Contrast Medium Reactions Treatment & Management

Updated: Jul 22, 2017
  • Author: Nasir H Siddiqi, MD; Chief Editor: Eugene C Lin, MD  more...
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Treatment

Approach Considerations

Most acute severe adverse reactions to ICM occur within 20 minutes of injection. For this reason, the patient should be monitored for a minimum of 20 minutes after an ICM injection. Furthermore, any physician who is responsible for an imaging study that requires the use of ICM must be able to recognize and treat acute adverse reactions.

Rooms in which contrast material is administered should be stocked with appropriate basic and advanced life support monitoring equipment and drugs. The equipment should be regularly checked.

In the examination of a patient with an adverse reaction, a brief history should be obtained, including a summary of the current symptoms, any medical conditions (eg, heart disease), and the patient's medications. Vital signs should be assessed, and any patient with an adverse reaction should be closely monitored until the symptoms have stabilized or resolved. Assessment of the patient's airway, breathing, and circulation (ABCs) remain the cornerstone of the management of moderate or severe adverse reactions to ICM.

In the treatment of adverse reactions, immediately discontinue ICM administration. Monitor the patient's cardiac rhythm, blood pressure, and oxygen saturation. Mild reactions are self-limiting and do not require treatment. However, the patient should be closely monitored until the symptoms resolve.

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Medical Care

Anaphylactic reactions

The treatment of most anaphylactic reactions, once they are recognized and differentiated from other types of reactions, is often straightforward. [34] These are summarized below.

A respiratory component to an adverse reaction requires more aggressive therapy. Oxygen administration, 10-12 L/min via a partial nonrebreathing mask, should be considered in any patient with respiratory difficulty. If bronchospasm is accelerating or severe, if it does not respond to inhalers, or if an upper airway edema (including laryngospasm) is present, epinephrine should be injected promptly. Intravenous use of epinephrine is optional in normotensive patients, but it is necessary in hypotensive patients with respiratory reactions.

Epinephrine must be administered with care to patients who have cardiac disease or those who are taking beta-blockers such as atenolol, propranolol, metoprolol, and nadolol, because the unopposed alpha effects of epinephrine in these patients may cause severe hypertension or angina.

H1 antihistamines, such as diphenhydramine, and H2-receptor blockers, such as cimetidine, do not have a major role in the treatment of respiratory reactions, but they may be administered after epinephrine.

Monitoring the vital signs can be helpful in determining the cause of the hypotension. Tachycardia (ie, heart rate more than 100 bpm) indicates that an anaphylactic reaction is more likely than other types of reactions. If the patient is bradycardic (ie, heart rate less than 60 bpm), a vasovagal reaction is probable, provided that the patient is not receiving beta-blockers.

Hypotension resulting from an anaphylactic reaction is treated with an intravenous iso-osmolar fluid (ie, normal saline, Ringer lactate solution) in large volumes. Several liters of fluid may be required. If fluid and oxygen are unsuccessful in reversing the patient's hypotension, the use of vasopressors should be considered. The most specifically effective vasopressor is dopamine; at infusion rates of 2-10 mcg/kg/min, the cerebral, renal, and splanchnic vessels remain dilated, whereas the peripheral vessels constrict. Epinephrine is less useful, its results are less predictable, and it has more adverse effects.

Urticaria

In asymptomatic patients, no treatment is needed.

In patient with symptomatic urticaria that is mild or moderate, diphenhydramine 50 mg may be administered orally, intramuscularly, or intravenously.

In severe cases, treatment is as above; consider adding cimetidine 300 mg by slow intravenous injection or ranitidine 50 mg by slow intravenous injection.

Bronchospasm

For mild bronchospasm, treatment includes oxygen 10-12 L by face mask, close observation, and/or 2 puffs of an albuterol or metaproterenol inhaler.

For moderate cases without hypotension, treatment is as above, with epinephrine 1:1000, 0.1-0.3 mL given subcutaneously, repeated every 10-15 minutes as needed until 1 mL is administered.

In patients with severe bronchospasm, administer epinephrine 1:10,000 1 mL slow intravenous injection over approximately 5 minutes, repeated every 5-10 minutes as needed.

Laryngeal edema

For mild to moderate laryngeal edema, treatment includes oxygen 10-12 L by face mask and epinephrine 1:1000 0.1-0.3 mL given subcutaneously, repeated every 10-15 minutes as needed until 1 mL is administered.

In moderate to severe cases, consider calling a code or intubating the patient. Consider adding diphenhydramine 50 mg slow intravenous injection and cimetidine 300 mg slow intravenous injection or ranitidine 50 mg slow intravenous injection.

Isolated hypotension

Raise the patient's legs as much as possible while preparing to administer intravenous fluids. The Trendelenburg position can also be effective, but many radiographic tables do not tilt. Oxygen should be administered in high doses.

Hypotension with tachycardia

In mild to moderate cases, elevate the patient's legs. Administer oxygen 10-12 L by face mask, and intravenous isotonic fluid (eg, 0.9% isotonic sodium chloride solution, Ringer lactate solution).

For patients with severe hypotension with tachycardia or patients who are unresponsive, treatment is as above, with dopamine 2-20 mcg/kg/min. Call a code if no response occurs.

Vasovagal reaction

In cases of mild to moderate vasovagal reactions, elevate the patient's legs. Administer oxygen 10-12 L by face mask, and intravenous isotonic fluid (eg, 0.9% isotonic sodium chloride solution, Ringer lactate solution).

For severe reactions or unresponsive patients, administer intravenous atropine 0.6-1 mg, repeated every 3-5 minutes as needed until a total of 3 mg is administered.

Unresponsive patient

In cases of unresponsive patients, do the following:

Treatment of nonidiosyncratic reactions

Treatments for nonidiosyncratic reactions depend on the type of reaction.

Vasovagal reaction

Hypotension resulting from a vasovagal reaction is also treated with iso-osmolar fluid; however, if the patient remains symptomatic, bradycardia can be reversed with intravenous atropine 0.6-1 mg, repeated every 3-5 minutes to a total dose of 3 mg, if needed. Low doses of atropine, those less than 0.5 mg, are contraindicated because they may have the paradoxical effect of accentuating bradycardia or causing sudden respiratory or cardiac arrest.

In these instances, as well as in other circumstances in which preliminary treatment of a moderate or severe reaction does not seem to be effective, call a code. Administer basic life support and, if necessary, advanced cardiac life support techniques should be initiated.

Cardiac arrhythmias

A defibrillator should be obtained immediately, and cardioversion or defibrillation should be performed. The response of ventricular fibrillation to defibrillation decreases dramatically in the first few minutes, and with the likelihood of a successful response diminishes by approximately 10% with each minute. For this reason, physicians who administer contrast material should be capable of using defibrillators.

Hypertensive reactions

Hypertensive reactions can be initially treated with oxygen and appropriate antihypertensive medications. In the past, nifedipine, a 10-mg tablet that was punctured with a needle tip and allowed to drip sublingually, was commonly used; however, nifedipine is no longer the favored drug because of the unpredictability of its response, its hemodynamic profile, and the risk of reflex sympathetic hyperactivity.

Additional doses of the patient's usual antihypertensive medications may be helpful. Intravenous fenoldopam, labetalol, and nitroglycerin, as well as oral clonidine or captopril, are reasonable choices, depending on the particular clinical situation. Intravenous furosemide 40 mg can also be used.

Seizure

Seizure can occur as a result of hypoxia due to respiratory insufficiency or an intrinsic central nervous system (CNS) response to the ICM. Patients should be turned on their side to prevent aspiration, and high-dose oxygen should be administered. When hypoxia is the cause of the seizure activity, intubation may be required for adequate oxygenation. In the case of primary CNS seizure activity, intravenous diazepam 5 mg may be injected and repeated if necessary. An emergency medical specialist should be consulted.

Pulmonary edema

Pulmonary edema is initially treated by elevating the patient's head, administering oxygen, and intravenous injection of furosemide and morphine 1-3 mg every 5-10 minutes as needed.

Angina

Patients with angina should be given sublingual nitroglycerin and oxygen. An electrocardiogram (ECG) may be obtained to assess ischemic changes. If the patient's symptoms persist or are new (ie, if the patient has no previous history of cardiac disease), a cardiologist should be consulted, or the patient should be transferred to an emergency department.

Contrast agent–induced nephropathy

In most cases, only watchful waiting, adequate hydration, and follow-up of serum chemical findings are required. In a few patients, temporary or permanent hemodialysis may be needed.

Interventions such as IV fluids, N-acetylcysteine, sodium bicarbonate, and statins to reduce the risk of contrast-induced nephropathy have been studied, but additional research is needed to determine benefit. [44, 45, 46, 47]

Delayed reactions

Delayed reactions are treated in a supportive manner, and analgesics are administered to treat headaches; antipyretics to treat high temperatures; meperidine to treat rigors; and isotonic fluid to treat hypotension. [36]

Extravasation injuries

Extravasation injuries are treated by elevating the affected extremity and applying cold compresses. A plastic surgeon should be consulted if the patient's pain gradually increases over 2-4 hours, if skin blistering or ulceration develops, or if the circulation or sensation changes at or distal to the level of the extravasation. No specific treatment is unequivocally effective;

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Prevention

Prophylactic medications

Corticosteroid prophylaxis is the standard of care in the United States [1]  for the prevention of allergic contrast reactions. However, corticosteroid prophylaxis is more controversial in Europe. For example, corticosteroid prophylaxis is only suggested by European guidelines [48] , and not recommended by United Kingdom guidelines. [49] Prophylaxis is controversial because there is no level I evidence supporting its use for the prevention of severe reactions to low osmolar contrast media (level I evidence only exists for high osmolar media). In addition, despite premedication, severe breakthrough reactions can occur. [50, 51]

Corticosteroid premedication before IV administration of iodinated contrast material has been found to reduce the overall risk of a contrast reaction, although its efficacy in the prevention of moderate and severe reactions is more controversial. [50] As severe contrast reactions—even in at-risk patients—are rare, a large number of patients would need to be premedicated to acheive any effect. In a study by Mervak et al, [51] it was estimated that 69 patients would need to be premedicated to prevent a reaction of any severity, and 569 patients would need to be premedicated to prevent a severe reaction.

In the same Mervak study, [51] patients premedicated for a previous allergic-like contrast reaction had a breakthrough rate 3 to 4 times the ordinary reaction rate when undergoing CT with iodinated low-osmolality contrast material. For comparison, in patients who have had a previous allergic-like reaction to the same class of contrast material, the risk of reaction to IV low osmolar contrast media in the absence of corticosteroid prophylaxis has been estimated to be 5 to 6 times that of the general population.

In a study of 190 breakthough allergic-like reactions to intravenous low osmolar contrast media, Davenport et al found that most premedicated patients will not experience breakthrough reactions, although premedication does not eliminate the risk. [52] The severity of breakthrough reactions is usually similar to the index reaction. For example, patients who experience a mild index reaction have a very low risk of a severe breakthrough reaction. Patients with moderate or severe index reactions are at high risk of experiencing another moderate or severe reaction if another breakthrough event occurs.

Kolbe et al suggest that premedication in patients with only an index reaction of urticaria is not necessary. [53] In these patients, premedication did not decrease the risk of repeat reactions, and most patients who were not premedicated did not have a subsequent reaction. When patients did experience a reaction, it was similar to the index event.

In a study by Lasser et al, methylprednisolone, 2 oral doses of 32 mg each administered at 12 and 2 hours before ICM administration, reduced the incidence of all adverse reactions to ionic ICM from 9% to 6.4%. [22] The frequency of severe reactions that required treatment was also reduced, from 2% to 1.2%. However, a single dose of 32 mg of methylprednisolone that was given 2 hours before ICM administration had virtually no effect. In the same study, oral corticosteroid premedication in 2 doses, one 6-24 hours before and the other 2 hours before ICM injection, significantly reduced the incidence of the total number of ICM-related adverse reactions from 5% to 2%. [22]

Greenberger et al showed that a premedication regimen of 50 mg of oral prednisolone at 13 hours, 7 hours, and 1 hour before injection of the contrast material and 50 mg of oral diphenhydramine at 1 hour before ICM injection substantially reduced the rate of adverse reactions from 9% to 7% in those with previous reactions, compared with historical control subjects. [54]

In another study, premedication with a single 100-mg tablet of hydroxyzine 12 hours before the intravenous injection of the ionic dimer ioxaglate reduced the incidence of adverse reactions compared with placebo (2 reactions in the treatment group vs 25 reactions in placebo group, all mild).

Studies of the potential role of H2 blockers, such as cimetidine, have shown a beneficial effect, no effect, or even adverse effects with the addition of H2 blockers to the premedication regimen.

Some investigators have incorporated ephedrine into their premedication regimens. Because of concern about the sympathomimetic cardiac effects of ephedrine, its use has not gained wide acceptance.

In a study by Dillman et al of allergic-like breakthrough reactions to IV gadolinium-containing contrast following premedication with corticosteroids and antihistamines, there were 9 breakthrough reactions (8 of which occurred in adults), with 6 being mild and 3 being moderate. All of the patients who had reactions had a previous history of reactions to either gadolinium- or iodine-containing contrast media. There were no severe or fatal breakthrough reactions. [2]

On September 9, 2010, the FDA announced the requirement that gadolinium-based contrast agents (GBCAs) carry new warnings on their labels about the risk for nephrogenic systemic fibrosis (NSF) and its association when administered to certain patients with kidney disease. The FDA’s review of the safety of the most widely used GBCAs determined that Magnevist, Omniscan, and Optimark were associated with a greater risk than other GBCAs for NSF and would be described as inappropriate for use in certain patients with kidney disease. [55]

Recommended prophylactic regimens

Methylprednisolone, one 32-mg tablet, may be orally administered at 12 and 2 hours before the study, or prednisone, one 50-mg tablet, may be orally administered 13 hours, 7 hours, and 1 hour before the contrast-enhanced study.

If the patient had a previous moderate or severe reaction to ICM or one that included a respiratory component, an alternative study, such as ultrasonography or magnetic resonance imaging (MRI), should be considered. Otherwise, the following may be used: H1 antihistamines; diphenhydramine, one 50-mg tablet orally administered 1 hour before the study; H2-histamine receptor blockers, which is optional; cimetidine, 300 mg orally administered 1 hour before the study; and/or ranitidine 50 mg orally administered 1 hour before the study.

Most authorities restrict corticosteroid pretreatment to patients in whom previous idiosyncratic adverse reactions to ICM were moderate or severe. Usually, corticosteroids are well tolerated and cause no adverse effects when only a few doses are administered.

Although the utility of H2-receptor blockers is questionable, these agents are well tolerated and might be of benefit, particularly because they are effective in the treatment of at least some allergic cutaneous reactions to agents other than ICM. However, H2 blockers should not be used without H1 blockers.

The treatment of the nonidiosyncratic adverse reactions of nausea and vomiting is not considered a routine indication for corticosteroid premedication or the use of nonionic ICM.

Reducing the incidence of ICM nephropathy

Other nephrotoxic drugs should be discontinued whenever possible, and the minimal amount of contrast material that is needed to perform a diagnostic study should be used. Nonionic agents are the ICM of choice. If multiple studies are required, time (as long as 5 days) should be allotted between the studies to allow the kidneys to recover fully from the ICM injection. Patients can be well hydrated until 12 hours before a contrast-enhanced study, and hydration should be continued for at least 2 hours after a contrast-enhanced procedure is performed. [29]

Other measures

Use of mannitol or furosemide is not recommended, at least in patients with diabetic nephropathy. In several studies, these medications were not effective in reducing the incidence of ICM nephropathy. In other studies, the incidence of nephropathy was higher in patients who were given mannitol or furosemide. The use of mannitol or dopamine at renal vasodilatory doses or atrial natriuretic peptide reduced the incidence of ICM nephropathy in nondiabetic azotemic patients, compared with azotemic patients who received only hydration with sodium chloride solution.

Several investigators have suggested that ICM nephrotoxicity can be reduced with the use of oral or intravenous theophylline, acetylcysteine, fenoldopam, or bosentan (an endothelin antagonist). Research with these agents is promising, but results are preliminary. [41] Some prospective studies have suggested that prophylactic administration of 600 mg acetylcysteine twice daily in combination with hydration reduces the incidence of ICM nephrotoxicity. [56]

Prophylaxis in nonvascular studies

Although rare, systemic reactions are reported after extravascular instillation of ICM (eg, during retrograde pyelography). [27]

When patients have had previous severe idiosyncratic or anaphylactic reactions to intravenous ICM, premedication with corticosteroids should be considered, even in nonvascular studies.

Rate and temperature of ICM injection

The perception that adverse reactions to ICM, particularly nausea and vomiting, are more common with a rapid rate of injection than with a slow injection has been refuted by findings from 2 studies. [57, 58]

Warming ICM to body temperature reduces their viscosity and may make the injection more comfortable for the patient.

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