Preventing, Mitigating, and Treating Radiological Injuries

"The number of known terrorist organizations with a global reach and the increased rate of proliferation and transfer of technical information through the Internet raise the possibility that more attacks with chemical, biological, radiological, or even nuclear weapons may occur in the years to come."

This assessment, from the NIH Strategic Plan and Research Agenda for Medical Countermeasures Against Radiological and Nuclear Threats, led the US Department of Health and Human Services, through the National Institutes of Health, to create eight Centers for Medical Countermeasures against Radiation (CMCRs), being funded by the National Institute of Allergy and Infectious Diseases (NIAID).

One of these Centers has been established at the Medical College of Wisconsin, where John Moulder, PhD, Professor of Radiation Oncology, serves as Principal Investigator. Dr. Moulder's work focuses on kidney injury, while Mary Otterson, MD, Professor of Gastrointestinal Surgery, acts as Associate Director of the Center and lead the gut injury project, and Meetha Medhora, PhD, Associate Professor of Pulmonary and Critical Care Medicine, directs the lung project.

Currently, relatively few medical treatments are available to counter radiological and nuclear threats, and most of those in development will need extensive preclinical testing before they can be evaluated for licensure, according to the NIH Strategic Plan.

The goals of the CMCRs are to prevent, mitigate, and treat radiological injuries, specifically in the event of a nuclear, biological, or radiological attack.

Preventive methods focus on developing radioprotective substances that will ready for use by first responders as an incident unfolds. Appropriate radioprotectors have to be fast-acting and easy to self-administer, and they must not affect work performance.

Mitigation measures are those that occur during or soon after radiation exposure, before evidence of injury is seen. Since most radiation injuries are not visible directly after release of radioactive compounds - symptoms might take hours or even weeks to develop - first responders need a method to determine who was actually exposed during an incident and their level of exposure. This method would have to take less than 1 hour to complete, which rules out the use of sophisticated techniques or equipment. Equipment and materials would have to be ready on the spot, and it is unlikely that advanced training will be available.

Measuring Exposure
One tool used for this process is a dosimeter, a small, portable device that can quickly test skin, teeth, or other samples to calculate the levels of radiation absorbed during an exposure. These instruments have not been perfected and research is still being conducted to refine them, but some type of dosimeter would likely be used if a radiation release occurred.

Biodosimetry quantifies radiation exposure, providing the biological information necessary for medical decision making," says NIAID in the NIH Strategic Plan. "Because the majority of assessment activities will take place in an acute care or emergency care setting, methods are urgently needed for rapid dose assessment of a large number of individuals within a short period."

Dosimetry will enable first responders to triage the exposed population and determine who needs decorporation - the process of getting radiological materials out of the body. Depending on the number of people involved, triage might take 1 to 2 days. When the needs for decorporation are made clear, says Dr. Moulder, health care providers "must be prepared to do something about it."

Use of Blood Pressure Medications in Radiation Injury
According to Dr. Moulder and E. P. Cohen, MD, in an article that appeared in the British Journal of Radiology in 2005, "clinical and experimental studies suggest that acute or chronic renal injury could occur after certain types of radiation accidents. Such renal injury could be life-threatening in its own right, could exacerbate other radiation injuries and could complicate the treatment of non-radiation injuries."

Dr. Moulder and his colleagues are currently studying the use of various agents to mitigate and treat the effects of radiation. Two types of high blood pressure medication - ACE inhibitors (Captopril) and AT1 blockers (Losartan) - are already being used to treat radiation injury to human kidneys, and part of Dr. Moulder's research involves using rat models to determine if these agents can also mitigate radiation injuries before they are well advanced.

"Both drugs suppress the renin-angiotensin system [a hormone system that helps regulate blood pressure and volume], thereby reducing blood pressure. However, their efficacy against renal radiation injury does not seem to be directly related to the blood pressure reduction," says Dr. Moulder. "Data from the MCW CMCR and elsewhere suggest that these agents can be used after irradiation to decrease the probability and severity not only of chronic renal injuries, but also of radiation-induced injury to the lungs and central nervous system."

The Course of Radiation Injury
Radiation dosages are measured in units called grays (Gy). In general, the type of injury caused by exposure to radioactive compounds is determined by the dose received. There are three typical syndromes associated with acute radiation injury:

• Bone marrow syndrome: (sometimes referred to as hematopoietic syndrome) usually occurs with a dose between 5 and 10 Gy, though mild symptoms may occur as low as 3 Gy. The survival rate of patients with this syndrome decreases with increasing dose. The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage.
• Gastrointestinal (GI) syndrome: the full syndrome will usually occur with a dose greater than 10 Gy, although some symptoms may occur as low as 6 Gy. Survival is extremely unlikely with this syndrome. Destructive and irreparable changes in the GI tract and bone marrow usually cause infection, dehydration, and electrolyte imbalance. Death usually occurs within 2 weeks.
• Cardiovascular (CV)/ Central Nervous System (CNS) syndrome: the full syndrome will usually occur with a dose greater than approximately 50 Gy, although some symptoms may occur as low as 20 Gy. Death occurs within 3 days. Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis.

The effects of radiation exposure can begin almost immediately after a radiation release has occurred, but might last for years. Although the specific syndrome depends on the type and amount of radiation received, Acute Radiation Sickness (ARS) generally has four distinct phases. These consist of:

• Prodromal stage: The classic symptoms for this stage are nausea, vomiting, anorexia and possibly diarrhea, which occur from minutes to days following exposure. The symptoms may last for minutes up to several days.
• Latent stage: In this stage, the patient looks and feels generally healthy for a few hours or even up to a few weeks.
• Manifest illness stage: In this stage the symptoms depend on the specific syndrome and last from hours to years.
• Recovery or death: The recovery process generally lasts from several weeks up to two years; but some injuries, such as those to the kidney and central nervous system, may take years to develop.

"Because many civilians might be exposed in an attack involving radiation, the development of therapeutic countermeasures to treat civilian victims after radiation exposure has occurred is a high priority. Promising candidate compounds must be moved expeditiously through development, licensure, and stockpiling", notes the NIH Strategic Plan. "Currently, the Strategic National Stockpile, a national repository of vaccines, antibiotics, antitoxins, chemical antidotes, and other essential materials needed for the medical response to a terrorist attack, includes only a limited number of medications specific for radiation exposure.

"Many more such agents are needed, based on the range of options that could be employed by terrorists, the need for urgent intervention following radiation exposure, and the medical complexities of acute and chronic radiation injury. "

Eileen Early, RN, BSN
HealthLink Editor
Medical College of Wisconsin Office of Clinical Informatics

This article includes information from the NIH Strategic Plan and Research Agenda for Medical Countermeasures Against Radiological and Nuclear Threats (PDF) and Radiation-induced multi-organ involvement and failure: the contribution of radiation effects on the renal system; J E Moulder, PhD and E P Cohen, MD. British Journal of Radiology Supplement_27(2005), 82-88.

For more information on this topic, see Part 1 of this article, MCW Center for Medical Countermeasures against Radiation.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.