Preparing for chaos: Hem/onc response crucial to radiation exposure incident

A mass casualty radiologic disaster would require immediate and full response from the medical community, with a specific need for the expertise of hematologists/oncologists.

Events in early January — including heightened tensions with North Korea, followed by an erroneous warning of a missile attack issued by Hawaii’s Emergency Management Agency — underscored the importance of the medical community’s preparedness in the event of a radiological disaster caused by a missile strike or nuclear detonation.

The radiological disasters of Chernobyl and Fukushima provided some indication of short- and long-term sequelae of radiation exposure. However, because each nuclear disaster occurred in areas with unique geography and health care infrastructure, it has been difficult to translate lessons learned from such events into coherent preparedness guidelines.

“There is always something to be learned from any of these disasters,” Donna Salzman, MD, professor of medicine and medical director of education and clinical services in the bone marrow transplantation and cellular therapy program at The University of Alabama at Birmingham, told HemOnc Today. “But every time we think we’re completely prepared, there’s always something we learn we can do better.”

Hem/oncs, radiation oncologists and hematopoietic stem cell transplant specialists would play a crucial role in several components of response, including the need for blood transfusions, the use of allogeneic HSCT as treatment for acute radiation syndrome (ARS), and the increased long-term risk for cancer from radiation exposure.

HemOnc Today spoke with experts about the role the hematology/oncology community would play in the response to a mass casualty radiologic disaster, lessons learned from previous events, and the need for continued education and readiness among the health care community and general public.

Role of hem/oncs

Because victims of radiation exposure often experience myelosuppression, hem/oncs are uniquely suited to help in such a situation.

“We don’t have the expertise to be first responders in such a situation, but we do have knowledge of how to take care of irradiated patients, at least in the area of allogeneic transplant,” Nelson J. Chao, MD, Donald D. and Elizabeth G. Cooke cancer research professor in immunology, research professor of global health, and chief of the division of cell therapy in the department of medicine at Duke University, told HemOnc Today.

Models have predicted that, if an event like Hiroshima were to occur in a U.S. city such as Washington, D.C., up to 175,000 victims would require intensive medical care and 30,000 would require treatment for myelosuppression.

“However, Hiroshima involved a 10-kiloton nuclear device,” Robert Peter Gale, MD, PhD, visiting professor of hematology at Imperial College London and a HemOnc Today Editorial Board Member, told HemOnc Today. “A typical Russian weapon is 1 megaton. This would not be an ‘event like Hiroshima.’”

“Initially, there would be chaos,” Cullen Case, EMPA, senior manager of logistics and emergency preparedness at National Marrow Donor Program and program manager of the Radiation Injury Treatment Network (RITN), told HemOnc Today.

Although the projected figures can seem overwhelming, Salzman suggested that hem/oncs focus on individual patients.

“Most of these patients will have mucosal irritation, infections, nausea and vomiting,” she said. “These are things that hem/oncs and radiation oncologists deal with every day.”

A 5-Gy dose of radiation would kill 50% of the exposed population in 60 days. Antibiotics and transfusions can help a person survive a 4.5-Gy to 7-Gy dose, and survival after doses greater than 10 Gy may be possible with HSCT or other methods.

Radiologists play an important role in these scenarios, according to Brian S. Englander, MD, chair in the department of radiology at Pennsylvania Hospital and associate professor of clinical radiology at Perelman School of Medicine.

“Imaging can assess critically ill patients and also more accurately triage victims,” Englander told HemOnc Today. “Our understanding of radiation, including radiation toxicity, is a part of the physics training provided to residents and should be expanded to address management of patients who have been exposed to a nuclear incident.”

Because those exposed to less than 2 Gy of radiation will likely recover without medical intervention, and those exposed to more than 12-Gy or 15-Gy whole-body doses will likely die, efforts should focus on those exposed to 2 Gy to 10 Gy, Gale and James O. Armitage, MD, Joe Shapiro professor of medicine at University of Nebraska Medical Center in the division of oncology & hematology, wrote in a special report in The New England Journal of Medicine.

Radiation exposure also poses long-term consequences, such as cancer risk, infertility and risk for cardiovascular disease, they wrote.

Source: Patricia Williams.

“Ninety percent of people will have percussion and thermal injuries and trauma from projectiles,” Gale told HemOnc Today. “Very few will have isolated radiation effects.”

Most victims will only require supportive care to help their hematopoietic system recover, Case said.

“Only a small percentage will likely go to transplant,” he said. “We estimate that 70% of ARS patients can be cared for in an outpatient setting with antibiotics, antifungals, cytokines and daily complete blood count with differential testing.”

Although these events are typically managed by emergency medicine and trauma, radiologists can be an important part of this team, Englander said.

“Residents should be taught the concept of minimum acceptable care with the need to allocate resources and assign efforts,” he said. “Intradepartmental and interdepartmental training is important to eliminate ‘silos’ and allow for discussion of appropriate responsibilities.”

It is imperative that physicians become engaged in their hospital’s emergency preparedness activities, Case said.

“We have found the only experience the hematology/oncology teams have with emergencies is the annual evacuation drill,” he said. “The vast majority are blind to the staggering amount of preparedness activities that are already in place.”

Most general practitioners do not understand the signs of ARS, Case added.

“Following a radiological disaster, there will need to be an intense training initiative to ensure ARS patients are triaged and cared for effectively,” he said. “Hem/onc specialists work with irradiated patients daily, but most do not think about this and may not have considered their potential involvement in a disaster.”

However, training after the fact may be too late, Gale said.

“At Hiroshima, 50% of physicians and 80% of nurses died,” he added. “They were not around to help anyone.”

Lessons learned

Previous radiologic disasters have prompted preparedness activities around the country.

Last year’s ASH Annual Meeting featured a special session titled Hematologic response to Mass Casualty Radiological Disasters.

Despite their emergency planning, hospitals themselves are vulnerable in the wake of a disaster, Kenneth E. Nollet, MD, PhD, professor in the department of blood transfusion and transplantation immunology at Fukushima Medical University, and director of international cooperation at their Radiation Medical Science Center, said during the ASH session.

He explained what happened after the Fukushima Daiichi nuclear disaster in 2011, which occurred after an earthquake and tsunami disabled the power plant’s triple-redundant backup power, leading to insufficient cooling and nuclear meltdowns.

“At least 118 medical facilities along the coast of Japan became unusable,” he said. “Eight major hospitals were designated for disaster response for anywhere from 11 to 24 days, during which routine outpatient appointments and elective surgeries were postponed.

“Schools became shelters, which have their own hazards, including many people using few toilets, creating potential hygiene issues,” Nollet added. “People were on voluntary fluid restrictions and many were immobile in shelters, often without their medications. As anticipated, deep vein thrombosis was a major issue for us in the shelters.”

Fukushima Medical University was prepared to collect blood for emergency transfusions and irradiate it to prevent transfusion-associated graft-versus-host disease, Nollet said, but the Japanese Red Cross was able to coordinate a national response that met demand in disaster-affected areas.

“Fukushima Medical University was the first institution in the world to introduce universal irradiation of allogeneic blood for transfusion,” he said. “It is now the standard of care in Japan because the risk for an HLA one-way match is especially high among Japanese individuals.”

Despite the significance of the event, major exposure to radiation was limited. Although exposure did exceed industry limits for some nuclear workers, no cases of ARS or myelosuppression have been reported among workers.

That was not the case after the Chernobyl Nuclear Power Plant incident in April 1986, which led to 134 cases of ARS among individuals exposed to high doses of radiation following a failed safety systems test. Some victims exposed to the highest levels of radiation underwent HSCT.

Baranov and colleagues reported data on 13 victims who underwent HSCT 4 to 16 days after the accident. Researchers estimated they had been exposed to median radiation dose of 8.3 Gy. Two of these patients were alive more than 3 years after transplant. The other 11 victims died of various causes, including GVHD, burns and interstitial pneumonitis.

Chao said knowledge of early symptoms of radiation exposure can be gleaned from these events.

“We know from the industrial accidents in Chernobyl, as well as from clinical practice, the early signs are nausea and vomiting,” he said.

There are more than short-term consequences, Nollet said.

“Kids downwind from the Chernobyl plant showed excess incidence of thyroid cancer,” he said. “Bear in mind that with Chernobyl, [people nearby were] milking the cows and drinking the milk. By way of contrast, Japan’s food supply was immediately and properly managed, with radiation safety standards now in place that exceed those of the United States and Europe.”

According to WHO data, there have been nearly 5,000 cases of thyroid cancer among children aged younger than 18 years at the time of the Chernobyl incident who lived in nearby Belarus, Russia and Ukraine. Reports also suggest increased incidence of leukemia among recovery workers.

Despite the research done since these events, most experts with whom HemOnc Today spoke agreed the lessons are often limited in their applicability to future events.

“The Chernobyl and Fukushima nuclear power plant incidents have improved readiness at other nuclear power plants and nuclear processing facilities,” Case said. “The event in Goiânia, Brazil highlighted that public panic can be a significant factor. Goiânia also demonstrated the need to secure abandoned irradiators around the world.

“But, even though we have learned much from history, in the end the number of people who are aware of these reports and then those who actually read them and apply the lessons are very few,” Case added.

The main lesson learned is simple, Chao said.

“The most important lesson is to stay in place and seek shelter,” he said.

Preparation, simulation, education

The National Marrow Donor Program and American Society for Blood and Marrow Transplantation established RITN in 2006.

The goals of the network — comprised of 80 voluntary HSCT centers, donor centers and umbilical cord blood banks — include to develop treatment guidelines for hematologic toxicity management among victims of radiation exposure, educate health care professionals about pertinent aspects of radiation exposure management, coordinate situation response after a radiation event, and provide comprehensive evaluation and treatment for victims at participating HSCT centers.

“Since 2006, RITN has conducted more than 650 exercises and educated more than 16,500 medical personnel,” Case said. “Within the RITN, there are more than 16,900 granulocyte-colony stimulating factor doses on hand.”

Exercises have been conducted throughout the country.

“We always have a hem/onc, ethicist and emergency management expert present,” Salzman added. “We can learn so much from these different perspectives. When there is a surge of patients in a hospital running at 120%, we can learn how to react to those high-occupancy situations, how we can increase the availability of resources and leverage the resources we have.”

The organization also provides a guidebook for hospital preparedness and simulations, as well as instructional videos, regional contacts, and treatment guidelines.

Understanding which health care personnel need protection and how to triage patients is a key component of hospital preparedness, Salzman said.

“There is a level of sophistication and thoroughness to these procedures that is impressive,” Salzman said, acknowledging this is not always the case at institutions that are not level-one trauma centers. “There are less than 100 facilities that are part of RITN. So, although our institution is prepared, I don’t know if the U.S. is fully prepared for bioterrorism or a plant meltdown.”

However, the response likely would be nationwide.

“If something were to happen within New York, we would be dispersing patients outside, to Boston, Philadelphia or Pittsburgh, or even as far south as Georgia or Florida,” Case said. “If something happened in Boston, centers in New York feel they can accept up to 20,000 casualties easily, based on their ability to surge. Based on 63,000 casualties, two-thirds would likely be cared for outpatient, about 29% would need inpatient care, and about 1% could possibly benefit from transplant, based on Chernobyl and other radiation incidents from the past 40 years.”

An additional goal of prevention exercises is to maintain a functional equivalent of routine care, Chao said.

“We don’t have a surplus of beds anymore,” he said. “Most hospitals run at pretty close to maximum capacity, and the idea of being able to take an additional 50 or 100 patients in 24 to 48 hours would be prohibitive without some sort of plan.”

Given the increasing incidence of natural disasters and their impact on health care delivery, it is not surprising that there has been an increase in disaster-related educational activities at multiple levels of medical training, Stephen C. Morris, MD, MPH, assistant professor of emergency medicine and lead for disaster preparedness and education at Washington University in St. Louis, told HemOnc Today.

“Although there are many similarities between normal trauma and mass gathering medical presentations, the epidemiology, logistics, social implications and many other aspects of natural disasters are different from normal health care delivery,” Morris said. “As such, appropriate preparation and planning — as well as a background in the principles of emergency management — can facilitate medical care in these situations.

“Additionally, there are some very unique medical concerns for disasters, such as the specialized training needed for radiological emergencies and those involving highly pathological diseases, such as influenza or Ebola,” Morris added. “Given the impact a large-scale disaster could have on a local or regional health system, more broad training in these areas should be considered for all medical providers.”

Still, medical preparation would be complicated by the nature of such an event, according to Gale and Armitage.

“Although stockpiling drugs such as antibiotics, antivirals and hematopoietic growth factors seems wise, deciding who needs these interventions and determining who is alive to estimate the radiation doses or to give parenteral drugs will be complicated if many or most health care and technical personnel are casualties and if a substantial part of the infrastructure, including hospitals, clinics, transportation facilities and communications, is destroyed,” they wrote.

“Storing hematopoietic cells — for example, in a bank of umbilical cord blood cells — seems sensible, but not if the cells are exposed to the same high-dose ionizing radiation as the victims who might benefit from receiving them,” they added. “It can be argued that cells could be transported from unexposed sites; this may be difficult in some instances and almost certainly would be impossible in the context of a multisite nuclear attack.”

Many potential related donors also would likely have been exposed to radiation or injured.

“Identifying potential unrelated donors elsewhere in the United States or overseas is time consuming and requires intact telecommunications and computer networks, resources that are unlikely to be available soon after a major nuclear event,” they wrote.

In addition to RITN, the International Atomic Energy Agency’s Incident and Emergency Centre coordinates international responses to nuclear or radiologic incidents and publishes preparedness guidelines, the WHO’s Radiation Emergency Medical Preparedness and Assistance Network has subject matter experts participating in response planning around the globe, and there are additional guidelines available from the National Council on Radiation Protection and Measurements and the Health Physics Society.

“However, our experience after much smaller nuclear events, such as the Chernobyl and Fukushima nuclear power facility accidents and the accidents and incidents in Tokaimura, Japan, and Goiânia, Brazil, suggests that much of this planning is unrealistic and unlikely to be effective, especially in the instances of a large nuclear or radiologic terrorist event, and it is obviously useless in the context of the detonation of a nuclear weapon or even a limited nuclear war,” Gale and Armitage wrote.

“We should not expect these events to play out as planned for, and prevention is key,” they added.

Chao disagreed.

“I do not doubt that there will be major problems and many deaths with a massive nuclear blast, but to say that to prepare does nothing is not only wrong, but nihilistic,” he said.

Initial impact

Health care emergency preparedness is highly regulated, such as through The Joint Commission, a not-for-profit organization that accredits and certifies health care programs in the United States, according to Wesley Light, director of emergency preparedness and security at Temple University Hospital.

“The Joint Commission has an entire chapter dedicated to emergency management,” he said. “They have requirements for managing utilities, communications, safety and security, patient and clinical support activities, resources and assets, and staff responsibilities in a disaster, such as The Joint Commission’s six areas of emergency response.”

These six areas are communication, resources and assets, safety and security, staff responsibilities, utilities management, and patient clinical and support activities.

CMS also has requirements, as well as local offices and state and federal agencies with resources for such events.

“Since the Joint Commission began discussing emergency management, they have really emphasized that hospitals should have an ‘all-hazard emergency operations plan’ to encompass anything that can go wrong in the facility,” Light said. “The plan should be designed to address all of the Joint Commission’s six areas of emergency response and should definitely include things like emergency communications, notifying stakeholders — including blood banks — in a disaster, and ensuring appropriate staffing.

“At Temple Hospital, we have a notification system that could quickly alert stakeholders of an event so they can respond to the disaster,” he added. “Our blood bank has a disaster plan. We also test our surge procedures so that we know how to manage beds.”

Like in Fukushima, most centers plan to handle the surge of patients within hotels, schools or mass shelters, Case said.

“Some cities hope to use transportation to bring patients in periodically for their daily blood tests,” he said. “Others would send nurses and phlebotomists to each of those hotels, take everyone’s blood draws, and send them to the lab. Some also have point-of-care devices where the full testing is entered into electronic health records to track daily blood counts.”

The primary response to such an event is coordinated through the federal government.

“There is a team that goes through a site, and patients are triaged and decontaminated depending on the accident,” Salzman said. “Hospitals have been designated to accept these patients. There are secure telephone lines and other tools provided by the RITN that allow for quick education on the nature of the event.”

Triage would be critical.

“Patients with trauma will be prioritized for care first,” Case said. “Patients with trauma and significant radiation exposure, or combined injury, will likely be triaged as expectant.”

Patients only with radiation exposure will be triaged for specialized care and then moved by the National Disaster Medical System to distant cancer centers for continued evaluation and treatment.

“This may take 5 to 10 days to begin moving these ARS patients out of the disaster area,” Case said. “That is not to say they will be left to wallow in the rubble, but they will be in assembly centers awaiting the availability of transportation assets to transport them to receive the care they need.”

Hematologists will play a crucial role in estimating a victim’s radiation exposure to determine whether patients do not require medical intervention; should receive supportive care, such as granulocyte colony-stimulating factor to facilitate autologous marrow recovery; should undergo evaluation for HSCT to treat marrow aplasia; or cannot be salvaged.

“Because many survivors have smartphones, it is possible to perform electron paramagnetic resonance spectroscopy on the display glass of smartphones and to perform optically stimulated luminescence analysis of smartphone resistors in order to estimate the dose of radiation,” Gale and Armitage wrote. “Other physical measurements include electron spin resonance measurements of dental enamel and some clothes (such as clothing made of cotton but not synthetic fibers) and neutron capture of urine samples.”

Other methods include biologic dosimetry on blood or bone marrow samples, as well as computer-based dose reconstruction. However, dose estimates may be inaccurate and may be more useful for triage than treatment strategies, they wrote.

Once the initial wave is past, clinicians must understand treatment strategies, Chao said.

“The idea is to try to use a nonradiation regimen,” he said. “For those who have received a significant dose of radiation, we would recommend standard prophylactic approaches, such as antibacterial and antifungal prophylaxis. Even after they recover from neutropenia, one would consider antiviral reactivation. The current view we have is that there is a very narrow band of patients who will actually need a true stem cell transplant.”

It is important to educate the public that these resources are available, Salzman said.

“Hospital employees also need to be educated about the emergency management plan,” she said. “Everyone involved needs to be ready for whatever comes through the door.”

For Chao, this lack of education and preparation is understandable.

“One of the problems is that this isn’t part of our daily lives, so there is not an impetus to have this in the forefront [of our minds],” he said. “But, education is really needed in all levels of health care. If no one shows up to clean the hospital because they are worried they are going to get irradiated from these patients, we may not be able to take care of them very well.”

Public understanding

An understanding of public perception regarding consequences of radiologic fallout, and the plans in place for such events, is necessary to inform awareness campaigns.

“Increasing awareness of the type of patients and how to care for them, as well as the existence of plans already in place from the federal level down to local metropolitan cities, would be ideal,” Chao said.

In extreme situations, medical preparedness will likely not be enough to handle the mass numbers of casualties, according to Gale and Armitage.

“We believe the best approach is a carefully conceived, long-term plan within the public education system to provide lessons on radiation biology,” they wrote. “Because this subject is usually not well taught in medical schools, health care providers, including physicians, also should be required to take an informational course.”

Greater public education is crucial for countries and locations with nuclear facilities.

“Most people, from the general public to medical personnel, are terrified of radiation,” Case said. “Radiation is dangerous, but the level of fear is not appropriate. This comes from misunderstanding. The public needs to know that radiation is readily detectable and contamination is easily removable, and they need to listen to their public officials during a disaster.”

Light was unequivocal in his assessment of the challenges clinicians will face.

“The biggest problem after a radiologic event is the public reaction,” he said.

Salzman said she believes preparation is improving through the efforts of RITN and other organizations.

“We haven’t had a radiation disaster in a while, but I think the community is pulling together to identify where we can be of assistance,” she said. “It’s not just happening in the United States. Our counterparts in Europe and the Asia-Pacific region are running scenarios and asking questions. The education level is increasing.”

Understanding natural hazards also is key, Nollet said.

“Japan does not have a monopoly on earthquakes,” he said. “Oklahoma had a magnitude 5.6 earthquake in 2011. Our Pacific Northwest is vulnerable to an incident of this magnitude.”

Still, preparation must go beyond natural disasters.

“Fukushima reminds us that nuclear accidents did not end with Chernobyl, and that any nuclear event may be part of a compound disaster,” Nollet said. “North Korea reminds us that nuclear weapon threats did not end with the Cold War. RITN is here to remind us that we can prepare.” – by Rob Volansky

Click here to read the , “Should preparation for a nuclear or natural disaster be part of physician residency?”

References:

Baranov A, et al. N Engl J Med. 1989;doi:10.1056/NEJM198907273210401.

Gale RP and Armitage JO. N Engl J Med. 2018;doi:10.1056/NEJMsr1714289.

Gale RP and Lax E. Radiation: What It Is, What You Need to Know. New York: Knopf; 2013.

Knebel AR, et al. Disaster Med Public Health Prep. 2011;5 (Suppl 1):S20-S31.

Nollet KE. Hell and High Water. 2017 and 2018. Available at: fmu-global.jp/2018/03/07/hell-and-high-water-presentations-at-the-59th-ash-annual-meeting-in-atlanta-and-tiara-in-tokyo/. Accessed on Aug. 9, 2018.

Nollet KE, et al. Transfus Apher Sci. 2016;doi:10.1016/j.transci.2016.09.009.

Weinstock DM, et al. Blood. 2008;doi:10.1182/blood-2008-01-134817.

WHO. Health effects of the Chernobyl accident: An overview. 2006. Available at: www.who.int/ionizing_radiation/chernobyl/backgrounder/en. Accessed on Aug. 1, 2018.

For more information:

Cullen Case, EMPA, can be reached at ccase@nmdp.org.

Nelson J. Chao, MD, can be reached at chao0002@mc.duke.edu.

Brian S. Englander, MD, can be reached at brian.englander@uphs.upenn.edu.

Robert Peter Gale, MD, PhD, can be reached at robertpetergale@gmail.com.

Wesley Light can be reached at Temple University Hospital, 3401 N. Broad St., Philadelphia, PA 19140.

Stephen C. Morris, MD, MPH, can be reached at scmorris@uw.edu.

Donna Salzman, MD, can be reached at dsalzman@uabmc.edu.

Disclosures: Case, Chao, Englander, Gale, Light, Morris and Salzman report no relevant financial disclosures.