1. health and fitness

Death by
Polonium-210
By Robin B. McFee, DO,
MPH, FACPM, &
Jerrold B. Leikin, MD,
FACEP, FAACT, FACP,
FACOEM, FACMT
Alexander Litvinenko in
the ICU on Nov. 20, 2006.
“T
he chilling reality is that nuclear materials and technologies are
more accessible now than at any other time in history,” said former CIA Director John Deutch in testimony before the Permanent Subcommittee on Investigations of the Senate Committee on Government
Affairs on March 20, 1996.1 This reality became all too evident in
November 2006 when Alexander Litvinenko, a Russian dissident who had
publicly criticized the leadership in Moscow, was murdered by poisoning
with radioactive Polonium-210 in the United Kingdom.2-5
Litvinenko, a former KGB agent, was tasked with investigating political corruption as a member of the elite organized crime unit of the Russian Federal Security Service (FSB)
prior to defecting to London. His former job took on greater
significance than is generally credited to the time-honored
but often underappreciated component of the assessment
and diagnostic process—the occupational history.
Health-care professionals often overlook a patient’s
travel history and obtain less-than-thorough occupational
histories. A recent study showed that among patients pre-
18
PHOTO NATASJA WEITSZ/GETTY IMAGES
Lessons learned from the murder of
former Soviet spy Alexander Litvinenko
senting to the emergency department (ED) with a travel-related
illness, only 16% were asked
about recent travel, resulting in
missed diagnoses.6-8 In this era of
emerging pathogens, global travel
and high-risk occupations, such
information can offer important
clinical clues and prove critical to
patient diagnosis.
Case report
On Nov. 1, 2006, a previously healthy, athletic, 43-year-old
Russian male who had emigrated to London five years
earlier, presented to a North London hospital with acute,
severe, progressive gastrointestinal symptoms. He was a
writer. Of course, we now know what his prior occupation
was. Whether Litvinenko intentionally withheld his prior
occupational history or it was not initially pursued by clinicians remains unclear.
Litvinenko’s health rapidly deteriorated: his hair fell out
Response Guide for Chemical & Radiologic Threats
and he developed pancytopenia (i.e., a shortage of all types
of blood cells, including red and white blood cells, as well as
platelets). Because his symptoms were consistent with radiation or thallium toxicity, physicians obtained urine and
blood samples and subjected them to gamma spectrometry.2,5 But the tests did not register anything unusual.5
While clinicians began searching for other causes of illness, including exotic toxins, biologicals and poisons, the
patient’s condition steadily declined. Because Litvinenko
was not responding to treatment, his urine was sent for more
advanced laboratory analysis to Britain’s Atomic Weapons
Establishment (BAWE), where tests revealed significant
amounts of alpha particle radiation.5 Not long thereafter, on
Nov. 23, Litvinenko died of internal contamination from
Polonium-210 (210Po).
In the aftermath, Litvinenko’s death was classified as murder. An international investigation identified several other
victims, and numerous locations in the UK tested positive for
traces of 210Po contamination. 210Po was found at a London
restaurant and bar that Litvinenko visited,2 and some traces
were found on British Airways aircraft; fortunately none of
the 1,700 passengers or 250 patrons of the restaurants were
contaminated or became sick. However, another former KGB
agent and a former Russian army officer both tested positive
for 210Po in Moscow.3 A substantial amount of 210Po must have
been used to cause such widespread contamination.5
Weeks elapsed between the poisoning and realization
that radioactive materials were utilized,21 and as of January
2007 at least 12 people had tested positive for contamination.3 The incidental exposure of these individuals did not
appear to pose a risk.3 However, fears of 210Po contamination
led thousands of people to contact the National Health
Services direct helpline, established in the aftermath of the
assassination.3
Understanding Polonium-210
Po is considered one of the most hazardous radioactive
materials, but it must be internalized to pose a toxic threat.
Patients affected by 210Po do not pose a health risk to
responders.
Emergency responders should think about two concepts
associated with radiation as a threat, especially as related to
detection and protection: the source as a contaminant,
although certain radiation sources can harm without direct
contact, and the source as a toxicant, affecting the patient.13
In the case of alpha emitters, such as 210Po, identifying the
source’s nature as a contaminant on the victim or in the
area—especially if the responder is in proximity to a radioactive source (alpha, beta, gamma ray or X-ray)—requires
equipment capable of detecting the full range of ionizing
radiation types.
The good news about alpha threats: Intact skin is a good
barrier. However, inhalation and ingestion are access points.
Also, in the case of alpha emitters as toxicants, once inside the
patient, especially if the victim is not externally contaminated,
further investigation to determine the etiology should be
recommended on the basis of the clinical picture because
external detection methods are unlikely to be of value for an
210
internal toxicant. Advanced laboratory testing is required to
evaluate biological samples and conduct blood tests.
Although Litvinenko’s symptoms were consistent with
radiation illness, as a result of the initial hospital assessment,
which apparently focused on gamma radiation, radiation
was abandoned and other diagnoses were sought. Of note,
the CDC recommends a 24-hour urine collection to assay for
the presence of 210Po when suspected; levels in excess of
background are suggestive of internal contamination. The
essential issue is suspecting radiation toxicity early and
employing a full range of testing until it can be ruled out.
Few human data are available on the health effects of
210
Po, but the toxicity of orally administered 210Po appears to
be consistent with the amount reaching blood (bioavailability). Damage to the gut mucosa is a probable contributory
cause of death after oral administration.
In a Russian case of interest, a male worker accidentally
inhaled an aerosol of 210Po.9 Death occurred after 13 days.
Vomiting was severe at the time of admittance to a clinic, two
to three days after the intake. A high fever was reported, but
there was no diarrhea. Thrombocyte counts were 150 x 109 l-1
on day 6 and 80 x 109 l-1 on day 8.
Within minutes of ingesting 210Po, the cells lining the victim’s gastrointestinal tract would begin to die and slough off,
which would cause nausea, pain and severe gastrointestinal
bleeding.4,10,11,14 Other systems would be affected by 210Po, and,
unless early decorporative (chelation) treatment is initiated
to lower the body burden and other medical interventions
are provided, significant morbidity and ultimately death can
be anticipated.
The earlier the initial symptoms of radiation poisoning
(nausea and vomiting) occur, the more likely it’s a severe
exposure. Although profound fear response and/or psychological exposure without actual radiation exposure can also
cause nausea and vomiting, these don’t tend to cause rapid
hair loss and disruption of blood counts. In the presence of
an actual exposure, persistent gastrointestinal symptoms
within the first two hours of exposure portends a poor prognosis and potentially fatal outcome.
Two basic models can be used to understand the health
effects of ionizing radiation (IR): the deterministic model
and stochastic model. The deterministic model states that as
radiation dose increases, the severity of health effect increases; there is a threshold dose. All health effects of IR,
except cancer and birth defects, follow this model. Cancer
follows the stochastic model: as the dose of IR increases, the
risk (not severity) of cancer increases. It does not have a
threshold, and there is no “zero” risk of cancer from IR.
Measurements in radiation science
Radiation can be measured in terms of emission from a
radioactive source, absorption by a person or risk that
a person might suffer health effects—the biological
risks. Depending on the aspect of radiation under discussion,
different units of measure are used.
Radioactivity occurs because the nucleus of the atom is unstable, resulting in emission of energy. A release in the form
of radiation is in proportion to the number of disintegrations
Response Guide for Chemical & Radiologic Threats
19
protection (NIOSH-approved mask for radionuclides) should
provide adequate protection. Removing victims’ clothes can
reduce the particle load by upward of 90%.
Rays do not pose a contamination risk and cannot be
transferred from person to person. However, they can pass
through most materials, unless proper shielding with lead,
depleted uranium and/or thick concrete barriers intervenes.
Alpha particles are essentially helium nuclei consisting
of two protons and two neutrons.4,10,11,13,15-17,20 They have significant mass and kinetic energy that can cause direct ionization of other atoms or molecules. Because they are so
Time
Distance
Shielding
massive and have a +2 charge, they have little penetrating
power. They are incapable of penetrating a few sheets of
of radioactive atoms in a radioactive material over a period of paper or the epidermis of skin. Alpha particles can be
time.10,11,13,15 The amount of radiation emitted by a radioactive stopped by clothing and intact skin. Therefore, alpha radiamaterial is measured using the conventional (U.S.) term curie tion represents an internal contamination and internal irra(Ci) or System Internationale (SI) term becquerel (Bq). One Ci diation hazard only if the particles are inhaled, ingested or
= 3.7 x 1010 disintegrations per second. One Bq = 1 disintegra- injected by penetrating wounds.11,13
tion per second. One Ci = 3.7 x 1010 Bq. The Ci or Bq may be
As demonstrated in the Litvinenko case, it’s important to
used to refer to the amount of radioactive materials released make certain before an event that radiation detectors can
into the environment. Example: An estimated 81 million Ci of identify alpha emissions. Not all Geiger-Muller detectors can
radioactive cesium was released into the atmosphere during identify alpha IR. Usually special wands or sensor attachthe Chernobyl disaster.15
ments are necessary and must be used as directed. Although
Radioactivity is a naturally occurring phenomenon; we seemingly obvious, preparedness has been significantly comare exposed to small amounts on a daily basis. When a per- promised because of uncharged batteries, lack of spare batson is exposed to radiation, energy is deposited in the body. teries and forgetting to calibrate a detector. Lack of familiarity
with the proper use of
The amount deposited
210
the equipment may also
per unit of weight is called
compromise the ability to
the RAD, or radiation
detect the presence of IR.
absorbed dose; the basic
unit of measuring expoBeta particles have a
sure dose is defined as the
spectrum of energy levels;
deposition of 0.01 joules
high-energy beta particles
of energy into one kilogram of tissue. The SI unit of meas- can penetrate a few meters in the air and millimeters into tisure is the gray (Gy); 1 Gy = 100 RAD. The number of RADs a sue.10,11,13,15 Severe beta burns are possible on skin or eyes upon
patient has been subjected to allows clinicians to anticipate contact. Cesium 137 (137Cs) is an example of a beta particle.15
the potential severity of acute radiation syndrome (ARS) Like alpha particles, beta particles pose a significant internal
hazard. Aluminum or thick plastic protection with hospital
and plan clinical management accordingly.
The risk that a person will suffer adverse health effects protective clothing is necessary to prevent injury. It’s imporfrom radiation is measured using the unit REM (roentgen tant to make certain before an event that radiation detectors
equivalent man). The REM quantifies the amount of damage can identify beta emissions and that your agency has a protosuspected from a radiation exposure. The SI unit is the Sievert col for testing biological samples.
(Sv); 1 Sv = 100 REM. The REM is adjusted to reflect the type
Gamma rays consist of electromagnetic radiation and are
of radiation absorbed and the likely damage produced.
high-energy uncharged particles similar to X-rays.10,11,13,16,19
They readily pass through matter, including skin and clothing,
Types of radiation
resulting in total body exposure and posing a significant risk to
The type of radiation refers to whether a source is ionizing health. Lead, including lead aprons, concrete and uranium are
used for shielding. In the field, thick barriers, limiting time
radiation (IR) or nonionizing.
IR comprises alpha and beta particles, gamma rays and near exposure and increased distance from the source are
X-rays (high energy). The types of IR vary in their ability to essential protective measures, especially if no other escape or
penetrate materials. This is important for first responders protective material is available (see illustration above).
because the risk to health, depth of penetration and need for Doubling the distance results in a 75% reduction in exposure.
PPE can vary by type.
X-rays are similar to gamma rays in that they are highly
Particles pose an external contamination risk and, if penetrating and require special shielding.10,11,13
internalized, have the same capability to destroy tissue as
gamma and X-rays. Moreover, as contaminants, alpha or beta Polonium & alpha emission
particles can be transferred from patient to provider and There are several important alpha emitters of concern.
inhaled. Universal precautions and appropriate respiratory These include polonium; Americium, which can be found
Basic Concepts of Radiation Protection
One gram of Po could kill
50 million people &
sicken another 50 million.
20
Response Guide for Chemical & Radiologic Threats
Acute radiation syndrome
Radiation sickness exhibits a distinct pattern of
injury.9,10,11,15,16 ARS represents signs and symptoms after
total body irradiation from penetrating radiation or internal contamination and is usually associated with greater
than 100 RAD (1 Gy) exposure.10,11,13,24,25 The clinical course of
ARS is predictable and dose-dependent, and occurs within
a few hours to weeks after exposure to IR. Severity is based
on significance of and time to symptoms, usually with the
following four phases:10,11,15
1: Prodrome (minutes to days)—Nausea and vomiting
are usually early signs. The development of gastrointestinal
(GI) symptoms within two hours of exposure portends a
serious and potentially fatal outcome. However, a psychological and traumatic component exists, so determining
whether the origin of the GI symptoms is psychological,
due to radiation or both is critical.
2: Latent (none to weeks depending on dose)—mostly
hematopoietic; white cells and platelets decrease due to
bone marrow damage.
3. Illness (days, weeks or longer)—relates to systems
involved (see below).
4. Recovery or death (weeks to months).
Hematopoietic effects: These generally occur at total
body exposures of 100–800 RAD11,15,24 because the
hematopoietic system is highly radiosensitive.13 Thus, ARS
results in a rapid decline of white cells, platelets and red
cells. Immune deficiency and vulnerability to infection,
PHOTO KEITH CULLOM
in smoke detectors; and plutonium, which is a highly
controlled commodity produced from uranium (239, 238U) in
reactors, often contaminated with Americium and used
in thermonuclear devices.4,10,11,15,20
Polonium was discovered in 1897 by Marie and Pierre
Curie; Madame Curie named it after her native Poland. There
are more than 20 isotopes of Po; 210Po, the most stable form, is
an alpha-particle- (5.3 MeV) emitting radionuclide with a
radiodecay half-life (t 1⁄2) of 138 days.4 Unlike other radioactive
elements, 210Po is relatively safe to transport.4 However, if
these high-energy particles are inhaled, ingested or inserted
into abraded skins or wounds, they can damage tissue.10,11
As a poison 210Po is several orders of magnitude more
toxic, on a milligram per milligram basis, than hydrogen
cyanide. Estimates suggest one gram of 210Po could kill 50 million individuals and sicken another 50 million, and less than
a microgram of Polonium could have caused Litvinenko’s
death.4 (Note: The production of just 1 g of plutonium would
require a nuclear reactor.)
210
Po is soluble in aqueous solution and forms simple salts
(e.g., chloride) in dilute acids. Its effectiveness as a poison
relies on its chemical characteristics only to the extent that
they determine its distribution and retention in organs and
tissues; the alpha particles do the damage.
Ingested 210Po is more readily absorbed than some other
alpha-emitting radionuclides. It is deposited predominantly
in soft tissues, with the greatest concentrations in the
reticuloendothelial system, principally the liver, spleen and
bone marrow, as well as in the kidneys and skin, particularly
hair follicles.22 Concentrations in circulating blood are also
important, with activity being associated with erythrocytes as
well as plasma proteins. Retention times differ among organs
and perhaps between forms of polonium taken into the body,
but whole-body retention typically has a half-time of about
one to two months. It is eliminated primarily through the
fecal route (after ingestion), with urine and dermal elimination constituting minor routes of excretion.
Doses from 210Po are generally assumed to be delivered
uniformly to the organs/tissues in which the radionuclide
is retained,23 despite the short range of the alpha particles
(5.3 MeV) of about 40–50 µm.
Radiation at sufficiently high doses is lethal within days or
weeks. Organs and tissues vary substantially in their sensitivity to damage by radiation. Particularly sensitive is the
haemopoietic (blood-related) tissue of the bone marrow,
followed by the epithelial lining of the alimentary tract. The
dose to the stomach and other regions of the gut during
the first day is estimated as about 0.04 Gy.
Response vehicles should carry detectors that can detect small
amounts of radiation and produce an audible alarm.
hemorrhage and impaired wound healing occur unless
treatment with reverse isolation, hematologic growth factor
stimulation and aggressive symptomatic and supportive
care are given. Reverse isolation should be considered until
immunodeficiency resolves.
Gastrointestinal (GI) syndrome: GI effects usually occur
after exposures of 800–3,000 RAD, resulting from damage to
the cells lining the small intestines. Fluid loss, hemorrhagic
diarrhea, nausea and vomiting (often hematemesis)
occur.11,15,24 The rapidity of GI symptom onset can mark the
severity of exposure: The earlier such symptoms appear, the
more likely it was a high-level radiological exposure. Such
was the clinical course of Litvinenko. Given the interventions
available, assume patients may be salvageable with aggressive fluid replacement, prevention of infection by bacterial
transmigration and appropriate antidotes or decorporative
countermeasures, such as chelation.25,26
Cerebrovascular or CNS effects occur with exposures of
3,000 RAD and are associated with death. Vomiting, diarrhea,
Response Guide for Chemical & Radiologic Threats
21
confusion, convulsion and coma can occur within minutes.10,11,24 Neurological involvement is irreversible.
Detection technology
FYI
There are different methods to assess 210Po, depending on the
sample, urgency of results and sensitivity of tests. Generally
increased precision takes time. In the UK, the Health
Protection Agency testing took two to three days from receipt
of the 24-hour sample.
Urine and blood testing are beyond the scope of EMS, so
other issues must be considered, such as having appropriate
detectors and knowledge about their use. (See www.
jems.com/chemical_threats for a discussion of radiation
detection equipment for first responders.) Not all Geiger
counters are capable of detecting alpha particles;14 consultation with health physicists or the Radiation Emergency
Assistance Center/Training Site (REAC/TS) should facilitate
procurement of appropriate equipment.10,11,13
Although many agencies have preparedness plans in
place, few have been tested in terms of radiation. It’s also
important to have such plans vetted by REAC/TS. Plans
should include current and regularly updated recommendations on the use of an electronic personal dosimeter
(EPD), dosimetry and detectors.27
For more information, call
865/576-3131 or 865/576-1005
(emergency number; ask for
REAC/TS) or visit REAC/TS online
at http://orise.orau.gov/reacts/.
Clinical care of the radiation victim
No health-care worker providing medical care to radiation
injured or ill patients has ever received a significant dose of
IR or been significantly contaminated with radiological
materials in the history of the atomic age.10,13,15 Traumatic
injuries usually take precedence over radiation in order of
treatment urgency. Moreover, there are few currently available prehospital interventions that the paramedic can
offer. Nevertheless, early diagnosis and the use of antidotes,
chelation or colony-stimulating factors may confer a survival advantage. Forward deployable treatments are under
development.
Treatment for the radiation poisoned patient, such as
colony-stimulating factors to increase blood cell counts
and decorporative antidotes (chelators) to decrease the
body burden, must be initiated early.
Chelators are drugs used to bind to certain metal ions,
thus enhancing body elimination. Currently available
chelators include dimercaptosuccinic acid (DMSA) and
N,N’-di (2-hydroxyethyl) ethylenediamine-N,N’-bisdithiocarbamate (HOEtTTC). These and other chelators demonstrate varying degrees of effectiveness in reducing body
burden and toxicity.25,26 Under laboratory conditions,
HOEtTTC appears to be superior to other options.25,26,28 But
DMSA is the only oral chelating agent that is FDA-approved
in the U.S. for human use as a heavy metal treatment (e.g.,
22
for lead, oral and intravenous mercury). It has a longstanding safety record with adults and children. Studies
indicate DMSA (i.e., Succimer) has the potential to treat
certain radionuclide exposures including 210Po.25,26
Currently the Strategic National Stockpile contains the
following medications for radiation exposure: DTPA (parenteral), KI (oral, but for 131I only), Prussian Blue (137Cs),
antiemetics and blood cell colony stimulating agents.
Discussion
The Litvinenko case demonstrates our vulnerability to radiation threats.19 Although hindsight is always 20/20, we can
learn key lessons from this case. The diagnosis delay underscores the need to consider radiation and exotic toxicants,
especially in the context of a victim who has been involved in
a dangerous occupation that might predispose the patient to
increased risk.
Radioactive materials are ubiquitous and available from
medical, industrial, university, research and military
sources. Often, these materials are in poorly secured locations, including classroom labs. They are daily transported
nationwide. Widespread proliferation of nuclear materials
worldwide increases the likelihood of a radiological event.
Thus, experience with and training in enhanced resources/
equipment for such events will avoid delays in identification, and assist in risk assessment, remediation and early
implementation of appropriate environmental, medical,
psychological and public health countermeasures.
Of all WMD categories, radiological agents and thermonuclear devices represent the ultimate lethal mass casualty,
yet remain the most underemphasized and least prepared
for.1,10-13,15-18,24,29,30 Almost half of hospitals lack a plan for
nuclear terrorism.12 Even when plans exist, few have been
practiced and such plans are not well known by health professionals, making them less than ideally placed to advise or
protect their patients.24 Most first responders and general
practitioners are uncertain about the health consequences
of exposure to IR and the medical management of exposed
patients.13,15,29,30
Conclusion
Responding to a radiation incident requires advance planning and routine training. Be alert to possible contaminants,
inhalation or contact. First responders represent the eyes
and ears on the street for downstream health-care facilities
and other responder agencies.
Being attuned to global threats and radiation-related
events, such as the Litvinenko case, can sensitize us to
potential threats and increase our index of suspicion.
Observing your surroundings carefully is always critical
because terrorists often target emergency responders via
secondary devices. Obtaining a detailed event history as well
as travel and occupational history that characterizes the
employment history well enough to unmask potential risks
associated with victims’ work can shorten the time between
symptom presentation and diagnosis.
First responders must be able to rapidly identify a possible
radiologic event, control public anxiety or outright panic and
Response Guide for Chemical & Radiologic Threats
protect themselves with appropriate PPE.1,13,15,16 Review your
agency’s radiation plans or assist in the development of such
a plan. Along with identifying the radiation resources/threats
in your community, work with key stakeholders to reduce risk
and elevate the potential for an appropriate response. One
could argue that in surreptitious releases, the potential public health outcome rests on the clinical acumen of first
responders and health-care professionals.1,12,29,30 ■
Robin B. McFee, DO, MPH, FACPM, is the medical director of
Threat Science and also a toxicologist and professional education coordinator of the Long Island Regional Poison Information
Center, Winthrop University Hospital, Mineola, N.Y. Contact her
at [email protected]. Disclosure statement: Dr. McFee is on the
national nerve agent advisory group for King Pharmaceutical,
the parent company of Meridian Medical Technologies.
Jerrold B. Leikin, MD, FACEP, FAACT, FACP, FACOEM,
FACMT, is the director of medical toxicology, ENH/OMEGA, at
Glenbrook Hospital in Glenview, Ill. Contact him via e-mail
at [email protected]. Disclosure statement: No conflicts to disclose.
References
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Recommended Reading
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establishing maximum single and multiple exposure to polonium.”
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Casarett GW: Pathology of orally administered polonium. Radiation
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