Iodinated contrast is a form of water-soluble, intravenous

radiocontrast agent 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 iod ...

containing

iodine Iodine is a chemical element; it has symbol I and atomic number 53. The heaviest of the stable halogens, it exists at standard conditions as a semi-lustrous, non-metallic solid that melts to form a deep violet liquid at , and boils to a vi ...

, which enhances the visibility of vascular structures and organs during

radiographic Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical ("diagnostic" radiography and "therapeu ...

procedures. Some pathologies, such as

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

, have particularly improved visibility with iodinated contrast. The

radiodensity Radiodensity (or radiopacity) is opacity to the radio wave and X-ray portion of the electromagnetic spectrum: that is, the relative inability of those kinds of electromagnetic radiation to pass through a particular material. Radiolucency or hypod ...

of iodinated contrast is 25–30

Hounsfield units The Hounsfield scale ( ), named after Sir Godfrey Hounsfield, is a quantitative scale for describing radiodensity. It is frequently used in CT scans, where its value is also termed CT number. Definition The Hounsfield unit (HU) scale is a linear t ...

(HU) per milligram of iodine per milliliter at a

tube voltage An X-ray tube is a vacuum tube that converts electrical input power into X-rays. The availability of this controllable source of X-rays created the field of radiography, the imaging of partly opaque objects with penetrating radiation. In contras ...

of 100–120 kVp.

Types

Iodine-based contrast media are usually classified as ionic or nonionic. Both types are used most commonly in radiology due to their relatively harmless interaction with the body and their solubility. Contrast media are primarily used to visualize vessels and changes in tissues on radiography and CT (computerized tomography). Contrast media can also be used for tests of the

urinary tract The human urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressu ...

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

and

fallopian tubes The fallopian tubes, also known as uterine tubes, oviducts or salpinges (: salpinx), are paired tubular sex organs in the human female body that stretch from the ovaries to the uterus. The fallopian tubes are part of the female reproductive sy ...

. 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. The iodine may be bound either in an organic (nonionic) 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 due to the high concentration of ions ( hyperosmolality). Organic agents which

covalent A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...

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. Organic iodine molecules used for contrast include

iohexol Iohexol, sold under the trade name Iodaque among others, is a contrast agent used for X-ray imaging. This includes when visualizing arteries, veins, ventricles of the brain, the urinary system, and joints, as well as during computed tomograph ...

iodixanol Iodixanol, sold under the brand name Visipaque, is an iodine-containing non-ionic radiocontrast agent. It is available as a generic medication. Medical uses The radio contrast agent is given intravenously for computed tomography (CT) imaging ...

, and

ioversol Ioversol ( INN; trade name Optiray) is an organoiodine compound that is used as a contrast medium. It features both a high iodine content, as well as several hydrophilic groups. It is used in clinical diagnostics including arthrography, angioca ...

. Iodine-based contrast media used nowadays 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 Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

, but for various purposes they can also be used intra-arterially, intrathecally (as in diskography of the spine) and intra-abdominally – just about any

body cavity A body cavity is any space or compartment, or potential space, in an animal body. Cavities accommodate organs and other structures; cavities as potential spaces contain fluid. The two largest human body cavities are the ventral body cavity, a ...

potential space In anatomy, a potential space is a space between two adjacent structures that are normally pressed together (directly apposed). Many anatomic spaces are potential spaces, which means that they are potential rather than realized (with their realiz ...

. Heating non-ionic contrast agent to human body temperature reduces its viscosity. The amount of iodine administered in children in the United States in 2010 was 272 to 740 mg/kg for CT scan. Iodine contrast agents are used for the following: *

Contrast CT Contrast CT, or contrast-enhanced computed tomography (CECT), is CT scan, X-ray computed tomography (CT) using radiocontrast. Radiocontrasts for X-ray CT are generally Iodinated contrast, iodine-based types. This is useful to highlight structure ...

s *

Angiography Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perfo ...

(''arterial investigations'') *

Venography Venography (also called phlebography or ascending phlebography) is a procedure in which an X-ray of the veins, a venogram, is taken after a special dye is injected into the bone marrow or veins. The dye has to be injected constantly via a cathete ...

(''venous investigations'') * VCUG (''

voiding cystourethrography Urination is the release of urine from the bladder through the urethra in placental mammals, or through the cloaca in other vertebrates. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, ...

'') * HSG ('' hysterosalpingogram'') * IVU (''intravenous

urography Pyelogram (or pyelography or urography) is a form of imaging of the renal pelvis and ureter. Types include: * Intravenous pyelogram – In which a contrast solution is introduced through a vein into the circulatory system. * Retrograde pyelogra ...

'')

Adverse effects

Iodinated contrast agents may cause allergic reactions, contrast-induced nephropathy,

hyperthyroidism Hyperthyroidism is a endocrine disease in which the thyroid gland produces excessive amounts of thyroid hormones. Thyrotoxicosis is a condition that occurs due to elevated levels of thyroid hormones of any cause and therefore includes hyperth ...

and possibly

metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome, ...

accumulation. However, there are no absolute contraindications to iodinated contrast, so the benefits needs to be weighted against the risks. Hypersensitivity towards iodinated contrast agent is associated with increase in

histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...

and

tryptase Tryptase () is the most abundant secretory granule-derived serine proteinase contained in mast cells and has been used as a marker for mast cell activation. Club cells contain tryptase, which is believed to be responsible for cleaving the hemagglu ...

concentration in blood.

Diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

(Benadryl) 50 mg orally or intravenously one hour before contrast administration can reduce the risk of

urticaria Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and typically ...

angioedema Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are ...

, and respiratory symptoms. An observational study conducted across 133,331 patients concluded that iodinated contrast injected through veins has more hypersensitivity reactions than when injected through arteries. However, the cause for this phenomenon is unknown. In people with

myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, ...

, older forms of iodinated contrast have caused an increased risk of exacerbation of the disease, but modern (low-osmolar) forms have no immediate increased risk.

Hypersensitivity reactions

Anaphylactoid reactions occur rarely, but can occur in response to injected as well as oral and rectal contrast and even retrograde

pyelography Pyelogram (or pyelography or urography) is a form of imaging of the renal pelvis and ureter. Types include: * Intravenous pyelogram – In which a contrast solution is introduced through a vein into the circulatory system. * Retrograde pyelogra ...

. They are similar in presentation to 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. Pretreatment with corticosteroids has been shown to decrease the incidence of adverse reactions. Anaphylactoid reactions range from

and itching, to

bronchospasm Bronchospasm or a bronchial spasm is a sudden bronchoconstriction, constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylat ...

and facial and laryngeal

edema Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

. For simple cases of urticaria and itching, an oral or intravenous antihistamine such as

diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

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 Radiology ( ) is the medical specialty that uses medical imaging to diagnose diseases and guide treatment within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiation), but tod ...

'' 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. 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. 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. The most significant study, proving that injections of ionic (high osmolar) agents are at least as safe as the newer, very expensive nonionic agents was published in ''Radiology'' in 1997. 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. Seafood "allergy" is not a contraindication for the use of iodinated contrast materials, because in seafood allergy the immune system is directed against the muscle protein

tropomyosin Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in many animal and fungal cells. In animals, it is an important component of the muscular system which works in conjunction with troponin to regulate muscle contraction. It ...

. 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. 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. In addition, those with an intolerance to alcohol should avoid use of this product due to chemical breakdown similar to ethyl alcohol. Studies show that B.A.C. has been shown to increase exponentially for up to 72 hours after contrast is administered, resulting in altered results of urine, blood, and breath alcohol screens. Those with history of severe contrast reaction will have six-fold increase risk of adverse reaction. Those with history of asthma will have six-fold increased risk to low-osmolar contrast media and 10-fold increased risk to high-osmolar contrast media. Over 85% of patients with seafood allergies will not have an adverse reaction to iodinated contrast. Finally, there is no evidence that adverse skin reactions to iodine-containing topical antiseptics (e.g.,

povidone-iodine Povidone-iodine (PVP-I), also known as iodopovidone, is an antiseptic used for skin disinfection before and after surgery. It may be used both to disinfect the hands of healthcare providers and the skin of the person they are caring for. It may ...

) are of any specific relevance to administration of I.V. contrast material. IL-2 medication poses no risk for the acquisition of adverse events by radiocontrast agents.

Contrast-induced nephropathy

Contrast-induced

nephropathy Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipap ...

is defined as either a greater than 25% increase of serum creatinine or an absolute increase in serum creatinine of 0.5 mg/dL. Iodinated contrast may be toxic to the kidneys, especially when given via the arteries prior to studies such as catheter coronary angiography. Nonionic contrast agents, which are almost exclusively used in

CT scan A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...

s, have not been shown to cause CIN when given intravenously at doses needed for CT studies.

Effects on thyroid function

Iodinated contrast media exposure can potentially cause incident

and incident overt

hypothyroidism Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...

." Hyperthyroidism is the effect of iodine being a substrate of thyroid hormones, and is then called the

Jod-Basedow phenomenon The Jod-Basedow effect (also Jod-Basedow syndrome and Jod-Basedow phenomenon) is hyperthyroidism following administration of iodine or iodide, either as a dietary supplement, for iodinated contrast medical imaging, or as a medication (mainly amio ...

. The risk is higher in those with an underlying

thyroid disease Thyroid disease is a medical condition that affects the structure and/or function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other ...

, such as

toxic multinodular goiter Toxic multinodular goiter (TMNG), also known as multinodular toxic goiter (MNTG), is an active multinodular goiter associated with hyperthyroidism. It is a common cause of hyperthyroidism in which there is excess production of thyroid hormones f ...

Graves' disease Graves' disease, also known as toxic diffuse goiter or Basedow's disease, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyro ...

, or

Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, Hashimoto's disease and autoimmune thyroiditis, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over ti ...

, where thyroid monitoring is indicated. Otherwise, for the general population, routine screening with thyroid function tests is generally not feasible.

Drug interactions

It has been recommended that

, 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 kidney 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 Lactic acidosis refers to the process leading to the production of lactate by anaerobic metabolism. It increases hydrogen ion concentration tending to the state of acidemia or low pH. The result can be detected with high levels of lactate and lo ...

, a dangerous complication. However, guidelines published by the American College of Radiologists suggest this is not as important for patients who have normal kidney function and no evidence of acute kidney injury. If kidney impairment is found before administration of the contrast, metformin should be withheld for 48 hours following the procedure and until kidney function has returned to normal. Contrast exposure may interfere with subsequent radioiodine treatment, causing unwanted delays in the management of

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck, ...

. 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 increase the frequency of adverse reactions in concert with radiocontrast agents.

Pregnancy

Iodinated contrast in

medical imaging in pregnancy Medical imaging in pregnancy may be Indication (medicine), indicated because of complications of pregnancy, pregnancy complications, intercurrent disease in pregnancy, intercurrent diseases or routine prenatal care. Options Options for medical ...

, when orally administered, is harmless. February 2016

Intravenous administration Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

of iodinated radiocontrast agents can cross the

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

and enter the

fetal circulation In humans, the circulatory system is different before and after birth. The fetal circulation is composed of the placenta, umbilical blood vessels encapsulated by the umbilical cord, heart and systemic blood vessels. A major difference between the ...

, but animal studies have reported no

teratogenic Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology caused by ...

mutagenic In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...

effects from its use. There have been theoretical concerns about potential harm of free iodide on the fetal

thyroid gland The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...

, but multiple studies have shown that a single dose of intravenously administered iodinated contrast medium to a pregnant mother has no effect on neonatal thyroid function. Nevertheless, it generally is recommended that radiocontrast only be used if absolutely required to obtain additional diagnostic information that will improve the care of the fetus or mother.

Breastfeeding

American College of Radiology The American College of Radiology (ACR), founded in 1923, is a professional medical society representing nearly 40,000 diagnostic radiologists, radiation oncologists, interventional radiologists, nuclear medicine physicians and medical physicists ...

(ACR) guidelines state that iodinated contrast administration to a breastfeeding mother is considered safe for both the mother and child. Still, mothers who remain concerned about any potential adverse effects to the child are recommended to have the option of abstaining from breastfeeding for 24 hours, with continued milk extraction such as by a

breast pump A breast pump is a mechanical device that Lactation, lactating women use to milking, extract milk from their breasts. They may be manual devices powered by hand or foot movements or automatic devices powered by electricity. Breast pumps come in sev ...

during that period. Mothers that opt for this for non-emergent exams may also use a breast pump to obtain milk before the exam in order to feed the child during the 24-hour abstinence period. What is also important, breastfeeding women should be asked whether they want to take a break from breastfeeding after CM administration.