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Minimizing Adverse Reactions to Contrast Agents
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Although
significant adverse reactions to iodinated contrast agents are rare,
they do, justifiably, arouse concern among patients, referring
physicians, and radiologists. Most reactions are mild and
self-limiting, such as flushing, nausea, vomiting, pain at the
injections site, pruritis, headache, and mild urticaria. They are,
nevertheless, unpleasant for the patient. The very rare severe
reactions, estimated to occur in 0.004 – 0.04% of patients, include
life-threatening anaphylactoid reactions, cardiac dysrythmias and
arrest, and cardiovascular and pulmonary collapse. These reactions are
idiosyncratic and difficult to predict since they may happen once but
never again.
In contrast, nephrotoxic reactions to
iodinated contrast reagents are more predictable and, with a high
enough dose, would be seen in everyone. Increased levels of serum
creatinine can be detected 24 hours after a contrast CT in
approximately 1% of the healthy outpatient population, returning to
baseline within 1-2 weeks. Nephrotoxic reactions are much more likely
in patients with impaired renal function. In one study, increased
levels of serum creatinine were detected in 23% of those with a
baseline serum creatinine > 2 mg/dl and almost 100% of patients with
serum creatinine levels > 4.5 mg/dl and diabetes. Fortunately,
permanent renal damage is rare. However, contrast medium nephrotoxicity
can prolong the patient’s stay in hospital and increase the risk of
non-renal complications.
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Sagittal
view of a CT angiogram of the abdominal aorta. The 3-D image is
reconstructed from axial CT images performed with intravenous contrast.
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Is Contrast Imaging Necessary?
The
best way to preclude the occurrence of adverse reactions is to avoid
the use of contrast reagent. However, contrast agents play an important
and sometimes essential role in many kinds of imaging. Thus, the
advantages of using iodinated contrast agents for the evaluation of the
patient must be weighed against the disadvantages. This is not always a
simple decision. MGH radiologists may use a contrast agent unless its
use is specifically contraindicated. Clinicians are given the option of
specifying the whether contrast is to be used at the time of
scheduling. However, if nothing is specified, the radiologist will make
the decision at the time the examination is reviewed. We recommend that
the use of contrast be left to the radiologist unless there is a true
contra-indication.
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Factors that Increase the Risk of Adverse Reactions to Iodinated Contrast Agents
A. Systemic Reactions
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- Previous adverse reaction
- History of asthma or bronchospasm
- History of allergy or atopy
- Anxiety
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- Cardiac disease*
- Medication (b-blockers)
- Hematologic and metabolic disease (sickle cell anemia, patients with thrombotic tendency, multiple myeloma, pheochromocytoma)
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B. Nephrotoxicity
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- Congestive heart failure (New York Heart Association class 3 & 4)
- Dehydration
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- Renal disease, especially in diabetics treated with metformin (Glucophage)
- Medications (aspirin, NSAIDs)
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*Symptoms
of angina or congestive heart failure with minimal exercise, severe
aortic stenosis, primary pulmonary hypertension, or severe but well
compensated cardiomyopathy.
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Immediate Adverse Reactions to CT Contrast Agents
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Mild
(Incidence, 3%) |
Self limited without evidence of progression
Hives, nasal stuffiness, itching, headache, shaking, dizziness
Not necessarily due to contrast but reported as adverse event: Nausea and vomiting
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Moderate
(Incidence, 0.04%) |
Clinical findings require treatment and careful observation for progression
Tachycardia, bradycardia, hypertension,
hypotension, dyspnea, bronchospasm, wheezing,
laryngeal edema, pronounced cutaneous reaction
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Severe
(Incidence, 0.0004%) |
Severe, life threatening symptoms, usually requires hospitalization
Laryngeal edema, convulsions, profound hypertension, unresponsiveness
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Pre-medication Recommendations
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| Immediate Adverse Reaction* |
Prednisone, 50 mg PO at 13 hr, 7 hr, and 1 hr before scan
Diphenhydramine (Benadryl), 50 mg PO, 1 hr before scan
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Nephrotoxicity
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If creatinine level > 2 mg/dl, consult radiologist
Discontinue metformin before and for 48 hrs after scan(diabetics)
Hydrate well (all patients)
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*Patients
with history of severe reaction should not receive CT contrast agents.
Contact radiologist to discuss alternate imaging options.
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Identifying the At-Risk Patient
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The
risk of a general adverse reaction is increased somewhat by several
factors (see box) that should be considered before administering
iodinated contrast agents. For this reason, all patients who are
scheduled to receive contrast agents are asked to fill in a
questionnaire to alert the radiology technologist to potential
problems. The technologist will discuss any concerns with a
radiologist, who will make an informed decision for that patient or
contact the referring physician to discuss imaging without contrast,
using an alternate contrast agent containing gadolinium, or using an
alternative imaging modality.
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High-risk
patients include those who have experienced a previous anaphylactoid
reaction to contrast agents or an anaphylactic reaction to an allergen.
Although patients with asthma have a 3-fold increase in the likelihood
of a contrast reaction, they are not considered to be at high risk,
except for severe cases. Children have a lower frequency of contrast
reactions than do adults.
Although the incidence of
contrast agent nephrotoxicity is low in patients with normal renal
function, it is a significant concern for those with poor renal
function, diabetes, congestive heart failure, dehydration, or the
concurrent use of nephrotoxic drugs.
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Minimizing Contrast Agent Reactions and Nephrotoxicity
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MGH
radiologists routinely use non-ionic iodinated contrast agents, which
have about one fifth the incidence rate of general adverse reactions
(around 3%) compared to the older ionic agents. For patients that are
at high risk of an anphylactoid reaction, pretreatment (prednisone 50
mg PO at 13, 7, and 1 hr before, and diphenhydramine (Benadryl) 50 mg,
1 hr before) decreases the chance that a reaction will occur. In cases
in which the use of iodinated contrast agent is deemed the best option,
despite a severe risk of an anaphylactoid reaction, the presence of an
anesthesiologist to monitor the patient is required.
In order to minimize nephrotoxicity, all adult patients scheduled to
receive an iodinated contrast agent must have had a recent test to
measure serum creatinine. If one is not available or if there is any
reason to think that there might have been a recent change, blood will
be drawn before the imaging procedure and the serum creatinine level
measured. If the level is 2 mg/dl or more, the radiology technologist
must consult a radiologist before proceeding with the study.
Hydration lowers the risk of renal failure and is especially important
in patients who have mild renal insufficiency, diabetes, or multiple
myeloma. Patients should be encouraged to drink plenty of clear fluids
both before and after the procedure. In those patients unable to take
oral fluids, hydration is ensured through IV saline infusion.
N-acetyl-cysteine is routinely used to reduce the chance of
nephrotoxicity in cases of mild renal insufficiency. Other prophylactic
drugs are available but these are only suitable for inpatient use.
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Diabetic
patients who are taking metformin (Glucophage) are at an increased risk
for lactic acidosis if they suffer nephrotoxicity after contrast
administration. For this reason, they must discontinue the drug at the
time of the procedure until at least 48 hours afterwards and after it
has been confirmed that the serum creatinine level remains within the
normal range.
Preliminary data suggests that the
newer (and more expensive) iso-osmolar contrast agents cause fewer
nephrotoxic effects and their use is being considered for those most at
risk as an additional precautionary measure. Alternatively, gadolinium contrast agents can be used safely for imaging in patients with marginal renal function or who are at significant risk for other adverse reactions. Gadolinium contrast agents have a much lower renal
toxicity than iodinated agents at the doses necessary for imaging and
anaphylactic reactions to gadolinium containing agents are extremely
rare. However, the doses of gadolinium needed for angiographic imaging
are higher than those necessary for MRI; these doses have not been
proven safe, and their use should be carefully considered.
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Further Information
MGH
radiologists welcome all questions regarding the use of contrast agents
and the choice of imaging modality. Please contact a radiologist in the
appropriate Division of the Department.
For general questions about web-based Radiology scheduling, call 617-726-0304
For general questions about Radiology Services, call 617-724-4902
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Scheduling and Reporting
CT
imaging with contrast can be performed at Mass General West Imaging in
Waltham, Mass General Imaging in Chelsea or the main MGH campus and can
be ordered online via the Radiology Order Entry (ROE) system
(http://mghroe
) or by calling 4-XRAY (617-724-9729). Results are made
available to physicians online within 24-48 hours.
Acknowledgements
Thanks to Alan Greenfield, M.D.
, Vascular Division, MGH Department of Radiology, for his advice in preparing this issue.
This article provided useful information about the appropriate use of imaging studies:
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References
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Bettmann, MA, Heeren, T, Greenfield, A and Goudey, C. (1997) Adverse events with radiographic contrast agents: results of the SCVIR Contrast Agent Registry. Radiology 203: 611-20
Hash, RB. (1999) Intravascular radiographic contrast media: issues for family physicians. J Am Board Fam Pract 12: 32-42
Tippins, RB, Torres, WE, Baumgartner, BR and Baumgarten, DA. (2000) Are screening serum creatinine levels necessary prior to outpatient CT examinations? Radiology 216: 481-4
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Morcos, SK and Thomsen, HS. (2001) Adverse reactions to iodinated contrast media. Eur Radiol 11: 1267-75
Maddox, TG. (2002) Adverse reactions to contrast material: recognition, prevention, and treatment. Am Fam Physician 66: 1229-34
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