Q1: Is my body type prone to allergy to iodine-containing contrast media?
A1: The risk factors I mentioned below are all risk factors that predispose to allergy. Having these risk factors does not necessarily lead to the development of allergy, but having one of these conditions should be highly noted for the development of any allergic reaction. The first factor is age. Infants and patients older than 60 years of age are more likely to develop allergies. The second is the gender factor, with women being more likely to develop allergies than men. The third is the underlying disease factor, such as asthma, heart disease, dehydration, kidney disease, diabetes mellitus and glucose obesity (i.e. diabetic obesity = Diabesity), which predispose to allergic-like/atopic reactions. The fourth is hematologic disease factors, such as multiple myeloma, sickle cell anemia, and erythrocytosis. The fifth is medication factors, such as ongoing use of non-steroidal anti-inflammatory drugs (NSAIDs), interleukin-2 (IL-2), beta-blockers (beta-blockers) and biguanides (glucose-lowering drugs). The sixth is contrast-related factors, such as more than 20 mg of iodine at a time, high fast injection rate, intra-arterial injection and previous contrast reactions If you have had a contrast reaction before, the likelihood of side effects occurring again is 8% to 25%, and if the previous contrast reaction was a true allergic reaction, the risk of reoccurrence will be 100%.
Q2: I have high risk factors for contrast allergy, can I prevent it in advance?
A2: At present, contrast agent test doses and mandatory pre-test medication are rare in clinical work in Japan and abroad. However, patients who have previously experienced allergic reactions or are now at increased risk for allergic reactions when intravenous contrast is administered need pre-test medication for prevention. Pre-examination medication mainly involves the use of glucocorticoids and antihistamines, and the recommended doses are as follows: [glucocorticoids in one of the three options] prednisone 50 mg orally 13 hours, 7 hours and 1 hour before contrast injection; hydrocortisone 200 mg intravenously 1 hour before contrast injection; methylprednisone 32 mg orally 12 hours and 2 hours before contrast injection; [selective use Antihistamines] Diphenhydramine 50 mg orally, intravenously, or intramuscularly 1 hour before contrast injection. glucocorticoids have relative contraindications: active tuberculosis, diabetes mellitus, peptic ulcer disease, acute lymphoblastic leukocytes, and non-Hodgkin’s lymphoma.
Note: Patients with seafood allergy are more likely to have contrast reactions, but this is more likely due to cross-reactivity between shellfish and iodine-containing contrast agents rather than an inherent allergy of the patient. This is the same reason why asthma patients are more likely to have iodine-containing contrast reactions].
Q3: What exactly are the allergies that can occur with iodine-containing contrast media?
A3: Iodine-containing contrast reactions can be divided into two categories: one is allergic-like reactions or atopic reactions, and the other is non-allergic-like reactions. Iodine-containing contrast reactions can be either one of these categories or both.
(1) As the name implies, allergic-like/atopic reactions are those whose exact etiology remains unknown, and they resemble allergic reactions. Its mechanism may be enzyme-induced reactions leading to the release of vasoactive substances such as histamine and 5-hydroxytryptamine and the activation of physiological cascades and ultimately the complement system.
Allergic-like/atopic reactions are the most common contrast side effects, which can have serious complications and can occasionally be fatal. These are most commonly associated with the underlying disease factors mentioned earlier, while anxiety, restlessness and fear that occur prior to contrast injection and are not related to the dose injected can also cause such reactions. Symptoms associated with such reactions can be mild (rash, pruritus, runny nose, nausea and vomiting), moderate (persistent mild symptoms, facial/pharyngeal edema, bronchospasm, dyspnea, tachycardia or bradycardia) and severe (life-threatening arrhythmias, hypotension, pharyngeal edema, pulmonary edema, seizures, fainting and death).
(2) Non-allergic-like reactions are thought to be caused by the ability of the contrast agent to disrupt the body’s internal environment, especially the blood circulation, and are also referred to as biochemical toxic reactions or non-specific reactions. Such reactions depend on the physical properties of the contrast agent, such as ionization (i.e., the formation of free ions in the blood circulation, which in turn interfere with the electrical charge associated with nerve or myocardial activity) and osmolarity (which can lead to a large transfer of fluid volume). Elevated iodine concentrations can also increase the risk of non-allergic-like reactions. The volume and route of contrast injection may also increase the likelihood of non-allergic reactions (large volumes or intra-arterial injections are more likely to cause such reactions).
Physiologic changes resulting from iodine-containing contrast media most often affect the cardiovascular, respiratory, urinary, gastrointestinal, and nervous systems. Symptoms of non-allergic-like reactions include body warmth, metallic taste in the mouth, nausea, vomiting, bradycardia, hypotension, vasovagal reaction, nephropathy, and delayed reactions.
Note: In clinical work, due to the large number of our patients, we often encounter CT-enhanced patients with mild to moderate drug allergies. We are happy that the patients I encountered are very understanding, many of them are not medical students, but they are very clear about this kind of allergic reactions, and they can also say a thing or two or three or four about its principles, and at the same time they can be heartily tolerant and understanding. Doctors face a dilemma in treating patients and saving lives. In fact, this is the ultimate pursuit of our medical workers, the current domestic medical environment doctors really do not ask for thanks, but for understanding.
Q4: What are the differences in side effects caused by different osmotic pressure of iodine-containing contrast media?
A4: The side effects of iodine-containing contrast agents are like all other drugs and their risks and side effects cannot be completely avoided. The incidence of side effects with hypertonic contrast media ranges from 5% to 12%, while with hypotonic contrast media it is 1% to 3%. The incidence of mild to moderate contrast side effects with hypertonic contrast agents is 6% to 8%, which is higher than the incidence of 0.2% with hypotonic contrast agents, but the incidence of severe contrast side effects is similar between the two. Allergic-like reactions occur more frequently with hypertonic contrast agents, while hypotonic contrast agents are more likely to cause cardiovascular decompensation.
When talking about the osmotic pressure of iodine-containing contrast agents, I think it is necessary to give a brief introduction to the classification of iodine-containing contrast agents and their chemical properties.
Iodine-containing contrast agents can be classified into hypertonic, hypotonic and isotonic contrast agents according to their osmolarity, and into ionic and nonionic contrast agents if based on their ionization degree, of which only nonionic contrast agents have isotonic contrast agents.
Contrast agents are generally thicker (i.e., more viscous) and have greater osmotic pressure (i.e., more molecules per kilogram of water) than blood, plasma, and cerebrospinal fluid. The viscosity and osmolarity play a role in the development of side effects of contrast media. The degree of ionization of the contrast agent means that the breakdown of a molecule into a cation and an anion can result in more molecules per kilogram of water, thus increasing the osmotic pressure of the contrast agent. Non-ionic contrast agents are not ionized, so they have a lower osmotic pressure than ionic contrast agents.
The osmolarity of hypertonic contrast media is 5-8 times that of normal plasma, the osmolarity of hypotonic contrast media is 2-3 times that of normal serum, and the use of isotonic contrast media is increasing as it has the same osmolarity as blood, plasma and cerebrospinal fluid. 2012 bulk data study by Davenport et al. found that a 37oC thermostatic contrast media was useful for intravenous injection rates below 6 mL/s of 300 mgI/mL iodine-containing contrast medium did not affect the incidence of contrast side effects, while the more viscous 370 mgI/mL iodine-containing contrast medium significantly reduced the incidence of contrast extravasation and overall side effects.
Q5: What happened when I had contrast extravasation during my enhancement CT? How should I treat it?
A5: Contrast extravasation is one of the most common side effects in clinical work, and occurs in about 0.1% to 0.9% of cases, whether by hand push [this method has become less common as economic conditions improve] or by using a high-pressure syringe. Older patients, infants, children, patients with altered consciousness, and patients with underlying vascular lesions are more likely to experience contrast extravasation. Small amounts of contrast extravasation usually result in a limited inflammatory skin reaction with no serious sequelae. Large amounts of contrast extravasation (50-75 mL) can result in tissue necrosis due to chemical toxicity or the resulting luminal syndrome.
Patients often present with a persistent burning sensation and edema at the injection site. Looking for a pulse distal to the patient’s injection site and recording the degree of initial edema and erythema is essential in early treatment. Small amounts of contrast extravasation can be avoided by applying injection site compression to avoid worsening the extravasation, applying a wet dressing of 50% magnesium sulfate and dexamethasone immediately, and instructing the patient to elevate the affected limb to promote venous return for absorption. If persistent edema, pain and skin color do not return to normal, a surgeon’s consultation is required for further management. Contrast extravasation is more common when using hypertonic contrast media. As mentioned earlier, a constant temperature of 37oC for contrast media can reduce the incidence of extravasation, especially in winter to reduce the overall incidence of side effects.
Note: Patients with saline needles are under 20G in diameter (e.g., generally finer 22G), whereas enhanced CT hyperbaric contrast agents require needles that are thicker in diameter than those used for IV drips and are 20G and larger (e.g., CTA at rates above 5 mL/s generally uses 18G). If a saline hung needle is used to inject high pressure and high speed contrast agent, the needle will often fall off or the contrast agent will leak out.
Q6: Can iodine-containing contrast agents cause serious nephropathy?
A6: Iodine-containing contrast agent-induced nephropathy is defined as the development of renal failure in patients with serum creatinine levels above 0.5 mg/dL or 50% of baseline within 1 to 3 days after contrast agent injection. Nephropathy induced by iodine-containing contrast agents essentially never occurs in patients with truly normal renal function. However, iodine-containing contrast-induced nephropathy can occur in patients with abnormal renal function prior to contrast injection, with an incidence of 2% to 7%. It is usually not serious and often returns to normal within 4-7 days after contrast injection, but a persistent rise in serum creatinine levels is abnormal and it can progress to end-stage renal. The etiology of contrast-induced nephropathy includes renal vasoconstriction due to altered renal hemodynamics or tubular toxicity induced directly by contrast agents.
The main risk factors for contrast-induced nephropathy are the elderly, antibiotics (aminoglycosides such as gentamicin), cardiovascular disease, chemotherapy, collagen vascular disease, elevated serum creatinine levels (1.3 to 2.0 mg/dL), dehydration, diabetes mellitus (insulin-dependent >2 years; non-insulin-dependent >5 years), NSAIDs, heteroproteinemia (e.g., myeloma), nephropathy, and renal transplantation. When these risk factors are present, careful consideration and balancing of the risks and benefits of contrast nephrotoxicity must be performed prior to intravenous contrast administration. In the event of contrast-induced nephropathy, it is best to refer to a nephrologist.
Patients with non-insulin-dependent diabetes mellitus are at a very high risk of contrast-induced nephropathy while on biguanide therapy. Such patients must discontinue taking the medication immediately after contrast injection and restart it only after 48 hours of confirming normal liver and kidney function under the supervision of a physician.
Note: The following points should be noted when confirming iodine-containing contrast-induced nephropathy: First, this nephropathy actually occurs only in those patients with abnormal kidney function prior to contrast injection. Second, the parameters used in clinical practice are not entirely accurate, as serum creatinine levels vary with age, muscle mass and gender. A normal serum creatinine value of 1.2 mg/dL for a 20-year-old male or female would imply a normal glomerular filtration rate in the range of 60 to 120 mL/min, more likely near or even above 100 mL/min, whereas the same serum creatinine value for an 80-year-old female with 50 Kg would correspond to a significant decrease in glomerular filtration rate, even below 40 mL/min. This difference occurs because the glomerular filtration rate decreases with age, while muscle production of creatinine products also decreases. In short, serum creatinine value is a reasonable screening parameter because it is inexpensive and easy to check, but it is not particularly accurate. In fact, many hospitals routinely do serum creatinine clearance and serum creatinine levels because the diagnosis of iodine-containing contrast-induced nephropathy is not only the value of glomerular filtration rate, but requires a combination of concomitant risk factors such as dehydration, surgery, and the application of other nephrotoxic substances].
Q7: Can patients with poor renal function undergo enhanced CT? Can nephropathy induced by iodine-containing contrast agents be prevented?
A7: Yes. Iodine-containing contrast-induced nephropathy basically never occurs in patients with truly normal renal function. In most patients with very poor renal function (e.g., patients on dialysis in nephrology), dialysis is done after enhanced CT in order to eliminate the effects of iodine-containing contrast-induced nephropathy. In a study of more than 600 patients who all had elevated serum creatinine levels after cardiac catheterization, only seven patients required dialysis, and only three patients required permanent dialysis.
The first step in preventing iodine-containing contrast-induced nephropathy is to drink more water. Patients may be allowed to drink several liters of water for 12 to 24 hours prior to contrast injection. However, drinking water as the enhanced CT exam approaches is not an option, either because the patient cannot drink on their own or because it is a contraindication because the patient needs sedation or anesthesia. In this way, intravenous fluids are a practical and very effective way to rehydrate. The recommended intravenous rehydration regimen is at least 1 mL of normal saline per kilogram of body weight per hour, continuously for 12 hours before and 12 hours after the contrast injection for a total of 24 hours. Remember that patients often do not adequately hydrate themselves, so intravenous rehydration should be initiated 12 hours prior to contrast injection for patients at risk for nephropathy, if feasible. There is evidence that normal saline is more effective than semi-normal saline. Recent studies have shown that the use of sodium bicarbonate rehydration is more effective in reducing the incidence of nephropathy induced by iodine-containing contrast media compared to normal saline (sodium chloride). Newer agents such as nonionic isotonic contrast agents (e.g., Visipaque) and N-acetyl cysteine (n-AC), which is both a vasodilator and a free radical scavenger, have promising applications. Of course, there are other ways to stop or weaken the occurrence and severity of nephropathy, which will not be listed here.
Q8: What is the delayed reaction to iodine-containing contrast media?
A8: Contrast side effects that occur within 1 hour to 7 days of iodine-containing contrast injection are called delayed allergic reactions. 2003 literature abroad reported that delayed reactions occurred in about 2% of patients, and the proportion of delayed allergic reactions we see in domestic clinics at present should be significantly lower than this data. Common delayed allergic reactions present with flu-like symptoms (such as fever, chills, rash, pruritus and nausea) and, relatively rarely, mumps, arthralgia and depression. Of course these symptoms may not seem to be related to the contrast agent at all, but the rash is certainly attributable to the contrast agent. Delayed allergic reactions are more common in patients treated with IL-2 chemotherapy and with nonionic dimeric contrast agents (i.e., the isotonic contrast agent Visipaque, mentioned earlier). These allergic reactions usually subside on their own, and clinical treatment is mainly supportive: analgesia for headache, antipyretic for fever, sedation for tonicity, and isotonic fluid infusion for hypotension.
Q9: Are there any side effects of contrast agents when pregnant or breastfeeding women have enhanced CT?
A9: The safety of intravenous iodine-containing contrast agents during pregnancy is still unclear, but there is no doubt that contrast agents can enter the fetal circulatory system through the placenta and cause thyroid disease. It is now well established that a very low level of contrast agent can enter the fetal circulation and that very little of it is indeed absorbed by the infant. Therefore, intravenous iodine-containing contrast should only be considered in pregnant women when the possible benefits clearly outweigh the risks; otherwise, ultrasound and MRI are generally considered, and any elective examination requiring intravenous iodine-containing contrast should be postponed until after delivery. Although lactating women can stop breastfeeding for 24 hours after contrast injection, the basis for this procedure is questionable.
Q10: Are there any side effects of contrast media in children undergoing enhanced CT?
A10: Contrast reactions in children are often allergic-like and mild, with an incidence of 0.18% for hypotonic contrast compared to 3% for hypertonic contrast. Contrast reactions in children are more difficult to detect than in adults, and children are unable to describe their symptoms. The management of contrast reactions in children is similar to that in adults, but special attention should be paid to age-appropriate doses and parents should always check the child’s weight to determine the injection dose with the appropriate application forms and equipment from the physician.