Updated 4/17/12

Brett Elicker, Fergus Coakley, Kerry Cho, Charlene Fong, Tina Hampton, Roy Gordon, and John Mackenzie

Overview

• Practical aspects of contrast administration
• Patient screening prior to administration of iodinated contrast
• Administrative Process
• 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
• References
• Useful Links

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 Patient Screening Form For Iodinated Contrast (Appendix A). 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, pheochromocytoma, solitary kidney, kidney or other transplant, or myeloma.
5. Current use of any metformin-containing medications.
6. For women of child-bearing age, if they are or may be pregnant or if they are breast-feeding.
7. The technologist reviews the form and enters the date and value of the most recent eGFR (if available or required).

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Administrative process

1. The requisition form for the exam with pertinent indication is scanned into ImageCast at or shortly after the time of scheduling.
2. 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.
3. Upon arrival to the department, the patient completes the “Patient Screening Form For Iodinated Contrast (Appendix A)”.
4. 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.
5. 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.
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 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 test 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.

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Vascular access and use of central lines and ports

Intravenous Administration of Contrast Agents for Enhanced CT or MR Scans in Adults.

1. Peripheral IVs
2. PICCS (peripherally inserted central catheters)
3. Chest Ports
4. Central Lines
5. Dialysis catheters should not be used to administer contrast agents
6. IV cannulas inserted into the Internal or External Jugular Vein

 

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 below. The follow flowchart will assist in the decision of obtaining proper venous access for contrast administration.

1) Peripheral IV

Doctors, nurses and Radiology technologists can insert peripheral IV catheters in the adult arm for the purpose of contrast administration.  A peripheral intravenous line (20 gauge) in the antecubital or forearm area is preferred when power injections are needed in adults.  Although 22-gauge catheters may be able to tolerate flow rates up to 5 ml/sec, the 20-gauge or larger catheter is preferable for flow rates of 3 ml/sec or higher. When a 22-gauge catheter is used, the technologist should adjust the injection rate to < 3.0 cc/sec in adults (2.0 cc/sec. in pediatrics) to suit the smaller bore catheter.

A small peripheral line  IV of 24 gauge, may only be used for contrast by hand injection.

Before initiating the injection, the position of the catheter tip should be checked for venous backflow by withdrawing blood and flushing with normal saline.  A saline test flush may be used to test the power injection. Standard procedures should be used to clear the syringe and pressure tubing of air before connecting to the catheter.  A critical step in preventing significant extravasation is direct monitoring of the venipuncture site by palpation during the initial portion of the contrast medium injection. If no problem is encountered during the initial injection, the individual monitoring the injection exits the CT scan room before the scanning begins. If extravasation is detected, the injection is stopped immediately. If the patient complains of pain the injection should be stopped and the patient examined for signs of extravasation.

2) PICCs (peripherally inserted central catheters)

PICCs that are power injectable are clearly marked "power injectable" and have a maximum flow rate printed on the catheter lumen or hub itself. They can be power injected by a trained MD or RN. and should only be be used according to manufacturer's guidelines in the presence of appropriately trained personnel. These lines include, but are not limited to the following:

• The 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 in adults and children. Refer to the marking on the hub of the catheter to determine the maximum rate of injection and to choose the correct lumen for power injection. Power PICCs of 4Fr single lumen, 5Fr single or double lumen and 6Fr single or double lumen can be power injected at 5 mls/sec and a maximum power injector pressure setting of 300 psi.  For more information, see: http://www.bardaccess.com/powerpicc/ 
  
• Cook Spectrum PICC. The line with the red hub should be used for power injection. All catheter tube extensions are labeled with port name, gauge, and flush volume. A 4Fr single lumen can be injected at 4mls/see, a 5Fr single lumen at 7 mls/sec and a double lumen at 5 mls/sec at a Maximum Injector Pressure limit of 325 psi.For more information, see: http://www.cookmedical.com/ir/dataSheet.do?id=5485
  
• The Navilyst Power injectable PICC has the max ml/sec marked on the clamp on the lumen of the power injectable lumen. Depending on the lumen of the catheter the rate ranges from 3.5 mls/sec to 5 mls/sec at a Maximum Power Injector pressure of 300 psi.  It has a clear extension tubing to visualize the blood return.  Patients may come with this PICC line placed at an outside hospital.  For more information, see: http://www.navilystmedical.com/Products/index.cfm/4
  
• Morpheus Smart PICC by AngioDynamics has the max ml/sec marked on the clamp on the lumen of the power injectable lumen, which is usually 5 mls/sec.   A patient may come with this PICC line placed at an outside hospital.  For more information, see: http://www.angiodynamics.com/products/morpheus-smart-picc
  

3) Chest Ports

• 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. Note the “CT” is visible on x-ray image of the newer models of ports as an identifier that this port is power injectable. It is indicated for power injection of contrast media up to 5 mL/sec. and 300 psi pressure limit setting, when used with a Gripper Plus Huber needle. They are MRI conditional at 3 Tesla. This is the most common adult chest port currently placed at UCSF.  For more information, see: http://www.angiodynamics.com/products/smart-port-ct
  
• Smith Medical has power P.A.C. port that is power injectable up to 5 ml/sec. when used with a Gripper Plus power P.A.C. Huber needle. They are MRI conditional at 3 Tesla. There are single-lumen and dual-lumen ports that are power injectable.  Note that the word “CT” is visible on a x-ray image of the newer models of ports as an identifier that this port is power injectable.  For more information, see: http://www.smiths-medical.com/catalog/implantable-ports/port-cath-p-s.html
  
• 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” under the triangle).  It is indicated for power injection of contrast media up to 5 mL/sec and a 300 psi pressure limit setting, when used with a Gripper Plus Huber needle.  There are also dual-lumen PowerPorts by BARD.  For more information, see http://www.bardaccess.com/port-powerport.php?section=Specifications
  
  

4) Central Lines

• The ARROWgard Blue plus pressure injectable CVC is pressure injectable for CT scanning for up to 10 mL/sec.  The center lumen is marked with the max ml/sec on the hub of the catheter.  The words “No CT” are marked on the lumen that is not to be used for power injection.  For more information, see http://www.arrowintl.com/products/PressureCVC/help_prevent_infection/research.asp
  
  
• Power Hickman catheter by BARD is a tunneled central venous catheter that can be injected up to maximum flow rate of 5 mL/sec.  and 300 psi pressure limits setting.  For more information, see: http://www.bardaccess.com/products.php?category=Central%20Venous%20Catheters
  
  
• Power Hohn by BARD comes in single, double, and triple lumen catheters.  The specific lumen is marked if it is power injectable, up to a maximum of 5 mL/sec at a maximum of 300 psi. http://www.bardaccess.com/picc-powerhohn.php?section=Features
  

Criteria to POWER INJECT through a power injectable CVC

• The CVC must be verified as compatible for power injection (see above).
• A trained Radiology RN/MD will help the imaging technologist connect the power injectable CVC to the power injector when the following conditions are met.
• The 5 rights for medication administration are satisfied. Check patient identification to ensure the Right Patient, check the Right Contrast (medication), check the Right Dose, check the Right Route, and check the Right Time.
• Do a visual inspection of the external portion of the catheter for integrity and proper position.
• Check that the catheter flushes properly with normal saline and withdraws properly.
• The technologist will perform the power injection after the power injector has been connected to the power injector catheter by the radiology nurse/MD using aseptic technique.
• The maximum flow rate and psi for adult injection is 5 mL/sec at <300 psi, and the maximum flow rate and psi for Pediatric is 2 mL/sec at <300 psi.  The injection rate will be dependant on the specific catheter type, size, and specific exam protocol.

Criteria to POWER INJECT through a power injectable CVC

The Radiology nurse will determine the catheter type and size by visual inspection and review of documentation. Hand injection of contrast is acceptable only if the examination does not require arterial phase of injection (CTA). Adult patients with non-power injectable central line, may undergo contrast injection for a CT/MRI by hand injection into the CVC, except into dialysis catheters.

A trained Radiology RN/MD will perform the hand injection into the non-power injectable CVC per protocol followed by 10 mL 0.9 sodium chloride flush when the following conditions are met.

• The 5 rights for medication administration are satisfied. Check patient identification to ensure the Right Patient, check the Right Contrast (medication), check the Right Dose, check the Right Route, and check the Right Time.
• Do a visual inspection of the external portion of the catheter for integrity and proper position.
• Check that the catheter flushes properly with normal saline and withdraws properly.

5) Dialysis catheters

Dialysis catheters are NOT to be used, with the exception of the BARD Trialysis catheter as described below. Dialysis or apheresis catheters should never be accessed without the explicit approval of the responsible attending or fellow in Nephrology or Hematology/Oncology.

• BARD Trialysis catheter has a power injectable third lumen.  Only this lumen may be used for contrast administration.  The maximum flow rate is marked on this purple lumen.  For more information, see http://www.bardaccess.com/dial-power-trialysis.php
  
  

6)  IV cannulas inserted into the Internal or External Jugular Vein

Short IV cannulas placed in the jugular vein should not be power injected by the technologist or RN because of the dangers of extravasation in the neck.  The preference is to attempt a peripheral IV in the patient for contrast administration.  If this is not possible and it is deemed necessary for the patient to receive a contrast scan, then contact the Radiologist.  The line will be checked for blood return and flushed with saline bolus.  It can be hand injected by a Radiology RN or MD for contrast enhanced scan but not for a CT angiogram.

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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. The risk of contrast nephropathy requiring dialysis significantly increases in patients with an estimated glomerular filtration rate below 30 ml/min/1.73² as shown in figure [3].

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. McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997; 103 (5): 368-75

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 Creatinine testing prior to contrast administration

UCSF guidelines for creatinine testing prior to contrast administration Laboratory results should be checked for the most recent serum creatinine on ALL patients (by the technologist performing the study). If serum creatinine is not available, it should be performed IF the patient has ANY of the following risk factors: •    Age over 60 •    History of “kidney disease” as an adult, including tumor and transplant •    Family history of kidney failure •    Diabetes treated with insulin or other prescribed medications •    Hypertension (high blood pressure) •    Paraproteinemia syndromes or diseases (e.g., myeloma) •    Collagen vascular disease (e.g., SLE, scleroderma, rheumatoid arthritis) •    Solid organ transplant. If creatinine testing is required, a creatinine level within the prior 6 weeks is sufficient in most clinical settings.

Background: Routine creatinine testing prior to contrast administration is NOT necessary in all patients [1, 2]. The indications for creatinine testing include those listed in the table above.  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 risk factors should be expanded to include chemotherapy, since many of these drugs are nephrotoxic [7].
5. Estimated glomerular filtration rate (eGFR) is likely a more reliable indicator of renal function compared to creatinine alone as it takes into account age, race and sex.  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].  The exact eGFR threshold below which withholding intravenous contrast should be considered is unclear. The risk of contrast nephropathy rises from a low baseline in patients with an eGFR < 60 ml/min/1.732, however the majority of these patients will only have a temporary rise in creatinine. Also, there is no convincing data to support an increased morbidity or mortality in patients who do not require dialysis for the treatment of contrast nephropathy. The risk of dialysis after receiving contrast significantly increases in patients with an eGFR < 30 ml/min/1.732 [9]. The eGFR threshold below which withholding contrast should be considered is thus between 60 and 30 ml/min/1.732.  In one article [10], the rate of contrast nephropathy in patients with a GFR<40 ml/min was 0.6% and >40 ml/min/1.732 was 7.8%, thus a threshold of 45 ml/min/1.732 seems an appropriate cut-off.  A creatinine of 1.6 in a 70 year old, non-African American male corresponds to an estimated GFR of approximately 45 ml/min/1.732.
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.  Estimated glomerular filtration rate is a better predicator of renal dysfunction than creatinine alone.

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.
9. McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997; 103 (5): 368-75.
10. Thomsen HS, Morcos SK.  Risk of contrast-medium-induced nephropathy in high-risk patients undergoing MDCT – A pooled analysis of two randomized trials.  Eur Radiol 2009; 19: 891-897.

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Contrast administration in patients with an elevated creatinine

The decision to proceed with contrast administration in patients with an estimated GFR < 45 ml/min/1.73² 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.

• Hydration. This is one of the most important methods for decreasing the incidence of contrast nephropathy, however the exact hydration protocol is unclear.  The regimen which is considered most ideal is 1/2 normal saline at 1 mL/kg per hour for 12 hours before and 12 hours after contrast administration [1].  This regimen, however, is very impractical in an outpatient setting.  Additionally, there is little data to either support or refute the effectiveness of oral compared to intravenous hydration regimens.  The exact hydration protocol is probably not nearly as important as the fact that some form hydration is administered.
• Decrease total amount of contrast administered.
• Increase the amount of time between contrast-enhanced studies.
• Infuse sodium bicarbonate solution. One of the first randomized bicarbonate trials performed [2] evaluated patients with a baseline creatinine of at least 1.1 mg/dL and 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. Additionally, a recent meta-analysis [3] comparing patients receiving sodium bicarbonate vs. sodium chloride showed that bicarbonate significantly reduced the incidence of contrast nephropathy (odds ratio = 0.46, 95% confidence interval = 0.26-0.82).  Of note, however, there was no significant difference in the need for renal replacement therapy or in-hospital mortality comparing the two groups.
• Discontinue other nephrotoxic drugs.
• 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). Since that original study there have been multiple randomized controlled trials and meta-analyses which have shown conflicting results [7], some supporting the use of acetylcysteine and others not.  Many of the controlled trials have been hampered by poor study design including small patient numbers.  Given the heterogeneity of data, it is difficult to support the administration of acetylcysteine as a proven and effective means by which to prevent contrast nephropathy. 

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.

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 hydration, reduction of contrast dose, hydration, sodium bicarbonate infusion and discontinuation of nephrotoxic drugs.

References

1. 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.
2. 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.
3. Navaneethan SD, Singh S, Appasamy S, Wing RE, Seghal AR. Sodium Bicarbonate Therapy for Prevention of Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis. Am J Kidney Dis 2008. In press.
4. 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.
5. Bagshaw SM, McAlister FA, Manns BJ, Ghali WA.  Acetylcysteine in the prevention of contrast-induced nephropathy: a case study of the pitfalls in the evolution of evidence. Arch Intern Med 2006; 166 (2): 161-6

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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 1998 ACR recommendation for contrast administration in patients receiving metformin was 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 was dropped in the 1998 update). More recently, the ACR has adopted a more relaxed policy that varies according to renal dysfunction and presence of co-morbidities [2]. The Safety Committee of the UCSF Department of Radiology and Biomedical Imaging reviewed the latest ACR recommendations related to metformin in October 2011. Given the substantial complexity and challenges in implementing the new guidelines, the Committee decided that the Department would continue to follow the more conservative and simpler 1998 policy. Of note, this is also concordant with the cautious approach taken by the FDA [3].

Key point: The UCSF Department of Radiology and Biomedical Imaging 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.
2. Manual on Contrast Media, Edition 7.0, 2010: 33-35. American College of Radiology.
3. http://depts.washington.edu/druginfo/Alerts/Details/metformin_bulletin.html.

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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.

“Hives” (urticaria)	Discontinue injection if not completed No treatment needed in most cases - reassure the patient Consider diphenhydramine (Benadryl®) PO/IM/IV 25-50 mg If severe/widely disseminated: Epinephrine SC (1:1,000) 0.1-0.3 ml (=0.1-0.3 mg) (if no cardiac contraindications)
Facial or laryngeal edema	0.1-0.3 ml epinephrine SC or IM (1:1,000) (=0.1-0.3 mg) or, if hypotensive, 1 ml epinephrine IV (1:10,000) slowly (=0.1 mg). Repeat as needed up to 1 mg. Give oxygen 6-10 L/min (via mask) If not responsive to therapy or if there is obvious acute laryngeal edema, seek appropriate assistance (e.g., cardiopulmonary arrest response team).
Bronchospasm	Give oxygen 6-10 L/min (via mask) Monitor: ECG, O2 saturation (pulse oximeter), and BP Give beta-agonist inhalers, such as metaproterenol (Alupent®), terbutaline (Brethaire®), or albuterol (Proventil®)(Ventolin®) 2-3 puffs; repeat as needed If unresponsive, epinephrine SC or IM (1:1,000) 0.1-0.3 ml (=0.1-0.3 mg) or, if hypotensive, epinephrine (1:10,000) slowly IV 1 ml (=0.1 mg) - Repeat up to 1 mg Alternatively, give aminophylline 6 mg/kg IV in D5W over 10-20 minutes (loading dose), then 0.4-1 mg/kg/hr, as needed (caution: hypotension) Call for assistance for severe bronchospasm or if O2 saturation < 88% persists
Hypotension with tachycardia	Legs elevated 60° or more (preferred) or Trendelenburg position Monitor: ECG, O2 saturation (pulse oximeter), and BP Give oxygen 6-10 L/min (via mask) Rapid large volumes of IV isotonic Ringer’s lactate or normal saline If poorly responsive: Epinephrine (1:10,000) slowly IV 1 ml (=0.1 mg) (if no cardiac contraindications). Repeat as needed up to a maximum of 1 mg If still poorly responsive seek appropriate assistance (e.g., arrest team).
Hypotension with bradycardia (vagal reaction)	Monitor: ECG, O2 saturation (pulse oximeter), and BP Legs elevated 60° or more (preferred) or Trendelenburg position Secure airway and give oxygen 6-10 L/min (via mask) Rapid large volumes of IV isotonic Ringer’s lactate or normal saline If unresponsive, atropine 0.6-1 mg IV slowly - repeat up to 2-3 mg in adult Ensure complete resolution of hypotension and bradycardia prior to discharge.
Severe hypertension	Give oxygen 6-10 L/min (via mask) Monitor: ECG, O2 saturation (pulse oximeter), and BP Give nitroglycerine 0.4-mg tablet, sublingual (may repeat x 3) Transfer to intensive care unit or emergency department For pheochromocytoma—phentolamine 5 mg IV
Seizures or convulsions	May be consequence of hypotension, primary treatment should be as indicated Lateral decubitus position, give oxygen, 6-10 L/min by mask Consider diazepam (Valium®) 5 mg or more or midazolam (Versed®) 0.5-1 mg IV If longer effect needed, obtain consultation; consider phenytoin (Dilantin®) infusion – 15-18 mg/kg at 50 mg/min. Careful monitoring of vital signs, particularly of pO2 (respiratory depression) Consider using cardiopulmonary arrest response team for intubation
Pulmonary edema	Elevate torso; rotating tourniquets (venous compression) Give O2 6-10 liters/min (via mask) Give diuretics – furosemide (Lasix®) 20-40 mg IV, slow push Consider giving morphine (1-3 mg IV) Transfer to intensive care unit or emergency department Corticosteroids optional
Unconscious/ unresponsive/ pulseless/ collapsed patient	CALL CODE (6-1234) Institute Basic Life Support Establish airway, head tilt, chin lift Initiate ventilation and external chest compression Continue uninterrupted until help arrives

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.

12 hours before	50 mg prednisone OR 32 mg methylprednisolone (Medrol®)
AND
2 hours before	50 mg prednisone OR 32 mg methylprednisolone (Medrol®) 50 mg Diphenhydramine (Benadryl®)

 
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), an iso-osmolar dimeric nonionic contrast medium.  There is a theoretical benefit to administering an agent that is iso-osmolar to serum, compared to low osmolar agents which have an osmolarity significant higher than serum.  One of the first randomized trials to compare iso-osmolar to low osmolar contrast agents demonstrated that 15% of patients who received the iso-osmolar agent showed a >10% rise in creatinine within the week following contrast administration, compared to 31% in the low-osmolar group.  Similar to the acetylcysteine trials there have been conflicting data regarding the effectiveness of iodixanol to reduce the incidence of contrast nephropathy compared to low osmolar agents.  In fact, in a recent meta-analysis [2] the overall relative risk of contrast nephropathy in patients receiving iso-osmolar agents was not significantly different than low osmolar agents (odds ratio 0.8, 95% confidence interval 0.61 to 1.04).  In the subset of patients who received intravenous contrast the effect was even less convincing (odds ratio 1.08, 95% confidence interval 0.62-1.89).

Key point: It is unclear whether Visipaque is associated with a decreased incidence of contrast nephropathy compared to low osmolar agents, and thus its routine administration in at-risk patients is not yet recommended based upon current data.

References

1. Chalmers and Jackson. Comparison of iodixanol and iohexol in renal impairment. The British journal of radiology (1999) vol. 72 (859) pp. 701-3
2. Heinrich et al. Nephrotoxicity of Iso-osmolar Iodixanol Compared with Nonionic Low-osmolar Contrast Media: Meta-analysis of Randomized Controlled Trials. Radiology (2009) vol. 250 (1) pp. 68-86

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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.

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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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