Radiological contrast

Femoral Angiography with CO2 as a contrast.

Radiological contrasts are radiopaque substances, which applied by different routes of administration (oral, rectal, intravenous, etc.) can be used, during an X-ray or radiographic examination, to facilitate and/or improve the visualization of different organs or fluids of our body for diagnostic purposes. Radiological contrasts are also used for magnetic resonance techniques.

These substances improve visualization as they produce an increase in the difference in density between the various tissues.

For the selection of substances as a radiological contrast medium, some characteristics have been defined that a supposed ideal contrast medium should have:

• It must be pharmacologically inert and chemically stable.
• preferably non-ionic.
• It must be hydrosoluble and have the same osmolarity as blood.
• It should not be toxic, nor should it be degraded or metabolized, and should be eliminated as quickly as possible.

However, not all contrast media currently used in the clinic meet all these characteristics.

We distinguish two types of contrasts: negative and positive.

Negative radiological contrasts

Their name is due to the fact that they absorb less radiation than organs and body fluids; in such a way that the organs or tissues appear more opaque than the cavities where the contrast medium is found.

The main radiological contrast media belonging to this group are gases, soluble in blood and rapidly eliminable, such as oxygen and carbon dioxide.

They are mainly used to visualize the gastrointestinal tract, and can be administered both orally and rectally.

Other examples of negative contrasts are: air (generally administered rectally to visualize the colon) and effervescent powder or sodium bicarbonate (used orally to visualize structures between the esophagus and duodenum).

Carbon dioxide

Carbon dioxide is well tolerated by patients since it is not absorbed, and its most frequent indications are in patients with renal failure and/or with a history of allergy to iodinated contrast.

Positive radiological contrasts

Positive radiological contrasts are characterized by being substances that are more radiopaque than the organs or fluids in their vicinity; This is because they usually have a high atomic number, which allows them to absorb or attenuate a large amount of radiation. Within this group, barylated and iodinated contrasts stand out mainly.

• Positrons: This is radiopharmacs.

Gadolinium

It is a chemical element that is part of the lanthanide family. As a contrast medium it is mainly used in magnetic resonance imaging; It is characterized by being administered intravenously, and is eliminated via the kidneys.

It must be taken into account that gallidonium in its free form is toxic, therefore its use as a contrast medium requires binding to a chelating agent; in such a way that this union makes it a non-toxic substance, although it is true that this union depends directly on the structure that the chelator presents.

At the usual dose of this contrast medium (0.1 to 0.2 mmol/kg) most reactions are mild, such as feeling hot or cold, nausea, headache, dizziness, or itching. Allergic reactions such as rash, urticaria or bronchospasm are very rare. Gadolinium has also been related to nephrotoxicity, causing nephrogenic systemic fibrosis, which is a rare but very serious disease that can endanger the patient's life; It is fundamentally characterized by an increase in the formation of connective tissue in the skin, joints, muscles and internal organs.

Many drugs with gadolinium have been withdrawn from the market because it was observed that part of the gadolinium was not completely eliminated, and those that released more gave rise to the formation of brain deposits. although it is true that no symptoms or disorders related to said deposits have been identified.

Even so, and as a precaution, these drugs were withdrawn by the AEMPS (Spanish Agency for Medicines and Health Products), and those that have been maintained have been recommended to be used when strictly necessary, and at the lowest possible dose.

It has also been observed that these deposits can form in other organs, and have been related to side effects that these drugs can cause.

Nephrogenic systemic fibrosis is the mechanism by which gadolinium causes such damage, it is believed to be due to its ability to cause the release of cytokines through stimulation of skin macrophages (by free Gd ions) or peripheral blood monocytes (by chelator-Gd complexes).

These processes of macrophage activation, release of proinflammatory cytokines cause the differentiation of fibrocytes in the blood and the activation of fibroblasts, consequently generating a response that creates collagen deposits and fibrosis. It has been proven that the presence of renal failure contributes to the release of gadolinium through increased transmetalation. The greater the proportion of gadolinium not bound to the chelator (free gadolinium), the greater the damage because it has a greater activation capacity.

Radiological barium contrasts

The barium is used in the form of barium sulfate powder (BaSO₄), which is mixed with water to form a suspension.

Regarding its main characteristics, it stands out the absence of activity (it has no pharmacological activity) and toxicity (since it is not absorbed), in addition, it has an excellent opacification capacity and does not produce false positives.

It is used as a contrast medium to visualize structures in the gastrointestinal tract, and can be administered both orally and rectally.

It is contraindicated in situations in which any alteration of the gastrointestinal system is suspected, such as intestinal perforation, gastrointestinal tract obstruction, peritoneal irritation, pyloric stenosis, fistulas, etc.

Barium sulfate is the positive radiological contrast that presents the least toxicity. Although a priori it seems a paradox since barium is a heavy metal, whose soluble compounds present a high toxicity, these compounds practically lack toxicity due to their low solubility and consequently the impossibility of absorption. Hence, it is contraindicated in those situations in which there may be absorption of this compound, such as intestinal perforation. Likewise, allergic reactions are very rare.

Iodinated radiological contrasts

This is the most important group of contrast media, since they are the most widely used. They are characterized by high contrast density and low toxicity.

Its chemical structure corresponds to an iodinated benzoic nucleus.

Classification

Thus, they can be divided into monomeric (they have a single benzoic nucleus) and dimeric (two benzoic nuclei); thus giving rise to four groups of iodinated contrasts:

• Monomeric Ionics: They have a high osmolarity.

• Dimeric Ionics: They have low osmolarity.

• Non-ionic monomericals: they have low osmolarity and a higher rate of efficacy compared to monomeric ion, resulting in a greater attenuation of X-rays.

• Non ionic dimeric: are isoosmolars. Its main advantages are a higher rate of efficacy, and a lower renal toxicity; however, they have the inconvenience of more viscosity; they also have a higher incidence of skin-type adverse effects.

The main difference between ionic and non-ionic is the replacement of the carboxyl radical (-COOH) of ionic, by a hydroxyl radical (-OH), which means that they do not dissociate and therefore have lower osmolarity.

Also, due to this characteristic, they present better neural tolerance, bind less to plasmatic proteins, and have a lower incidence of adverse effects; however, they are more expensive.

Features

Iodinated contrasts can be administered both orally and intravenously, and depending on the route of administration, they will present different pharmacokinetic characteristics.

Iodinated contrasts administered orally are poorly absorbed and are easily eliminated rectally, while those administered intravenously are practically completely eliminated by the kidneys, and only 2% is excreted through the bile.

It is necessary to distinguish between ionic and non-ionic contrast media in terms of their toxicity.

• The non-ionic contrast media, by incorporating in its structure a group that prevents the dissociation of the radical carboxyl, are to behave as an electrically neutral substance in dissolution (then its name). This physicochemical property prevents them from presenting the electric charge, and therefore they will not present the toxicity of the ion compounds.

• Ionic contrast media when contacting the aqueous solution of the organism is dissociated, this gives rise to the formation of anion (which is the one that exerts the action of contrast) hence it is known as ionic. This anion presents the ability to influence different electrophysiological processes of the organism, responsible for the toxic effects:
  • effects on hemodynamics (especially in arteryography and coronaryography, since it is in these tests for longer and more directly with these structures): to cause a displacement of sodium electrolytes, potassium and calcium, which is a negative inotropo effect that explains cardiac depression.
  • Modification of the volume of circulating blood: after the injection of contrast media there is an increase in the volume of circulating blood (hypervolemia), which is due to the hyperosmolality of the contrast media, resulting in a water displacement from extravascular space to intravascular. Therefore the greater the osmolarity (which expresses the number of particles in solution) of the greater contrast medium will be its influence on the volume of blood.
  • effects on the morphology of erythrocytes: erythrocytes suffer a deformation from hyperosmolality. This causes dehydration of the same giving rise to a retraction and with it a change of form.
  • effects on CNS (central nervous system): may cause an injury to BHE, although this depends on the concentration of MC, the hypersomolality of the solution, the changes of viscosity of the blood, the contact time of MC over the cerebral vessels and the chemotoxicity of the molecule. They influence the entry of the phosphorus into the brain, as well as the micro circulation, also affect the content of sodium, calcium and meglumina, causing a change in the permeability of the BHE. All these toxicodynamic processes are expressed with: vasovagal reaction, headache, dizziness, impairment of the sensory, decreased vision, seizures.
  • hypersensitivity reactions: through pseudo-allergic mechanisms that involve a direct release of different mediators, as well as active processes of various plasma protein systems, including activation of the Complement, interaction with the Coagulation and Fibrinolysis System. A true antigen-antibody reaction has not been demonstrated.
  • kidney effects: nephrotoxicity. Renal perfusion at the presence of the contrast medium experiences biphasic behavior: in the first 20 minutes the perfusion increases and then follows a decrease in the medulla perfusion, which can last hours until days. This presupposes that by increasing perfusion, more toxicity is in contact with the structures of the kidney but also this lasting for a very long time due to the decrease in perfusion that occurs later. In addition, it causes an imbalance of local vasoactive mediators, vasoconstrictors and vasodilators (such as nitric oxide, prostaglandins, adenosine, endothelin and reactive oxygen species (ROS)), predominating renal vasoconstriction. The increase in tubular viscosity causes obstruction of the tubular light of the nephrene, followed by release of ROS and generating acute tubular damage. In addition, the increase in osmolarity causes a very marked excretion of water and sodium, which raises the intratubular pressure that ultimately reduces TFG and contributes to the pathogenesis of IRA (Aguda Renal Insufficiency).

They are responsible for the toxic sign: contrast-induced nephropathy, which is the most important adverse reaction caused by iodinated contrasts. Although the exact mechanism is not fully understood, it is thought that the toxicodynamic mechanism is as follows: the chemotoxicity exerted by the contrast medium on the nephron generates the production of ROS (oxygen free radicals) and therefore a cytotoxic effect that It presents with oxidative stress and activation of proinflammatory cytokines. This leads to inhibition of tubular protein reabsorption, vacuolation, apoptosis, and necrosis. The oxidative cascade ends in hypoxia in the renal tubules and loss of nephrons.