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See also: Contrast medium

Radiocontrast agents (also simply contrast agents or contrast materials) are compounds used to improve the visibility of internal bodily structures in an X-ray image. RadiocontrastIn a medical setting a contrast medium is any Substance that is used to enhance the visibility of structures or fluids within the body X-radiation (composed of X-rays) is a form of Electromagnetic radiation.

Contrast agents are also used in MRI (Magnetic Resonance Imaging). Although MRI is usually considered a branch of radiology, it is not based on X-rays. MRI contrast agents are usually gadolinium-based, and work not by being radioopaque, but rather by altering the magnetic properties of nearby hydrogen nuclei. Gadolinium (ˌgædəˈlɪniəm is a Chemical element that has the symbol Gd and Atomic number 64

Contents

Types and uses

There are two basic types of contrast agents used in X-ray examinations. X-radiation (composed of X-rays) is a form of Electromagnetic radiation.

One type of contrast agent is based on barium sulfate, an insoluble white powder. Barium sulfate is a white crystalline solid with the chemical formula BaSO4 This is mixed with water and some additional ingredients to make the contrast agent. Water is a common Chemical substance that is essential for the survival of all known forms of Life. 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. Feces, faeces, or fæces (see spelling differences) is a waste product from an animal's digestive tract expelled through the Anus

The other type of contrast agent is based on iodine. Iodine (ˈaɪədaɪn ˈaɪədɪn or /ˈaɪədiːn/ from ιώδης iodes "violet" is a Chemical element that has the symbol I and Atomic 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 examination they are required for. Ionic agents have a poorer side effect profile. Organic compounds 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. There are many different molecules. Some examples of organic iodine molecules are iohexol, iodixanol, ioversol. Iodine based contrast media are water soluble and harmless to the body. These contrast agents are sold as clear colorless water solutions, the concentration is 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 (the spine) and intraabdominally - just about any body cavity or potential space. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein.

An older type of contrast agent, Thorotrast was based on thorium dioxide, but this was abandoned since it turned out to be carcinogenic. Thorotrast is a suspension containing particles of the radioactive compound Thorium dioxide, ThO2 used as a Contrast medium in Thorium dioxide (ThO2 also called thorium(IV oxide (IUPAC is a white crystalline powder The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation

Commonly used iodinated contrast agents
Compound Name Type Iodine Content Osmolality Level
Ionic Diatrizoate (Hypaque 50) Ionic Monomer 300 1550 High Osmolar
Ionic Metrizoate (Isopaque Coronar 370) Ionic 370 2100 High Osmolar
Ionic Ioxaglate (Hexabrix) Ionic dimer 320 580 Low Osmolar
Non-Ionic Iopamidol (Isovue 370) Non-ionic monomer 370 796 Low Osmolar
Non-Ionic Iohexol (Omnipaque 350) Non-ionic 350 884 Low Osmolar
Non-Ionic Ioxilan (Oxilan) Non-ionic Low Osmolar
Non-Ionic Iopromide Non-ionic Low Osmolar
Non-Ionic Iodixanol (Visipaque 320) Non-ionic dimer 320 290 Iso Osmolar

Adverse effects

Modern iodinated contrast agents are safe drugs; adverse reactions exist but they are uncommon. Diatrizoic acid (or its anionic form Diatrizoate) also known as amidotrizoic acid or 35-Diacetamido-246-triiodobenzoic acid is a Radiocontrast agent containing Iohexol is a contrast agent, sold under the trade name Omnipaque. Ioxilan is a diagnostic Contrast agent. It is injected Intravenously before taking X-ray images to increase arterial contrast in the final Iodixanol, is a contrast agent sold under the trade name Visipaque. The major side effects of radiocontrast are anaphylactoid reactions and contrast-induced nephropathy.

Anaphylactoid reactions

Anaphylactoid reactions occur rarely (Karnegis and Heinz, 1979; Lasser et al, 1987; Greenberger and Patterson, 1988), but can occur in response to injected as well as oral and rectal contrast and even retrograde pyelography. Anaphylaxis is an acute systemic (multi-system and severe Type I Hypersensitivity allergic reaction in humans and other Mammals They are similar in presentation to anaphylactic reactions, but are not caused by an IgE-mediated immune response. Anaphylaxis is an acute systemic (multi-system and severe Type I Hypersensitivity allergic reaction in humans and other Mammals Patients with a history of contrast reactions, however, are at increased risk of anaphylactoid reactions (Greenberger and Patterson, 1988; Lang et al, 1993). Pretreatment with corticosteroids has been shown to decrease the incidence of adverse reactions (Lasser et al, 1988; Greenberger et al, 1985; Wittbrodt and Spinler, 1994).

Anaphylactoid reactions range from urticaria and itching, to bronchospasm and facial and laryngeal edema. Bronchospasm is a sudden constriction of the muscles in the walls of the Bronchioles It is caused by the release ( Degranulation) of substances from Mast cells Oedema (or Edema in American English formerly known as dropsy or hydropsy, is the increase of Interstitial fluid in any organ &mdash swelling For simple cases of urticaria and itching, Benadryl (diphenhydramine) oral or IV is appropriate. Pharmacological action Diphenhydramine (dye fen hye' dra meen works by blocking the effect of histamine at H1 receptor sites 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.

Contribution of seafood and other allergies

It must be noted that suspicion of seafood "allergy", often based more on medical myth than fact, is not a sufficient contraindication to the use of iodinated contrast material. A relationship between iodine levels in seafood and seafood allergy is part of medical lore. 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. [1] Available data suggests that seafood allergy increases the risk of a contrast-mediated reaction by approximately the same amount as allergies to fruits or those with asthma. [2] In other words, over 85% of patients with seafood allergies will not have an adverse reaction to iodinated contrast. [1] Finally, there is no evidence that adverse skin reactions to iodine-containing topical antiseptics (e. g. , Betadine, Povidine) are of any specific relevance to administration of I. V. contrast material. [1][3]

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. Nephropathy refers to damage to or disease of the Kidney. An older term for this is nephrosis. 5 mg/dL. [4]

To minimize the risk for contrast-induced nephropathy, various actions can be taken if the patient has predisposing conditions. These have been reviewed in a meta-analysis. In Statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses [5] A separate meta-analysis addresses interventions in for emergent patients with baseline renal insufficiency. In Statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses [6]

Three factors have been associated with an increased risk of contrast-induced nephropathy: preexisting renal insufficiency (such as Creatinine clearance < 60 mL/min [1. Renal failure or kidney Renal function, in Nephrology, is an indication of the state of the Kidney and its role in Renal physiology. 00 mL/s] - online calculator), preexisting diabetes, and reduced intravascular volume. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc [7][8]

A clinical prediction rule is available to estimate probability of nephropathy (increase ≥25% and/or ≥0. A clinical prediction rule is type of medical research study in which researchers try to identify the best combination of Medical sign, Symptoms, and other findings 5 mg/dl in serum creatinine at 48 h)[9]:

Risk Factors:

or
  • 2 for 40–60 mL/min/1. Renal function, in Nephrology, is an indication of the state of the Kidney and its role in Renal physiology. 73 m2
  • 4 for 20–40 mL/min/1. 73 m2
  • 6 for < 20 mL/min/1. 73 m2

Scoring:
5 or less points

6–10 points

11–16 points

>16 points

Choice of contrast agent

The osmolality of the contrast agent is believed to be of great importance in contrast-induced nephropathy. Osmolarity is a measure of the osmoles of solute per Liter of solution while the osmolality is a measure of the osmoles of Solute per Kilogram Ideally, the contrast agent should be iso-osmolar to blood. Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products Modern iodinated contrast agents are non-ionic, the older ionic types caused more adverse effects and are not used much anymore.

Iso-osmolar, nonionic contrast media may be the best according to a randomized controlled trial. A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare [10]

Hypo-osmolar, non-ionic contrast agents are beneficial if iso-osmolar, nonionic contrast media is not available due to costs. [11]

Hydration with or without bicarbonate

Administration of sodium bicarbonate 3 mL/kg per hour for 1 hour before , followed by 1 mL/kg per hour for 6 hours after contrast was found superior to plain saline on one randomized controlled trial of patients with a creatinne of at least 1. A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare 1 mg/dL (97. 2 µmol/L) . [12] To make the solution, the study used 154 mL of 1000 mEq/L sodium bicarbonate to 846 mL of 5% dextrose. This is approximately three 50 ml ampules of bicarbonate in 850 ml of water with 5% dextrose. This was subsequently corroborated by a multi-center randomized controlled trial, which also demonstrated that IV hydration with sodium bicarbonate was superior to 0. A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare 9% normal saline[13]. The renoprotective effects of bicarbonate are thought to be due to urinary alkalinization, which creates an environment less amenable to the formation of harmful free radicals. In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell [14].

Alternatively, one randomized controlled trial of patients with a creatinine over 1. A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare 6 mg per deciliter (140 µmol per liter) or creatinine clearance below 60 ml per minute used 1 ml/kg of 0. 45 percent saline per per hour for 6-12 hours before and after the contrast. [15]

Methylxanthines

Adenosine antagonists such as the methylxanthines theophylline and aminophylline, may help[6] although studies have conflicting results. Adenosine is a Nucleoside composed of a Molecule of Adenine attached to a Ribose sugar molecule ( Ribofuranose) moiety via a β-N9- Xanthine (ˈzænθiːn ˈzænθaɪn] (37-dihydro-purine-26-dione is a Purine base found in most body tissues and fluids and in other organisms Theophylline, also known as dimethylxanthine, is a Methylxanthine drug used in therapy for Respiratory diseases such as COPD or Asthma Aminophylline is a Bronchodilator Drug combination that contains Theophylline and Ethylenediamine in 21 ratio [16] The best studied dose is 200 mg of theophylline given IV 30 minutes before contrast administration. [17][18]

N-acetylcysteine

N-acetylcysteine (NAC) 600 mg orally twice a day, on the day before and of the procedure if creatinine clearance is estimated to be less than 60 mL/min [1. 00 mL/s]) may reduce nephropathy. [19]. A randomized controlled trial found higher doses of NAC (1200-mg IV bolus and 1200 mg orally twice daily for 2 days) benefited (relative risk reduction of 74%) patients receiving coronary angioplasty with higher volumes of contrast[20]. A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare The relative risk reduction is a measure used in Epidemiology.

Since publication of the meta-analyses, two small and underpowered negative studies, one of IV NAC[21] and one of 600 mg give four times around coronary angiography[22], found statistically insignificant trends towards benefit. In Statistics, a result is called statistically significant if it is unlikely to have occurred by Chance.

Some authors believe the benefit is not overwhelming. [23] The strongest results were from an unblinded randomized controlled trial that used NAC intravenously. The blind method is a part of the Scientific method, used to prevent research outcomes from being influenced by either the Placebo effect or the Observer A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare [24] A systematic review by Clinical Evidence concluded that NAC is "likely to beneficial" but did not recommend a specific dose. A systematic review is a Literature review focused on a single question which tries to identify appraise select and synthesize all high quality research evidence relevant to [25] One study found that the apparent benefits of NAC may be due to its interference with the creatinine laboratory test itself. [26] This is supported by a lack of correlation between creatinine levels and cystatin C levels. Cystatin C or Cystatin 3 (formerly Gamma trace, post-gamma-globulin or neuroendocrine basic polypeptide a Protein encoded by the CST3

In one study 15% of patients receiving NAC intravenously had allergic reactions. [24]

Prophylactic hemodialysis

Patients with chronic renal insufficiency and a creatinine over 309. Renal failure or kidney 4 µmol/L (3. 5 mg. dl) who have elective coronary catheterization, a randomized controlled trial found benefit from prophylactic hemodialysis[27]

Other interventions

Other pharmacological agents, such as furosemide, mannitol, dopamine, and atrial natriuretic peptide have been tried, but have either not had beneficial effects, or had detrimental effects. A coronary catheterization is a Minimally invasive procedure to access the Coronary circulation and blood filled chambers of the Heart using a Catheter A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare Furosemide ( INN) or frusemide (former BAN) is a Loop diuretic used in the treatment of congestive Heart failure and Edema Mannitol or hexan-123456-hexol (C6H8(OH6 is a Polyol that is used as an osmotic Diuretic agent and a Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Atrial natriuretic peptide ( ANP) atrial natriuretic factor ( ANF) or atriopeptin, is a protein ( Polypeptide) Hormone secreted [15][28] Of course, limiting the total contrast volume also aids greatly in reducing the incidence of contrast nephropathy.

References

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See also

RadiocontrastIn a medical setting a contrast medium is any Substance that is used to enhance the visibility of structures or fluids within the body
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