Side effects of contrast agents

The use of radiocontrast preparations poses the greatest danger for patients because of the high incidence and severity of complications. The harmful effects of water-soluble radiocontrast agents (RCS) used for excretory urography, renal CT, AGP and CT angiography, as well as other studies of the kidneys and urinary tracts, are related to the chemotactic effect of iodine and carboxyl groups on cells; with osmotic toxicity and local ion imbalance arising in the lumen of the vessel during the bolus injection of ionic radiopaque agents. The phenomenon of osmotic toxicity is a multiple increase in osmotic pressure at the injection site, which causes dehydration and damage to endothelial cells and blood cells. As a result, red blood cells lose their elasticity and the ability to change shape when moving through capillaries, an imbalance exists between the formation of endothelin, the endothelial relaxing factor (NO), the activation of other biologically active molecules is activated, regulation of vascular tone and microcirculation is disturbed, thromboses occur.

The toxicity of PKC is determined by the structure of their molecule and its ability to dissociate in an aqueous solution into ions. Until recently, only ionic or dissociating  radiopaque agents (urographine, veropain, etc.) were used, which consisted of salts dissociating into cations and anions. They are characterized by high osmolarity (5 times higher than in blood plasma), so also called vysokoosmolyarnymi contrast media and may cause local ion imbalance. When they are used, side effects often develop, even to the heaviest. More safe are nonionic or nondissociating, low osmolar  radiocontrast agents (yogexol, iopromide, iodixanol). They do not dissociate into ions, are characterized by a higher ratio of the number of iodine atoms to the amount of drug particles per unit volume of solution (i.e., good contrast is provided at lower osmotic pressures), iodine atoms are protected by hydroxyl groups, which reduces chemotoxicity. At the same time, the cost of low osmolar radiocontrast agents is several times higher than that of high osmolarity. In addition, radiopaque agents are divided in their structure into monomeric and dimeric, depending on the number of benzene rings with built-in iodine atoms. With the use of dimeric preparations containing six instead of three iodine atoms in one molecule, a lower dose of the drug is required, which reduces the osmotoxicity. By the mechanism of development, side effects are divided into:

• anaphylactoid, or unpredictable (anaphylactic shock, Quincke edema, urticaria, bronchospasm, hypotension);
• direct toxic (nephrotoxicity, neurotoxicity, cardiotoxicity, etc.);
• local (phlebitis, necrosis of soft tissues at the injection site).

Anaphylactoid, or unpredictable, reactions to iodine-containing contrast media are named because the cause and exact mechanism of their development are not known, although certain conditions increase their risk. There is no clear relationship between their severity and the dose of the drug administered. A certain role is played by the activation of the secretion of serotonin and histamine. The difference between anaphylactoid reactions and true anaphylaxis in practice is not significant, since the symptoms and treatment measures do not differ with them.

By severity, side effects are divided into mild (not requiring intervention), moderate (requiring treatment, but not life-threatening) and severe (life-threatening or disabling).

To light side effects include the appearance of sensations of heat, dry mouth, nausea, lack of air, headache, mild dizziness. They do not require treatment, but they can be harbingers of more severe effects. If they come before the completion of the contrast agent, it is necessary to stop it. Without removing the needle from the vein, continue to monitor the patient, prepare medicines in case of development of more severe complications.

With the development of side effects of moderate severity (severe nausea, vomiting, rhinoconjunctivitis, chills, itching, urticaria, edema Quincke), antidote - sodium thiosulfate (10-30 ml 30% solution intravenously), adrenaline (0.5-1.0 ml 0.1% solution subcutaneously), antihistamines - diphenhydramine (1-5,0 ml 1% solution intramuscularly), chloropyramine (1-2,0 ml 2% solution intramuscularly), prednisolone (30-90 mg intravenously in glucose solution) . In the case of tachycardia, a drop in blood pressure, the appearance of pallor, adrenaline (0.5-1.0 ml intravenously) is added, oxygen inhalation in a volume of 2-6 l / min is started. When signs of bronchospasm appear, bronchodilators are prescribed in the form of inhalations.

With the development of severe anaphylactoid reaction or true anaphylactic shock (pallor, sharp drop in blood pressure, collapse, tachycardia, asthmatic status, convulsions), it is necessary to call a resuscitator, establish a system for intravenous infusions and begin inhalation of oxygen 2-6 l / min. Intravenously injected sodium thiosulfate (10-30 ml 30% solution), adrenaline 0.5-1.0 ml 0.1% solution, chloropyramine 1-2.0 ml 2% solution or diphenhydramine 1-2.0 ml 1% solution , hydrocortisone 250 mg in isotonic sodium chloride solution. If necessary, an intubation and artificial ventilation of the lungs is performed by the resuscitator.

The development of such a serious complication as acute heart failure can lead to a disruption in the regulation of the heart (hyperactivation of the parasympathetic effect, leading to severe bradycardia and a decrease in cardiac output), myocardial damage due to its ischemia and direct toxic action of the contrast agent with the development of arrhythmia and the drop in pump function heart, a sharp increase in postnagruzka in the large and small circle of circulation due to vasoconstriction and disturbance of microcirculation. With hypotension, resulting from vagal vascular reaction and associated, in contrast to anaphylactoid hypotension, with pronounced bradycardia, in addition to intravenous administration of isotonic sodium chloride solution, atropine (0.5-1.0 mg intravenously) is used. In acute left ventricular failure, intravenously injected inotropic drugs (dopamine, 5-20 mkg / kg / min). At normal or high blood pressure, nitroglycerin (0.4 mg under the tongue every 5 minutes or 10-100 μg / min), sodium nitroprusside (0.1-5 μg / kg / min) to reduce afterload is used to reduce afterload.

NB! Adverse reactions to contrast agents in an anamnesis are an absolute contraindication for their repeated application.

Risk factors for complications when using iodine-containing contrast media:

• previous allergic reactions to medications;
• an allergy in the anamnesis;
• bronchial asthma;
• severe diseases of the heart, lungs;
• dehydration;
• chronic renal failure;
• elderly and senile age.

Prevention of complications consists in careful collection of anamnesis and examination before examination by the attending physician in order to identify risk factors. In the presence of at least one of them, and especially when combined, a careful and rigorous assessment of the relationship between the potential benefits and the dangers of the planned study is required. It should only be carried out if its results can affect the tactics of treatment and, by doing so, improve the prognosis and quality of life of the patient. The most important preventive measure is the use of low-osmolar (non-ionic) PCs, at least in patients at risk. According to numerous studies, the incidence of side effects with the use of high osmolarity contrast agents is 5-12%, low-osmolar contrast media - 1-3%. In the event of a reaction, the assistance is already in the diagnostic room, where the necessary set of medicines must be available. In some centers, prednisolone is premedicated to patients at risk for the prevention of anaphylactoid reactions (50 mg orally for 13, 5 and 1 hour before the contrast agent is administered). However, there is no conclusive evidence that this preventive measure significantly reduces the risk of complications, therefore, its wide implementation should be considered insufficiently justified.

Nephrotoxicity of PKC requires special consideration. It consists of a direct toxic effect of the drug on the epithelium of the renal tubules and the renal endothelium, as well as osmotic toxicity. There is severe endothelial dysfunction with increased production of both vasopressor and vasodilating agents of endothelin, vasopressin, prostaglandin E ₂, endothelial relaxing factor (NO), atrial natriuretic peptide; However, there is an earlier depletion of the depressor system with a predominance of vasoconstriction. Because of this, as well as increasing blood viscosity and worsening of microcirculation, glomerular perfusion is broken, ischemia and hypoxia tubulointerstitia develop. In conditions of hypoxia and increased osmotic loading of the epithelial cells of the renal tubules, their death occurs. One of the factors affecting the epithelium of the renal tubules is the activation of lipid peroxidation and the formation of free radicals. Fragments of the destroyed cells form protein cylinders and can cause obstruction of the renal tubules. Clinically, kidney damage is manifested by proteinuria and impaired renal function - from reversible hypercreatininaemia to severe acute renal failure, which can occur with or without oliguria. The prognosis for the development of acute renal failure in response to the introduction of radiocontrast agents is serious. Each third patient with an oliguric acute renal failure has an irreversible decrease in kidney function, while half need constant treatment with hemodialysis. In the absence of oliguria, chronic renal failure develops in every fourth patient, and one in three of them needs constant hemodialysis treatment.

The proven risk factors for acute renal failure with the use of radiocontrast agents largely coincide with the risk factors for extrarenal complications. These include:

• chronic renal insufficiency;
• diabetic nephropathy;
• severe congestive heart failure;
• dehydration and hypotension;
• high dose and frequency of repeated administration of radiocontrast agents.

If in the general population the nephrotoxicity of radiocontrast agents, defined as the increase in serum creatinine level by more than 0.5 mg / dl or more than 50% of the baseline level, is observed in 2-7% of cases, in patients with impaired renal function (creatinine serum more than 1.5 mg / dL) or other proven risk factors, it is observed in 10-35% of cases. In addition, it should take into account such possible risk factors for impaired renal function, such as hypertension, widespread atherosclerosis, impaired liver function, hyperuricemia. The adverse effect on the risk of nephrotoxicity of myeloma and diabetes mellitus without kidney damage has not been proven.

Prevention of acute renal failure with PKC includes:

• accounting for risk factors and contraindications;
• conducting research with CSW in patients at risk, only in cases where its results can significantly affect the prognosis;
• use of safer low-osmolar drugs;
• the use of the lowest possible doses;
• hydration of patients [1.5 ml Dkgxh)] for 12 h before and after the study;
• normalization of blood pressure.

Among the medical prescriptions offered for the prevention of acute renal failure with the use of radiocontrast agents, only hydration significantly improves the prognosis of patients. The effectiveness of other methods based on prospective clinical studies is questionable (administration of dopamine, mannitol, calcium antagonists) or insufficient evidence (the appointment of acetylcysteine).

In MRI for the purpose of contrasting, preparations containing rare-earth metal gadolinium, whose atoms possess special magnetic properties, are used. The toxicity of gadolinium preparations is significantly lower (by 10 or more times compared with iodine-containing PKCs) due to the fact that its atoms are surrounded by chelate complexes of diethylenetriamide pentaacetic acid. However, when it is used, severe side effects of anaphylactoid type, similar to the side effects of iodine-containing PKC, as well as cases of acute renal failure are described. The tactics of treating these complications have no fundamental differences in comparison with the complications of radiocontrast agents.

[1], [2], [3], [4], [5], [6], [7],