the kidneys]], especially when given via the arteries prior to studies such as catheter coronary angiography. Non-ionic contrast agents, which are almost exclusively used in [[computed tomography]] studies, have not been shown to cause CIN when given intravenously at doses needed for CT studies.<ref name="CIN_not_a_risk_factor">{{cite journal |last1=McDonald |first1=Robert |last2=McDonald |first2=Jennifer S. |last3=Carter |first3=Rickey E. |last4=Hartman |first4=Robert P. |last5=Katzberg |first5=Richard W. |last6=Kallmes |first6=David F. |last7=Williamson |first7=Eric E. |date=December 2014 |title=Intravenous Contrast Material Exposure Is Not an Independent Risk Factor for Dialysis or Mortality |journal=Radiology |volume=273 |issue=3 |pages=714–725 |pmid=25203000 |doi=10.1148/radiol.14132418 |doi-access= }}</ref>


===Thyroid dysfunction===
Previously, beta blockers have been assumed as risk factor for the acquisition of contrast medium-induced adverse reactions/hypersensitivity reactions. Due to recent investigations it became clear that beta blockers do not have the ability to increase the frequency of adverse reactions in concert with radiocontrast agents.<ref name="pmid27531627">{{cite journal |vauthors=Boehm I, Morelli J, Nairz K, Silva Hasembank Keller P, Heverhagen JT |title=Beta blockers and intravenous roentgen contrast materials; which risks do exist? |journal=Eur J Intern Med |volume=35 |issue=November |pages=e17-e18 |year=2016 |pmid=27531627 |doi=10.1016/j.ejim.2016.08.003}}</ref>
Iodinated radiocontrast can induce [[hyperthyroidism|overactivity]] (hyperthyroidism) and [[hypothyroidism|underactivity]] (hypothyroidism) of the thyroid gland. The risk of either condition developing after a single examination is 2–3 times that of those who have not undergone a scan with iodinated contrast. Thyroid underactivity is mediated by two phenomena called the [[Plummer effect|Plummer]] and [[Wolff–Chaikoff effect]], where iodine suppresses the production of thyroid hormones; this is usually temporary but there is an association with longer-term thyroid underactivity. Some other people show the opposite effect, called [[Jod-Basedow phenomenon]], where the iodine induces overproduction of thyroid hormone; this may be the result of underlying thyroid disease (such as nodules or [[Graves' disease]]) or previous iodine deficiency. Children exposed to iodinated contrast during pregnancy may develop hypothyroidism after birth and monitoring of the thyroid function is recommended.<ref>{{cite journal |vauthors=Lee SY, Rhee CM, Leung AM, Braverman LE, Brent GA, Pearce EN | title=A Review: Radiographic Iodinated Contrast Media-Induced Thyroid Dysfunction | journal=J Clin Endocrinol Metab | date=6 Nov 2014 | volume= 100| issue=2 | pmid=25375985 | doi=10.1210/jc.2014-3292 | pages=376–83 | pmc=4318903}}</ref>


==See also==
==See also==
{{Portal|Medicine}}
{{Portal|Medicine}}
*[[Contrast medium]]


==References==
==References==
{{Reflist|2}}
{{Reflist}}


==External links==
==External links==
*{{Commons category-inline|Radiocontrast agents}}
* {{Commons category-inline|Radiocontrast agents}}


{{Contrast media}}
{{Contrast media}}


{{Authority control}}
{{Authority control}}
{{Use dmy dates|date=August 2019}}


[[Category:Radiocontrast agents| ]]
[[Category:Radiocontrast agents| ]]
[[Category:Nephrotoxins]]

Latest revision as of 08:20, 16 October 2024

Radiocontrast agents are substances used to enhance the visibility of internal structures in X-ray-based imaging techniques such as computed tomography (contrast CT), projectional radiography, and fluoroscopy. Radiocontrast agents are typically iodine, or more rarely barium sulfate. The contrast agents absorb external X-rays, resulting in decreased exposure on the X-ray detector. This is different from radiopharmaceuticals used in nuclear medicine which emit radiation.

Magnetic resonance imaging (MRI) functions through different principles and thus MRI contrast agents have a different mode of action. These compounds work by altering the magnetic properties of nearby hydrogen nuclei.

Types and uses

[edit]

Radiocontrast agents used in X-ray examinations can be grouped in positive (iodinated agents, barium sulfate), and negative agents (air, carbon dioxide, methylcellulose).[1]

Iodine (circulatory system)

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Example of iodine based contrast in cerebral angiography
Main article: Iodinated contrast

Iodinated contrast contains iodine. It is the main type of radiocontrast used for intravenous administration. Iodine has a particular advantage as a contrast agent for radiography because its innermost electron ("k-shell") binding energy is 33.2 keV, similar to the average energy of x-rays used in diagnostic radiography. When the incident x-ray energy is closer to the k-edge of the atom it encounters, photoelectric absorption is more likely to occur. Its uses include:

Organic iodine molecules used for contrast include iohexol, iodixanol and ioversol.

Barium sulfate (digestive system)

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Example of a DCBE

Barium sulfate is mainly used in the imaging of the digestive system. The substance exists as a water-insoluble white powder that is made into a slurry with water and administered directly into the gastrointestinal tract.[citation needed]

  • Upper gastrointestinal series
  • Barium enema (large bowel investigation) and DCBE (double contrast barium enema).
  • Barium swallow (oesophageal investigation)
  • Barium meal (stomach investigation) and double contrast barium meal
  • Barium follow through (stomach and small bowel investigation)
  • CT pneumocolon / virtual colonoscopy

Barium sulfate, an insoluble white powder, is typically used for enhancing contrast in the GI tract. Depending on how it is to be administered the compound is mixed with water, thickeners, de-clumping agents, and flavourings to make the contrast agent. As the barium sulfate doesn't dissolve, this type of contrast agent is an opaque white mixture. It is only used in the digestive tract; it is usually swallowed as a barium sulfate suspension or administered as an enema. After the examination, it leaves the body with the feces.

Air

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As in the picture on the right where both air and barium are used together (hence the term "double-contrast" barium enema) air can be used as a contrast material because it is less radio-opaque than the tissues it is defining. In the picture it highlights the interior of the colon. An example of a technique using purely air for the contrast medium is an air arthrogram where the injection of air into a joint cavity allows the cartilage covering the ends of the bones to be visualized.

Before the advent of modern neuroimaging techniques, air or other gases were used as contrast agents employed to displace the cerebrospinal fluid in the brain while performing a pneumoencephalography. Sometimes called an "air study", this once common yet highly-unpleasant procedure was used to enhance the outline of structures in the brain, looking for shape distortions caused by the presence of lesions.

Carbon dioxide

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Main article: Carbon-dioxide angiography

Carbon dioxide also has a role in angioplasty. It is low-risk as it is a natural product with no risk of allergic potential. However, it can be used only below the diaphragm as there is a risk of embolism in neurovascular procedures. It must be used carefully to avoid contamination with room air when injected. It is a negative contrast agent in that it displaces blood when injected intravascularly.

Discontinued agents

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Thorotrast

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Thorotrast was a contrast agent based on thorium dioxide, which is radioactive. It was first introduced in 1929. While it provided good image enhancement, its use was abandoned in the late 1950s since it turned out to be carcinogenic. Given that the substance remained in the bodies of those to whom it was administered, it gave a continuous radiation exposure and was associated with a risk of cancers of the liver, bile ducts and bones, as well as higher rates of hematological malignancy (leukemia and lymphoma).[2] Thorotrast may have been administered to millions of patients prior to being disused.[citation needed]

Nonsoluble substances

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In the past, some non water-soluble contrast agents were used. One such substance was iofendylate (trade names: Pantopaque, Myodil) which was an iodinated oil-based substance that was commonly used in myelography. Due to it being oil-based, it was recommended that the physician remove it from the patient at the end of the procedure. This was a painful and difficult step and because complete removal could not always be achieved, iofendylate's persistence in the body might sometimes lead to arachnoiditis, a potentially painful and debilitating lifelong disorder of the spine.[3][4] Iofendylate's use ceased when water-soluble agents (such as metrizamide) became available in the late 1970s. Also, with the advent of MRI, myelography became much less-commonly performed.

Adverse effects

[edit]
Further information: Iodinated contrast

Modern iodinated contrast agents – especially non-ionic compounds – are generally well tolerated.[5] The adverse effects of radiocontrast can be subdivided into type A reactions (e.g. thyrotoxicosis), and type B reactions (hypersensitivity reactions: allergy and non-allergy reactions [formerly called anaphylactoid reactions]).[6]

Patients receiving contrast via IV typically experience a hot feeling around the throat, and this hot sensation gradually moves down to the pelvic area.

The documentation of adverse drug reactions to contrast media should be documented precisely so that the patient receives adequate prophylaxis if contrast medium is administered again. [7]

Contrast induced nephropathy

[edit]
Main article: Contrast-induced nephropathy

Iodinated contrast may be toxic to the kidneys, especially when given via the arteries prior to studies such as catheter coronary angiography. Non-ionic contrast agents, which are almost exclusively used in computed tomography studies, have not been shown to cause CIN when given intravenously at doses needed for CT studies.[8]

Thyroid dysfunction

[edit]

Iodinated radiocontrast can induce overactivity (hyperthyroidism) and underactivity (hypothyroidism) of the thyroid gland. The risk of either condition developing after a single examination is 2–3 times that of those who have not undergone a scan with iodinated contrast. Thyroid underactivity is mediated by two phenomena called the Plummer and Wolff–Chaikoff effect, where iodine suppresses the production of thyroid hormones; this is usually temporary but there is an association with longer-term thyroid underactivity. Some other people show the opposite effect, called Jod-Basedow phenomenon, where the iodine induces overproduction of thyroid hormone; this may be the result of underlying thyroid disease (such as nodules or Graves' disease) or previous iodine deficiency. Children exposed to iodinated contrast during pregnancy may develop hypothyroidism after birth and monitoring of the thyroid function is recommended.[9]

See also

[edit]

References

[edit]
  1. ^ Dong, Yuxy C; Cormode, David P. (2021). "Chapter 17. Heavy Elements for X-Ray Contrast". Metal Ions in Bio-Imaging Techniques. Springer. pp. 457–484. doi:10.1515/9783110685701-023. S2CID 233676619.
  2. ^ Grosche, B.; Birschwilks, M.; Wesch, H.; Kaul, A.; van Kaick, G. (6 May 2016). "The German Thorotrast Cohort Study: a review and how to get access to the data". Radiation and Environmental Biophysics. 55 (3): 281–289. doi:10.1007/s00411-016-0651-8. PMID 27154786. S2CID 45053720.
  3. ^ Dunlevy, Sue (10 December 2016). "Australians crippled and in chronic pain from dye used in toxic X-rays". The Daily Telegraph (Sydney). Retrieved 27 October 2017.
  4. ^ William P. Dillon; Christopher F. Dowd (2014). "Chapter 53 – Neurologic Complications of Imaging Procedures". Aminoff's Neurology and General Medicine (5th ed.). pp. 1089–1105.
  5. ^ Haberfeld, H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 978-3-85200-196-8.
  6. ^ Boehm I, Morelli J, Nairz K, Silva Hasembank Keller P, Heverhagen JT (2017). "Myths and misconceptions concerning contrast media induced anaphylaxis: a narrative review". Postgrad Med. 129 (2): 259–266. doi:10.1080/00325481.2017.1282296. PMID 28085538. S2CID 205452727.
  7. ^ Böhm IB, van der Molen AJ (2020). "Recommendations for Standardized Documentation of Contrast Medium-Induced Hypersensitivity". J Am Coll Radiol. 17 (8): 1027–1028. doi:10.1016/j.jacr.2020.02.007. hdl:1887/3184447. PMID 32142634.
  8. ^ McDonald, Robert; McDonald, Jennifer S.; Carter, Rickey E.; Hartman, Robert P.; Katzberg, Richard W.; Kallmes, David F.; Williamson, Eric E. (December 2014). "Intravenous Contrast Material Exposure Is Not an Independent Risk Factor for Dialysis or Mortality". Radiology. 273 (3): 714–725. doi:10.1148/radiol.14132418. PMID 25203000.
  9. ^ Lee SY, Rhee CM, Leung AM, Braverman LE, Brent GA, Pearce EN (6 November 2014). "A Review: Radiographic Iodinated Contrast Media-Induced Thyroid Dysfunction". J Clin Endocrinol Metab. 100 (2): 376–83. doi:10.1210/jc.2014-3292. PMC 4318903. PMID 25375985.
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