CT and X-ray Contrast Guidelines

A Radiology nurse or a Radiology technologist may administer intravenous contrast media under the general supervision of a physician. This policy applies for all areas in the Department of Radiology and Biomedical Imaging where intravenous iodinated contrast media is given. In order to provide for the safe administration of contrast media, those persons administering contrast media and those performing the imaging procedures must have an understanding of indications for use of contrast media as well as the potential side effects (contrast reactions) and their management.

Key Points

• The supervising physician must be physically present in the facility or office suite and available in order to provide immediate medical intervention to prevent or mitigate injury to the patient in the event of an adverse contrast reaction.
• Iodinated intravenous contrast media are pharmaceuticals and have potentially dangerous and life-threatening adverse reactions.
• Most major and minor reactions will occur in patients without any known risk factors. Virtually all life-threatening reactions occur immediately or within 20 minutes after contrast injection.
• All areas where contrast is given must be equipped with emergency treatment supplies required for the treatment of common contrast reactions.

Nurses, technologists, and/or radiologists administering intravascular iodinated contrast media must first assess the patient for risk factors predisposing them to an adverse reaction to iodine contrast. This is achieved by completion of the Patient Screening Form For Iodinated Contrast (pdf). Patients also receive the Patient Information Leaflet for CT (Appendix B) at this time. The patient (or their parent/guardian) indicates:

1. Previous reactions to iodinated contrast media.
2. All severe allergies and reactions (both medications and food).
3. If they are age 60 years or over.
4. History of diabetes, kidney disease, solitary kidney, or prior kidney or other transplant
5. History of hypertension requiring medication
6. Current use of any metformin-containing medications.
7. For women of child-bearing age, if they are or may be pregnant or if they are breast-feeding.
8. The technologist reviews the form and enters the date and value of the most recent eGFR (if available or required).

1. An electronic order for an imaging study is placed by a referring physician in the electronic medical record.
2. The radiology team will review the imaging study order, determine whether the study requires iodinated contrast administration or not, and select an appropriate imaging protocol. This protocol will be for the technologist to follow when performing the examination.  
3. Upon arrival to the department, the patient completes the “Patient Screening Form For Iodinated Contrast.”
4. The RN/RT reviews the completed form and notifies the Radiologist of any contraindications or serious risk factors noted. The pharmacist may be consulted as necessary.
5. Most patients have some degree of anxiety and fear concerning imaging procedures. The RN/RT questions the patient regarding their expectations, explains the iodinated contrast procedure and reassures the patient. The patient should be offered the opportunity to speak with a radiologist if questions persist or anxiety seems pronounced.
6. The RN/RT check orders for contrast administration, verify the five rights (right patient, right medication, right dose, right route, right time). Dosage is determined by scan protocol and body weight per manufacturer's recommendations.
7. Transient minor reactions such as warm flushing and altered sense of taste are common. Before beginning injection, the RN/RT explains that these may occur and reassures the patient.
8. The patency of the IV catheter is checked by flushing with 0.9% normal saline (using the injector at the same rate as the actual contrast injection). If there is resistance, pain, or the catheter does not flush, do not proceed. Otherwise, connect the fluid filled high-pressure tubing to the catheter at the hub closest to the catheter. Contrast flow is manually tested to ensure patency. Proceed with contrast injection.
9. At the completion of the injection, the catheter is flushed with 10cc 0.9% normal saline, the high-pressure tubing is disconnected, and the IV site is inspected for any swelling or indication of extravasation. The patient is observed for any indications of contrast reaction throughout the administrative process.

Safe intravenous access, for the injection of intravenous contrast, is vital in obtaining high quality contrast enhanced or angiographic studies. Proper technique is used to avoid the potentially serious complications of contrast media extravasation and/or air embolism. When the proper technique is used, contrast medium can safely be administered intravenously by power injector, at high-flow rates of up to 5 mls/second. A short peripheral IV catheter in the antecubital or forearm area is the preferred route for contrast administration. However other routes may need to be used and each is considered separately.  Learn more

Safe intravenous access, for the injection of intravenous contrast, is vital in obtaining high quality contrast enhanced or angiographic studies. Proper technique is used to avoid the potentially serious complications of contrast media extravasation, air embolism, and damage to the catheter. When the proper technique is used, contrast medium can safely be administered intravenously by power injector, at high-flow rates of up to 2 mls/second (depending on size of patient). A short peripheral IV catheter in the antecubital or forearm area is the preferred route for intravenous contrast administration. However other routes may need to be used and each is considered separately.   Learn more

Historically, the greatest concern over the use of intravascular iodinated contrast for imaging studies has been the possibility that contrast could have an adverse effect on kidney function. This possible adverse effect has been termed contrast-induced nephropathy (CIN). Concern for CIN is rooted in early literature suggesting a correlation between intravascular iodinated contrast administration and subsequent decreases in kidney function (as measured by serum creatinine tests). However these early studies were limited in several ways: 1) they did not include control groups of patients who did not receive intravascular iodinated contrast, 2) many studies were performed in the era of older high-osmolar contrast media whereas contrast media in current use are universally low- or iso-osmolar, 3) the definition of CIN varied between studies, and 4) many studies evaluated the effects of intra-arterial administration of iodinated contrast rather than intravenous administration, as is commonly performed for non-invasive imaging studies. Given the confounding factors present in these previous studies, the American College of Radiology has adopted the term post-contrast acute kidney injury (PC-AKI) for any sudden deterioration in renal function that occurs within 48 hours following intravascular administration of iodinated contrast and reserves the term contrast-induced nephropathy (CIN) for PC-AKI that is caused by intravascular administration of iodinated contrast.

Recent studies [2-8] suggest that historical concern for CIN after administration of intravenous iodinated contrast was likely overstated. Studies utilizing unmatched control groups published in the last two decades have found no correlation between intravascular contrast administration and subsequent abnormal kidney function. The common limitation of these studies is that patients were not randomized to either receive or not receive iodinated contrast and that the control groups were not matched by patient-specific factors to patients receiving iodinated contrast. These studies are thus limited by selection bias. 

Multiple subsequent studies have since used propensity score adjustment and propensity score matching to correct for selection bias that may have limited prior studies [9-13]. Taken collectively, we can conclude from these studies that intravenous iodinated contrast administration is only rarely associated with acute kidney injury in patients with stable eGFR >30mL/min/1.73m². These studies have come to conflicting conclusions as to whether intravenous administration of iodinated contrast is associated with acute kidney injury in patients with eGFR < 30 mL/min/1.73m². 

Many patient-specific factors have been proposed as placing patients at risk for CIN. At present the most studied and accepted risk factor for CIN is pre-existing severe renal insufficiency, as described above. Other proposed risk factors in the literature (but with weaker support) include a history of diabetes mellitus, dehydration, cardiovascular disease, diuretic use, advanced age, multiple myeloma, hypertension, hyperuricemia, and multiple iodinated contrast medium doses in a short time interval. Therefore, screening of patients at risk for CIN is targeted to identify patients with pre-existing severe renal insufficiency.

The incidence and risk factors for contrast-induced nephropathy have not been well-studied in pediatric patients. The effect of intravascular iodinated contrast on kidney function is generally assumed to be similar between children and adults.

Finally, it is important to consider the morbidity and mortality resulting from post-contrast acute kidney injury. The usual course of post-contrast acute kidney injury consists of a transient asymptomatic elevation in serum creatinine. Serum creatinine usually begins to rise within 24 hours of intravascular iodinated contrast medium administration, peaks within 4 days, and often returns to baseline within 7 to 10 days. It is unusual for patients to develop permanent renal dysfunction.

However several studies have shown that in patients who receive intravascular iodinated contrast, those that develop post-contrast acute kidney injury (PC-AKI) tend to have longer hospital stays, higher mortality, and higher incidence of cardiac and neurologic events than patients who do not develop acute kidney injury. These results must be interpreted with caution however: these studies did not include cohorts of patients who did not receive iodinated contrast. It is therefore not possible to conclude if patients who developed acute kidney injury did so as a result of receiving contrast versus alternative causes of acute kidney injury. It also impossible to conclude whether the increased morbidity and mortality seen in patients with PC-AKI is associated with intravascular iodinated contrast exposure or due to some other factor such as the underlying comorbid diseases present in these patients. 

Key Points

1. Historical concern over the association between intravascular administration of iodinated contrast and subsequent decrement in kidney function (contrast-induced nephropathy, or CIN) has been overstated and was based on early studies with a number of limitations.
2. Based on recent studies, we can conclude that intravenous iodinated contrast administration is is only rarely associated with acute kidney injury in patients with stable eGFR >30mL/min/1.73m². Existing studies have come to conflicting conclusions as to whether intravenous administration of iodinated contrast is associated with acute kidney injury in patients with eGFR < 30 mL/min/1.73m².
3. The most rigorously studied and accepted risk factor for the development of contrast-induced nephropathy is pre-existing severe renal insufficiency. Screening of patients at risk for contrast-induced nephropathy is therefore targeted to identifying patients with this risk factor.
4. The incidence of contrast-induced nephropathy and risk factors for development of contrast-induced nephropathy have not been well-studied in pediatric patients. The effect of intravascular iodinated contrast on kidney function in pediatric patients is generally assumed to be similar between children and adults.
5. The usual course of post-contrast acute kidney injury is an asymptomatic elevation in serum creatinine that returns to baseline within 7-10 days. It is unusual for patients to develop permanent renal dysfunction. However it should be noted that amongst patients who receive intravascular iodinated contrast, those that develop post-contrast acute kidney injury (PC-AKI) tend to have longer hospital stays, higher mortality, and higher incidence of cardiac and neurologic events than patients who do not develop acute kidney injury. Because the studies demonstrating these adverse outcomes did not include groups of patients who were not exposed to contrast, it is impossible to conclude whether the increased morbidity and mortality seen in patients with PC-AKI is associated with intravascular iodinated contrast exposure or due to some other factor such as the underlying comorbid diseases present in these patients.

⁺In order to standardize understanding of the effects of nephrotoxic events on kidney function, the diagnosis of acute kidney injury (AKI) should be used according to the Acute Kidney Injury Network criteria. These criteria define specific changes in serum creatinine or urine output within 48 hours of a nephrotoxic event necessary to make the diagnosis of acute kidney injury.

*Estimated glomerular filtration rate (eGFR) is estimated from serum creatinine levels and is considered the best overall index of kidney function. In adults, the CKD-EPI equation is used to estimate GFR. In pediatric patients, the Bedside Schwartz equation is considered the best equation for estimating glomerular filtration rates. This equation requires knowledge of the patient’s height in addition to serum creatinine.

1. ACR Manual on Contrast Media Version 10.3, 2017: 35-46. American College of Radiology
2. Bruce RJ, Djamali A, Shinki K et al. Background fluctuation of kidney function versus contrast-induced nephrotoxicity. AJR Am J Roentgenol. 2009;192(3):711-718.
3. Heller CA, Knapp J, Halliday J et al. Failure to demonstrate contrast nephrotoxicity. Med J Aust 1991;155(5):329-332.
4. Langer S, Stumpe S, Kirsch M et al. No increased risk for contrast-induced nephropathy after multiple CT perfusion studies of the brain with a nonionic, dimeric, iso-osmolal contrast medium. AJNR Am J Neuroradiol. 2008;29(8):1525-1529.
5. Lima FO, Lev MH, Levy RA et al. Functional contrast-enhanced CT for evaluation of acute ischemic stroke does not increase the risk of contrast-induced nephropathy. AJNR Am J Neuroradiol. 2010;31(5):817-821.
6. McGillicuddy EA, Schuster KM, Kaplan LJ et al. Contrast-induced nephropathy in elderly trauma patients. J Trauma. 2010;68(2):294-297.
7. Oleinik A, Romero JM, Schwab K et al. CT angiography for intracerebral hemorrhage does not increase the risk of acute nephropathy. Stroke. 2009;40(7):2393-2397.
8. Tremblay LN, Tien H, Hamilton P et al. Risk and benefit of intravenous contrast in trauma patients with an elevated serum creatinine. J Trauma. 2005;59(5):1162-1166.
9. Davenport MS, Khalatbari S, Cohan RH et al. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material: risk stratification by using estimated glomerular filtration rate. Radiology. 2013;268(3):719-728.
10. Davenport MS, Khalatbari S, Dillman JR et al. Contrast-material induced nephrotoxicity and intravenous low-osmolality iodinated contrast material. Radiology 2013;267(1):94-105.
11. McDonald JS, McDonald RJ, Carter RE et al. Risk of intravenous contrast material-mediated acute kidney injury: a propensity score-matched study stratified by baseline-estimated glomerular filtration rate. Radiology. 2014;271(1):65-73.
12. McDonald RJ, McDonald JS, Bida JP et al. Intravenous contrast material-induced nephropathy: causal or coincident phenomenon? Radiology. 2013;267(1):106-118.
13. Hinson JH, Ehmann MR, Fine DM et al. Risk of acute kidney injury after intravenous contrast media administration. Ann Emerg Med. 2017 May;69(5):577-586.

The UCSF Department of Radiology routinely screens patients undergoing CT examinations to identify those individuals with chronic kidney disease and thus at potential risk of acute kidney injury and recommends volume expansion therapy to mitigate the risk in this subgroup.

First, the patient’s electronic medical record is searched to determine whether a serum creatinine and an estimated glomerular filtration rate (eGFR) acquired within the past 6 weeks are available for outpatients and within the last 7 days for inpatients.

If this information is not available, the information from the patient’s screening form is reviewed, focusing on four key questions to identify patients who are most likely to have underlying chronic kidney disease:  

1. What is your current age?
2. Do you have diabetes?
3. Do you have hypertension requiring medication?
4. Do you have ANY problems with your kidneys (such as transplant, single kidney, kidney cancer, kidney surgery, dialysis)?

• If patient is less than 60 years of age and answers NO to questions 2-4, IV contrast will be administered.
• If a patient is older than 60 years of age and/or answers YES to any of these questions, an assessment of renal function will be performed before administering IV contrast.

The decision to administer contrast in patients undergoing CT should always be a matter of clinical judgment based on the individual circumstances of the patient and following consultation between the radiologist and requesting provider when necessary. Patients with chronic kidney disease (CKD) whose estimated glomerular filtration rates* are < 30 mL/min/1.73m² may be at risk for developing post-contrast acute kidney injury, an uncommon but potentially serious form of acute kidney injury (AKI). The method of contrast delivery is also important; the incidence of post-contrast acute kidney injury is higher after intra-arterial contrast administration than after intravenous contrast administration.

There are two primary strategies to reduce the incidence of post-contrast acute kidney injury in at-risk patients. The first strategy is to avoid contrast entirely when it is not required to establish the diagnosis or when another imaging modality may be used to answer a clinical question. The second strategy is to utilize peri-exposure volume expansion therapy. The use of volume expansion therapy is based upon studies that have shown decreased rates of post-contrast acute kidney injury in patients receiving volume expansion therapy. But it should be noted that these studies are heterogeneous, with many performed in patients undergoing intra-arterial administration of iodinated contrast.

The ideal route, rate, and volume for volume expansion therapy are unknown. The intravenous route is preferred to the oral route for patients at risk for post-contrast acute kidney injury as this route has been more well-studied. Isotonic intravenous fluids (0.9% normal saline, lactated Ringers solution) are preferred. There is no clear superiority of 0.9% normal saline or sodium bicarbonate solutions for prophylaxis in this setting.

Based on existing evidence, the UCSF Department of Radiology employs a practical but conservative approach to screening and volume expansion for the prevention of post-contrast acute kidney injury:

Many other interventions have previously been proposed to reduce the incidence in patients and are deserving of further mention:

Choice of contrast medium: Iodinated contrast agents in modern use are universally low-osmolar solutions. There is no clear advantage of iso-osmolar contrast agents compared with modern low-osmolar contrast agents for the prevention of post-contrast acute kidney injury.

Contrast medium dose: There is no clear dose-toxicity relationship for contrast medium injected INTRAVENOUSLY. Therefore, there is no defined threshold of contrast administration above which additional intravenous iodinated contrast should be withheld. The decision to administer closely spaced contrast-enhanced studies is thus considered by the American College of Radiology to be clinical and subjective, where high-risk patients are treated with greater caution than the general population.

N-acetylcysteine: The American College of Radiology and the European Society of Urogential Radiology concur that there is insufficient evidence of the efficacy of this medication for reducing the incidence of post-contrast acute kidney injury to recommend its use.

1. ACR Manual on Contrast Media Version 10.3, 2017: 35-46. American College of Radiology

Patients on dialysis can receive IV contrast, but the fact that a patient is on dialysis should NOT be regarded as automatically allowing the administration IV contrast, because of several potential hazards, including:

• In the setting of acute renal failure, where dialysis is being performed with the expectation of renal recovery, it may be inappropriate to administer a nephrotoxic agent that may jeopardize the reversal of renal impairment.
• In the setting of chronic renal failure where patients are still producing a small amount of urine, the small amount of residual renal function could be imperiled by IV contrast, potentially increasing the required frequency of dialysis and hastening the complications of severe renal impairment – neither of which are trivial considerations. Patients with renal insufficiency who require only intermittent or occasional dialysis are at substantial risk for contrast media-induced nephrotoxicity with further worsening of their renal function. Alternative imaging studies not requiring contrast media should be strongly considered.
• In either setting, the volume of IV contrast may add to fluid overload, potentially adding to circulatory compromise. The volumes of both oral and IV contrast should be included in the fluid intake of dialysis patients.

While these hazards of giving IV contrast to dialysis patients may be relatively small, these risks should be weighed against the likely diagnostic benefit of contrast administration. The Nephrology Service is readily available for consultation in cases where the risk/benefit assessment is complicated, and closely follows all hospitalized dialysis patients.

It should also be noted that the common belief that dialysis patients require early post-procedural dialysis is unsupported by clinical studies and expert guidelines. Dialysis pre-procedure may be desirable, particularly if a large dose of contrast is anticipated or in patients with heart failure.

Key Point

Patients on dialysis can receive IV contrast, and early post-procedural dialysis is NOT routinely required. However, the fact that a patient is on dialysis should NOT be regarded as automatically allowing the administration IV contrast. The Nephrology Service is readily available for consultation in problematic cases.

References

1. ACR Manual on Contrast Media Version 10.3, 2017:35-46. American College of Radiology.
2. Younathan CM, Kaude JV, Cook MD, Shaw GS, Peterson JC. Dialysis is not indicated immediately after administration of nonionic contrast agents in patients with end-stage renal disease treated by maintenance dialysis. AJR Am J Roentgenol 1994; 163: 969-71.
3. Morcos SK, Thomsen HS, Webb JAW, and members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR). Dialysis and Contrast Media. Eur Radiol 2002; 12: 3026-3030.

Metformin (Glucophage®) is an oral hypoglycemic agent that is eliminated by renal excretion. The most significant potential adverse effect of metformin therapy is the development of metformin-associated lactic acidosis, a rare but serious condition that can be fatal. Any factors that decrease metformin excretion from the kidney or increase blood lactate levels may theoretically increase the risks for patients to develop metformin-associated lactic acidosis.

Prior guidelines from the American College of Radiology recommended withholding metformin when a patient was planned to receive intravascular iodinated contrast based on the theoretical risk of patients developing contrast-induced nephropathy and therefore retaining metformin within the body. However further examinations of the rare cases of metformin-associated lactic acidosis have revealed that almost all cases occurred when patients were receiving metformin despite having one or more patient-associated contraindications to receiving this drug. There have been no reports of lactic acidosis in patients properly selected for metformin therapy. As a result, recent guidelines from the American College of Radiology are more measured in the management of this medication around the time of intravascular iodinated contrast administration: 

Category I

In patients with no evidence of AKI and with eGFR ≥30 mL / min/1.73m2 , there is no need to discontinue metformin either prior to or following the intravenous administration of iodinated contrast media, nor is there an obligatory need to reassess the patient’s renal function following the test or procedure.

Category II

In patients taking metformin who are known to have acute kidney injury or severe chronic kidney disease (stage IV or stage V; i.e., eGFR< 30), or are undergoing arterial catheter studies that might result in emboli (atheromatous or other) to the renal arteries, metformin should be temporarily discontinued at the time of or prior to the procedure, and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been re-evaluated and found to be normal.

Reference

1. ACR Manual on Contrast Media Version 10.3, 2017: 47-49. American College of Radiology. 

Acute adverse reactions to the intravascular administration of iodinated contrast material occur in < 1% of patients. The majority of reactions are mild non-life-threatening events that usually only require observation, reassurance, and/or supportive measures. Severe and potentially life-threatening adverse events do occur rarely (~0.04%) and unpredictably however. Nearly all life-threatening reactions occur within the first 20 minutes after contrast medium injection.

Acute contrast reactions can be categorized as allergic-like (e.g. urticaria, bronchospasm, erythema, facial edema, laryngeal edema, anaphylactic shock) or physiologic (e.g. nausea/vomiting, hypertension, vasovagal reactions, arrhythmia). Reactions are further classified as mild, moderate, or severe in nature (Table 1).

Caring for patients with acute contrast reactions requires a prepared team, adequate resources available for immediate management, and knowledge of how to activate additional resources to assist in caring for severely ill patients. Initial assessment of a patient experiencing an acute contrast reaction should include an assessment of how the patient looks, whether the patient can speak and how his or her voice sounds, an assessment of the patient’s breathing, and measurement of vital signs. Treatment should then proceed as indicated based on the nature and severity of the acute contrast reaction.

Specific ACR guidelines recommendations for management of acute contrast reactions based on category and severity:

• For adults (Management of Acute Reactions to Contrast Media in Adults)
• For children (Treatment of Acute Reactions to Contrast Media in Children)

After managing an acute adverse event to intravascular contrast exposure, it is critical to analyze the event and determine whether the patient experienced an allergic-like reaction. Allergic-type reactions should be further classified by severity. The most substantial risk factor for the development of an acute allergic-like reaction to intravascular iodinated contrast is a prior allergic-like reaction to intravascular iodinated contrast. Thus, any allergic-like reaction should be documented as an allergy in the patient’s electronic medical record so that appropriate prophylaxis (reviewed in the next section) can be considered prior to future administration of intravascular iodinated contrast material. 

(Table 1)

Mild

Signs and symtoms are self-limited without evidence of progression.  Mild reactions include:

Moderate

Signs and symtoms are more pronounced and commonly require medical management.  Some of these reactions have the potiential to become severe if not treated.  Moderate reactions include:

Severe

Signs and symtoms are often life-threatening and can result in permanent morbidity or death if not managed appropriately. 

Cardiopulmonary arrest is a nonspecific end-stage result that can be caused by a variety of the following severe reactions, both allergic-like and physiologic.  If it is unclear what etiology caused the cardiopulmonary arrest, it may be judicious to assume that the reaction is/was an allergic-like one.

Pulmonary edema is a rare severe reaction that can occur in patients with tenuous cardiac reserve (cardiogenic pulmonary edema) or in patients with normal cardiac function (noncardiogenic pulmonary edema).  Noncardiogenic pulmonary edema can be allergic-like or physiologic; if the etiology is unclear, it may be judicious to assume that the reaction is/was an allergic-like one.

Severe reactions include:

1. ACR Manual on Contrast Media Version 10.3, 2017: 96-97, 104-121. American College of Radiology

A prior allergic-like reaction to intravascular iodinated contrast is the most substantial risk factor for a recurrent reaction upon future contrast administration. Up to 35% of patient will experience a recurrence if no premedication prophylaxis is given. Importantly, patients with a mild index reaction have a very low risk (< 1%) of developing a moderate or severe reaction in the future (2).

The use of premedication to prevent recurrent allergic reactions to intravascular iodinated contrast remains controversial. One randomized controlled trial showed that premedication decreased the rate of allergic-like reactions in average-risk (with or without prior history of allergic-like reaction) patients exposed to older high-osmolar iodinated contrast (3). This trial is not directly applicable to modern practice since the contrast medium (high osmolar contrast) is no longer in clinical use and because the patients studied included all patients rather than the patients with a history of prior allergic-type reaction who are targeted for premedication in modern practice. A second smaller randomized controlled trial did investigate prevention of allergic-type reactions in patients exposed to modern low-osmolar iodinated contrast, however this trial again enrolled average risk patients rather than only patients with a history of prior allergic-type reaction (4). This trial showed that in average risk patients premedication prophylaxis did decrease the overall rate of allergic-type reaction (4.7% vs. 1.7%) and of mild reactions (1.9% vs 0.2%) but did not show statistically significant reductions in moderate or severe reactions. It remains an open question whether this trial failed to show a reduction in moderate or severe reactions because premedication prophylaxis is not effective in this regard or whether the trial was underpowered to capture a difference in these uncommon events. Finally, it is important to note that at least 2% of patients with a history of prior allergic-type reaction will still experience a recurrent reaction (“breakthrough reaction”) despite receiving premedication prophylaxis. In most cases the severity of the breakthrough reaction will be similar to that of the index reaction.

The UCSF Department of Radiology employs a practical but conservative approach to managing patients with a prior history of allergic-type reaction to intravascular iodinated contrast, stratified by severity of prior reaction.

In patients with a history of prior mild reaction (limited hives/itching, limited cutaneous edema, limited “itchy/scratchy” throat, nasal congestion, or sneezing/conjunctivitis/rhinorrhea), either no premedication prophylaxis or premedication consisting of only an antihistamine prior to the planned imaging study is recommended (protocol below). This recommendation is based on the following rationale: 1) mild allergic-type reactions do not typically require medical treatment, 2) patients with a mild allergic-type reaction have a very low risk (< 1%) of developing moderate or severe reactions in the future, 3) the effectiveness of corticosteroid prophylaxis for preventing this type of reaction is uncertain. In fact, in one retrospective study, patients with a history of prior mild allergic-type contrast reaction had lower rates of breakthrough reactions when they had received an antihistamine alone as opposed to either a corticosteroid alone or a corticosteroid and antihistamine (2).

In patients with a history of prior moderate or severe prior allergic-type reaction to iodinated contrast or in patients in whom the severity of a prior allergic-type contrast reaction is unknown, oral premedication prophylaxis with a corticosteroid and an antihistamine beginning 12 hours prior to expected contrast administration as outlined below should be strongly considered. In patients in whom more rapid imaging must be obtained, the accelerated premedication protocol outlined below showed non-inferiority to a more traditional longer protocol in a recent retrospective single institution series (5). For several reasons, it is preferable for referring physicians to prescribe the premedication regimen, although other arrangements may be possible depending on individual circumstances. 

For several reasons, it is preferable for referring physicians to prescribe the premedication regimen, although other arrangements may be possible depending on individual circumstances. An APEX smartset has been created to facilitate prescribing of recommended premedication regimens and can be accessed by searching for “contrast premedication".  Patients with a history of prior severe reaction will be imaged at a facility where rapid access to a higher level of care is available (Moffitt-Long Hospital, Mount Zion Hospital, Mission Bay Hospital). 

Prior Mild Contrast Reaction - Premedication Protocol

Prior Moderate, Severe, or Unknown Severity Contrast Reaction - Premedication Protocol

IV Alternatives for Patients Who CANNOT Take Oral Medications

Accelerated Premedication Protocol

For use in patient with prior moderate, severe, or unknown contrast reaction when clinical situation warrants imaging sooner than allowed (12 hrs) with standard protocol

* Cetirizine is a selective antagonist of the histamine H1 receptor. The use of cetirizine (Zyrtec®) instead of the previously recommended antihistamine diphenhydramine (Benadryl®) is preferred in adults due to the side effects associated with diphenhydramine (drowsiness). Substituting diphenhydramine (50 mg PO or IV 1 hour prior to imaging study) for cetirizine is acceptable in situations where a patient or referring clinician has a strong preference for this antihistamine.

**Cetirizine (Zyrtec®) is a selective antagonist of the histamine H1 receptor. Previous protocols for premedication in pediatric patients with a history of allergic-type reactions to iodinated contrast have recommended the use of diphenhydramine (Benadryl®) instead of cetirizine. The advantage of cetirizine is that it is not associated with the side effect of drowsiness that accompanies the use of diphenhydramine (Benadryl®).  For families or referring providers who have a preference for the use of diphenhydramine (Benadryl®), pediatric dosing is as follows: Diphenhydramine 1 mg/kg by mouth 1 hour prior to imaging study.

***Prior UCSF recommendations for corticosteroid prophylaxis recommended the use of EITHER methylprednisolone (Solu-Medrol®) OR prednisone to be given 12 and 2 hours prior to imaging studies. We have simplified this recommendation to only include methylprednisolone for two reasons: 1) To simplify the recommended premedication protocol by only including one medication, and 2) the relevant randomized control trial utilizing prednisone did so with dosing at 13, 7, and 1 hours prior to contrast administration (not 12 and 2 hours as per prior and current UCSF protocols). In situations where a patient or referring clinician strongly prefers to use prednisone instead of methylprednisolone for corticosteroid prophylaxis, this should ideally be given as prednisone 50 mg orally 13, 7, and 1 hour prior to imaging study.

Learn more about iodine allergies and cross-reactivity

Key Point

1. Prior allergic-type reaction to intravascular iodinated contrast is the greatest risk factor for subsequent reaction, with up to 35% of patients experiencing recurrent reactions in the absence of premedication prophylaxis.
2. Patients with a mild severity index reaction have a very low risk of developing a moderate or severe future reaction.
3. Premedication prophylaxis regimens in use today are based on extrapolations from studies in different patient populations and weak support for their use with modern low-osmolar iodinated contrast material.
4. In patients with a history of mild severity prior allergic-type reaction, either no premedication or antihistamine alone should be considered, as outlined above.
5. In patients with a history of moderate or severe prior allergic-type reaction, oral premedication with a corticosteroid and antihistamine beginning 12 hours prior to contrast administration should be considered (as outlined above). An accelerated premedication regimen (also outlined above) beginning 5 hours prior to contrast administration should be considered in patients in whom clinical grounds necessitate earlier imaging.
6. “Breakthrough” reactions occur in at least 2% of patients with a history of prior allergic-type reaction who receive premedication prophylaxis. Patients with a history of severe prior reaction will be imaged at a facility with rapid access to a higher level of care (Moffitt-Long Hospital, Mt. Zion Hospital, Mission Bay Hospital). 

References

1. ACR Manual on Contrast Media Version 10.3, 2017: 6-15, 24-30. American College of Radiology
2. Park S, Kang D, Sohn K et al. Immediate mild reactions to CT with iodinated contrast media: strategy of contrast readministration without corticosteroids. Radiology. 2018 May 16 [Epub ahead of print]
3. Lasser EC, Berry CC, Mishkin MM et al. Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material. N Engl J Med 1987;317:845-9.
4. Lasser EC, Berry CC, Mishkin MM et al. Pretreatment with corticosteroids to prevent adverse reactions to nonionic contrast media. AJR Am J Roentgenol 1994;162:523-6.
5. Kolbe AB, Hartman RP, Hoskin TL et al. Premedication of patients for prior urticarial reaction to iodinated contrast medium. Abdom Imaging. 2014;39:432-7.
6. Davenport MS, Cohan RH. The evidence for and against corticosteroid prophylaxis in at-risk patients. Radiol Clin N Am. 2017;55:413-21.

Background

Contrast extravasation is the accidental extravascular injection of intravascular contrast media caused by dislodgment of the cannula, contrast leakage from the vessel puncture site, or rupture of the vessel wall. Contrast extravasation is a well-recognized complication, with reported frequencies of 0.25% (56/22,254), 0.7% (475/69,657) and 0.9% (48/5,106) in three large CT series where power injectors were used [1-3]. Extravasation usually causes some combination of immediate pain, erythema, and swelling, but fortunately these are usually self-limiting and long-term major morbidity is rare [4]. However, severe skin and subcutaneous ulceration can occur, and subfascial extravasation may cause compartment syndrome (neurovascular signs and symptoms due to increased volume in the confined spaces formed by the deep fascia). These major complications may occur even with small volume (< 10cc) extravasations and non-ionic contrast media [4, 5]. Only 1 patient required fasciotomy for compartment syndrome in a series of 475 extravasations [2].

Risk Factors and Prevention

Small children, the elderly, and unconscious patients are at higher risk for extravasation, partially because of reduced reporting of injection site pain [4]. Other risk factors are use of an injection site other than the antecubital fossa, use of an indwelling venous cannula that has been in place for over 24 hours, and multiple attempts at venous access [4, 6]. When extravasation does occur, complications are more severe in extremities with poor vascular or lymphatic circulation (e.g., on the side of a prior mastectomy with radiation or lymph node dissection) or when extravasation occurs on the dorsum of the hand of foot [4]. Based on these considerations, and realizing that prevention is the key to avoiding contrast extravasation, the following practice guidelines are suggested:

• Ensure the IV site is properly selected, placed, secured, and tested. Make sure the vein is not obstructed when repositioning the arm.
• Consider a lower flow rate in patients at particular risk (while high flow rates do not seem to increase the risk of extravasation, they while result in a more rapid accumulation of extravasated contrast) [3, 7].
• Warn the patient to report any unusual sensations at the IV site immediately.
• Observation of the IV site by the technologist for the first 10-20 seconds of the injection.
• STOP the injection if there is ANY concern or question of extravasation.

Management of Extravasation

As soon as an extravasation is detected, the contrast infusion should be stopped immediately, the catheter removed, and the local overseeing radiologist notified. The affected extremity should be elevated above the heart and cold compresses applied topically. The radiologist evaluating the patient will decide whether the patient can be managed by observation in Radiology for 1-2 hours or requires transfer to the Emergency Department for possible review by Plastic Surgery. Indications for transfer to Emergency Department include skin blistering, altered tissue perfusion, increasing pain, or change in sensation distal to the site of extravasation. Given that there is only a limited relationship between the volume extravasated and the severity of complications, it has been suggested that “only signs and symptoms should be used as criteria for plastic surgery consultation and additional treatment”, and ED referral based purely on the volume extravasated is probably unjustified [2]. Similarly, performing a CT or radiograph of the extremity for large extravasation is of doubtful utility, other than in cases where the extravasation may be subfascial and may cause a compartment syndrome. If the patient is transferred to the Emergency Department, the patient must be escorted. Irrespective of the treatment plan, it is CRITICAL that the radiologist communicates appropriately with the referring physician and the Emergency department. In addition a radiologist at Moffitt from the responsible imaging section should be notified so that the patient can be visited as soon as possible in the Emergency Department. All evaluations and communications must be documented, either in the dictated report or medical record. Patients who are sent home after observation should be given discharge instructions that include the phone number for the patient to call a nurse in Radiology, 353-1564, or go to the nearest Emergency Department if severe problems develop. The technologist or nurse must complete an incident report on-line. The Radiology safety nurse will follow up on all cases of extravasation.

Key Point

Patients with extravasation should be assessed and reassured by a radiologist, and referred to the Emergency Department if there is skin blistering, altered tissue perfusion, increasing pain, or change in sensation distal to the site of extravasation. In all cases, it is critical that the responsible radiologist communicates directly with the patient, referring physician, and Emergency Department as appropriate and documents these communications in the report or medical record.

References

1. Cohan RH, Bullard MA, Ellis JH, Jan SC, Francis IR, Garner WL, Dunnick NR. Local reactions after injection of iodinated contrast material: detection, management, and outcome. Acad Radiol 1997; 4: 711-8.
2. Wang CL, Cohan RH, Ellis JH, Adusumilli S, Dunnick NR. Frequency, management, and outcome of extravasation of nonionic iodinated contrast medium in 69,657 intravenous injections. Radiology 2007; 243: 80-7.
3. Federle MP, Chang PJ, Confer S, Ozgun B. Frequency and effects of extravasation of ionic and nonionic CT contrast media during rapid bolus injection. Radiology 1998; 206: 637-40.
4. Cohan RH, Ellis JH, Garner WL. Extravasation of radiographic contrast material: recognition, prevention, and treatment. Radiology 1996; 200: 593-604.
5. Ayre-Smith G. Tissue necrosis following extravasation of contrast material. J Can Assoc Radiol 1982; 33: 104.
6. Lewis GB, Hecker JF. Radiological examination of failure of intravenous infusions. Br J Surg 1991; 78: 500-1.
7. Jacobs JE, Birnbaum BA, Langlotz CP. Contrast media reactions and extravasation: relationship to intravenous injection rates. Radiology 1998; 209: 411-6.

ACR Contrast Manual

eGFR Caluclators:  GFR Calculator for Adults (for patients 18 and older) and GFR Calculator for Children, from the National Kidney Disease Education Program website.

Adult Glomerular Filtration Rate (GFR) Calculator (National Kidney Foundation website)

Contrast Screening Form (pdf)