if the attachment doesn't come through, go to the NEJM website for charts.
R.
Current Concepts
http://www.nejm.org/doi/full/10.1056/NEJMra1103676
Short-Term and Long-Term Health Risks of Nuclear-Power-Plant Accidents
John P. Christodouleas, M.D., M.P.H., Robert D. Forrest, C.H.P.,
Christopher G. Ainsley, Ph.D., Zelig Tochner, M.D., Stephen M. Hahn,
M.D., and Eli Glatstein, M.D.
April 20, 2011 (10.1056/NEJMra1103676)
Article
References
On March 11, 2011, a 9.0-magnitude earthquake struck the east
coast of Japan. The total number of people who died in the earthquake
and the tsunami that it generated is still being assessed, but the
official estimation already exceeds 14,000.1 The natural disaster also
caused substantial damage to the Fukushima Daiichi nuclear power
plant, the consequences of which are still unclear. The purpose of
this review is to put the emergency at the Japanese power plant, even
as it is evolving, into the context of the extensive literature on
nuclear-reactor accidents by analyzing the mechanisms and major
short-term and long-term health risks of radiation exposure. In
addition, we briefly discuss the accidents at Three Mile Island in
Pennsylvania in 1979 and at Chernobyl in Ukraine in 1986 because they
illustrate the broad range of potential outcomes.
Mechanisms of Exposure
Reactor Accidents and the Release of Radioactive Materials
In a nuclear power plant, the fuel, an isotope of either uranium
or plutonium, undergoes fission to produce the energy that is used to
heat water and turn steam-driven turbine generators. In addition to
the release of energy, the split fuel creates radioactive fission
products. In the event of an accident, the primary concern is that the
support structure (core) containing the fuel and the fission products
may become damaged and allow radioactive elements to escape into the
environment. One mechanism by which this can happen is failure of the
core cooling system. In such a circumstance, the reactor core and even
the fuel itself can partially or completely melt. Elevated
temperatures and pressures can result in explosions within the
reactor, dispersing radioactive material. In most plants, the
potential effects of a cooling-system failure are minimized by
surrounding the reactor core with a steel-walled vessel, which in turn
is surrounded by an airtight, steel-reinforced concrete containment
structure that is designed to contain the radioactive material
indefinitely (Figure 1Figure 1Key Components of a Nuclear Power
Plant.). Of note, the explosions that have been seen in reactor
accidents are not the same as those seen after the detonation of a
nuclear weapon, since the latter requires highly enriched uranium or
plutonium isotopes in concentrations and configurations that are not
present in power plants.
In the partial meltdown at Three Mile Island, the plant's
containment structure fulfilled its purpose, and a minimal amount of
radiation was released.2 However, there was no such containment
structure in place at the Chernobyl reactor — the explosions and the
subsequent fire sent a giant plume of radioactive material into the
atmosphere. Although the Three Mile Island accident has not yet led to
identifiable health effects,3-5 the Chernobyl accident resulted in 28
deaths related to radiation exposure in the year after the
accident.6,7 The long-term effects of the Chernobyl accident are still
being characterized, as we discuss in more detail below. The situation
at Fukushima, though still in daily flux, will probably end up ranking
between these two historical accidents in terms of radiation releases
and health consequences.
Types of Radiation Exposure
Human radiation exposure as a result of reactor accidents is
generally characterized in three ways: total or partial body exposure
as a result of close proximity to a radiation source, external
contamination, and internal contamination. All three types can affect
a given person in a radiation accident. Total or partial body exposure
occurs when an external source irradiates the body either
superficially to the skin or deeply into internal organs, with the
depth depending on the type and energy of the radiation involved. For
example, beta radiation travels only a short distance in tissue,
depending on its energy, and can be a significant source of dose to
skin. High-energy gamma radiation, however, can penetrate deeply. In
previous reactor accidents, only plant workers and emergency personnel
who were involved in the aftermath had substantial total or partial
body exposure. Persons who have had total or partial body exposure but
no contamination are not radioactive and therefore cannot expose their
caregivers to radiation. External contamination occurs when the
fission products settle on human beings, thereby exposing skin or
internal organs. Populations living near a reactor accident may be
advised to remain indoors for a period to minimize the risk of
external contamination. Internal contamination occurs when fission
products are ingested or inhaled or enter the body through open
wounds. This is the primary mechanism through which large populations
around a reactor accident can be exposed to radiation. After
Chernobyl, approximately 5 million people in the region may have had
excess radiation exposure, primarily through internal contamination.7
Reactor accidents can release a variety of radioisotopes into the
environment. Table 1Table 1Estimated Releases of Isotopes during the
Chernobyl Accident. lists the radioisotopes that were released during
the Chernobyl accident.8 The health threat from each radioisotope
depends on an assortment of factors. Radioisotopes with a very short
half-life (e.g., 67 hours for molybdenum-99) or a very long half-life
(e.g., 24,400 years for plutonium-239), those that are gaseous (e.g.,
xenon-133), and those that are not released in substantial quantities
(e.g., plutonium-238) do not cause substantial internal or external
contamination in reactor accidents. In contrast, iodine-131 can be an
important source of morbidity because of its prevalence in reactor
discharges and its tendency to settle on the ground. When iodine-131
is released, it can be inhaled or consumed after it enters the food
chain, primarily through contaminated fruits, vegetables, milk, and
groundwater. Once it enters the body, iodine-131 rapidly accumulates
in the thyroid gland, where it can be a source of substantial doses of
beta radiation.
The release of radioactive water into the sea at the Fukushima
plant has resulted in an additional route whereby the food chain may
be affected, through contaminated seafood. Although the radioactivity
in seawater close to the plant may be transiently higher than usual by
several orders of magnitude, it diffuses rapidly with distance and
decays over time, according to half-life, both before and after
ingestion by marine life.
Clinical Consequences of Radiation Exposure
Type of Radiation and Dose Rates
At a molecular level, the primary consequence of radiation
exposure is DNA damage. This damage will be fully repaired or
innocuous or will result in dysfunction, carcinogenesis, or cell
death. The clinical effect of radiation exposure will depend on
numerous variables, including the type of exposure (total or partial
body exposure vs. internal or external contamination), the type of
tissue exposed (tissue that is sensitive to radiation vs. tissue that
is insensitive), the type of radiation (e.g., gamma vs. beta), the
depth of penetration of radiation in the body (low vs. high energy),
the total absorbed dose, and the period over which the dose is
absorbed (dose rate). The type of radiation and the dose rates that
are involved in a reactor accident would typically be very different
from those seen in the detonation of a nuclear bomb, which is why the
biologic consequences of these events may differ substantially.
The literature on radiation refers to dose in terms of both gray
(Gy), the unit of measurement for the absorbed dose, and sievert (Sv),
the unit of measurement for the effective dose, which is the absorbed
dose multiplied by factors accounting for the biologic effect of
different types of radiation and the radiation sensitivities of
different tissues. For high-energy gamma radiation and whole-body
exposures, 1 Gy equals 1 Sv. Table 2Table 2Effective Doses of
Radiation, According to Source of Exposure. shows estimated effective
doses received during common medical and nonmedical activities and how
these doses relate to those received by the populations around Three
Mile Island and Chernobyl.9-15
Radiation exposure can potentially result in short-term and
long-term effects in every organ system in the body. Comprehensive
reviews of the literature on radiation exposure have been produced by
the International Atomic Energy Agency and the World Health
Organization.7,15 In this review, we focus on the two potential
outcomes of radiation exposure that have garnered much of the media
attention in the wake of the ongoing crisis in Fukushima: acute
radiation sickness and increased long-term cancer risks.
Acute Radiation Sickness and Its Treatment
When most or all of the human body is exposed to a single dose of
more than 1 Gy of radiation, acute radiation sickness can occur. Much
of our understanding of acute radiation sickness is based on the
clinical experience of more than 800 patients who have been described
in national and international registries of radiation accidents that
have been predominantly medical in source.16 Acute radiation sickness
has not been seen in the general population in association with a
nuclear-reactor accident. All 134 patients with confirmed acute
radiation sickness at Chernobyl were either plant workers or members
of the emergency response team.6 No confirmed diagnoses of acute
radiation sickness were noted in workers or in the general population
at Three Mile Island.17
Much of the short-term morbidity and mortality associated with a
high total or near-total body dose is due to hematologic,
gastrointestinal, or cutaneous sequelae. In the Chernobyl accident,
all 134 patients with acute radiation sickness had bone marrow
depression, 19 had widespread radiation dermatitis, and 15 had severe
gastrointestinal complications.18 Hematologic and gastrointestinal
complications are common because bone marrow and intestinal epithelium
are especially radiosensitive as a result of their high intrinsic
replication rate. Cutaneous toxic effects are common because external
low-energy gamma radiation and beta radiation are chiefly absorbed in
the skin. In Chernobyl, estimated skin doses in some patients were 10
to 30 times the bone marrow doses.18 If total body doses are extremely
high (>20 Gy), severe acute neurovascular compromise can occur. At
Chernobyl, the highest absorbed dose in a worker was 16 Gy.19
Acute radiation sickness can be categorized into three phases:
prodrome, latency, and illness. Table 3Table 3Signs and Symptoms of
Acute Radiation Sickness in the Three Phases after Exposure.
summarizes the constellation of hematologic, gastrointestinal, and
neurologic symptoms, along with the time to onset and dose dependence,
associated with each of these phases. Cutaneous manifestations of
acute radiation injury include mild erythema and pruritus with limited
skin doses (3 to 15 Gy) and blistering and ulceration with very high
skin doses (>15 Gy).6
The first step in the care of any patient who is exposed to
radiation is to manage immediate life-threatening injuries, such as
those from trauma or burns. The next step is to address external and
internal radiation contamination, if any. Decontamination protocols
are available from several sources.20,21 Once these issues have been
addressed and acute radiation sickness is suspected, treatment is
guided by the estimated total dose, which is determined on the basis
of the initial clinical symptoms, lymphocyte depletion kinetics, and
cytogenetic analyses, when available.22,23
Patients with modest whole-body doses (<2 Gy) may require only
symptomatic support for nausea and vomiting. In patients with
whole-body doses of more than 2 Gy, the treatment of the consequences
of bone marrow depletion is paramount. Strategies include management
of infections with antibiotics and antiviral and antifungal agents,
the use of hematopoietic growth factors, and possibly bone marrow
transplantation.20 The use of bone marrow transplantation is
controversial, since outcomes after radiation accidents have been
poor. After Chernobyl, only 2 of the 13 patients who underwent bone
marrow transplantation survived long term. Among the 11 patients who
died, complications from transplantation appeared to be the primary
cause of death in 2 patients.24 Gastrointestinal radiation sequelae
are managed with supportive care and possibly with the use of
prophylactic probiotics.25 Cutaneous radiation injuries may evolve
over the course of weeks. Treatment of such lesions involves
minimizing acute and chronic inflammation with topical glucocorticoids
while avoiding secondary infections. Several organizations have
developed detailed treatment algorithms for acute radiation sickness
that are publicly available.6,20,26,27
Increased Long-Term Cancer Risks
In the region around Chernobyl, more than 5 million people may
have been exposed to excess radiation, mainly through contamination by
iodine-131 and cesium isotopes.7 Although exposure to nuclear-reactor
fallout does not cause acute illness, it may elevate long-term cancer
risks. Studies of the Japanese atomic-bomb survivors showed clearly
elevated rates of leukemia and solid cancers, even at relatively low
total body doses.28,29 However, there are important differences
between the type of radiation and dose rate associated with
atomic-bomb exposure and those associated with a reactor accident.
These differences may explain why studies evaluating leukemia30-36 and
nonthyroid solid cancers37-40 have not shown consistently elevated
risks in the regions around Chernobyl. Alternatively, small increases
in the risks of leukemia and nonthyroid solid cancers may become more
apparent with improved cancer registries or longer follow-up. In the
population around Three Mile Island, there was a notable temporary
increase in cancer diagnoses in the years immediately after the
accident, but this increase may have been the result of intensified
cancer screening in the area. Long-term follow-up has shown no
increases in cancer mortality.4
However, there is strong evidence of an increased rate of
secondary thyroid cancers among children who have ingested iodine-131.
Careful studies of children living near the Chernobyl plant (which
included estimates of the thyroid radiation dose) suggest that the
risk of thyroid cancer increased by a factor of 2 to 5 per 1 Gy of
thyroid dose.41-43 Although this relative increase in incidence is
large, the baseline incidence of thyroid cancer in children is low (<1
case per 100,000 children). Factors that increase the carcinogenic
effect of iodine-131 include a young age and iodine deficiency at the
time of exposure. Among children in regions with endemic iodine
deficiency, the risk of thyroid cancer per 1 Gy of thyroid dose was
two to three times that among children in regions in which iodine
intake was normal.44,45 Moreover, the risk of thyroid cancer among
children who were given stable iodine after the Chernobyl accident was
one third that among children who did not receive iodine.45 Studies of
the effect of thyroid exposure to radiation in utero46,47 and in
adulthood48-50 have been inconclusive.
In accidents in which iodine-131 is released, persons in affected
areas should attempt to minimize their consumption of locally grown
produce and groundwater. However, since the half-life of iodine-131 is
only 8 days, these local resources should not contain substantial
amounts of iodine-131 after 2 to 3 months. On the advice of public
health officials, area residents may take potassium iodide to block
the uptake of iodine-131 in the thyroid. To be most effective,
prophylactic administration of potassium iodide should occur before or
within a few hours after iodine-131 exposure. The administration of
the drug more than a day after exposure probably has limited effect,
unless additional or continuing exposure is expected.51 Although
potassium iodide can have toxic effects, the Polish experience with en
masse administration of the drug after Chernobyl was reassuring. More
than 10 million children and adolescents in Poland were given a single
dose of prophylactic potassium iodide, with very limited morbidity.52
The Food and Drug Administration has issued guidelines for the
administration of potassium iodide according to age and expected
radiation exposure.53
Conclusions
Because nuclear-reactor accidents are very rare events, few
medical practitioners have direct experience in treating patients who
have been exposed to radiation or in the overall public health
response. Organizations that could be involved in either activity —
because of their proximity to a power plant or their role in the
health system — must put detailed algorithmic response plans in place
and practice them regularly. A critical component of the response,
with respect to both treatment of individual patients and interaction
with the community, is clear communication about exposure levels and
corresponding risk, with an eye toward widespread public apprehension
about acute radiation sickness and long-term cancer risks.
Disclosure forms provided by the authors are available with the
full text of this article at NEJM.org.
No potential conflict of interest relevant to this article was reported.
This article (10.1056/NEJMra1103676) was published on April 20,
2011, at NEJM.org.
Source Information
From the Departments of Radiation Oncology (J.P.C., C.G.A., Z.T.,
S.M.H., E.G.) and Radiation Safety (R.D.F.), University of
Pennsylvania, Philadelphia.
Address reprint requests to Dr. Glatstein at the University of
Pennsylvania Department of Radiation Oncology, 2 Donner, 3400 Spruce
St., Philadelphia, PA 19104-4283, or at glatstein@uphs.upenn.edu.
Attachment:
nejmra1103676.pdf
Description: Adobe PDF document