In the aftermath of 9/11 and more recent acts of unrelenting terrorism, such as the mass killings in Paris, Brussels, and Orlando, as well as the recent conflict in Eastern Europe, the possibility of the use of nuclear weapons or crude nuclear devices in attacks on nuclear facilities and use of chemical agents cannot be ignored. Given the devastating medical consequences that would follow the use of such weapons, the training of medical personnel will be a crucial factor in the effective management of such casualties. In such a devastating scenario, preparation will be crucial for optimal care of those exposed to radiation.

Only 4 months after Roentgen reported the discovery of x-rays, Dr. John Daniel observed that irradiation of his colleague’s skull caused hair loss. Since this finding was reported in 1896, many biomedical effects of radiation have been described. Knowledge of nuclear physics was rapidly amassed in the early part of the 20th century, leading eventually to the Manhattan project and the development of the atomic bomb. The use of this weapon over Japanese cities Hiroshima and Nagasaki in 1945 produced at least 129,000 direct casualties and many more long-term sequelae; it still stands as the most gruesome demonstration of the impact and threat that nuclear weapons hold. The past 50 years have also seen widespread deployment of energy-generating nuclear reactors and the expanding use of radioactive isotopes in industry, science, and health care. In 2011, a tsunami following an earthquake near the Fukushima 1 power plant in Japan led to severe equipment failures, three nuclear meltdowns, and the subsequent release of radioactive material with contaminative consequences. This incidence was preceded by other notable, major industrial accidents at Three Mile Island in Pennsylvania, Chernobyl in the Ukraine, and Goiânia, Brazil, all of which have resulted in acute, life-threatening radiation injuries to hundreds of people. This is not to mention the longer-term health consequences, such as cancer and genetic effects (termed stochastic effects ), likely endured by countless others. According to the latest National Council on Radiation Protection & Measurements report on radiation exposure to US citizens, the most significant increase in ionizing radiation exposure over the past 20 years has been through medical imaging.

Exposure to ionizing radiation can follow one of three patterns:

• 1.

  Small-scale accidents, or cumulative exposures, as might occur in a laboratory or from an x-ray device in a hospital setting with access to sufficient resources and definitive clinical care

• 2.

  Large industrial accidents (such as those already mentioned), stretching the need for treatment beyond available resources

• 3.

  Detonation of a nuclear device in a military conflict producing complex polytrauma, during which resources are totally overwhelmed or unavailable

Damage to biologic tissue by ionizing radiation is mediated by energy transference. This can be the result of exposure to electromagnetic radiation (e.g., x-rays and γ-rays) or particulate radiation (e.g., α- and β-particles or neutrons). The severity of tissue damage is determined by the energy deposited per unit track length, known as linear energy transfer (LET). Electromagnetic radiation passes through tissue almost unimpeded by the skin and is called low LET because little energy is left behind. In contrast, neutron exposure has high LET, resulting in significant energy absorption within the first few centimeters of the body. α-Particles and low-energy β-particles do not penetrate the skin and represent a hazard only when internalized by inhalation, ingestion, or absorption through a wound.

The biologic effect of ionizing radiation is measured by the radiation absorbed dose (rad). The newer SI unit of absorbed dose is the gray (1 Gy = 100 rad). Not all radiation is equally effective in causing biologic damage, although it may cause the same energy deposition in tissue. For example, 1 Gy of neutron radiation will not have the same effect as 1 Gy of γ- or x-radiation. For this reason, a unit of dose equivalence was derived that allows radiations with different LET values to be compared. One such unit is the rem (acronym of roentgen equivalent man). The dose in rem is equal to the dose in rads multiplied by a quality factor (QF). The QF takes into account the LET and has a different value for different radiations; for x-rays it is 1.0, and for neutrons it is 10. The international unit, now more widely in use, is the sievert (Sv); 1 Sv equals 100 rem, and 1 rem equals 10 mSv. This allows radiations with different LET values to be compared because 1 Sv of neutron radiation has the same biologic effect as 1 Sv of low LET γ- or x-radiation.

The source of the most abundant type of biologically relevant electromagnetic radiation is the sun. Ultraviolet (UV) light with a wavelength of 315 to 400 nm (UVA), 280 to 315 nm (UVB), and 10 to 280 nm (UVC) would normally be absorbed by 98% in the atmosphere’s ozone layer, which extends about 20 miles above sea level. However, mostly because of human-made pollution and the resulting increase in local permeability of this protective layer, UV radiation can reach the surface of the skin and unfold its hazardous effects. Although not technically ionizing, UV light can severely irritate dermal structures in terms of first- and second-degree burns. Simultaneously, the formation of pyrimidine dimers in the DNA of dermal cells can be induced, which in the long term can result in malignancies. ^,

Another important cause of cutaneous radiation injury is secondary to radiotherapy, which is often used in cancer patients. A systematic review has indicated that ∼85% of radiotherapy patients will experience some level of reaction in the skin, which can range from erythema and mild discomfort to severe ulcerations and necrosis. Several scoring criteria exist that are unique to cutaneous radiation injury, which have been developed by, for example, the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer. These scoring systems have significant overlap, and both include life-threatening consequences at the more severe end of the scale. These scoring systems have been used to evaluate the potential benefit of different topical agents.

In clinical practice, there are concerns that relatively low levels of radiation delivered over a long period of time might induce cancer or exert genetic or teratogenic effects. Although most of the literature that explores this issue refers to case studies, it confirms that exposure at a younger age increases the risk of cancer. Even more important, this risk is not reduced with time. Exposure to radiation through computed tomography imaging is now commonplace, and healthcare personnel should not disregard the cumulative effects of these examinations, which can approximate levels seen in atomic bomb survivors (30 mSv). Because distance and radiation intensity obey the inverse square law, radiation dose can be limited most effectively by increasing the distance from the source of radiation. Additionally, incorporation of lead aprons and other shielding devices also blocks 90% to 99% of x-rays from clinical diagnostic sources.

Cumulative doses of radiation can be recorded on radiation badges containing photographic emulsion. The personnel dosimeter is relatively cheap and accurate but has limitations. The smallest exposure that can be measured is 10 millirem; film badges can be exposed by heat, giving false readings, and they are analyzed only at monthly intervals.

Exposure to higher levels of irradiation can occur after a significant radiation accident, which is defined as one in which an individual exceeds at least one of the following criteria:

• ■

  Whole-body doses ≥25 rem (≥0.25 Sv)

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  Skin doses ≥600 rem (≥6 Sv)

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  Absorbed dose ≥75 rem (≥0.75 Sv) to other tissues or organs from an external source

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  Internal contamination equal to or exceeding one-half the maximum permissible body burden as defined by the International Commission on Radiological Protection (this number is different for each radionuclide)

• ■

  Medical misadministration provided it results in a dose or burden equal to or greater than the previously listed criteria.

The number of accidents, the number of persons involved, and the number of fatalities in the United States and worldwide are shown in Table 34.1 . There have been 128 fatalities recorded by the REAC/TS Registry worldwide. The majority of the radiation deaths occurred as a result of the Chernobyl accident in 1986 (>40). The classification of radiation accident by device for the period 1944 to 2016 is shown in Table 34.2 .

The detonation of a nuclear device over a population center will produce an extremely hot, luminous fireball that emits intense thermal radiation capable of causing thermal burns and starting fires at considerable distance. This is accompanied by a destructive blast wave moving away from the fireball at supersonic speed and the emission of irradiation in the form of mainly γ-rays and neutrons. The result of a combination of thermal and radiation injuries can have a synergistic effect on the outcome. Several animal experiments have demonstrated a significant increase in mortality rate when a standard burn wound model is irradiated, over and above that expected from either injury alone.

Exact information about the cause of fatalities in a nuclear blast is not available, but from the nuclear attack on Japan it has been estimated that 50% of deaths were caused by burns, and some 20% to 30% were flash burns. The clinical picture may range from an erythema of exposed areas to a charring of the superficial layers of the skin. Secondary flame burns may be present after the ignition of the victim’s clothing or environment. The physicians at Hiroshima and Nagasaki observed that the “flame” burn wound seemed to heal at first. However, between 1 and 2 weeks later, a serious relapse occurred. Wound infection set in; there was disorder in granulation tissue formation; and a gray, greasy coating would form on the wounds. Thrombocytopenia resulted in spontaneous bleeding both into the wound and elsewhere. Histologically, the normal collection of leukocytes delineating a necrotic area was found to be absent because of agranulocytosis, and gross bacterial invasion was evident; both of these changes obviously affected the prognosis of these otherwise relatively small injuries.

The transference of radiation energy can damage critical parts of the cell directly or indirectly by formation of free radicals. The primary targets are cellular and nuclear membranes as well as DNA strand breaks.

The morbidity of radiation depends on the dose received, the dose rate, and the sensitivity of the cell exposed. Cells are most sensitive when undergoing mitosis so that those that divide rapidly such as those found in bone marrow, skin, and the gastrointestinal (GI) tract are more susceptible to radiation damage. Radiation to an organ such as brain or liver, which has parenchymal cells with a slow turnover rate, results in damage to the more sensitive connective tissue and microcirculation.

The overall effect on the organism depends on the extent of the body involved (e.g., total vs. partial body exposure, depth of energy penetration, whether the thymus is involved), duration of exposure, and homogeneity of the radiation field. It is convenient to consider radiation injuries as whether there is localized or whole body exposure, which will dictate which subtypes of acute radiation syndrome (ARS) occur (see later).

Long-term effects of radiation exposure include the formation of cancer and wound-healing deficits. These have been studied in various venues, including exposure to tanning beds, which have been linked to an increase in melanoma in young females of up to 16%. These changes are thought to be caused by a defect in the p53 tumor suppressor pathway. Children are particularly at risk for radiation-induced injuries because they have a proportionally larger amount of replicating cells and will live long enough to see the effects of radiation, which can have upward of a 30-year latency period.

In cutaneous radiation injury, while higher doses are typically required, only a relatively small part of the body is affected without significant systemic effects. The skin and subcutaneous tissue alone may be involved after exposure to low-energy radiation, whereas exposure to high-energy radiation may injure deeper structures. Although we use the term cutaneous radiation injury , it is of note that other terms have been used to describe the same phenomenon, including radiation burns , local radiation injury , radiation dermatitis , and radiation-induced skin injury . These terms have recently been reviewed elsewhere, with a call to standardize terminology to better coordinate studies.

Radiation damage depends on the dose of exposure, and several progressive features are observed in skin: Erythema is equivalent to a first-degree thermal burn and occurs in two stages. Mild erythema appears within minutes or hours after the initial exposure and subsides in 2 to 3 days. Given high enough dose, the second onset of erythema occurs 2 to 3 weeks after exposure and is accompanied by dry desquamation of the epidermal keratinocytes. Epilation (loss of hair) may occur as soon as 7 days after injury. It is usually temporary with doses less than 5 Gy, but may be permanent with higher doses.

Moist desquamation is equivalent to a second-degree thermal burn and develops after a latent period of about 3 weeks with a dose of 12 to 20 Gy. The latency period may be shorter with higher doses. Blisters form, which are susceptible to infection if not treated.

Full-thickness skin ulceration and necrosis are caused by doses in excess of about 25 Gy. Onset varies from a few weeks to a few months after exposure. Blood vessels become telangiectatic, and deeper vessels occlude. Obliterating endarteritis results in fibrosis, atrophy, and necrosis. Skin cancers may be evident after months or years.

One of the most closely studied instances of cutaneous radiation injury involves the treatment of breast cancer. It is well known that radiation therapy improves postmastectomy outcomes in females with multiple nodal involvement. This outcome comes at a cost as significantly increased rates of tissue contracture, hyperpigmentation, and asymmetry after all types of reconstruction paired with radiation. Although there is no consensus for the optimal treatment of cutaneous radiation injury, there a variety of topical agents that have been studied to date. These have been recently reviewed elsewhere and include treatments familiar to the burn field (silver sulfadiazine, etc.).

The physiologic effects of whole body radiation are described as ARS. The clinical course usually begins within hours of exposure. Prodromal symptoms include nausea, vomiting, diarrhea, fatigue, fever, and headache. There then follows a latent period, the duration of which is related to the dose, where lower doses received have a longer latency period that ends in recovery. On the contrary, higher doses lead to an accelerated latency that ultimately may lead to manifest illness and death. The LD ₅₀ dose for humans spans 4 to 6 Gy depending on the amount of supportive care offered. ARS can be subdivided into three overlapping subsyndromes, which are related to the dose exposure.

At lower doses (1–4 Gy) hematopoietic complications ensue. The bone marrow is the most sensitive, and pancytopenia develops, with the rate of the depletion of lymphocytes holding diagnostic value. Opportunistic infections result from the granulocytopenia and spontaneous bleeding from thrombocytopenia. Hemorrhage and infection can cause death.

GI-ARS requires a larger dose exposure (usually in the range of 6–12 Gy). Severe nausea and vomiting associated with bowel cramps and watery diarrhea occur within hours of irradiation. Similarly to lymphocyte depletion, the time to vomiting and severity of GI symptoms are also used as a parameter aiding the estimate of dose received. There is a shorter latent period of 5 to 7 days, which reflects the turnover time of the gut epithelium (3–5 days). The epithelial damage results in loss of transport capability, bacterial translocation with septicemia, bowel ischemia, and bloody diarrhea. Large fluid imbalances can result in hypovolemia, acute renal failure, and anemia from both bleeding and the loss of erythropoiesis. Critical exposure will lead to rapid deterioration with unrelenting bloody diarrhea, fever, refractive hypovolemic shock, sepsis, and death. ^,

Even higher exposures to doses of 15 to 30 Gy or greater can cause neurovascular ARS, with an immediate total collapse of the vascular system superimposed on the aforementioned syndromes. This may be caused by the massive release of mediator substances, nitric oxide abnormalities, or destruction of endothelium. This syndrome can progress rapidly with variable neurologic symptoms, respiratory distress, cardiovascular collapse, and is usually lethal within a couple of days.

Triage is the initial classification of casualties into priority groups for treatment and is essential in the management of large numbers of casualties. All first responders should take into account their own safety and remember that exposure to radiation is reduced by reduced time, increased distance, and shielding. Therefore a perimeter should be established beyond which those without shielding should remain until the donning of personal protection equipment is complete. In most circumstances, ionizing radiation is not immediately life threatening, and after life-saving measures have been carried out and the patient stabilized, assessment of radiation exposure can proceed.

If large-scale casualties are encountered, triage may, of necessity, seem to be draconian. Patients who are unlikely to survive should not be allowed to overwhelm available resources, so that adequate treatment reaches those most likely to survive. In conventional warfare with limited medical resources, 50% of soldiers with thermal injuries of up to 70% total body surface area (TBSA) are expected to survive ( Table 34.3 ).

This survival rate should be improved upon in a smaller civilian accident. Thus patients with burns alone over 70% TBSA should receive expectant treatment, and those with burns under 20% can have their treatment delayed. If there has been a significant exposure to radiation as well as a thermal injury, individuals with over 30% TBSA burns are unlikely to survive without the use of major resources.

The victims must be evacuated from the source of radiation to limit exposure. Normal resuscitation procedures must be followed. Contaminated clothing must be removed, and the skin wounds must be decontaminated by copious but gentle irrigation with water or saline. The goal of decontamination is to dilute and neutralize particles without spreading them to unexposed areas. Thus patients should not be immersed in tubs. Irrigation should be continued until a dosimeter, such as a Geiger-Müller counter, indicates a steady state or minimum radiation count has been reached.

Intact skin may also be irrigated with a soft brush or surgical sponge, preferably under a stream of warm tap water. If this is inadequate, a second scrubbing with mild soap or detergent (with a pH of 7) for 3 to 4 minutes is recommended. This is followed by application of povidone-iodine solution or hexachlorophene soap, which is then rinsed again for 2 to 3 minutes and dried. If the patient is known to have had exposure to less than 100 rem (1 Sv/Gy), they can be followed as an outpatient. Exposures greater than 100 rem (1 Sv/Gy) require full evaluation in the hospital. Patients with exposures greater than 200 rem (2 Sv/Gy) or who have symptoms of ARS should preferably be sent to specialist centers with facilities to treat bone marrow failure.

The assessment of thermal injury has been covered in preceding chapters. Exposure to radiation can be estimated clinically by noting the onset of symptoms of ARS, supported by biologic parameters. A complete blood count, including platelets and differential count, should be performed immediately and repeated at 12 to 24 hours if indicated by a change in the absolute lymphocyte count. If the patient sustains a fall in lymphocyte count of 50% or a count less than 1 × 10 ⁹ /L in a time period of 48 hours postexposure, a moderate dose of radiation has been encountered. Levels of serum amylase and diamine oxidase (produced by intestinal villi) may be useful biologic dosimeters of the future. Amylase levels are only reliable when the salivary glands have been exposed, and diamine oxidase has not yet been fully assessed in humans. Lymphocyte chromosomal analysis allows for accurate measurement even at low levels of exposure. However, this test is impractical with large numbers of casualties. Practically speaking, time to emesis is a crude metric that can be used to estimate dose, as 2- to 4-Gy exposure results in vomiting within a couple of hours, with higher doses occurring earlier. AFRRI has developed a biodosimetry assessment tool to incorporate as many parameters as possible in dose estimation ( https://afrri.usuhs.edu/research-assessment-of-radiation-injury ).