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The GREENWATER study: patients’ green sensitivity and potential recovery of injected contrast agents
Abstract
The environmental footprint of iodinated contrast agents (ICAs) and gadolinium-based contrast agents (GBCAs) is noteworthy. This study assesses: (1) patients’ “green sensitivity” as measured by their acceptance in a sustainability study and (2) the resulting potential reduction of contrast residuals in wastewater.
After ethical approval, participants scheduled for administration of ICAs or GBCAs for diagnostic purposes were enrolled in this prospective observational study from July 2022 to October 2023. They were asked to prolong their hospital stay by up to 60 min to collect their first urine in dedicated canisters, thereby measuring the recovery rates of ICAs and GBCAs as found/theoretical ratio of concentrations. Mann–Whitney U, χ2 tests, and multivariable regression analysis were used.
Patients scheduled for contrast-enhanced CT or MRI (n = 455) were screened; 422 (92.7%) accepted to participate. We enrolled 212 patients administered with ICAs and 210 administered with GBCAs. The median recovery rate was 51.2% (interquartile range 29.2–77.9%) for ICAs and 12.9% (9.0–19.3%) for GBCAs. At multivariable analysis, a significant effect of patient age (ICAs, p = 0.001; GBCAs, p = 0.014), urine volume (p < 0.001 for both), and time interval from contrast administration to urine collection (p < 0.001 for both) on recovery rates was found for both contrast agents; injected contrast volume (p = 0.046) and saline flushing usage (p = 0.008) showed a significant effect only for ICAs.
The high patient enrollment compliance (93%) and potential recovery rates of 51% (ICAs) and 13% (GBCAs) play in favor of sustainable practices in reducing the environmental footprint of contrast agents.
Question How many patients are willing to extend their stay in radiology by up to 60 min to help reduce the environmental impact of contrast agents?
Findings Over 90% of screened patients agreed to extend their stay by up to 60 min and collect their urine in dedicated containers.
Clinical relevance Patients demonstrated a high willingness to cooperate in reducing the environmental impact of contrast agents, allowing for a potential recovery of approximately 51% for iodinated and 13% for gadolinium-based contrast agents.
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Background
Anthropogenic gadolinium (Gd), originating from Gd-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI), is widely identified in the aquatic environment with concerns about toxicity and accumulation. We aimed to present new data on anthropogenic Gd in the Tone River, which has the largest drainage area in Japan, and then to compare the current data with those obtained in 1996.
Methods
The water samples were collected on August 9−10, 2020, at 15 different locations of the Tone River in Japan. The concentrations of the rare earth elements (REEs) were measured by inductively coupled plasma-mass spectrometry and normalized to Post-Archean Australian Shale to construct shale-normalized REE patterns. The degree of Gd-anomaly was defined as the percentage of anthropogenic Gd to the geogenic background and used to compare the water samples from different locations. Pearson’s correlation coefficients were calculated.
Results
All the samples displayed positive Gd anomalies. The Gd-anomaly ranged from 121 to 6,545% and displayed a repeating decrease-and-increase trend. The Gd-anomaly showed strong positive correlations to the number of hospitals ( r = 0.88; p < 0.001) and their MRI units ( r = 0.89; p < 0.001).
Conclusions
Our study revealed notable anomalies of Gd concentrations in river water in Japan, with strong positive correlations to the number of major hospitals and their MRI units. Compared with the previous report in 2000, the Gd-anomaly in Tone River increased from 851% (sampled in 1996) to 6,545%, i.e., 7.7 times, reflecting the increased use of GBCAs in hospitals.
Relevance statement
Notable Gd concentration anomalies in river water in Japan were observed. This result underlines the importance of more extensive research on anthropogenic gadolinium, and investigations of risks to human health as well as the development of effective removal technologies may be necessary.
Key points
• All water samples from Tone River displayed positive Gd anomalies.
• The Gd anomalies increased to 7.7 times higher over the past 24 years.
• Correlations between Gd values and the number of hospitals and MRI units were observed.
Graphical Abstract
Objectives
Energy consumption and carbon emissions from medical equipment like CT/MRI scanners and workstations contribute to the environmental impact of healthcare facilities. The aim of this systematic review was to identify all strategies to reduce energy use and carbon emissions in radiology.
Methods
In June 2023, a systematic review (Medline/Embase/Web of Science) was performed to search original articles on environmental sustainability in radiology. The extracted data include environmental sustainability topics (e.g., energy consumption, carbon footprint) and radiological devices involved. Sustainable actions and environmental impact in radiology settings were analyzed. Study quality was assessed using the QualSyst tool.
Results
From 918 retrieved articles, 16 met the inclusion criteria. Among them, main topics were energy consumption (10/16, 62.5%), life-cycle assessment (4/16, 25.0%), and carbon footprint (2/16, 12.5%). Eleven studies reported that 40–91% of the energy consumed by radiological devices can be defined as “nonproductive” (devices “on” but not working). Turning-off devices during idle periods 9/16 (56.2%) and implementing workflow informatic tools (2/16, 12.5%) were the sustainable actions identified. Energy-saving strategies were reported in 8/16 articles (50%), estimating annual savings of thousand kilowatt-hours (14,180–171,000 kWh). Cost-savings were identified in 7/16 (43.7%) articles, ranging from US $9,225 to 14,328 per device. Study quality was over or equal the 80% of high-quality level in 14/16 (87.5%) articles.
Conclusion
Energy consumption and environmental sustainability in radiology received attention in literature. Sustainable actions include turning-off radiological devices during idle periods, favoring the most energy-efficient imaging devices, and educating radiological staff on energy-saving practices, without compromising service quality.
Relevance statement
A non-negligible number of articles — mainly coming from North America and Europe — highlighted the need for energy-saving strategies, attention to equipment life-cycle assessment, and carbon footprint reduction in radiology, with a potential for cost-saving outcome.
Key points
• Energy consumption and environmental sustainability in radiology received attention in the literature (16 articles published from 2010 to 2023).
• A substantial portion (40–91%) of the energy consumed by radiological devices was classified as “non-productive” (devices “on” but not working).
• Sustainable action such as shutting down devices during idle periods was identified, with potential annual energy savings ranging from 14,180 to 171,000 kWh.
Graphical Abstract
Supplementary Information
The online version contains supplementary material available at 10.1186/s41747-024-00424-6.
Gadolinium-based contrast agents (GBCA) are essential for diagnostic MRI examinations. GBCA are only used in small quantities on a per-patient basis; however, the acquisition of contrast-enhanced MRI examinations worldwide results in the use of many thousands of litres of GBCA per year. Data shows that these GBCA are present in sewage water, surface water, and drinking water in many regions of the world. Therefore, there is growing concern regarding the environmental impact of GBCA because of their ubiquitous presence in the aquatic environment. To address the problem of GBCA in the water system as a whole, collaboration is necessary between all stakeholders, including the producers of GBCA, medical professionals and importantly, the consumers of drinking water, i.e. the patients. This paper aims to make healthcare professionals aware of the opportunity to take the lead in making informed decisions about the use of GBCA and provides an overview of the different options for action.
In this paper, we first provide a summary on the metabolism and clinical use of GBCA, then the environmental fate and observations of GBCA, followed by measures to reduce the use of GBCA. The environmental impact of GBCA can be reduced by (1) measures focusing on the application of GBCA by means of weight-based contrast volume reduction, GBCA with higher relaxivity per mmol of Gd, contrast-enhancing sequences, and post-processing; and (2) measures that reduce the waste of GBCA, including the use of bulk packaging and collecting residues of GBCA at the point of application.
Critical relevance statement This review aims to make healthcare professionals aware of the environmental impact of GBCA and the opportunity for them to take the lead in making informed decisions about GBCA use and the different options to reduce its environmental burden.
Key points
• Gadolinium-based contrast agents are found in sources of drinking water and constitute an environmental risk.
• Radiologists have a wide spectrum of options to reduce GBCA use without compromising diagnostic quality.
• Radiology can become more sustainable by adopting such measures in clinical practice.
Graphical Abstract
The pharmacokinetics of contrast media (CM) will determine how long safe waiting intervals between successive CT or MRI examinations should be. The Contrast Media Safety Committee has reviewed the data on pharmacokinetics of contrast media to suggest safe waiting intervals between successive contrast-enhanced imaging studies in relation to the renal function of the patient.
Clinical relevance statement
Consider a waiting time between elective contrast-enhanced CT and (coronary) angiography with successive iodine-based contrast media administrations in patients with normal renal function (eGFR > 60 mL/min/1.73 m ² ) of optimally 12 h (near complete clearance of the previously administered iodine-based contrast media) and minimally 4 h (if clinical indication requires rapid follow-up).
Key Points
• Pharmacokinetics of contrast media will guide safe waiting times between successive administrations.
• Safe waiting times increase with increasing renal insufficiency.
• Iodine-based contrast media influence MRI signal intensities and gadolinium-based contrast agents influence CT attenuation.
The potential enviromental impact of iodinated (ICAs) and gadolinium-based contrast agents (GBCAs) have recently come under scrutiny, considering the current nonselective wastewater treatment. However, their rapid excretion after intravenous administration could allow their potential recovery by targeting hospital sewage. The GREENWATER study aims to appraise the effective quantities of ICAs and GBCAs retrievable from patients’ urine collected after computed tomography (CT) and magnetic resonance imaging (MRI) exams, selecting ICA/GBCA per-patient urinary excretion and patients’ acceptance rate as study endpoints. Within a prospective, observational, single-centre, 1-year framework, we will enrol outpatients aged ≥ 18 years, scheduled to perform contrast-enhanced CT or MRI, willing to collect post-examination urine in dedicated canisters by prolonging their hospital stay to 1 h after injection. Collected urine will be processed and partially stored in the institutional biobank. Patient-based analysis will be performed for the first 100 CT and 100 MRI patients, and then, all analyses will be conducted on the pooled urinary sample. Quantification of urinary iodine and gadolinium will be performed with spectroscopy after oxidative digestion. The evaluation of the acceptance rate will assess the “environmental awareness” of patients and will aid to model how procedures to reduce ICA/GBCA enviromental impact could be adapted in different settings.
Key points
• Enviromental impact of iodinated and gadolinium-based contrast agents represents a growing point of attention.
• Current wastewater treatment is unable to retrieve and recycle contrast agents.
• Prolonging hospital stay may allow contrast agents retrieval from patients’ urine.
• The GREENWATER study will assess the effectively retrievable contrast agents’ quantities.
• The enrolment acceptance rate will allow to evaluate patients’ “green sensitivity”.
Gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI) are highly resistant in the environment. They pass through wastewater treatment plants (WWTPs) unhindered escaping degradation. Although GBCAs are subjects of intensive research, we recognized that a quantitative approach to the mass balance of gadolinium, based on known input and output data, is missing. The administered amount of Gd as GBCAs, the number of out- and inpatients and the concentration of rare earth elements (REEs) in wastewater were monitored for 45 days in a medium sized city (ca. 203,000 inhabitants) with two MRI centres. An advection-dispersion type model was established to describe the transport of Gd in the wastewater system. The model calculates with patient locality, excretion kinetics of Gd and the yield of wastewater. The estimated and measured daily amount of anthropogenic gadolinium released to the WWTP were compared. GBCAs (Omniscan and Dotarem) were administered to 1008 patients representing a total of 700 ± 1 g Gd. The amount of total Gd entering the WWTP was 531 ± 2 g, of which the anthropogenic contribution (i.e. GBCAs) was 261 ± 6 g (49 ± 1 % of the total Gd) during the sampling campaign. Local residents and inpatients should fully release Gd in the city, but outpatients only partially. Overall, 37 ± 1 % of the total administered Gd was recovered in the wastewater, so the remaining 63 ± 1 % of administered Gd is expected to be dispensed outside of the sewer system. Our approach enables to better understand the dispersion of GBCAs originated Gd in an urban environment.
Contrast media are essential for diagnostic and interventional procedures. Iodinated contrast media are the most commonly used agents, with CT requiring the largest overall quantities. Data show that these iodinated contrast media are found in sewage water, surface water and drinking water in many regions in the world. Because standard drinking water purification techniques only provide poor to moderate removal of iodinated contrast media, these substances pose a problem for drinking water preparation that has not yet been solved. There is a growing body of evidence supporting the negative environmental effects of iodinated contrast media via their breakdown products. The environmental impact of iodinated contrast media can be mitigated by measures focusing on the application of contrast media or the excretion of contrast media. Measures with respect to contrast application include reducing the utilization of contrast media, reducing the waste of contrast media and collecting residues of contrast media at the point of application. The amount of contrast media excreted into the sewage water can be decreased by introducing urine bags and/or special urine collection and waste-water processing techniques in the hospital. To tackle the problem of contrast media in the water system in its entirety, it is necessary for all parties involved to cooperate, from the producer of contrast medium to the consumer of drinking water. This paper aims to make health professionals aware of the opportunity to take the lead now in more conscious decisions regarding use of contrast media and gives an overview of the different perspectives for action.
Rare Earth Elements (REEs) are used in increasing amounts in technical applications and consumer products. However, to date, the contribution of industrial sources to the loads of individual REEs in wastewater streams have not been quantified. Here, we determine the REE contents in sludge collected from 63 wastewater treatment plants (WWTPs) across Switzerland. To quantify the industrial fraction of individual REEs in the sewage sludge, we develop two complementary approaches, based on REE ratios and REE pattern fitting. Unspecific (background) inputs, with REE patterns similar to the averaged REE pattern of soils collected across Switzerland, dominate the REE budget of most WWTPs. A few WWTPs receive significant REE inputs from specific industrial sources. Based on population equivalents of Switzerland, we estimate a total annual load of 4200 kg Ce (0.5 g Ce year⁻¹ capita⁻¹), with an industrial contribution of 2000 kg year⁻¹. The latter agrees with estimates of probabilistic mass flow models for engineered nanoscale CeO2 particles discharged to the sewer network. About 7 kg year⁻¹ of Sm (total for Switzerland: 184 kg year⁻¹ or 0.02 g Sm year⁻¹ capita⁻¹) and 3 kg year⁻¹ of Eu (total for Switzerland: 44 kg year⁻¹ or 0.005 g Eu year⁻¹ capita⁻¹) are assigned to industrial inputs from single WWTPs. Gd is used in the form of a stable complex as contrast agent in magnetic resonance imaging. Assuming 10% removal of Gd during wastewater treatment, we calculate an annual discharge of 90 kg of Gd from one individual WWTP to surface waters. WWTPs with exceptionally high industrial inputs of specific REEs warrant detailed investigations to identify the respective sources and to assess whether REE concentrations in effluents are elevated to the same degree.
The increasing use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging is leading to widespread contamination of freshwater and drinking water systems. Contrary to previous assumptions that GBCAs are stable throughout the water cycle, they can degrade. The stability of GBCAs depends largely on their organic ligands, but also on the physicochemical conditions. There is specific concern regarding UV end-of-pipe water treatments, which may degrade GBCAs. Degradation products in drinking water supplies can increase the risk of adverse health effects. This is of particular relevance where the raw water for drinking water production has a higher proportion of recycled wastewater. GBCAs concentrations in aquatic systems, often referred to as anthropogenic gadolinium, are determined using a variety of calculation methods. Where anthropogenic gadolinium concentrations are low, the inconsistent use of these methods results in high discrepancies and high levels of uncertainty. The current COVID-19 crisis will, in the short-term, drastically decrease the input of GBCAs to freshwater systems. Temporal variations in anthropogenic gadolinium concentrations in river water can be used to better understand river-aquifer interactions and groundwater flow velocities. Collecting urine from all patients following MRI examinations could be a way forward to halt the generally increasing concentrations of Gd in drinking water systems and recover this technologically critical element.
Iodinated X-ray contrast media (ICM) such as diatrizoate, iohexol, iomeprol, iopamidol, and iopromide are commonly used in medical imaging for radiological visualization of a variety of anatomic structures. Because of their highly persistent nature and poor removal by conventional wastewater treatment, ICM can often remain unchanged after entering the environment or they are transformed into many different by-products in complex physical, chemical, and biological processes. Large amounts of ICM and their by-products are found in natural waters, groundwater, drinking water (up to 100 µg/L), and even in soil, where they can be a potential threat to the inhabitants of these environments. Because knowledge about the fate of ICM in various environments is dispersed and it concerns specific areas, the main purpose of this review is to summarize the available information about their occurrence, chemical and biological transformation/degradation, and toxicity to living organisms. The topics discussed particularly focus on mechanisms of ICM degradation/transformation in water using advanced oxidation processes and the biotransformation/biodegradation of ICM by microorganisms under different conditions, as well as the toxicity of ICM and their transformation by-products to humans and other organisms. Although environmental risk is not expected from the parent compounds of ICM, their continuous input to the water and the formation of toxic by-products may constitute a long-term potential risk for living organisms. Therefore, monitoring the transport and fate of ICM in various environments seems necessary.
Here, we summarise the unresolved debate about p value and its dichotomisation. We present the statement of the American Statistical Association against the misuse of statistical significance as well as the proposals to abandon the use of p value and to reduce the significance threshold from 0.05 to 0.005. We highlight reasons for a conservative approach, as clinical research needs dichotomic answers to guide decision-making, in particular in the case of diagnostic imaging and interventional radiology. With a reduced p value threshold, the cost of research could increase while spontaneous research could be reduced. Secondary evidence from systematic reviews/meta-analyses, data sharing, and cost-effective analyses are better ways to mitigate the false discovery rate and lack of reproducibility associated with the use of the 0.05 threshold. Importantly, when reporting p values, authors should always provide the actual value, not only statements of “p < 0.05” or “p ≥ 0.05”, because p values give a measure of the degree of data compatibility with the null hypothesis. Notably, radiomics and big data, fuelled by the application of artificial intelligence, involve hundreds/thousands of tested features similarly to other “omics” such as genomics, where a reduction in the significance threshold, based on well-known corrections for multiple testing, has been already adopted.
As a result of high doses of paramagnetic gadolinium (Gd) chelates administered in magnetic resonance imaging (MRI) exams, their unmetabolized excretion, and insufficient removal in wastewater treatment plants (WWTPs), large amounts of anthropogenic Gd (Gdanth) are released into surface water. The upward trend of gadolinium-based contrast agent (Gd-CA) administrations is expected to continue growing and consequently higher and higher anthropogenic Gd concentrations are annually recorded in water resources, which can pose a great threat to aquatic organisms and human beings. In addition, the feasibility of Gd retention in patients administered with Gd-CAs repeatedly, and even potentially fatal diseases, including nephrogenic systemic fibrosis (NSF), due to trace amounts of Gd have recently arisen severe health concerns. Thus, there is a need to investigate probable adverse health effects of currently marketed Gd-CAs meticulously and to modify the actual approach in using Gd contrast media in daily practice in order to minimize unknown possible health risks. Furthermore, the employment of enhanced wastewater treatment processes that are capable of removing the stable contrast agents, and the evaluation of the ecotoxicity of Gd chelates and human exposure to these emerging contaminants through dermal and ingestion pathways deserve more attention. On the other hand, point source releases of anthropogenic Gd into the aquatic environment presents the opportunity to assess surface water—groundwater interactions and trace the fate of wastewater plume as a proxy for the potential presence of other microcontaminants associated with treated wastewater in freshwater and marine systems.
In 1988, the first contrast agent specifically designed for magnetic resonance imaging (MRI), gadopentetate dimeglumine (Magnevist®), became available for clinical use. Since then, a plethora of studies have investigated the potential of MRI contrast agents for diagnostic imaging across the body, including the central nervous system, heart and circulation, breast, lungs, the gastrointestinal, genitourinary, musculoskeletal and lymphatic systems, and even the skin. Today, after 25 years of contrast-enhanced (CE-) MRI in clinical practice, the utility of this diagnostic imaging modality has expanded beyond initial expectations to become an essential tool for disease diagnosis and management worldwide. CE-MRI continues to evolve, with new techniques, advanced technologies, and novel contrast agents bringing exciting opportunities for more sensitive, targeted imaging and improved patient management, along with associated clinical challenges. This review aims to provide an overview on the history of MRI and contrast media development, to highlight certain key advances in the clinical development of CE-MRI, to outline current technical trends and clinical challenges, and to suggest some important future perspectives.
Funding
Bayer HealthCare.
Modern iodinated contrast media (CM) consist of one or two tri-iodobenzene rings. They differ from each other in the composition of the side chains, creating different molecules and thus different brand substances. After intravascular administration, all CM are distributed rapidly into intravascular and extracellular fluids. They are eliminated solely by glomerular filtration. In patients with normal renal function, CMs are eliminated within 24 h. The pathophysiology of contrast-induced nephropathy (CIN) is based on three distinct but interacting mechanisms: medullary ischaemia, formation of reactive oxygen species and direct tubular cell toxicity. The contribution of each of these mechanisms to the development of CIN in the individual patient remains unclear. CIN prevention is extensively described in guidelines, such as the recently updated guideline from the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR). The recent update is briefly discussed. Furthermore, it remains unclear if volume expansion with either NaCl 0.9 % or NaHCO3 1.4 % is superior.
Teaching points
• After intravascular injection, CM are distributed over intravascular and extracellular fluids.
• CM are eliminated by glomerular filtration in patients with normal kidney function.
• CIN pathophysiology is based on medullary ischaemia, formation of reactive oxygen species (ROS) and tubular cell toxicity.
• It remains unclear if volume expansion with either NaCl 0.9 % or NaHCO31.4 % is superior.
We performed a Monte Carlo study to evaluate the effect of the number of events per variable (EPV) analyzed in logistic regression analysis. The simulations were based on data from a cardiac trial of 673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality; the number of events per predictive variable was (252/7 =) 36 for the full sample. For the simulations, at values of EPV = 2, 5, 10, 15, 20, and 25, we randomly generated 500 samples of the 673 patients, chosen with replacement, according to a logistic model derived from the full sample. Simulation results for the regression coefficients for each variable in each group of 500 samples were compared for bias, precision, and significance testing against the results of the model fitted to the original sample. For EPV values of 10 or greater, no major problems occurred. For EPV values less than 10, however, the regression coefficients were biased in both positive and negative directions; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coefficients; the 90% confidence limits about the estimated values did not have proper coverage; the Wald statistic was conservative under the null hypothesis; and paradoxical associations (significance in the wrong direction) were increased. Although other factors (such as the total number of events, or sample size) may influence the validity of the logistic model, our findings indicate that low EPV can lead to major problems.
Purpose:
Covid-19 related lockdowns have resulted in a shortage of iodinated contrast media (ICM) in 2022. Health care providers have reacted with implementing conservation strategies to stay operational without compromising patient care. Although articles describing the implemented Interventions have been published, possible chances of the shortage have not yet been mentioned in the literature.
Methods:
We conducted a literature search in PubMed and Google Scholar, and analysed the background, interventions, and possible benefits of low-dose ICM regimens.
Results:
We included 22 articles dealing with "ICM shortage" for the analysis. The delivery bottlenecks in the USA and Australia led to two different countermeasures, 1. reduction of the number of contrast-enhanced image-guided examinations and 2. reduction of the (single) ICM dose. Interventions from both groups have resulted in significant reduction of ICM usage; however, group 1 has contributed more to overall ICM reduction. As benefit of the ICM reduction, we revealed an increased safety for patients at risk (e.g. hypersensitivity reactions, contrast-induced acute kidney injury, thyroid toxic effects).
Conclusion:
The ICM shortage of 2022 has forced health care providers to implement conservation strategies to stay operational. Although there were already proposals for dose reduction before the corona pandemic and the associated supply bottlenecks, this situation led to the use of a reduced amount of contrast agent on a large scale. This presents a good opportunity to reconsider protocols and the use of contrast-enhanced imaging in general for future practice as it offers chances and advantages regarding costs, environmental impact, and patient safety.
A production facility shutdown related to containment measures during the COVID-19 pandemic has resulted in a global shortage of iodinated contrast media. This article describes the strategies implemented at one large U.S. health system to maintain care continuity during the ongoing shortage. The strategies have included attempts to procure additional stock, repackage existing stock for use in larger numbers of patients, use of non-contrast CT or alternative imaging modalities in place of contrast-enhanced CT, and collaboration with specialties outside of radiology to participate in conservation efforts. In addition, individual CT protocols underwent tailored modifications to use dual-energy technique and/or lower tube voltages, to allow lower contrast media doses with maintained visualization of tissue enhancement. The experiences during this period will provide insights to facilitate long-term reductions in contrast media doses and ongoing CT protocol optimization after supplies return to normal levels. Critical throughout the efforts to mitigate the impact of the shortage have been system-level action, operational flexibility, and close communication by the health system's radiologists, technologists, physicists, pharmacists, and ordering providers.
Iodinated contrast media (ICM) are drugs which are used in medical examinations for organ imaging purposes. Wastewater treatment plants (WWTPs) have shown incapability to remove ICM, and as a consequence, ICM and their transformation products (TPs) have been detected in environmental waters. ICM show limited biotransformation and low sorption potential. ICM can act as iodine source and can react with commonly used disinfectants such as chlorine in presence of organic matter to yield iodinated disinfection byproducts (IDBPs) which are more cytotoxic and genotoxic than conventionally known disinfection byproducts (DBPs). Even highly efficient advanced treatment systems have failed to completely mineralize ICM, and TPs that are more toxic than parent ICM are produced. This raises issues regarding the efficacy of existing treatment technologies and serious concern over disinfection of ICM containing waters. Realizing this, the current review aims to capture the attention of scientific community on areas of less focus. The review features in depth knowledge regarding complete environmental fate of ICM along with their existing treatment options.
Gadolinium-based contrast agents used in magnetic resonance imaging are difficult to impossible to remove in wastewater treatment plants, and may enter groundwater production wells and hence municipal tap water via bank filtration. As anthropogenic gadolinium (Gd) may be accompanied by other, more harmful waste water-derived (micro)pollutants such as endocrine disruptors, we investigated the potential pathway of anthropogenic Gd into popular tap water-based beverages sold in highly frequented fast food restaurants. We, therefore, determined the concentration and distribution of geogenic and anthropogenic rare earth elements (REE) in tap water and in a related tap water-based popular soft drink (Coca Cola) from two fast food franchises (McDonalds and Burger King) in six major German cities. We observed anthropogenic Gd in both tap water and corresponding soft drinks in all investigated cities, extending the database for anthropogenic Gd in tap waters and highlighting its widespread distribution. In Berlin and Düsseldorf, where tap water is (mainly) produced by river bank filtration, 85 to 99% of the total Gd is of anthropogenic origin. The surprisingly high anthropogenic fraction (91%) in tap water from Munich reveals that even the shallow groundwater tapped in two Alpine valleys is eventually exposed to anthropogenic pollution. The REE distribution in post-mix soft drinks generally follows that of the corresponding tap water, except for enrichments of ytterbium (Yb), lutetium (Lu) and cerium (Ce), which are derived from the syrup. The concentration of anthropogenic Gd is similar in the soft drinks and in the corresponding tap water, demonstrating that the highly stable Gd-based contrast agents are not removed in soda fountains but are directly transferred to the beverages. This study highlights a pathway for anthropogenic waste water-derived xenobiotics such as pharmaceuticals and endocrine disruptors into the food chain, and hence, reveals the potential for human exposure to potentially harmful anthropogenic compounds.
Background Acute allergic-like and physiologic reactions occur following administration of gadolinium-based contrast agents (GBCAs) for MRI examinations. Because these reactions are uncommon, it is challenging to compare reaction rates between GBCAs and to determine risk factors. Purpose To compare reaction rates between the four GBCAs gadodiamide, gadobutrol, gadobenate dimeglumine, and gadoterate meglumine, and to determine potential risk factors for reactions. Materials and Methods This retrospective study identified all intravenous GBCA injections for MRI examinations performed at a single institution from June 1, 2009, to May 9, 2017. Reactions were identified by reviewing records from the MRI technologist, MRI nursing staff, radiologist, emergency department, and provider. Reactions were classified as allergic-like or physiologic and as mild, moderate, or severe by using American College of Radiology criteria. GBCA reaction rates and other potential risk factors were examined by using multivariable regression models with generalized estimating equations. Results Analysis included a total of 158 100 patients (median age, 55 years [interquartile range, 40-67 years], 51% women) who received a total of 281 945 GBCA injections (140 645 gadodiamide, 94 109 gadobutrol, 39 138 gadobenate, and 8053 gadoterate). At multivariate analysis, gadobenate or gadobutrol had higher rates of allergic-like reactions compared with gadodiamide (gadobenate: odds ratio [OR], 3.9 [95% confidence interval {CI}: 3.0, 5.1]; P < .001; gadobutrol: OR, 2.3 [95% CI: 1.8, 2.9]; P < .001) or gadoterate (gadobenate: OR, 4.8 [95% CI: 1.0, 23]; P = .049; gadobutrol: OR, 2.8 [95% CI: 0.6, 14]; P = .20). Physiologic reactions were more frequently observed with gadoterate (OR, 7.7 [95% CI: 2.3, 25; P = .001), gadobenate (OR, 1.8 [95% CI: 1.3, 2.5; P < .001), and gadobutrol (OR, 1.6 [95% CI: 1.3, 2.1; P < .001) administration compared with gadodiamide. Six severe allergic-like reactions (three gadobutrol, three gadobenate) occurred requiring hospitalization. Patient age (P values .025 to < .001), sex (P < .001), location (P = .006), and MRI type (P = .003 and P = .006) were associated with acute reactions. Conclusion Gadobenate and gadobutrol are associated with higher rates of allergic-like reactions compared with gadodiamide or gadoterate, and gadoterate, gadobenate, and gadobutrol are associated with higher rates of physiologic reactions compared with gadodiamide. Patient sex, age, location, and MRI type correlate with acute reaction rates. © RSNA, 2019 Online supplemental material is available for this article.
Objectives:
To evaluate the value of spectral-detector CT (SDCT) in the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), its differentiation against other etiologies of pulmonary hypertension (PH) and in the prediction of disease severity.
Materials and methods:
60 patients with suspected PH underwent SDCT. Additional diagnostic tests in accordance with the ESC guidelines including right heart catherization and VQ-SPECT were performed. After full diagnostic work-up patients were classified as: 21 precapillary PH, 5 postcapillary PH, 6 combined pre- and postcapillary PH, 19 CTEPH, 9 no PH. SDCT examinations were analyzed by two blinded readers deciding on the diagnosis of CTEPH and scoring the extent of perfusion abnormalities on iodine density images. An additional reading was performed using conventional CTPA images only.
Results:
With access to SDCT data, both readers reached a sensitivity of 100% for the diagnosis of CTEPH with a specificity of 95.1% and 87.8%. On analysis of conventional CTPA images alone, specificity and diagnostic confidence decreased for both readers (Specificity 90.2 and 85.3%) while sensitivity dropped for the less experienced reader only (Sensitivity 78.9%). Patients with PH showed significantly more perfusion abnormalities than patients without PH (16.6 ± 8.4 vs. 9.5 ± 8.9 p < 0.001) and the extent of perfusion abnormalities correlated with the mean pulmonary artery pressure (r = 0.37 p = 0.008).
Conclusions:
SDCT offers confident identification of patients with CTEPH and enables a comprehensive analysis of pulmonary vasculature, pulmonary perfusion and the lung parenchyma in a single examination for patients with suspected PH.
Introduction:
The potential adverse renal outcome among patients undergoing iodine-based contrast-enhanced computerized tomography (CT) has been questioned recently, given the caution undertaken in patients' selection, hydration protocols, and the low radiocontrast volume, used with advanced imaging equipment.
Materials and methods:
This study is a retrospective assessment of renal outcome in 12,580 hospitalized patients undergoing contrast-enhanced CT, compared with 754 patients subjected to gadolinium-based magnetic resonance imaging, with subsequent propensity matching for clinical characteristics and potential risk factors.
Results:
The risk of postcontrast acute kidney injury (PC-AKI) was found to be negligible as compared with patients undergoing enhanced magnetic resonance imaging studies, before and after propensity matching (8% vs 7.3% rate of AKI in the nonmatched iodine-based contrast agents [IBCAs] and gadolinium-based contrast agents [GBCAs], respectively, P = 0.3, and 7% in the matched IBCA group, P = 0.9), including comparisons among subgroups with well-defined risk factors such as chronic renal failure, diabetes, older age, and hypertension. However, lower systolic blood pressure before imaging was associated with higher risk to develop PC-AKI after IBCA administration but not with GBCA (for systolic blood pressure lower than 110 mm Hg, odds ratio for AKI after IBCA was 1.49; 95% confidence interval, 1.16-1.88, and after GBCA; odds ratio, 0.12; 95% confidence interval, 0.003-0.73).
Conclusions:
With the current precautions undertaken, the real-life risk of PC-AKI among inpatients undergoing CT is insignificant. Possible reasons for the diverse impact of blood pressure on the propensity to develop acute kidney failure after iodine-based but not gadolinium-based enhancement imaging are discussed.
Objectives:
Recently, safety guidelines for the use of intravascular iodinated contrast material have been updated, and the recommended threshold for giving prophylaxis to prevent contrast-induced nephropathy (CIN) has been reduced to estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m. Data on this population in the context of CIN, especially evidence for efficacy of the recommendation of prophylactic intravenous hydration, are lacking. The aim of the current study was to test implicit assumptions underlying the guideline update: (1) patients with eGFR <30 mL/min/1.73 m, as opposed to former high-risk patients with eGFR ≥30 mL/min/1.73 m, are at high risk of CIN and other unfavorable outcomes after intravascular iodinated contrast material administration; (2) prophylactic intravenous hydration mitigates this risk; and (3) the risk of administering prophylactic intravenous hydration does not outweigh the positive preventive effect.
Materials and methods:
Retrospectively, data were collected from all patients with eGFR <30 mL/min/1.73 m referred for an elective procedure with intravascular iodinated contrast material administration and excluded from the AMACING trial (A MAastricht Contrast-Induced Nephropathy Guideline trial). We compared these patients with those prospectively included in the AMACING trial (with eGFR 30-59 mL/min/1.73 m and risk factors). Main outcomes were CIN (defined as an increase in serum creatinine by more than 25% or 44 μmol/L within 2-6 days postcontrast exposure), dialysis and mortality within 35 days postcontrast exposure, and complications of prophylactic intravenous hydration.
Results:
A total of 28,803 patients referred for an elective procedure with intravascular iodinated contrast administration were prospectively screened for inclusion in the AMACING trial. One hundred fifty-seven (0.5%) patients had eGFR <30 mL/min/1.73 m, and 155 received intravascular iodinated contrast material. Standard prophylaxis was given to 119/155 of these patients. Data on 2- to 6-day serum creatinine, 35-day dialysis 35-day mortality, and complications of prophylactic intravenous hydration were available for 59/119 (50%), 118/119 (99%), 119/119 (100%), and 119/119 (100%) standard prophylaxis patients, respectively. Incidences in eGFR <30 mL/min/1.73 m versus AMACING patients are as follows: CIN 13.6% versus 2.7% (P = 0.0019); 35-day dialysis 0.9% versus 0.0% (P = 0.2646); 35-day mortality 9.2% versus 0.0% (P < 0.0001); complications of prophylactic intravenous hydration 5.9% versus 5.5% (P = 0.8529).
Conclusions:
Postcontrast incidences of CIN and mortality at 35 days are significantly higher in the population with eGFR <30 mL/min/1.73 m than in the former high-risk population with eGFR 30 to 59 mL/min/1.73 m, even after prophylactic intravenous hydration. The risk of complications of prophylactic intravenous hydration is similar and substantial in both populations. Obtaining evidence from a randomized trial that efficacy of prophylactic intravenous hydration outweighs the risk of complications is important but may not be feasible.
Since the 1980 s, gadolinium based contrast agents (GBCA) are routinely used in magnetic resonance imaging (MRI) as stable chelates of the Gd3+ ion, without toxic effects. Generally, GBCAs are considered as some of the safest contrast agents. However, it has been observed that they can accumulate in patients tissue, bone and probably in brain (causing nephrogenic systemic fibrosis in patients with kidney failure, insufficiency and disturbance of calcium homeostasis in the organism). The GBCAs are predominantly removed renally without metabolization. Subsequent, they do not undergo degradation processes in wastewater plants (WTPs) and are emitted into the aquatic ecosystem. Their occurrence was confirmed in surface waters (up to 1100 ng/L), sediments (up to 90.5 µg/g) and living organisms. Based on literature review, there is a need to investigate the contamination of different ecosystems and to ascertain the environmental fate of gadolinium. Long-term ecotoxicological data, degradation, metabolism, bioaccumulation processes and biochemical effects of the Gd-complexes should be explored. These data can be used to assess detailed environmental risks (ERA), because currently only hotspots with high level of Gd can be marked as dangerous for aquatic environments according to performed ERA. This article is protected by copyright. All rights reserved
Millions of radiologic examinations requiring the use of iodinated contrast are performed yearly in North America. Triiodobenzoic acid, the contrast agent molecule currently in use, is a benzene ring covalently bonded to the 3 iodine atoms. Iodinated contrast media can be divided in 4 categories: ionic monomers, ionic dimers, nonionic monomer, and nonionic dimers. Currently, second- and third-generation nonionic low-osmolar and iso-osmolar contrast media are used in clinical practice. The search for a safer and more effective iodinated contrast agents remains an ongoing challenge and important research topic.
Background
Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher levels.
Rare earth elements (REEs) are important for green and a large variety of high-tech technologies and are, therefore, in high demand. As a result, supply with REEs is likely to be disrupted (the degree of depends on the REE) in the near future. The 17 REEs are divided into heavy and light REEs. Other critical elements besides REEs, identified by the European Commission, are also becoming less easily available. Although there is no deficiency in the earth's crust of rare earth oxides, the economic accessibility is limited. The increased demand for REEs, the decreasing export from China, and geopolitical concerns on availability contributed to the (re)opening of mines in Australia and the USA and other mines are slow to follow. As a result, short supply of particularly terbium, dysprosium, praseodymium, and neodymium is expected to be problematic for at least the short term, also because they cannot be substituted. Recycling REEs from electronic waste would be a solution, but so far there are hardly any established REE recycling methods. Decreasing the dependency on REEs, for example, by identifying possible replacements or increasing their efficient use, represents another possibility.
Importance Patients who undergo radiographic studies with contrast receive an enormous bolus of iodine. This can delay subsequent use of radioactive iodine (RAI) therapy because the iodine can compete for uptake. There is a paucity of literature on the minimum interval between contrast administration and RAI therapy.
Objective To better characterize how long it takes for the iodine load from an intravenous contrast bolus to clear from the body.
Design, Setting, and Participants A prospective cohort of 21 adults undergoing intravenous contrast CT studies at a tertiary academic medical center; exclusion criteria included history of thyroid disease or thyroidectomy, history of renal insufficiency, pregnancy, and other contrast administration within 1 year.
Intervention Morning urine samples were taken before the scan for analysis and then every 2 weeks thereafter for 12 weeks.
Results The median baseline iodine level was 135 μg/L (range, 29-1680 μg/L), and median peak level was 552 μg/L (range, 62-6172 μg/L). Median time for urinary iodine level to normalize was 43 days, with 75% of subjects returning to baseline within 60 days, and 90% of subjects within 75 days. Baseline iodine level was a significant predictor of postcontrast iodine levels. Age, sex, weight, and estimated glomerular filtration rate were not significant.
Conclusions and Relevance These results may be used for guidance on the timing of RAI use following contrast exposure. The practice at our institution is to wait 2 months and then check a 24-hour urinary iodine level. This alleviates concerns about contrast use in patients with thyroid carcinoma interfering with adjuvant radioiodine therapy.
A LC tandem MS method was developed for the simultaneous determination of four iodinated X-ray contrast media (ICM) and 46 ICM biotransformation products (TPs) in raw and treated wastewater, surface water, groundwater, and drinking water. Recoveries ranged from 70% to 130%, and limits of quantification (LOQ) varied between 1 ng/L and 3 ng/L for surface water, groundwater and drinking water, and between 10 ng/L and 30 ng/L for wastewater. In a conventional wastewater treatment plant, iohexol, iomeprol, and iopromide were transformed to >80%, while iopamidol was transformed to 35%. In total, 26 TPs were detected above their LOQ in WWTP effluents. A significant change in the pattern of ICM TPs was observed after bank filtration and groundwater infiltration under aerobic conditions. Predominately, these TPs are formed at the end of the microbial transformation pathways in batch experiments with soil and sediment. These polar ICM TPs, such as iohexol TP599, iomeprol TP643, iopromide TP701A, and iopromide TP643, were not or only partially removed during drinking water treatment. As a consequence, several ICM TPs were detected in drinking water, at concentration levels exceeding 100 ng/L, with a maximum of 500 ng/L for iomeprol TP687.
Little is known about the significance of hospitals as point sources for emission of organic micropollutants into the aquatic environment. A mass flow analysis of pharmaceuticals and diagnostics used in hospitals was performed on the site of a representative Swiss cantonal hospital. Specifically, we analyzed the consumption of iodinated X-ray contrast media (ICM) and cytostatics in their corresponding medical applications of radiology and oncology, respectively, and their discharge into hospital wastewater and eventually into the wastewater of the municipal wastewater treatment plant. Emission levels within one day and over several days were found to correlate with the pharmacokinetic excretion pattern and the consumed amounts in the hospital during these days. ICM total emissions vary substantially from day to day from 255 to 1259 g/d, with a maximum on the day when the highest radiology treatment occurred. Parent cytostatic compounds reach maximal emissions of 8-10 mg/d. A total of 1.1%, 1.4%, and 3.7% of the excreted amounts of the cytostatics 5-fluorouracil, gemcitabine, and 2',2'-difluorodeoxyuridine (main metabolite of gemcitabine), respectively, were found in the hospital wastewater, whereas 49% of the total ICM was detected, showing a high variability among the compounds. These recoveries can essentially be explained by the high amount administered to out-patients (70% for cytostatics and 50% for ICM); therefore, only part of this dose is expected to be excreted on-site. In addition, this study emphasizes critical issues to consider when sampling in hospital sewer systems. Flow proportional sampling over a longer period is crucial to compute robust hospital mass flows.
The excretory behavior of nine nephrotropic contrast agents with varying physicochemical properties such as charge, lipophilicity, and molecular size was investigated. Renal clearance in comparison with inulin was determined by means of the continuous infusion method. Each contrast agent was infused at three dose levels in four to six rabbits. The investigations show that tubular transportation in proportion to glomerular filtration decreases with increasing dosages of all the contrast agents. Thus, with the highest concentration in plasma all contrast agents are eliminated at more or less the glomerular filtration rate (GFR). After administration of the low dosages the following differences are found: 1) Net tubular secretion increases for the monomeric contrast agent acids with increasing lipophilicity, in the order diatrizoate congruent to iothalamate less than iodamide less than acetrizoate. 2) The clearance studies do not reveal any tubular secretion or reabsorption for a hydrophilic cationic contrast agent. 3) The nonionic contrast agents do not show net secretion. The more lipophilic they are, the more they are reabsorbed. 4) Two dimeric contrast agents also do not reveal any tubular secretion. They seem to be reabsorbed more than monomers with the same charge.
Low-molecular-weight gadolinium (Gd) chelates are glomerular tracers but their role in evaluation of renal function with magnetic resonance (MR) imaging is still marginal. Because of their small size, they diffuse freely into the interstitium and the relationship between measured signal intensity and concentration is complex. New categories of contrast agents, such as large Gd-chelates or iron oxide particules, with different pharmacokinetic and magnetic properties have been developed. These large molecules could be useful for both functional (quantification of perfusion, quantification of glomerular filtration rate, estimation of tubular function) and cellular imaging (intrarenal phagocytosis in inflammatory renal diseases). Continuous development of new contrast agents remains worthwhile to get the best adequacy between the physiological phenomenon of interest and the pharmacokinetic of the agent.
Evaluation of safety guidelines on the use of iodinated contrast material
- E C Nijssen
- P J Nelemans
- R J Rennenberg
- EC Nijssen
ICH Q2(R2) validation of analytical procedures-scientific guideline
European Medicines Agency (2024) ICH Q2(R2) validation of analytical
procedures-scientific guideline. European Medicines Agency,
Amsterdam