Neurologic Effects of Gadolinium Retention in the Brain after Gadolinium-based Contrast Agent Administration.

Background Concerns over the neurotoxic potential of retained gadolinium in brain tissues after intravenous gadolinium-based contrast agent (GBCA) administration have led to pronounced worldwide use changes, yet the clinical sequelae of gadolinium retention remain undefined. Purpose To assess clinical and neurologic effects and potential neurotoxicity of gadolinium retention in rats after administration of various GBCAs. Materials and Methods From March 2017 through July 2018, 183 male Wistar rats received 20 intravenous injections of 2.5 mmol per kilogram of body weight (80 human equivalent doses) of various GBCAs (gadodiamide, gadobenate, gadopentetate, gadoxetate, gadobutrol, gadoterate, and gadoteridol) or saline over 4 weeks. Rats were evaluated 6 and 34 weeks after injection with five behavioral tests, and inductively coupled plasma mass spectrometry, transmission electron microscopy, and histopathology were performed on urine, serum, cerebrospinal fluid (CSF), basal ganglia, dentate nucleus, and kidney samples. Dunnett post hoc test and Wilcoxon rank sum test were used to compare differences between treatment groups. Results No evidence of differences in any behavioral test was observed between GBCA-exposed rats and control animals at either 6 or 34 weeks (P = .08 to P = .99). Gadolinium concentrations in both neuroanatomic locations were higher in linear GBCA-exposed rats than macrocyclic GBCA-exposed rats at 6 and 34 weeks (P < .001). Gadolinium clearance over time varied among GBCAs, with gadobutrol having the largest clearance (median: 62% for basal ganglia, 70% for dentate) and gadodiamide having no substantial clearance. At 34 weeks, gadolinium was largely cleared from the CSF and serum of gadodiamide-, gadobenate-, gadoterate-, and gadobutrol-exposed rats, especially for the macrocyclic agents (range: 70%-98% removal for CSF, 34%-94% removal for serum), and was nearly completely removed from urine (range: 96%-99% removal). Transmission electron microscopy was used to detect gadolinium foci in linear GBCA-exposed brain tissue, but no histopathologic differences were observed for any GBCA. Conclusion In this rat model, no clinical evidence of neurotoxicity was observed after exposure to linear and macrocyclic gadolinium-based contrast agents at supradiagnostic doses. © RSNA, 2022 Online supplemental material is available for this article.

Clinical and Ethical Considerations in Allocation of Ventilators in an Influenza Pandemic or Other Public Health Disaster: A Comparison of the 2007 and 2015 New York State Ventilator Allocation Guidelines.

OBJECTIVES: During an influenza or coronavirus disease 2019 (COVID-19) pandemic that results in acute respiratory distress, the number of available ventilators will not meet demand. In 2007, the New York State Task Force on Life and the Law and Department of Health released draft Guidelines for ethical allocation of ventilators for adults. In 2015, updated guidelines were released to ensure that: (1) revisions reflect the public's values and (2) the triage protocol is substantiated by evidence-based clinical data. We summarize the development and content of the 2015 Guidelines compared with the 2007 version, emphasizing new/revised aspects of the ethical considerations and clinical protocol. METHODS: We compared the 2007 and 2015 guidelines, with particular emphasis on the ethical issues and clinical protocols. RESULTS: The 2015 Guidelines retained much of the ethical and clinical framework of the 2007 draft. The triage protocol was revised using evidence-based clinical data. Patients with the highest likelihood of short-term survival with ventilator therapy have priority access. Protocol consists of exclusion criteria, the sequential organ failure assessment (SOFA) score, and periodic clinical assessments. Guidance is provided on secondary triage criteria. Other forms of medical intervention/palliative care and review of triage decisions are discussed. CONCLUSIONS: The 2015 Guidelines reflect advances in medicine and societal values and provide an evidenced-based framework to save the most lives. The framework could be adapted in other emergencies, such as the COVID-19 pandemic, that require ventilators.