Opinion article: the acute radiation syndrome – need for updated medical guidelines

Abstract The major immediate and severe medical consequences in man following exposure to high doses of ionizing radiation can be summarized within the concept of the acute radiation syndrome (ARS). In a dose-dependent fashion, a multitude of organ systems can be affected by such irradiation, presenting considerable medical challenges to treating physicians. Accidents or malevolent events leading to ARS can provoke devastating effects, but they occur at a low frequency and in a highly varying manner and magnitude. Thus, it is difficult to make precise medical predictions and planning, or to draw conclusive evidence from occurred events. Therefore, knowledge from on-going continuous developments within related medical areas needs to be acknowledged and incorporated into the ARS setting, enabling the creation of evidence-based guidelines. In 2011 the WHO published a first global consensus on the medical management of ARS among patients subjected to nontherapeutic radiation. During the recent decade the understanding of and capability to counteract organ damage related to radiation and other agents have improved considerably. Furthermore, legal and logistic hurdles in the process of formally approving appropriate medical countermeasures have been reduced. We believe the time is now ripe for developing an update of internationally consented medical guidelines on ARS.

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Investigating the Role of Inflammasome Caspases 1 and 11 in the Acute Radiation Syndrome

Radiation Research ◽

10.1667/rade-21-00141.1 ◽

2021 ◽

Author(s):

Andrea R. Daniel ◽

Lixia Luo ◽

Chang-Lung Lee ◽

David G. Kirsch

Keyword(s):

Cell Death ◽

Drug Targets ◽

Acute Radiation ◽

Rational Approach ◽

High Dose ◽

Acute Radiation Syndrome ◽

Alternative Pathways ◽

Caspase 1 ◽

Organ Systems ◽

Sensitive Organ

Exposure to high dose radiation causes life-threatening acute and delayed effects. Defining the mechanisms of lethal radiation-induced acute toxicity of gastrointestinal and hematopoietic tissues are critical steps to identify drug targets to mitigate and protect against the acute radiation syndrome (ARS). For example, one rational approach would be to design pharmaceuticals that block cell death pathways to preserve tissue integrity in radiation-sensitive organ systems including the gastrointestinal tract and hematopoietic compartment. A previous study reported that the inflammasome pathway, which mediates inflammatory cell death through pyroptosis, promotes ARS. However, we show that mice lacking the inflammatory executioner caspases, caspase-1 and caspase-11, are not protected from ARS when compared directly to littermates expressing caspase-1 and caspase-11. These results suggest that alternative pathways will need to be targeted by drugs that successfully mitigate and protect against the ARS.

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Opinion article: the METREPOL criteria – are they still relevant?

Journal of Radiological Protection ◽

10.1088/1361-6498/ac3bc2 ◽

2021 ◽

Author(s):

Laurence Lebaron-Jacobs ◽

Eduardo Daniel Herrera Reyes

Keyword(s):

Medical Management ◽

Acute Radiation ◽

Acute Radiation Syndrome ◽

Radiation Accidents ◽

Strategic Approach ◽

Organ Systems ◽

Radiation Induced ◽

Critical Organ ◽

Opinion Article ◽

Broad Overview

Abstract The Medical management of radiation accidents manual on the acute radiation syndrome (METREPOL) proposed a successful strategic approach to diagnosing and treating acute radiation syndrome: the response category concept. Based on clinical and laboratory parameters, this approach aimed to assess damage to critical organ systems as a function of time, categorising different therapeutical approaches. After 20 years of its publication, the following paper attempts to provide a broad overview of this important document and tries to respond if proposed criteria are still relevant for the medical management of radiation-induced injuries. In addition, a critical analysis of its limitations and perspectives is proposed.

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Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems

Disaster Medicine and Public Health Preparedness ◽

10.1001/dmp.2011.73 ◽

2011 ◽

Vol 5 (3) ◽

pp. 183-201 ◽

Cited By ~ 51

Author(s):

Nicholas Dainiak ◽

Robert Nicolas Gent ◽

Zhanat Carr ◽

Rita Schneider ◽

Judith Bader ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Acute Radiation ◽

World Health ◽

Controlled Trials ◽

Strong Recommendation ◽

Acute Radiation Syndrome ◽

Randomized Controlled ◽

Organ Systems ◽

Hypothetical Scenario ◽

Medical Countermeasures

ABSTRACTObjectives:The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature.Methods:English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made.Results:No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/or shock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients.Conclusions:High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future.(Disaster Med Public Health Preparedness. 2011;5:183–201)

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