Intravenous Imaging Contrast Media Complications: The Basics That Every Clinician Needs to Know

doi:10.1016/j.amjmed.2015.02.018

The American Journal of Medicine

Volume 128, Issue 9, September 2015, Pages 943-949

https://doi.org/10.1016/j.amjmed.2015.02.018 Get rights and content

Abstract

Intravenous contrast is commonly used in noninvasive imaging procedures such as magnetic resonance imaging and computed tomography and can evaluate blood vessels and better characterize soft-tissue lesions. Although the incidence of adverse events after administration of contrast is low, it is important that clinicians and radiologists minimize risks and respond quickly and effectively when reactions occur. We will discuss a range of adverse events to iodinated and gadolinium-based contrast agents, including allergic-like reactions, nephrotoxicity, extravasation, and nephrogenic systemic fibrosis. We will review risk stratification for patients, as well as premedication and treatment of adverse events.

Section snippets

Iodinated Contrast Reactions

Iodinated contrast has been used in radiographic studies for almost a century and is usually well tolerated. Adverse reactions are divided into 2 categories: allergic-like and physiologic. Allergic-like reactions are usually divided into 3 grades; mild, moderate, and severe (Table 1). The majority of reactions are non-life threatening, and 70% occur within the first 5 minutes of injection.1, 2 Early iodinated contrast agents were high-osmolarity, ionic compounds, and as a result, associated

Metformin

Metformin is an oral antihyperglycemic medication commonly used to control blood glucose in non-insulin-dependent diabetics. Patients taking metformin may develop lactic acidosis, although the incidence is very rare—estimated at 0 to 0.08 cases per 1000 patient-years.12, 16 Because most metformin is excreted in the kidney, renal insufficiency can increase the risk of lactic acidosis. Iodinated contrast is not an independent lactic acidosis risk factor in patients taking metformin, but because

Nephrotoxicity

As defined by the 2013 ACR Manual on Contrast Media,¹² contrast-induced nephrotoxicity is “a sudden deterioration in renal function after intravascular administration of iodinated contrast medium in the absence of another nephrotoxic event.” The most common laboratory-based definition of contrast-induced nephrotoxicity is an increase ≥25% in serum creatinine levels or an absolute serum creatinine increase ≥0.5 mg/dL after contrast administration.¹⁷

The pathophysiology of contrast-induced

Extravasation

Extravasation of IV contrast during power injection has a reported incidence of 0.1%-0.9%.⁵⁰ Increased risk for extravasation is observed in patients with altered circulation, prior radiation therapy, prior lymph node dissection, and severe debilitation. Certain access sites also are at increased risk, including the hand, foot, and ankle. Most patients complain of initial swelling and tightness, or burning, although some feel no discomfort. In the vast majority of patients the symptoms are

Gadolinium Agents

The increased availability and utilization of MRI has increased exposure to gadolinium-based contrast media. There are many different such agents, with different molecular structures leading to variations in stability, osmolality, and excretion. Gadolinium agents are not nephrotoxic in the approved recommended dose. However, as with any injected media there is risk for anaphylactoid-type reaction and physiologic reactions, although the frequency is less than for iodinated contrast.⁵²

Gadolinium Contrast Reaction

The frequency of adverse reactions (allergic-like and physiologic) in gadolinium-based contrast media is estimated to be 0.07%-2.4%. Allergic-like responses are very unusual. The reported incidence is 0.004%-0.007%, with the vast majority consisting of a few hives or minor rash.¹² Severe life-threatening reactions were extremely rare (0.001%-0.01%). Patients with previous reaction to gadolinium contrast agents have an 8-fold higher risk of developing an allergic-like reaction.¹² Patients with

Nephrogenic Systemic Fibrosis

Nephrogenic systemic fibrosis is a rare, multisystemic disease associated with certain types of gadolinium contrast in patients with reduced renal function. As the name implies, it is associated with increased collagen deposition in soft tissues, which can present with skin thickening and muscle contractures. Organs such as the heart, liver, and lungs can also be affected.53, 54

Most patients presenting with nephrogenic systemic fibrosis had received contrasted MRI within the previous 2 to 3

Conclusion

Intravenous contrast agents are among the most widely administered drugs in the world and are often necessary for optimal clinical imaging. Although not common, risks with using IV contrast media include allergic-like response, nephrotoxicity, and with gadolinium agents nephrogenic systemic fibrosis. Clinicians and radiologists must be aware of risk factors that may place their patients at increased risk of these adverse events. The first step is to ensure that contrast is necessary for the

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To evaluate the potential to reduce the amount of iodinated contrast media (CM) for computer tomographic pulmonary angiography (CTPA) with a novel photon-counting-detector CT (PCCT).
Overall, 105 patients referred for CTPA were retrospectively included in this study. CTPA was performed using bolus tracking and high-pitch dual-source scanning (FLASH mode) on a novel PCCT (Naeotom Alpha, Siemens Healthineers). CM (Accupaque 300, GE Healthcare) dose was lowered stepwise following the introduction of the new CT scanner. Thus, patients could be divided into 3 groups as follows: group 1, n = 29, 35 ml of CM; group 2, n = 62, 45 ml of CM and group 3, n = 14, 60 ml of CM.
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The subjective image quality was rated highest in group 1 with 4.6 compared to 4.5 (group 2) and 4.1 (group 3) with a significant difference between groups 1 and 3 (p < 0.001) and between groups 2 and 3 (p = 0.003). In all groups, almost all segmental pulmonary arteries could be assessed adequately without significant differences (18.5 vs. 18.7 vs. 18.4).
Mean attenuation in the pulmonary trunk did not differ significantly between groups 321 ± 92 HU versus 345 ± 93 HU versus 347 ± 88 HU (p = 0.69).
Significant CM dose reduction is possible without a reduction in image quality. PCCT enables diagnostic CTPA with 35 ml of CM.
Significance of Brain Imaging for Staging in Patients With Clinical Stage T1-2 N0 Non–Small-Cell Lung Cancer on Positron Emission Tomography/Computed Tomography
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We retrospectively investigated the frequency of extrathoracic metastasis in 466 consecutive patients with clinical stage T1-2 N0 NSCLC with the complete staging assessment comprised of thin-section CT, PET/CT, and brain contrast-enhanced magnetic resonance imaging between 2008 and 2016. All patients were reclassified according to the eighth edition of the tumor, node, and metastasis (TNM) classification.
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Routine screening of brain imaging is unnecessary in patients with early-stage NSCLC, assessed with the current staging protocol including PET/CT.
Adverse Events of Diagnostic Radiopharmaceuticals: A Systematic Review
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Citation Excerpt :
We found a median reported frequency of adverse events in diagnostic radiopharmaceuticals of 0.0016%, which is low compared to the 1%-2% reported for therapeutic drugs143,144 and the 5%-7% reported for drug reactions in hospitalized patients.145-147 This frequency is also lower than the earlier reported frequency range of 0.7%-3.1% with nonionic iodinated contrast media used in computed tomography (CT).148,149 For some individual radiopharmaceuticals, we found a frequency ranging from 0.125% to 40.9%, with the higher frequencies including products no longer in use such as I-131 human serum albumin and Tc-99m fanolesomab.
Diagnostic radiopharmaceuticals used in nuclear medicine can cause adverse events. Information on these adverse events is available in case reports and databases but may not be readily accessible to healthcare professionals. This systematic review provides an overview of adverse events of diagnostical radiopharmaceuticals and their characteristics. A median frequency for adverse events in diagnostical radiopharmaceuticals of 1.63 (interquartile range: 1.09-2.29) per 100,000 is reported. Most common are skin and subcutaneous tissue disorders, and general disorders and administration site conditions. Many adverse events reported are minor in severity, although 6.7% can be classified as important. In rare cases, adverse events are serious and potentially life-threatening. With the introduction of new radiopharmaceuticals and the increasing use of positron emission tomography-computed tomography, previously unknown adverse events may be detected in daily practice. Future work should cover the experience of the patient with adverse events from diagnostic radiopharmaceuticals.
An Initiative to Reduce Unnecessary Gadolinium-Based Contrast in Multiple Sclerosis Patients
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Patients with multiple sclerosis (MS) routinely undergo serial contrast-enhanced MRIs. Given concerns regarding tissue deposition of gadolinium-based contrast agents (GBCAs) and evidence that enhancement of lesions is only seen in patients with new disease activity on noncontrast imaging, we set out to implement a prospective quality improvement project whereby intravenous contrast would be reserved only for patients with evidence of new disease activity on noncontrast images.
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During a 2-month trial period, 153 patients were imaged under the new protocol. Technologists using the CAD software were able to identify patients with new or enlarging lesions on FLAIR images with 95% accuracy and 97% negative predictive value relative to final neuroradiologist interpretations, which allowed us to avoid the use of contrast and additional imaging sequences in 87% of patients.
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Provocation with a skin test–negative RCM was performed to exclude RCM allergy and to determine the reliability of a negative skin test result. General principles of our provocation protocol were as follows: (1) the time interval since immediate-type reactions was at least 4 weeks, and recovery from MPE was at least 8 weeks ago; (2) written informed consent was obtained from each patient; (3) before RCM injection, renal function and thyroid function were examined by measurement of serum creatinine and thyrotropin; (4) intake of metformin was discontinued 48 hours before RCM injection16,17; (5) patients were closely monitored and equipment for emergency treatment was available throughout the entire procedure. Incremental doses were given intravenously every 30 minutes.
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: Funding: None.

: Conflict of Interest: None.

: Authorship: Both authors had access to the data and a role in writing the manuscript.

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ReviewIntravenous Imaging Contrast Media Complications: The Basics That Every Clinician Needs to Know

Abstract

Section snippets

Iodinated Contrast Reactions

Metformin

Nephrotoxicity

Extravasation

Gadolinium Agents

Gadolinium Contrast Reaction

Nephrogenic Systemic Fibrosis

Conclusion

J Allergy Clin Immunol

Prog Cardiovasc Dis

Kidney Int

Kidney Int

Am J Med

Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media

Radiology

Anaphylaxis to iodinated contrast material: nonallergic hypersensitivity or IgE-mediated allergy?

AJR Am J Roentgenol

Current understanding of contrast media reactions and implications for clinical management

Drug Saf

Acute reactions to intravascular contrast media: types, risk factors, recognition, and specific treatment

AJR Am J Roentgenol

Intravascular contrast media: adverse reactions

AJR Am J Roentgenol

Pretreatment with corticosteroids to prevent adverse reactions to nonionic contrast media

AJR Am J Roentgenol

Reactions to radiocontrast material. Anaphylactoid events in radiology

Clin Rev Allergy Immunol

Increased risk for anaphylactoid reaction from contrast media in patients on beta-adrenergic blockers or with asthma

Ann Intern Med

Iodine allergy: an oyster without a pearl?

AJR Am J Roentgenol

Strategies for the prevention of asthmatic, anaphylactic and anaphylactoid reactions during the administration of anesthetics and/or contrast media

J Investig Allergol Clin Immunol

Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material

N Engl J Med

Breakthrough adverse reactions to low-osmolar contrast media after steroid premedication

AJR Am J Roentgenol

Use of IV epinephrine for treatment of patients with contrast reactions: lessons learned from a 5-year experience

AJR Am J Roentgenol

Metformin

N Engl J Med

Prophylaxis of contrast-induced nephrotoxicity

Biomed Res Int

Pathophysiology of renal tissue damage by iodinated contrast media

Clin Exp Pharmacol Physiol

Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media

Radiology

Is contrast medium osmolality a causal factor for contrast-induced nephropathy?

Biomed Res Int

Nephrotoxicity of iso-osmolar iodixanol compared with nonionic low-osmolar contrast media: meta-analysis of randomized controlled trials

Radiology

Background fluctuation of kidney function versus contrast-induced nephrotoxicity

AJR Am J Roentgenol

Renal function following infusion of radiologic contrast material. A prospective controlled study

Arch Intern Med

Failure to demonstrate contrast nephrotoxicity

Med J Aust

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

Functional contrast-enhanced CT for evaluation of acute ischemic stroke does not increase the risk of contrast-induced nephropathy

AJNR Am J Neuroradiol

Contrast-induced nephropathy in elderly trauma patients

J Trauma

Review
Intravenous Imaging Contrast Media Complications: The Basics That Every Clinician Needs to Know