Selecting a contrast medium for MDCT investigation

Most procedures performed with multidetector computed tomography (MDCT) require the administration of a contrast medium (CM). In choosing a CM, it is important to consider the tolerability profile of the CM and whether sufficient contrast enhancement will be achieved. Low-osmolar CM (LOCM) are the most widely used and are well tolerated in most patients. However, some patients (e. g. those with renal insufficiency, diabetes and the elderly) are at significant risk of contrast-induced nephropathy (CIN), which can compromise the benefits of the procedure. Iodixanol is an iso-osmolar CM that compares favourably with LOCM in terms of contrast enhancement and is also associated with less pain or discomfort on injection. In patients with renal impairment and diabetes undergoing angiography, a significantly lower incidence of CIN was reported with iodixanol compared with iohexol (iodixanol, 3.1%; iohexol, 26.2%; P = 0.002). A second study in patients with renal insufficiency undergoing CT angiography reported a 9% incidence of CIN; no patients developed renal failure and all recovered.     

Nephrotoxicity of ionic and non-ionic contrast media in aorto-femoral angiography

Nineteen patients examined with aorto-femoral angiography were randomized into two contrast medium groups (meglumine metrizoate and iohexol). Urine activity of beta-hexosaminidase, a specific renal enzyme, was determined before and on three occasions after angiography. No change of beta-hexosaminidase activity was found after angiography with iohexol, while there was a significant increase after examination with meglumine metrizoate. This indicates that meglumine metrizoate even following injection into the abdominal aorta damages renal cells which could not be shown with iohexol as contrast medium. We therefore recommend that at least patients with impaired renal function should be examined with the non-ionic contrast medium iohexol to minimize the danger of further damage to the kidneys and a possible renal failure.     

Induction of Upregulation and Downregulation of the T-Cell Activation Marker CD98 in Patients Undergoing Contrast-Enhanced CT with Iodinated Non-Ionic Dimeric Contrast Medium

Objective

This study was designed to determine prospectively the expression of the multifunctional CD98 protein in peripheral white blood cells in patients receiving iodinated contrast media (CM) for a computed tomography (CT) examination.

Materials and Methods

In 12 adult patients that received non-ionic dimeric CM (iosimenol or iodixanol), the expression of CD98 was analyzed from samples of peripheral white blood cells obtained prior to, one hour, and 24 hours after CM injection by the use of flow cytometry analysis and the use of the direct immunofluorescence technique.

Results

Overall, expression of CD98 was significantly downregulated 24 hours after CM injection (51.9%±10.8% vs. 38.8%±16.9%; p < 0.04). Patients that received iosimenol exhibited a more pronounced but not significant decrease of CD98 expression both one hour and 24 hours after CM injection. In an analysis of specific patient responses, CD98 downregulation occurred in eight patients. In two patients, CD98 was upregulated, and in the remaining two patients, expression remained unchanged. No patient acquired an adverse CM reaction.

Conclusion

This is the first demonstration that CM may be a regulator of CD98 expression. To determine if upregulation is associated with an increased risk for the acquisition of an adverse CM-induced hypersensitivity reaction and if downregulation is associated without a risk for the acquisition of an adverse CM-induced hypersensitivity reaction, further studies with a larger population of patients are required.     

Late adverse reactions to non-ionic contrast media: a cohort analytic study

In this cohort study early, intermediate and late reactions after intravenous injection of non-ionic contrast media were evaluated and compared with the nature and incidence of complaints stated by a control group investigated without contrast media. Study A was conducted by means of a questionnaire. In study B a physician interviewed a different group of patients. Early adverse reactions (day 1) occurred in 11.4% of patients to whom contrast (CM) media had previously been administered compared with 6.1% of patients who had not received a CM injection (study A). Late adverse reactions (up to day 7) were observed in 39.1% and 21.1% of the patients respectively. The incidence was 7.0% versus 0.9% on day 1 for the symptom increased diuresis. Between days 4 and 7, 4.8% and 2.6% of the patients respectively had this symptom, which is interpreted as an impairment of renal function. In study B the incidence of early adverse reactions was 3% and 1.5% respectively between days 2 and 3 (CM group). The authors conclude that more than half of the adverse reactions after (non-ionic) contrast media are due to the underlying disease and that a (clinically latent) impairment of renal function can be assumed.     

Contrast media in abdominal computed tomography. A double blind clinical trial comparing a non-ionic (iohexol) and an ionic (metrizoate) contrast medium

Abdominal computed tomography was performed in 55 patients before and after intravenous injection of 60 ml of a non-ionic (iohexol) or an ionic (metrizoate) contrast medium. The adverse effects were recorded and a series of measurements of attenuation values before and after the contrast medium injection was performed in the aorta and in hepatic and renal parenchyma. Only minor adverse effects were seen with both contrast media, but iohexol was clearly better tolerated than metrizoate. No difference in the enhancement properties was found between the two contrast media.     

Letter to the Editor re: Are intravenous injections of contrast media really less nephrotoxic than intra-arterial injections?

In a recent paper, the authors oppose the opinion that “ intra-arterial administration of iodinated-based contrast media (CM) appears to pose a greater risk of contrast-induced nephropathy (CIN) than intravenous administration” . As nephrologists, we are happy to have the opportunity to offer our expertise in the setting of renal disease aimed at optimizing diagnostic algorithm and preventive strategies. Our comment relies on the fact that, from a nephrologist’s point of view, there is no doubt that renal damage following CM intra-venous administration in patients not in intensive care or emergency department and treated with conventional preventive strategies not only occurs with low frequency, but also appears of negligible clinical impact; it is confined to an asymptomatic increase of serum creatinine of 25% or 0.5 mg/dL lacking any prognostic negative impact, and in some case not significantly different from controls. True CIN, just related to intravenous CM injection for diagnostic purpose, has to be differentiated from all the other cause of renal involvement in people stricken with sudden and acute illness also receiving intra-arterial CM injection, in order to avoid patients being denied necessary radiological examinations due to an inappropriate fear of risk. Key Points ? Contrast induced nephropathy (CIN) is not any nephropathy following contrast medium(CM). ? CIN should only refer to renal damage strictly due to CM infusion. ? True CIN following CM intravenous infusion is a clinically insignificant event. ? Renal damage following intra-arterial CM infusion in compromised patients is not CIN. ? Patients should not forego necessary radiological examinations for inappropriate understanding about risk.     

Et-A receptor antagonist BQ123 prevents radiocontrast media-induced renal medullary hypoxia

Purpose:
Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. Endothelin (ET) is released into the blood stream following CM injection and has been proposed as a potential mediator through its vasoconstrictive properties. Material and Methods:
To investigate the possible protective influence of ET-receptor antagonists against CM-induced reduction in renal function, we studied the effects of injection of iopromide with and without pretreatment with BQ123 (ET-A antagonist) or BQ788 (ET-B antagonist) on renal superficial cortical flow (CBF), outer medullary blood flow (OMBF) and outer medullary oxygen tension ( pO₂) in normal rats. Results:
Administration of CM (1600 mg I/kg b.w.) did not affect CBF in any of the groups. However, a transient decrease in OMBF occurred, which was unaffected by both BQ123 and BQ788. Also a transient decrease in outer medullary pO₂ was induced by CM administration. The pO₂ reduction was significantly smaller after pretreatment with BQ123, than after injection of CM alone or together with BQ788, and pO₂ returned more rapidly to the control level. Neither receptor antagonist had an effect on CM-mediated increases in electrolyte excretion. Conclusion: 
In the normal rat, activation of ET-A receptors is partly involved in the depression of outer medullary pO₂ caused by injection of iopromide. However, the decrease in OMBF after iopromide injection is not mediated by ET receptors. The beneficial effects of the ET-A receptor antagonist on CM-induced changes in outer medullary pO₂ seem therefore not primarily mediated on the hemodynamic level but may rather involve tubular transport mechanisms.     

Adenosine A1 receptors in contrast media-induced renal dysfunction in the normal rat

Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. In this study we investigated the effects of injection of the non-ionic low-osmolar CM iopromide with and without pretreatment with the selective adenosine A₁-receptor antagonist DPCPX. The effects were evaluated on regional renal blood flow, outer medullary oxygen tension (PO₂) and urine output in normal anaesthetised rats. A laser-Doppler technique was used for recording haemodynamic changes while oxygen microelectrodes were used for oxygen measurements. The A₁-receptor antagonist per se elevated glomerular filtration rate (+44%), cortical blood flow (+15%) and urine output (threefold) while reducing outer medullary PO₂ (–24%). Administration of CM reduced outer medullary blood flow (OMBF; –26%) and PO₂ (–80%) but did not affect cortical blood flow. Urine output increased 28-fold by CM while arterial blood pressure was reduced. The CM-mediated effect on haemodynamics, PO₂, urine output and blood pressure was unaffected by the A₁-receptor antagonist. Adenosine A₁-receptors are not important mediators of the depression of outer medullary blood flow and PO₂ caused by the CM iopromide in the normal rat; however, A₁-receptors are tonically active to regulate renal haemodynamics, PO₂ and urine production during normal physiological conditions.     

Effect of prostaglandin inhibition on the renal vascular response to ionic and non-ionic contrast media in the dog

In an attempt to study the role of prostaglandins in the renal vascular response to contrast media in mongrel dogs, renal arterial injections of 6 ml of either the non-ionic contrast medium Iopamidol or the ionic medium diatrizoate meglumine/Na+ were performed, before and after intravenous injection of a buffered solution of acetylsalicylic acid (10 mg/kg) (ASA). Renal blood flow was recorded using non-occluding electromagnetic flow probes. The resting renal blood flow was significantly reduced after ASA. The usual biphasic response to contrast injection was observed both before and after ASA, and using either contrast medium. Analysis of the results failed to show any difference in degree of vasodilation or vasoconstriction after ASA. We conclude that prostaglandins may affect the resting level of renal blood flow but are not mediators of the instantaneous changes in response to contrast injection.     

Tolerance data of Gd-DTPA: a review

Gd-DTPA is the first paramagnetic contrast agent approved for clinical use in cranial and spinal MRI in the F.R.G., U.S.A., Japan and several other countries. After submission 13,439 patients were enrolled in standardized protocolled clinical trials. The observed adverse drug reactions (ADRs) after i.v. injection of Gd-DTPA were comparable to those after administration of iodinated non-ionic roentgen contrast media (CM). However, the overall incidence of ADRs after intravenous injection of 0.1 or 0.2 mmol/kg body weight Gd-DTPA was found to be even lower. Adverse events were observed in only 1.46% of the patients - or 1.14% if localized warmth is excluded. None of them was critical. There was no correlation between patient age and the incidence of ADRs. In patients with a known history of allergy the incidence of ADRs was increased by a factor 3-4, which is still lower than the incidence reported after intravenous administration of iodinated non-ionic roentgen CM to patients without known allergy. Good renal tolerance was seen in all patients, irrespective of pre-existing renal impairment. Fast bolus injections of Gd-DTPA were tolerated without added risk. The favorable safety profile is also reflected in the post marketing surveillance reports since Gd-DTPA became available as a commercial drug.     

Urinary protein excretion following intravenously administered ionic and non-ionic contrast media in man

Urinary protein excretion following intravenous administration of the radiographic contrast media (CM) diatrizoate (ionic) and iopromide (non-ionic) was examined in 20 patients with normal renal function. Neither of the two CM had any effect on the 24-h urinary excretion of albumin (a marker of glomerular proteinuria). The 24-h urinary excretion of the retinol-binding protein (a marker of low molecular weight or tubular proteinuria) and the folate binding protein, a protein localized in the brush-border membranes of the proximal tubular cells, showed a statistically significant transient increase the day after diatrizoate injection, whereas no increase was observed after iopromide. Thus, only a minimal and temporary disturbance of the renal proximal tubular function was observed after diatrizoate injection in patients with normal renal function.     

Clearance of iopamidol, a non-ionic contrast medium, by CAPD in patients with end-stage renal failure.

In normal healthy subjects radiographic contrast media are cleared by the kidneys with a half-life of approximately 2 h and a total body clearance of 8 l/h. The mechanism of contrast clearance has not been previously investigated in chronic renal failure patients undergoing continuous ambulatory peritoneal dialysis (CAPD). A study was undertaken to investigate the pharmacokinetics of a non-ionic water soluble radiographic contrast medium (iopamidol) in 10 patients stabilized on CAPD. All patients (eight male, two female) aged 22-68 years (median 53 years) had injection of 30 ml of iopamidol 300 via a forearm vein to investigate subclavian vein patency following previous cannulation for haemodialysis. Venous blood samples, CAPD dialysate and urine were collected for seven days post injection. The mean plasma half-life was 37.9 h (SD 10.6) (range 24.1-57.2 h) for the CAPD patients and was greatly prolonged in comparison to healthy subjects. The total body clearance of iopamidol was also greatly reduced (0.377 l/h). CAPD removed an average of 53.6% of the administered dose (range 36.3-80.8%) whilst an average of 26.9% was excreted in the urine (range 1.3-56.3%). The combined renal and dialysate clearance was up to 93% of the administered dose over the period of the study. There is therefore some evidence for a small extra renal clearance of iopamidol in end-stage renal failure patients. This study has shown for the first time that patients with end-stage renal failure undergoing CAPD have significantly delayed elimination of contrast medium. This should be taken into consideration when extensive or prolonged investigations using contrast medium are proposed.     

Iosimenol, a new non-ionic dimeric contrast medium, does not induce immunoreactivity in the popliteal lymph node assay

Animal studies in mice were conducted to determine the potential immunoreactivity of the new non-ionic dimeric contrast medium (CM) iosimenol using the PLNA and flow cytometric analyses. Comparative studies were performed with iodixanol. The known immune-reactive substance strepozotocin (STZ) and vehicle injections served as positive and negative controls, respectively. Our experiments did not show any immunological effect of iosimenol, concluding that the new CM iosimenol may be beneficial for use in high-risk patients.     

Adverse reactions to non-ionic contrast media with special regard to high-risk patients

Non-ionic contrast media (CM) are proven to be significantly safer than the high osmolar ionic contrast media (HOCM). Nevertheless deaths are reported after administration of non-ionic agents. The aim of the study was to investigate the rate of adverse reactions to non-ionic CM with special regard to high-risk patients and the effects of premedication with H1-and H2-receptor antagonists.In a prospective study conducted over about 2 years 12 995 examinations with intravenous or intra-arterial non-ionic CM were evaluated. Premedication with H1-and H2-antagonists was used in 1276 high-risk patients with known adverse reaction to CM, history of allergy or severe cardiac or pulmonary disease. 229 patients received no premedication inspite of known risk factors. In total, there were 143 (1.10%) adverse reactions (mild in 0.58%, moderate in 0.41% and severe in 0.05%). In high-risk patients there were adverse reactions in 4.37% without and in 1.57% with premedication. There were no severe adverse reactions in the high-risk patients after premedication. The age of the patient, CM dosage and CM concentration were not shown to be risk factors in the present study. In conclusion, the additional premedication with H1- and H2-antagonists could be an effective agent to reduce the risk of mild and moderate adverse reactions and to avoid severe adverse reactions in high-risk patients. Correspondence to: U. Fink     

The effect of iodixanol, a new isotonic contrast agent, on femoral blood flow in man.

Both ionic and non-ionic contrast media (CM) injected intra-arterially produce peripheral vasodilatation and a sensation of heat or even pain. This effect has been considered to be predominantly related to the osmolality of the CM used. Iodixanol is a non-ionic dimeric CM which can be made isotonic with blood at iodine concentrations up to 400 mg/ml. To assess the degree of peripheral vasodilatation following aortic injection of iodixanol, the change in femoral artery blood flow has been assessed non-invasively. Dupex ultrasound flow-velocity records were taken from the contralateral femoral artery in 10 patients undergoing transfemoral aortography. Volume flow, mean velocity, pulsatility index and peak systolic velocity were continuously recorded before and up to 2 min after injection of 60 ml of iodixanol at an iodine concentration of 320 mg/ml (iodixanol 320). Transient changes consistent with vasodilatation were observed in all patients. The greatest changes were observed during the time period 18-24 s after injection. Volume flow, mean velocity and pulsatility index all changed significantly from baseline (mean changes of 80.6%, 73% and -42.7% respectively). Peak systolic velocity did not change significantly. Intra-arterial injections of isotonic iodixanol 320 produces a significant increase in femoral blood flow in man. Factors other than hypertonicity must therefore be implicated in the vasodilatory effect of contrast media.     

Immediate and non-immediate reaction after non-ionic X-ray contrast medium injection: Case report and review of the literature

Maculopapular rush (exanthema) is the most common contrast medium (CM)-induced non-immediate (delayed) reaction, accounting for over 50% of affected patients. In this article, we describe the clinical course of a 50-year-old female patient who underwent CM-enhanced computer tomography (CT). During non-ionic CM-injection (iopromide) she developed dyspnoea and itching. 24 h afterwards the patient presented with generalized small red macules that tended to confluence (maculopapular exanthema) and itching. Because in vivo testing was not possible, we analyzed blood cells by the cellular allergen stimulation test (CAST), and found slightly increased leukotriene production in the presence of iopromide, while another CM (iotrolan) did not induce leukotriene production. In addition we reviewed available literature for CM related maculopapular exanthema. This clinical feature due to CM is a characteristic delayed (non-immediate) reaction that usually occurs 24 h after CM administration and has been preferentially reported due to non-ionic dimeric CM. Laboratory tests like the CAST that are used in parallel with in vivo skin tests would be of great relevance but are currently not validated. As to whether intra-individual reactions with both immediate and delayed symptoms after CM-injection occur seldom or have been only rarely reported is currently unknown.     

Side effects and pharmacokinetics of nonionic iodinated contrast medium in hemodialyzed patients

We conducted contrast CT scanning on 22 dialysis patients using the same method as usually applied to cases with normal renal function and studied the incidences and types of side effects and the pharmacological kinetics of non-ionic iodine contrast medium (Iopamiron 370, 100 ml). During the followup period (five days at most), we found localized urtication as a side effect in only one case (4.5%). Therefore we speculate that non-ionic contrast medium is a safe agent in dialysis patients, as long as it is cautiously used. After contrast medium injection, we conducted dialysis twice, which definitely decreased total blood iodine content. The extraction ratio at first dialysis was particularly high (73% on average). We recognized a statistically positive correlation between this extraction ratio and dialyzer size. Although two cases studied proved the notable acceleration of vicarious excretion in dialysis patients, this acceleration appeared only with high total blood iodine content. This phenomenon was considered mainly due to excretion from the hepatobiliary tract. Vicarious excretion appeared relatively soon after contrast medium injection (within a few hours), but showed a slower decreasing tendency.     

Cytokine profiles after nonionic dimeric contrast medium injection

RATIONALE AND OBJECTIVES: Mediators of contrast media (CM)-induced allergic/pseudoallergic side effects are largely unknown. We evaluated the possibility of cytokines released as surrogate markers for allergic/pseudoallergic responses in patients who tolerated CM injection well. MATERIALS AND METHODS: Interleukin-1beta (IL-1beta), -2, -4, -5, -6; tumor necrosis factor-alpha; plasma histamine level; and the anaphylatoxin C5a were measured by enzyme-linked immunosorbent assay technique in 9 patients who received the nonionic dimeric iodinated CM iotrolan under routine computed tomography examination conditions. Serum samples were collected before, 1 hour, 6 hours, and 24 hours after contrast medium injection. RESULTS: The cytokine values did not correlate with the hematocrit. Kinetic studies revealed a trend, although not statistically significant (P>0.05), for an early increase of IL-2 (1 hour after CM), followed by delayed increase of IL-4 and IL-6. Histamine significantly decreased after iotrolan injection and C5a increased 6 hours (P>0.05) after CM administration in parallel to IL-6. IL-1beta decreased (with the lowest value measured 6 hours after CM injection; P>0.05), and tumor necrosis factor-alpha did not show any tendency. Patients with late adverse reactions had a T helper 1 to T helper 2 shift and 24 hours after CM injection had the highest histamine values. CONCLUSION: The results suggest CM-related liberation of cytokines with a sequential T helper type 1 (IL-2 after 1 hour), and T helper type 2-like pattern (IL-4, -5, and -6).     

Contrast-induced nephropathy in patients with renal insufficiency undergoing contrast-enhanced MDCT

Objectives

To evaluate the safety of contrast-enhanced MDCT in patients with renal impairment.

Methods

We conducted a retrospective review of 938 patients with stable renal insufficiency (eGFR between 15 and 60?ml/min) who underwent contrast-enhanced MDCT. SCr levels were measured at baseline and 48–72?h after contrast medium administration. The incidence of contrast-induced nephropathy (CIN) in the total study population was assessed. As a control group, 1,164 separate patients with renal insufficiency who did not receive contrast medium for CT were also reviewed.

Results

The overall incidence of CIN in the patient population with renal insufficiency was 6.1?%; the incidence was 4.4?%, 10.5?% and 10.0?% for patients whose eGFR was 45–60, 30–45 and ≤30?ml/min, respectively (P?P?=?0.82)

Conclusions

The risk of CIN from contrast-enhanced MDCT in patients with renal insufficiency appeared to be low, and there was no significant difference in the incidence of CIN in comparison with patients who did not receive CM.

Key Points

? The contrast medium used for multidetector CT can induce nephropathy. ? Contrast-induced nephropathy (CIN) developed in 6.1?% of patients with renal insufficiency. ? However, nephropathy developed in 5.8?% of similar patients not receiving contrast medium. ? Thus, the risk of CIN associated with MDCT appears to be low. ? Special care should still be taken in patients with renal insufficiency.     

Canadian Association of Radiologists Consensus Guidelines for the Prevention of Contrast-Induced Nephropathy: Update 2012

Purpose

Contrast-induced acute kidney injury or contrast-induced nephropathy (CIN) is a significant complication of intravascular contrast medium (CM). These guidelines are intended as a practical approach to risk stratification and prevention. The major risk factor that predicts CIN is pre-existing chronic kidney disease.

Methods

Members of the committee represent radiologists and nephrologists across Canada. The previous guidelines were reviewed, and an in-depth up-to-date literature review was carried out.

Results

A serum creatinine level (SCr) should be obtained, and an estimated glomerular filtration rate (eGFR) should be calculated within 6 months in the outpatient who is stable and within 1 week for inpatients and patients who are not stable. Patients with an eGFR of ≥ 60 mL/min have an extremely low risk of CIN. The risk of CIN after intra-arterial CM administration appears be at least twice that after intravenous administration. Fluid volume loading remains the single most important measure, and hydration regimens that use sodium bicarbonate or normal saline solution should be considered for all patients with GFR < 60 mL/min who receive intra-arterial contrast and when GFR < 45 mL/min in patients who receive intravenous contrast. Patients are most at risk for CIN when eGFR < 30 mL/min. Additional preventative measures include the following: avoid dehydration, avoid CM when appropriate, minimize CM volume and frequency, avoid high osmolar CM, and discontinue nephrotoxic medications 48 hours before administration of CM.