A systematic review of cost-effectiveness analyses across the acute kidney injury landscape.

Introduction: Acute kidney injury (AKI) is a complex and common condition associated with increased morbidity, mortality, and costs. Evidence from cost-effectiveness analysis (CEA) have targeted various aspects of AKI including detection with biomarkers, treatment with renal replacement therapy, and prevention when using contrast media. However, there has not been a systematic review of these studies across the entirety of AKI.Areas covered: PubMed, Embase, and Cochrane library were used to identify CEA studies that involved AKI from 2004 onwards. These studies compared AKI treatment through renal replacement therapies (n = 6), prevention of contrast-induced-AKI (CI-AKI) using different media (n = 3), and diagnosis with novel biomarkers (n = 2). Treatment strategies for AKI focused on continuous versus intermittent renal replacement therapy. While there was no consensus, the majority of studies favored the continuous form. For contrast media, both studies found iodixanol to be cost-effective compared to iohexol for preventing CI-AKI. Additionally, novel biomarkers showed potential to be cost-effective in risk assessment and detection of AKI.Expert opinion: Consistent criteria such as a lifetime time horizon would allow for better model comparisons. Further research on clinical parameters to capture transition probabilities between stages within AKI and progression to downstream kidney disease is needed.

A Custom Radiopaque Thermoresponsive Chemotherapy-Loaded Hydrogel for Intratumoural Injection: An In Vitro and Ex Vivo Assessment of Imaging Characteristics and Material Properties.

PURPOSE: Thermoresponsive hydrogels are gels which have different properties at varying temperatures. The objective of this study was to assess the material characteristics, imaging properties and chemotherapeutic drug release profile of a novel radiopaque thermoresponsive hydrogel in vitro, which is liquid at room temperature but solidifies at body temperature, to determine potential suitability for intratumoural delivery. MATERIALS AND METHODS: An iodinated radiopaque thermoresponsive hydrogel was formulated using iodixanol at a range of concentrations and assessed for sol-gel transition, radiopacity and imaging using CT and US. A lead formulation containing iodixanol at a concentration of 9.22% weight by weight (w/w, g of iodixanol per g of hydrogel) was evaluated in vitro for injectability, disintegration and dual drug release of cisplatin and paclitaxel from the hydrogel formulation. RESULTS: Radiopacity of the hydrogel increased in a concentration-dependent manner, but the highest concentration of iodixanol evaluated in this study (13.83% w/w) adversely affected the sol-gel transition of the hydrogel; therefore, 9.22% w/w iodixanol hydrogel was identified as the lead formulation. This formulation was readily visible on both CT and US. The formulation was hand injectable through a range of clinically relevant devices, had a sustained disintegration profile for up to 28 days and was able to deliver a sustained release of chemotherapeutic drug for up to 10 days. CONCLUSIONS: Favourable in vitro and ex vivo imaging and material characteristics of this thermoresponsive gel are demonstrated, suggesting potential interventional oncology applications for image-guided intratumoural delivery of sustained-release chemotherapy.

Assessment of an advanced virtual monoenergetic reconstruction technique in cerebral and cervical angiography with third-generation dual-source CT: Feasibility of using low-concentration contrast medium.

OBJECTIVES: To investigate the feasibility of low-concentration contrast media (LC-CM) in cerebral and cervical dual-energy CT angiography (DE-CTA) using an advanced monoenergetic (Mono+) reconstruction technique. METHODS: Sixty-five consecutive patients prospectively selected to undergo cerebral and cervical DE-CTA were randomised into two groups: 32 patients (63.7 ± 9.7 years) in the high-concentration contrast medium (HC-CM) group with iopromide 370 and 33 patients (60.7 ± 10.8 years) in the low-concentration contrast medium (LC-CM) group with iodixanol 270. Traditional monoenergetic (Mono) and Mono+ images from 40 to 100 keV levels (at 10-keV intervals) and the standard mixed (Mixed, 120 kVp equivalent) images were reconstructed. Subjective image quality parameters included the contrast-to-noise ratio (CNR) and objective image quality parameters were evaluated and compared between the two groups. RESULTS: The 40-keV Mono+ images in the LC-CM group showed comparable objective CNR (common carotid arteries: 83.7 ± 24.5 vs. 78.1 ± 23.2; internal carotid arteries: 82.2 ± 26.8 vs. 76.8 ± 24.1; middle cerebral arteries: 72.5 ± 24.6 vs. 70.6 ± 19.2; all p > 0.05) and subjective image scores (3.95 ± 0.19 vs. 3.83 ± 0.35; p > 0.05) compared with Mixed images in the HC-CM group. CONCLUSION: The Mono+ reconstruction technique could reduce the concentration of iodinated CM in the diagnosis of cerebral and cervical angiography. KEY POINTS: • Mono+ shows decreased noise and superior CNR compared with Mono. • The 40-keV Mono+ images show the highest CNR in the LC-CM group. • The Mono+ reconstruction technique could reduce the concentration of iodinated CM.

Myocardial Fractional Flow Reserve Measurement Using Contrast Media as a First-Line Assessment of Coronary Lesions in Current Practice.

BACKGROUND: Fractional flow reserve (FFR) measurement requires adenosine injection. However, adenosine can induce conductive and rhythmic complications, or be contraindicated in some patients. Contrast-induced hyperemia could provide a simple first-line method (contrast-enhanced FFR; cFFR) to assess coronary lesions. In this study we evaluated the accuracy of cFFR to predict lesion significance. METHODS: This prospective study included 104 patients with 138 coronary lesions. Each stenosis was evaluated using resting distal coronary pressure to aortic pressure ratio (Pd/Pa) measurements using intracoronary iodixanol (cFFR) and adenosine (FFR) injection. An FFR value ≤ 0.8 defined a significant lesion. RESULTS: Dose-ranging analysis (n = 12 lesions) showed that 10 mL iodixanol was required to obtain the lowest cFFR value. Intermeasurement reproducibility of cFFR (n = 18 lesions) showed limited variability and small mean estimated bias (0.001 ± 0.014). Values of cFFR and FFR were highly correlated in a first series of n = 36 lesions (r = 0.9; P < 0.001). Receiver-operating characteristic curve analysis showed an excellent accuracy of cFFR cutoff value of ≤ 0.85 in predicting FFR value ≤ 0.80 (area under the curve, 0.94; 95% confidence interval, 0.90-0.98; sensitivity, 95%; specificity, 73%). This threshold was then tested prospectively in an independent cohort of n = 72 lesions. A cFFR value ≤ 0.85 correctly identified hemodynamically significant lesions with a sensitivity of 100%, specificity of 78%, positive predictive value of 78%, and negative predictive value of 100%. CONCLUSIONS: cFFR is reproducible and can be achieved with usual volumes of contrast. A cFFR threshold value of 0.85 provides excellent sensitivity and negative predictive value in coronary artery stenosis.

Low-dose CT angiography of the abdominal aorta and reduced contrast medium volume: Assessment of image quality and radiation dose.

AIM: To determine the effect of using 80 kV tube voltage and a reduced amount of contrast medium on the image quality and radiation dose of computed tomography angiography (CTA) of the abdominal aorta. MATERIALS AND METHODS: Patients who were referred for a CTA examination of the abdominal aorta were included in this technical efficacy study. Thirty patients were divided randomly into two groups. Fifteen patients underwent a dual-energy CT (DECT) protocol (Group A). Fifteen patients were scanned with the use of an automated tube potential selection algorithm tool (Group B). In both protocols, a test bolus injection of 10 ml ioversol (350 mg iodine/ml) was used, followed by 20 ml of 1:1 saline-diluted contrast medium. Quantitative analysis comprised determination of the mean attenuation and contrast-to-noise ratio. Qualitative image analysis was performed independently by five radiologists. The estimated radiation dose in terms of CT dose index and effective dose was recorded and compared with a standard 120 kV protocol. RESULTS: In Group B, six patients underwent CTA at 80 kV, seven patients underwent CTA at 100 kV and two patients underwent CTA at 120 kV. The mean contrast-enhancement values of Group A (80 kV) and the 80 kV subgroup of Group B were 16.5% and 27.6% higher compared to the 100 kV subgroup of Group B, these differences were, however, not significant. There were no significant differences in mean image quality between groups. In patients undergoing CTA at 80 kV the effective dose decreased by up to 51.3% compared to a conventional 120 kV CTA protocol. CONCLUSIONS: The findings of this study support the hypothesis that 80 kV in CTA of the abdominal aorta can reliably be used with only 30 ml contrast medium in total and a 50% reduction in radiation dose. The overall image quality was diagnostically adequate; however, it appeared to be suboptimal in patients with a BMI above 28 kg/m(2).

Low-volume contrast medium protocol for comprehensive cardiac and aortoiliac CT assessment in the context of transcatheter aortic valve replacement.

RATIONALE AND OBJECTIVES: To investigate the diagnostic performance of a comprehensive computed tomography (CT) protocol for both cardiac and aortoiliac evaluation of patients considered for transcatheter aortic valve replacement (TAVR) using a single, low-volume contrast medium (CM) injection. MATERIALS AND METHODS: Forty-four TAVR candidates were retrospectively analyzed. All underwent retrospectively electrocardiogram-gated cardiac CT followed by high-pitch CT angiography of the aortoiliac vasculature using one of two single injection protocols of 320 mgI/mL iodine CM: group A (n = 22), iodine delivery rate-based (1.28 gI/s), 60-mL CM volume, 4.0 mL/s flow rate; group B (n = 22), clinical routine protocol, 100-mL CM volume, 4.0 mL/s flow rate. Mean arterial attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated. Subjective image quality was assessed. RESULTS: Aortic root and iliofemoral dimensions could be analyzed in all cases. Patient characteristics showed no significant differences. Mean attenuation at the levels of the aortic root (285.8 ± 83.0 HU vs 327.5 ± 70.8 HU, P = .080) and the iliofemoral access route (256.8 ± 88.5 HU vs 307.5 ± 93.2 HU, P = .071), as well as SNR and CNR were nonsignificantly lower in group A compared to group B. Subjective image quality was equivalent. CONCLUSIONS: In multimorbid TAVR patients, the performance of a combined CT protocol using a single low-volume CM bolus is feasible with maintained image quality compared to a standard protocol.

Discomfort assessment in peripheral angiography: randomized clinical trial of Iodixanol 270 versus Ioversol 320 in diabetics with critical limb ischemia.

OBJECTIVES: To assess and compare the intra-arterial injection-associated discomfort of iodinated contrast media (CM) and the impact on diagnostic efficacy in diabetics with critical limb ischemia (CLI). BACKGROUND: Arterial revascularization is a mainstay in patients with CLI. Previous diagnostic angiography is a crucial step that can be affected by CM injection discomfort compromising the revascularization results, and it could vary related to the CM agents. METHODS: One hundred forty-eight patients received Iodixanol 270 mg iodine pro ml or Ioversol 320 mg iodine pro ml in a prospective, double-blind, randomized, parallel-group clinical trial. Injection-associated discomfort was assessed by Visual Analogic Scale (VAS). Diagnostic efficacy and safety up to 1 week were evaluated. RESULTS: The incidence of pain has been around 50% of the all population in study, with lesser incidence of pain (25.7% vs 74.3%; P < 0.0001) and of heat sensation (55.4% vs 85.1%; P < 0.0001), after Iodixanol than after Ioversol injection. Discomfort mean score, according to VAS assessment, was less in the Iodixanol group (8.1 ± 15.3) than in the Ioversol group (36.0 ± 29.7), after first injection (P < 0.001) and for all injections (P < 0.001). A significant difference was also observed in favor of Iodixanol (P < 0.001), respect to mean score of discomfort and heat sensation, assessed by the operators after all the CM injections. CONCLUSIONS: Iodixanol caused less frequent and severe discomfort, characterized as pain and heat during intra-arterial administration compared with Ioversol. The pain severity is tightly related to image and diagnosis quality with an impact on the patients for additional injections and larger CM volumes.

Comparison of iodinated contrast media for the assessment of atherosclerotic plaque attenuation values by CT coronary angiography: observations in an ex vivo model.

OBJECTIVE: To compare the influence of different iodinated contrast media with several dilutions on plaque attenuation in an ex vivo coronary model studied by multislice CT coronary angiography. METHODS: In six ex vivo left anterior descending coronary arteries immersed in oil, CT (slices/collimation 64×0.625 mm, temporal resolution 210 ms, pitch 0.2) was performed after intracoronary injection of a saline solution, and solutions of a dimeric isosmolar contrast medium (Iodixanol 320 mgI ml(-1)) and a monomeric high-iodinated contrast medium (Iomeprol 400 mgI ml(-1)) with dilutions of 1/80 (low concentration), 1/50 (medium concentration), 1/40 (high concentration) and 1/20 (very high concentration). Two radiologists drew regions of interest in the lumen and in calcified and non-calcified plaques for each solution. 29 cross-sections with non-calcified plaques and 32 cross-sections with calcified plaques were evaluated. RESULTS: Both contrast media showed different attenuation values within lumen and plaque (p<0.0001). The correlation between lumen and non-calcified plaque values was good (Iodixanol r=0.793, Iomeprol r=0.647). Clustered medium- and high-concentration solutions showed similar plaque attenuation values, signal-to-noise ratios (SNRs) (non-calcified plaque: medium solution SNR 31.3±15 vs 31.4±20, high solution SNR 39.4±17 vs 37.4±22; calcified plaque: medium solution SNR 305.2±133 vs 298.8±132, high solution SNR 323.9±138 vs 293±123) and derived contrast-to-noise ratios (p>0.05). CONCLUSION: Differently iodinated contrast media have a similar influence on plaque attenuation profiles. ADVANCES IN KNOWLEDGE: Since iodine load affects coronary plaque attenuation linearly, different contrast media may be equally employed for coronary atherosclerotic plaque imaging.

[Oral administration of intravenous contrast media: a tasty alternative to conventional oral contrast media in computed tomography]. / Intravenöse Kontrastmittel oral appliziert: Eine wohlschmeckende Alternative zum herkömmlichen oralen Kontrastmittel in der Computertomografie.

PURPOSE: Many patients dislike oral contrast media due to their bad taste. The aim of the present study was to identify a solution that tastes better while providing the same opacification in order to offer oncological patients an alternative to the routinely used bad tasting oral contrast media. MATERIALS AND METHODS: In a single blinded, prospective clinical study, the orally administered intravenous contrast media iohexol (Omnipaque), iopromide (Ultravist), and iotrolan (Isovist) as well as the oral contrast media sodium amidotrizoate (Gastrografin) and ioxithalamate (Telebrix) were each compared to the oral contrast medium lysine amidotrizoate as the reference standard at a constant dilution. The density values of all contrast media with the same dilutions were first measured in a phantom study. The patient study included 160 patients who had undergone a prior abdominal CT scan with lysine amidotrizoate within 6 months. The patients rated their subjective taste impression on a scale of 0 (very bad) to 10 (excellent). In addition, adverse events and opacification were recorded and prices were compared. RESULTS: The phantom study revealed identical density values. Patients assigned much higher taste impression scores of 8 and 7 to iohexol and iotrolan, respectively, as compared to a score of 3 for the conventional lysine amidotrizoate (p< 0.05). Iopromide and sodium amidotrizoate did not differ significantly from lysine amidotrizoate. The opacification of all contrast media and experienced adverse events did not differ significantly. Iotrolan (ca. 120 euro/100 ml), Iohexol and Iopromide (ca. 70 euro/100 ml) are more expensive than the conventional oral contrast media (ca. 10 - 20 euro/100 ml). CONCLUSION: Orally administered solutions of non-ionic contrast media improve patient comfort due to the better taste and provide the same opacification in comparison to conventional oral contrast media. At present, their use should be limited to individual cases due to the higher costs.

Gadolinium as a CT contrast agent: assessment in a porcine model.

PURPOSE: To investigate the use of gadolinium as a computed tomographic (CT) contrast agent. MATERIALS AND METHODS: In vitro attenuation measurements of multiple dilutions of gadodiamide and ioversol were compared. In three pigs, 50-mL boluses of undiluted gadodiamide were injected intravenously at 2 mL/sec, and repeated single-level scans were obtained through the lung bases, liver, and kidneys. The doses of 0.8-1.0 mmol of gadolinium per kilogram of body weight were approximately three times the highest doses currently used in patients. Enhancement was determined from attenuation measurements in the aorta, pulmonary arteries, liver, and kidneys. RESULTS: In vitro, the attenuation of undiluted gadodiamide (3,069 HU) was equivalent to that of ioversol diluted to 106 mg of iodine per milliliter and at equimolar concentrations was 50% greater than that of ioversol. The magnitude of and time to peak enhancement were 141 HU and 27 seconds (n = 3) for the aorta; 168 HU and 21 seconds (n = 3) for the pulmonary arteries; 23 HU and 65 seconds (n = 2) for the liver; and 63 HU and 32 seconds (n = 1) for the kidneys. Time-attenuation curves revealed a useful duration of enhancement of 20-30 seconds for the aorta and pulmonary arteries. CONCLUSION: Gadolinium produces good vascular enhancement, adequate renal enhancement, and suboptimal hepatic enhancement. Further study is needed to determine the safety of the gadolinium dose required to produce similar enhancement in patients.

Quantitative contrast media dose evaluation for cranial computed tomography.

The goal of this study was to quantitatively evaluate the CT enhancement characteristics of selected intracranial blood vessels using four different volumes of a contrast medium under otherwise identical conditions in order to help determine a cost-effective dose. In a double blind, prospective manner, 100 patients referred for contrast-enhanced cranial CT were randomly assigned to receive one of four different volumes (50, 75, 100 or 120 ml) of ioversol 320 mg I/ml which was subsequently administered intravenously at a rate of 1 ml/s via a power injector. Unenhanced images were also obtained. Scanning times, slice thickness and other parameters were identical in all patients. Scanning was initiated immediately following delivery of the full volume of contrast. Region of interest Hounsfield unit measurements were acquired in a standardized manner using a 1 mm diameter circle on the pre- and post-contrast scans of the supraclinoid left internal carotid artery (LICA), supraclinoid right internal carotid artery (RICA), basilar artery (BA), and torcular region (TR). The mean enhancement value (in Hounsfield units) for the 50 ml, 75 ml, 100 ml and 120 ml dose groups respectively were as follows for each vessel: LICA 29.9, 41.5, 63.9, 64.6; RICA 30.1, 39.4, 62.6, 65.1; BA 30.0, 41.7, 66.0, 71.9; TR 31.7, 46.8, 68.9, 74.3. There was no statistically significant (p > 0.05) difference in enhancement in any of the four vessels when the 120 ml volume was delivered compared to the 100 ml volume. However, there was a statistically significant (p < 0.05) improvement in enhancement in all four vessels when 100 ml of contrast was administered compared to 75 ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Reducing the concentration of contrast medium in dynamic computed tomography of the neck: consequences for image quality, side effects and cost.

OBJECTIVE: To determine the efficacy of two concentrations of nonionic contrast medium (320 and 240 mg iodine/mL; Optiray [ioversol], Mallinckrodt Medical) for enhanced dynamic computed tomography (CT) of the neck. PATIENTS AND METHODS: Between March 1992 and August 1993, 50 patients undergoing dynamic CT of the neck were assigned randomly to receive either the higher-strength or the lower-strength contrast agent. The amount of opacification was measured objectively, and the quality of the scans was assessed subjectively by two radiologists without knowledge of which contrast agent had been administered. Both immediate and delayed side effects were recorded. RESULTS: The higher-strength contrast medium gave greater opacification (p = 0.0006, t-test), but both concentrations yielded images of excellent quality (p = 0.125, chi 2 test). The number of patients affected by immediate minor complications was lower with Optiray 240 (11 [44%]) than with Optiray 320 (23 [92%]) (p < 0.001, chi 2 test). The number of patients affected by delayed side effects was similar in the two groups (7 [28%] with Optiray 240 and 9 [36%] with Optiray 320; p > 0.70, chi 2 test). No predictive relation between immediate and delayed complications was observed. CONCLUSIONS: Because adequate contrast can be obtained with the lower-strength contrast medium, it can be used in dynamic CT of the neck as a means of reducing the cost and the side effects associated with such imaging.

Low-osmolality contrast media: dosage comparison of ioversol and iohexol for cranial computed tomography.

One hundred patients undergoing cranial computed tomography were evaluated in this prospective, randomized, double-blind comparative study. Patients received 50 mL of ioversol 320 (16 g iodine), 75 mL of ioversol 320 (24 g iodine), 100 mL of iohexol 240 (24 g iodine), 100 mL of iohexol 300 (30 g iodine) or 150 mL of iohexol 240 (36 g iodine). Twenty patients were enrolled in each treatment group. No patient in any treatment group experienced any contrast-media-related adverse reaction. Results of this study coupled with our prior work suggests that the lowest dose and optimal concentration of low-osmolality contrast media necessary to produce diagnostic cranial computed tomography is 32 g of iodine administered in a concentration of 320 mg/100 mL iodine.

Optimization of low-osmolality contrast media for cranial CT: a dose comparison of two contrast agents.

A prospective, randomized, double-blind comparative study of 200 patients was made to examine the image quality, safety, and costs of 100 ml of ioversol-320 (32 g iodine) and 150 ml of iohexol-300 (45 g iodine) in patients undergoing cranial CT. We found no statistically significant difference in image quality between the two low-osmolality, nonionic contrast agents at these doses. There was a statistically significant (p = .02) difference in the occurrence of minor to mild adverse effects caused by ioversol (n = 0) as compared with iohexol (n = 5). No patient in either group experienced any major contrast-induced reactions. Contrast media costs were 34% less in patients receiving 32 g of iodine as compared with those receiving 45 g of iodine. This study demonstrates that high-quality cranial CT scans are possible even with a reduced volume of low-osmolality contrast medium, and that the potential cost savings are significant.

Selection of intravascular contrast media in clinical radiology.

From previous experimental investigations and from the present clinical experience in more than 2000 examinations it is clear that the adverse reactions of Omnipaque are markedly less when compared with those of conventional contrast media for intravascular use. Similar observations have been made for other low osmolar contrast media. These new media should therefore replace the conventional media for intravascular use. The economical consequences are discussed.