GUIDELINES ON THE ADMINISTRATION OF INTRAVENOUS IODINATED CONTRAST MEDIA

Fergus Coakley, Glenn Chertow, Kerry Cho, Charlene Fong, Roy Gordon

Overview

• Practical aspects of contrast administration
• Patient screening prior to administration of iodinated contrast
• Vascular access and use of central lines and ports
• Background information on adverse effects of iodinated contrast
• Creatinine testing prior to contrast administration
• Contrast administration in patients with an elevated creatinine
• Contrast administration in patients with renal failure
• Contrast administration in patients receiving metformin
• Contrast administration in patients with multiple myeloma
• Management of acute contrast reactions
• Premedication
• Permissible doses
• Iso-osmolar dimeric contrast media (Visipaque)
• Contrast extravasation

Related links:

• http://www.radiology.ucsf.edu/dept/docs/Gad_UCSF6.20.07.doc
• http://manuals.ucsfmedicalcenter.org/AdminManual/IndividualPolicies/MedMgmtAdministrationofMedication.pdf
• http://manuals.ucsfmedicalcenter.org/NursingDept/AdultProcedures/PDFsafter12-29 2003/CVC_PartF_AccessingImplantedPort.pdf

Practical aspects of contrast administration

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 where 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 and their management.

Critical 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 reaction.
• Iodinated 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 an emergency anaphylactic box containing supplies required for the treatment of contrast reactions.

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Patient screening prior to administration of iodinated contrast

Nurses, technologists, and radiologists administering intravascular iodinated contrast media must first assess the patient for risk factors predisposing them to adverse reactions. This is achieved by completion of the Radiology Contrast Media History & Assessment form. The patient (or their parent/guardian) indicates:

1. Previous reactions to iodinated contrast media.
2. All allergies and reactions (both medications and food).
3. All current medications.
4. History of diabetes, kidney disease, asthma, pheochromocytoma, solitary kidney or transplant kidney, or myeloma.
5. Current use of any metformin-containing medications.
6. Weight, height, and time of last food or drink.
7. Possibility of pregnancy (for women of child-bearing age).
8. The technologist completes the date and level of the most recent creatinine level (if available).

Administrative process

1. The requisition form for the exam with pertinent indication is scanned into ImageCast at the time of scheduling.
2. The scheduling process includes an initial screening for allergies, pregnancy, age, and history of kidney disease. The scheduling nurse will be consulted for screening as necessary.
3. The radiologist entering the protocol into ImageCast will determine whether the study requires contrast or not. This protocol will be for the technologist to follow.
4. Upon arrival to the department, the patient completes the “Radiology Contrast Media History and Assessment” form #724-026Z.
5. The RN/RT reviews the completed form and notifies the Radiologist of any contraindications or risk factors noted. The pharmacist may be consulted as necessary.
6. Most patients have some degree of anxiety and fear concerning imaging procedures. The RN/RT questions the patient regarding their expectations, explains the procedure and reassures the patient. The patient should be offered the opportunity to speak with a radiologist if questions persist or anxiety seems pronounced.
7. 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 body weight per manufacturer's recommendations.
8. 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.
9. 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 test to ensure patency. Proceed with contrast injection.
10. 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.

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Vascular access and use of central lines and ports

Technologists can only insert peripheral IV catheters in the arm, and an unaccompanied technologist can only power inject a peripheral IV catheter in the arm. Power injection of other peripheral lines (including external jugular lines) should be done in the presence of an RN or MD. Intravenous access catheters placed peripherally for contrast injection should be 20 gauge or larger for CT studies. When a 22-gauge catheter is used, the technologist should adjust the injection rate to 2.5 cc/sec or less to suit the smaller bore catheter. Intravenous setup for mechanical power injection should include 0.9 % saline flush, high-pressure tubing, and contrast injection syringe.

Central lines and ports can only be hand injected by an MD or RN (including PICC lines - Peripherally Inserted Central Catheters), with the exception of the following three devices that can be power injected in the presence of an MD or RN:

1. The purple PowerPICC line by BARD Access Systems. The Power PICC is a purple central venous catheter that has been approved by the FDA for power injection of contrast.
2. The PowerPort by BARD is a subcutaneous indwelling central venous access port that is FDA-approved for power injection of contrast. It has a distinctive triangular shape that can be palpated (three palpable “bumps” arranged in a triangle) or seen on a CXR or scout view (either an opaque rounded triangle or a triangular outline with the letters “CT”).

3. The Smart Port by AngioDynamics is a subcutaneous indwelling central venous access port that is FDA-approved for power injection of contrast. It has distinctive scalloped edges that can be palpated or seen on a CXR or scout view.

The PowerPICC line is readily identifiable by visual inspection. Any of the following three methods can be used to verify the presence of a power injectable subcutaneous port (i.e., PowerPort or Smart Port):

1. Device card in the possession of the patient.
2. Report available in the patient record describing placement of a PowerPort or Smart Port.
3. Radiographic confirmation (recent CXR or CT scout view).

These lines are to be injected using appropriate sterile technique to prevent infection. The two power injectable ports require special equipment for power injectable access (LifeGuard Safety Infusion set and needle). After contrast injection, all central lines not in continuous use must be flushed with appropriate volumes and concentration of heparin-saline solution and capped with a sterile injection cap. This may be done by an RN or MD only. Additional details for using the approved power injectable central lines are given below:

Power injectable PICC line

1. The physician or RN with PowerPICC competency must be present for the power injection into the PowerPICC line. The maximum flow rate allowed is 5 ml/sec and the pressure is not to exceed 300 psi.
2. “Check blood return and flush” – This reminder is on the thumb clamp. Flush the PowerPICC catheter using a 10 cc sterile normal saline prior to and immediately following the completion of power injection studies. This will ensure the patency of the PowerPICC. Resistance to flushing may indicate partial or complete catheter occlusion. Do not proceed with power injection until occlusion has been cleared.
3. Remove the injection/needleless cap from the PowerPICC catheter.
4. Attach a 10 cc syringed filled with sterile normal saline.
5. Aspirate for adequate blood return and vigorously flush the catheter with the full 10 cc of sterile normal saline.
6. Clamp catheter and detach syringe.
7. Attach the high pressure tubing from the MedRad injector to the PowerPICC catheter.
8. Complete power injection study taking care not to exceed the flow rate limits of 5 cc/sec and 300 psi.
9. Disconnect the power injection device.
10. Flush the PowerPICC catheter with 10 cc of sterile normal saline.
11. Replace the injection/needleless cap on the PowerPICC catheter.
12. For catheter maintenance, flush PICC with 3 cc per lumen of heparinized saline.

Power injectable subcutaneous port

1. The physician or RN with power port competency must be present for the power injection into the port. The radiologist will verify the port as a power injectable port by the scout scan or CXR. The maximum flow rate allowed is 5 ml/sec and the pressure is not to exceed 300 psi.
2. Check blood return and flush. Flush the power port catheter using a 10 cc sterile normal saline prior to and immediately following the completion of power injection studies. This will ensure the patency of the port. Resistance to flushing may indicate partial or complete catheter occlusion. Do not proceed with power injection until occlusion has been cleared.
3. Access the power port with the Lifeguard Safety Infusion set. Refer to procedure for port access in the Nursing procedure manual.
4. Attach a 10 cc syringed filled with sterile normal saline.
5. Aspirate for adequate blood return and vigorously flush the catheter with the full 10 cc of sterile normal saline.
6. Clamp catheter and detach syringe.
7. Attach the high pressure tubing from the MedRad injector to the Power port catheter.
8. Complete power injection study taking care not to exceed the flow rate limits of 5 cc/ sec and 300 psi.
9. Disconnect the power injection device.
10. Flush the port catheter with 10 cc of sterile normal saline.
11. Replace the injection/needleless cap on the port.
12. For catheter maintenance, flush port with 3 cc per lumen of heparinized saline.

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Background information on adverse effects of iodinated contrast

Renal impairment is one of the major side effects of intravenous iodinated contrast administration. A wide variety of risk factors have been described, of which pre-existing renal impairment and diabetes mellitus are the most important. The true frequency of contrast nephropathy is difficult to establish because there are no standard diagnostic criteria. In two large series (n = 1114 and 443) of patients undergoing coronary angiography, 6 to 10% of patients had a post-procedural rise in serum creatinine of greater than 0.5 mg/dl [1, 2]. None of these patients became anuric or required hemodialysis. The major factors predictive of contrast nephropathy were elevated baseline serum creatinine and diabetes mellitus. Another study that only included patients with impaired renal function (creatinine greater than 1.35 mg/dl) found the frequency of contrast nephropathy (defined as a rise of at least 25% in serum creatinine) depended on the baseline creatinine level and presence of diabetes mellitus [3], as shown in the figure:

Key point: The true frequency of contrast nephropathy is difficult to establish because there are no standard diagnostic criteria, but it is clear that the primary risk factor is baseline renal impairment, especially with co-existent diabetes.

References

1. Davidson CJ, Hlatky M, Morris KG, et al. Cardiovascular and renal toxicity of a nonionic radiographic contrast agent after cardiac catheterization. A prospective trial. Ann Intern Med. 1989; 110:119-124.
2. Schwab SJ, Hlatky MA, Pieper KS, et al. Contrast nephrotoxicity: a radomized controlled trial of a nonionic and an ionic radiographic contrast agent. NEJM 1989; 320:149-153.
3. Barrett BJ, Parfrey PS, Vavasour HM, et al. Contrast nephropathy in patients with impaired renal function: high versus low osmolar media. Kidney Internat 1992; 41:1274-1279.

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Creatinine testing prior to contrast administration

Background: Routine creatinine testing prior to contrast administration is NOT necessary in all patients [1, 2]. With the exception of age and hypertension (see below), the indications for creatinine testing in the above guidelines are those suggested by the ACR [2]. However, these recommendations should be considered in the light of several confounding factors:

1. In a study of 2034 outpatients who all had routine creatinine testing prior to CT outpatient CT, 66 patients had a creatinine of 2.0 or above [1]. All but 2 of the 66 had one or more of 8 risk factors that were chosen based on published literature (history of renal insufficiency or renal disease, diabetes mellitus, advanced age, male gender, nephrotoxic-drug use, chemotherapy, HIV/AIDS, solitary kidney). The two cases that would have been “missed” by a policy of selective creatinine testing had a creatinine of 2.0 and 2.2. Two particularly notable findings in this study were that age alone was not an important risk factor, and that both IDDM and NIDDM were important risk factors.
2. The use of age as a risk factor and the choice of threshold are both controversial, with conflicting data in the literature. It is also important to distinguish between studies that address age as a risk factor for an elevated baseline serum creatinine BEFORE contrast administration (which is the topic of concern when considering measuring creatinine prior to imaging) and age as a risk factor for developing contrast-induced nephropathy AFTER contrast administration. Community based studies of serum creatinine suggest age, hypertension, and diabetes are important predictors of creatinine elevation [3-5]. In addition, many centers use age (with variable thresholds) to determine the need for creatinine testing and this practice is also engrained in the department culture at UCSF.
3. Standard practice is variable and often based on little to no evidence [6]. For example, there is little data on whether in-patients are substantively different to outpatients.
4. Arguably, the list of medications should be expanded to include chemotherapy, since many of these drugs are nephrotoxic [7].
5. The use of serum creatinine as a marker of renal insufficiency is in and of itself questionable, given that in one study, 15.2% of out-patients with a normal serum creatinine had an estimated creatinine clearance of 50 mL/min/1.73 m² or less (normal is 90 mL/min/1.73 m² or more) [8].
6. In general, these guidelines are simply guidelines, and slavish adherence in every case is neither expected nor appropriate. Physician discretion and judgment are paramount, and commonsense should be applied to individual patient circumstances. For example, creatinine testing can be omitted for an urgent study where time is critical, particularly a contrast-enhanced stroke CT protocol requested by the Emergency Department (this determination should be made by the requesting physician). Conversely, it may be prudent to check creatinine in a sick debilitated patient even if they do not have any of the specific factors listed above.

Key point: Routine creatinine testing prior to contrast administration is NOT necessary in all patients; the major indications are age over 70, history of preexistent renal insufficiency, diabetes mellitus, or hypertension.

References

1. Tippins RB, Torres WE, Baumgartner BR, Baumgarten DA. Are screening serum creatinine levels necessary prior to outpatient CT examinations? Radiology 2000; 216: 481-484.
2. Manual on Contrast Media, Edition 5.0, 2004. American College of Radiology.
3. Culleton BF, Larson MG, Evans JC, Wilson PW, Barrett BJ, Parfrey PS, Levy D. Prevalence and correlates of elevated serum creatinine levels: the Framingham Heart Study. Arch Intern Med 1999; 159: 1785-90.
4. Passos VM, Barreto SM, Lima-Costa MF; Bambui Health and Ageing Study (BHAS) Group. Detection of renal dysfunction based on serum creatinine levels in a Brazilian community: the Bambui Health and Ageing Study. Braz J Med Biol Res. 2003;36: 393-401.
5. Coresh J, Wei GL, McQuillan G, Brancati FL, Levey AS, Jones C, Klag MJ. Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med. 2001; 161: 1207-16.
6. Elicker BM, Cypel YS, Weinreb JC. IV contrast administration for CT: a survey of practices for the screening and prevention of contrast nephropathy. Am J Roentgenol 2006; 186: 1651-1658.
7. Kintzel, PE. Anticancer Drug-Induced Kidney Disorders. Drug Safety 2001; 24:19-38.
8. Duncan L, Heathcote J, Djurdjev O, Levin A. Screening for renal disease using serum creatinine: who are we missing? Nephrol Dial Transplant 2001; 16:1042 -1046.

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Contrast administration in patients with an elevated creatinine

The decision to proceed with contrast administration in patients with a creatinine greater than 1.5 mg/dL should ALWAYS be a matter of clinical judgment, based on the individual circumstances of the patient and following consultation between the radiologist and requesting physician. The radiologist is ultimately responsible for determining the most appropriate imaging algorithm. If contrast administration is considered essential, the following options should be considered.

• Acetylcysteine. A frequently cited study claimed a nine-fold reduction in contrast-induced nephropathy in chronic renal insufficiency patients receiving 600 mg acetylcysteine (Mucomyst®) orally twice daily on the day before and the day of a contrast-enhanced study, when compared to controls [1]. In the study, patients were randomly assigned to receive acetylcysteine and 0.45% saline intravenously or to receive placebo and saline. Only 1 of the 41 (2%) patients in the acetylcysteine group had an increase of at least 0.5 mg in serum creatinine at 48 hours after administration of contrast compared to 9 of 42 (21%) patients in the control group (p = 0.01). A more recent randomized study of 121 cardiac catheterization patients with chronic renal insufficiency (creatinine greater than 2.0) receiving a mean dose of 117ml of non-ionic contrast, showed 15 of 61 (24.6%) patients who received only saline infusion (0.45% at 1ml/kg/hr) from 12 hours before to 12 hours after angiography developed acute nephropathy (increase of creatinine by at least 0.5 at 48 hours after the procedure) compared to only 2 of 60 (3.3%) patients who received saline infusion and acetylcysteine 400 mg bid on the day before and the day of the procedure (p < 0.001) [2].
• Discontinue other nephrotoxic drugs.
• Hydration. IV hydration can be achieved with 1/2 normal saline at 75-100 cc/hour for 12 hours before and 12 hours after contrast administration [3].
• Decrease total amount of contrast administered.
• Increase the amount of time between contrast-enhanced studies.
• Infuse sodium bicarbonate solution. A recent trial [4] of patients with a baseline creatinine of at least 1.1 mg/dL study found a significant reduction (p = 0.02) in the frequency of nephrotoxicity (defined as an increase of 25% or more in serum creatinine within 2 days of contrast) in those randomized to sodium bicarbonate infusion (1 of 60) compared to sodium chloride (8 of 59). Patients received 154 mEq/L of either sodium chloride or sodium bicarbonate, as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure. The advantage of this regime is that is can be implemented rapidly, facilitating the early scanning of patients from the Emergency Department, for example.

While these options may be helpful, it should be remembered contrast nephropathy is uncommon and usually transient. A critical diagnostic study should NOT be delayed because of excessive concern regarding possible contrast nephropathy. In addition, it should be noted that there is little data on the combined use of these approaches, although the clinical setting may dictate which regimen is more practical in a patient with an elevated creatinine. For example, the two-day acetylcysteine regimen may be simplest to administer prior to an elective out-patient study, while a one hour infusion of sodium bicarbonate may be more appropriate before an unplanned emergency study. Of note, a recent meta-analysis comparing the protective effect of various regimens suggested that N-acetylcysteine is more renoprotective than hydration alone, and supported the administration of acetylcysteine prophylaxis, particularly in high-risk patients, given its low cost, availability, and few side effects [5].

Key point: Contrast nephropathy is uncommon and usually transient. A critical diagnostic study should NOT be delayed because of excessive concern regarding possible contrast nephropathy. Strategies to prevent nephropathy in patients with renal impairment include oral acetylcysteine, discontinuation of other nephrotoxic drugs, hydration, reduction of contrast dose, and sodium bicarbonate infusion.

References

1. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000; 343: 180-184.
2. Shyu KG, Cheng JJ, Kuan P. Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure. J Am Coll Cardiol 2002; 40: 1383-1388.
3. Solomon R, Werner C, Mann D, et al. Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents. NEJM 1994; 331: 1416-1420.
4. Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, Bersin RM, Van Moore A, Simonton CA 3rd, Rittase RA, Norton HJ, Kennedy TP. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004; 291: 2328-2334.
5. 5. Kelly AM, Dwamena B, Cronin P, Bernstein SJ, Carlos RC. Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy. Ann Intern Med 2008; 148: 284-94.

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Contrast administration in patients with renal failure

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 [1, 2]. 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. 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.
2. 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.

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Contrast administration in patients receiving metformin

Metformin (Glucophage®) is an oral hypoglycemic agent. Metformin is predominantly eliminated by renal excretion. Contrast-induced nephropathy can result in metformin accumulation and precipitate metformin-related lactacidosis, a rare but recognized side effect. The current ACR recommendation for contrast administration in patients receiving metformin is that the drug should be discontinued at the time of 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 [1] (the older recommendation that metformin should be stopped for 48 hours before the exam has been dropped).

Key point: The current ACR recommendation for contrast administration in patients receiving metformin is that the drug should be discontinued at the time of 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. Bush WH, Bettmann MA. Update on metformin (Glucophage®) therapy and the risk of lactic acidosis: change in FDA-approved package insert. ACR Bulletin 1998; 54: 15.

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Contrast administration in patients with multiple myeloma

There is a widespread perception that iodinated contrast media are contra-indicated in patients with multiple myeloma but this is unsupported by the available evidence. In a comprehensive review of this topic [1], it was noted that the primary risk factors for acute renal failure in patients with multiple myeloma are hypercalcemia, dehydration, infection, and Bence Jones proteinuria (rather than contrast media). This review identified seven retrospective studies reporting iodinated contrast administration in 476 myeloma patients for a total of 568 imaging studies. The frequency of acute renal failure was 0.6%-1.25%, as against a comparable frequency of 0.15% in the general population receiving iodinated contrast. Although the administration of contrast media to myeloma patients is not totally risk free, it may be performed if the clinical need arises and the patient is well hydrated.

Key point: The administration of contrast media to myeloma patients is not totally risk free, but the widespread perception of high risk is unfounded and contrast may be administered if the clinical indication is appropriate and the patient is well hydrated.

Reference

1. McCarthy CS, Becker JA. Multiple myeloma and contrast media. Radiology 1992; 183: 519-521.

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Management of acute contrast reactions

Management is organized by symptom complex [5, 14, 15]. No attempt has been made to integrate symptomatology into an etiological scheme. It is prudent to administer oxygen to all patients having a contrast reaction, however mild, since the reaction may progress and become potentially life-threatening.

Table 2. Management of acute contrast reactions.

References

1. Manual on Contrast Media, Edition 5.0, 2004. American College of Radiology.
2. Guidelines for the Management of Reactions to Intravenous Contrast Media. Royal College of Radiologists, London.
3. Chapters 1-6, in: Bush WH, Krecke KN, King BF, Bettmann MA. Radiology Life Support (Rad-LS): A Practical Approach. London / Arnold Publishers, New York / Oxford University Press, 1999. pp. 1-99.

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Premedication

Premedication is generally reserved for patients with a history of a significant prior contrast reaction. The risk of a repeat reaction in a patient with a history of prior severe reaction is 18.5%, even with non-ionic contrast media [1]. The use of pre-medication to prevent reactions to intravascular non-ionic contrast media is controversial [2, 3]. The most supportive study states pre-medication reduces the incidence of all reactions by approximately 60% [4], but it is unclear whether the statistical power and methodology of the study allows extrapolation of this risk reduction to patients developing moderate and severe reactions, i.e. those of most concern [2, 4]. Corticosteroids are the critical component of any premedication regime, and should be given at least 6 hours before the test. For several reasons, it is preferable for the referring physician to prescribe the premedication regime, although other arrangements may be possible depending on individual circumstances. For simplicity, an oral regime is recommended:

Table 3. Oral premedication regime in patients considered at high risk for adverse contrast reactions.

Key point: Pre-medication may help reduce, but does not eliminate, the risk of a serious contrast reaction in a patient considered to be at elevated risk.

References

1. Siegle RL, Halvorsen RA, Dillon J, et al. The use of iohexol in patients with previous reactions to ionic contrast material. A multicenter clinical trial. Inv Radiol 1991; 26: 411-416.
2. Dawson P, Sidhu PS. Is there a role for corticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents? Clin Radiol 1993; 48:225-226.
3. Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media. Radiology 1990; 175: 621-628.
4. Lasser EC, Berry CC, Mishkin MM, et al. Pretreatment with corticosteroids to prevent adverse reactions to nonionic contrast media. AJR 1994; 162:523-526.

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Permissible doses

Dose is considered a risk factor for adverse contrast reactions and nephropathy, although the data on this issue are limited [1]. The maximum recommended adult dose of iohexol (Omnipaque®; the main intravascular contrast agent used in our department) is of 250 mL of Omnipaque 350 or 291 mL of Omnipaque 300 [2]. In practice, dose is only a concern in patients undergoing catheter angiography and CT on the same day (e.g., a patient with metastatic colon cancer who requires a conventional arteriogram to assess arterial anatomy and a CT to define the site and number of lesions). In such circumstances, due regard should be given to the clinical need for an optimal study, rather than rigid adherence to a relatively empiric maximum recommended dose. It may be appropriate to discuss the relative risks and benefits with the patient.

Key point: There are no strict maximum permissible doses of contrast, but in general volumes of over 250-300 cc in a 24 hour period should be avoided.

References

1. Lasser EC, Lyon SG, Berry CC. Reports on contrast media reactions: analysis of data from reports to the U.S. Food and Drug Administration. Radiology 1997; 203: 605-610.
2. Omnipaque package insert. Nycomed-Amersham, Princeton, NJ.

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Iso-osmolar dimeric contrast media

Several recent studies have reported on the use of iodixanol (Visipaque, Nycomed, Princeton, NJ), which is a iso-osmolar dimeric nonionic contrast medium. No difference in nephrotoxicity was seen in either of 40 normal volunteers or 16 non-diabetic patients with sever renal failure randomized to receive iodixanol or iohexol (Omnipaque, Nycomed-Amersham, Princeton, NJ) [1-3]. A similar study in 64 patients with mild renal impairment (creatinine of 1.5 to 3.0) found no difference in nephrotoxicity between iodixanol or iopromide (Ultravist, Schering, Berlin, Germany) [4]. Conversely, a study in 124 patients with a creatinine over 1.7 mg/dL found an post-angiographic increase in serum creatinine of over 10% in 31% of patients receiving iohexol compared to only 15% of patients receiving iodixanol (p < 0.05) [5]. A randomized double-blind prospective multi-institutional trial of 129 diabetics with elevated serum creatinine of 1.5 to 3.5 mg/dL undergoing coronary angiography, found creatinine increased significantly less in patients who received iodixanol compared to iohexol [6]. These two larger studies suggest there may be some renal benefit to the use of iodixanol, but the data are not definitive. In addition, dimeric contrast media are probably associated with more delayed contrast reactions, such as T-cell mediated skin rashes [7]. Unfortunately, delayed contrast reactions are often poorly documented and reliable comparative data for different agents are not available.

Key point: Visipaque may help reduce the risk of contrast nephropathy in patients with an elevated creatinine.

References

1. Jakobsen, J.A., Renal experience with Visipaque. Eur Radiol, 1996. 6 Suppl 2: p. S16-9.
2. Jakobsen, J.A., Renal effects of iodixanol in healthy volunteers and patients with severe renal failure. Acta Radiol Suppl, 1995. 399: p. 191-5.
3. Jakobsen, J.A., et al., Evaluation of renal function with delayed CT after injection of nonionic monomeric and dimeric contrast media in healthy volunteers. Radiology, 1992. 182(2): p. 419-24.
4. Carraro, M., et al., Effects of a dimeric vs a monomeric nonionic contrast medium on renal function in patients with mild to moderate renal insufficiency: a double-blind, randomized clinical trial. Eur Radiol 1998; 8. 144-7.
5. Chalmers N, Jackson RW. Comparison of iodixanol and iohexol in renal impairment. Br J Radiol 1999; 72: 701-703.
   6.             
6. Aspelin, P., et al., Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med, 2003; 348: 491-9.

7. Webb JA, Stacul F, Thomsen HS, Morcos SK. Late adverse reactions to intravascular iodinated contrast media. Eur Radiol 2003; 13: 181-184.

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Contrast extravasation

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.

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