Article

Terrorism Involving Cyanide: The Prospect of Improving Preparedness in the Prehospital Setting

Abstract and Figures

The potential for domestic or international terrorism involving cyanide has not diminished and in fact may have increased in recent years. This paper discusses cyanide as a terrorist weapon and the current state of readiness for a cyanide attack in the United States. Many of the factors that render cyanide appealing to terrorists are difficult to modify sufficiently to decrease the probability of a cyanide attack. For example, the relative ease with which cyanide can be used as a weapon without special training, its versatile means of delivery to intended victims, and to a large degree, its ready availability cannot be significantly modified through preparedness efforts. On the other hand, the impact of an attack can be mitigated through preparedness measures designed to minimize the physical, psychological, and social consequences of cyanide exposure. Although the nation remains ill-equipped to manage a cyanide disaster, significant progress is being realized in some aspects of preparedness. Hydroxocobalamin-a cyanide antidote that may be appropriate for use in the prehospital setting for presumptive cases of cyanide poisoning-currently is under development for potential introduction in the US. If it becomes available in the US, hydroxocobalamin could enhance the role of the prehospital emergency responder in providing care to victims of a cyanide disaster. Additional progress is required in the areas of ensuring local and regional availability of antidotal treatment and supportive interventions, educating emergency healthcare providers about cyanide poisoning and its management, and raising public awareness of the potential for a cyanide attack and how to respond.
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Prehospital and Disaster Medicine http://pdm.medicine.wisc.edu Vol. 21, No. 2
ORIGINAL RESEARCH?
National Center of Environmental Health,
US Centers for Disease Control and
Prevention, Atlanta, Georgia USA, and
Department of International Health and
Development, Tulane University School of
Public Health and Tropical Medicine, New
Orleans, Louisiana USA, and Center for
International, Emergency, Disaster and
Refugee Studies, Johns Hopkins University
School of Medicine, Baltimore, Maryland
USA
Correspondence:
AU-please provide information!
Keywords: Cyanide Antidote Kit; cyanide
poisoning; preparedness; terrorism
Abbreviations:
CAK = Cyanide Antidote Kit
Web publication:
Disclaimer:
The material in this paper reflects solely the
views of the author. It does not necessarily
reflect the policies or recommendations of the
Centers for Disease Control and Prevention
or the US Department of Health and Human
Services.
Terrorism Involving Cyanide: The Prospect
of Improving Preparedness in the
Prehospital Setting
Mark E. Keim, MD
Introduction
The public health threat of disasters involving cyanide and the lack of pre-
paredness in the United States for such events was described in 2001.1In the
wake of the 11 September 2001 attacks on the World Trade Center and the
Pentagon,the threat of a disaster caused by chemical, biological, or other sub-
stances that can be used as weapons of mass destruction has become only
morepalpable.
The fact that cyanide, in particular,continues to pose a public health threat
is illustrated by several recent findings representative of a much larger num-
ber of incidents of intended or actual use of cyanide as a weapon.
1. May 2002: Ten tons of sodium cyanide were stolen during a truck
hijacking in Mexico. Weeks later, only one fifth of the cyanide had been
recovered, and the hijackers had not been found.
2. June 2002:Joseph Konopka (Dr. Chaos) was indicted by a US grand
jury on counts of possessing the chemical weapons sodium cyanide and
potassium cyanide, which he stored in the Chicago subway system.
3. November 2003:The US Department of Homeland Securityissued a
warning to law enforcement personnel about al-Qaeda’s development
of a device for producing cyanogen chloride and hydrogen cyanide
gases for dispersal through ventilationsystems.
Abstract
The potential for domestic or international terrorism involving cyanide has
not diminished and, in fact, may have increased in recent years. This paper
discusses cyanide as a terrorist weapon and the current state of readiness for
acyanide attack in the United States. Many of the factors that render cyanide
appealing to terrorists are difficult to modify sufficiently to decrease the prob-
ability of a cyanide attack. For example, the relative ease with which cyanide
can be used as a weapon without special training, its versatile means of deliv-
ery to intended victims, and to a large degree, its ready availability are not sig-
nificantly manipulable. On the other hand, the impact of an attack can be
mitigated through preparedness measures designed to minimize the physical,
psychological, and social consequences of cyanide exposure. Although the
nation remains ill-equipped to manage a cyanide disaster, significant progress
is being realized in some aspects of preparedness. Hydroxocobalamin—a
cyanide antidote that may be appropriate for use in the prehospital setting for
presumptive cases of cyanide poisoning— currently is under development for
potential introductionin the US. If it becomes available in the US, hydroxo-
cobalamin could enhance the role of the prehospital emergency responder in
providing care to victims of a cyanide disaster. Additional progress is required
in the areas of ensuring local and regional availability of antidotal treatment
and supportive interventions, educating emergency healthcare providers
about cyanide poisoning and its management, and raising public awareness of
the potential for a cyanide attackand howto respond.
Keim MJ: Terrorism involving cyanide: The prospect of improving pre-
paredness in the prehospital setting. Prehosp Disast Med 2006;21(2):s56–s60.
March April 2006 http://pdm.medicine.wisc.edu Prehospital and Disaster Medicine
Keim s57
that cyanide is carried in the blood and that its primary site
of action is the bloodstream.7This classification is outdat-
ed, and is somewhat misleading because the primary site of
action of cyanide is not necessarily the bloodstream.
Moreover, although cyanide is carried in the blood, so too
are other chemical weapons, including absorbed nerve
agents. Therefore, the term does not differentiate cyanide
from other categories of chemical weapons.
Cyanide has a long history of use as a murder weapon,
terrorist weapon, and weapon of war, as well as an agent of
suicide and attempted genocide. Characteristics of cyanide
are those of the ideal terrorist weapon.2,4 These character-
istics include the facts that: (1) cyanide can cause mass
physical and psychological casualties; (2) it is readily avail-
able; (3) it is versatile with respect to how it can be delivered;
and (4) it does not require specialized skills or knowledge for
effective use. Finally, effective management of moderate-
to-severe cyanide poisoning requires specific resources (i.e.,
an antidote) that are available typically in short supply.
Therefore, the chances of responding effectively to an
attackgenerally are low.
Cyanide kills cells by preventing them from using oxy-
gen, necessitating anaerobic cellular metabolism, which
generates cytotoxic byproducts.8The oxygen deprivation
and accumulation of cytotoxins are thought to be the prin-
cipal mechanisms of cyanide toxicity, although additional
mechanisms also may contribute. Acute cyanide poisoning
is manifested by symptoms including stupor, seizures, and
coma, and can culminate in death within seconds to hours,
depending onthe concentration, source, and route of
cyanide exposure.9The dramatic, alarming manifestations
of poisoning and the deadliness of cyanide make it suitable
for accomplishing the primary aim of terrorists of inciting
mass fear and panic by incapacitating or killing large num-
bers of individuals.
The ready availability of cyanide also renders it an
attractive terrorist weapon. Worldwide, an estimated 1.84
billion pounds of hydrogen cyanide are produced each
year.10 Cyanide is manufactured in large quantities in the
United States and other countries for use in industrial
processes including electroplation, extraction of gold and
silver from ores, fumigation, and the production of
nitriles.11 Cyanide also is available widely in research labo-
ratories. Cyanide is susceptible to theft from these labora-
tories and industrial sources, as well as from the railroads
and trucks used in transport. The May 2002 robbery of 10
tons of cyanide during the truck hijacking in Mexico illus-
trates the ease of obtaining cyanide.
Available in both gaseous and solid forms, cyanide is
versatile, with respect to mode of delivery to intended vic-
tims. Hydrogen cyanide gas can be released into enclosed
spaces such as stadiums, public transportation vehicles, and
office buildings. Al-Qaedasdevice for dispersing cyanide
through ventilation systems presumably was developed for
this application. In salt form, cyanide can be introduced
into the water supply, food, and pharmaceuticals, as exem-
plified by the plans of four Moroccans arrested in February
2002 in Rome to poisonthe US Embassy’s water supply
with cyanide; the morethan 900 deaths caused by cyanide-
4. September 2004: South Korea indicated that
North Korea imported approximately 175 tons of
sodium cyanide from South Korea through China
and Thailand in 2003. This amount of cyanide is
eclipsed by the nearly3,800 tons of sodium cyanide
exported from South Korea to Thailand from 2002
to the present. Exports such as these have been char-
acterized as a securitythreat, as most of the countries
that import sodium cyanide from Korea are not
members of, and do not consider themselves bound
by the directives of the Australia Group. The
Australia Group is a 38-member consortium that
attempts to ensurethat exported material does not
contribute to the proliferation of biological and
chemical weapons.
The potential for domestic or international terrorism
involving cyanide has not diminished and, in fact, it may
haveincreased in recent years. In the context of this con-
tinued threat, has the ability of the healthcare system to
manage a chemical terrorism attack involving cyanide
changed? This paper discusses cyanide as a potential ter-
rorist weaponand the current state of domestic readiness
for a cyanide attack.
Profile of Cyanide as a Terrorist Weapon
The Centers for Disease Control and Prevention (CDC)
and the Department of Homeland Security include
cyanide, known among many in the military as a blood
agent, among the most probable agents of chemical terror-
ism.2,3 Other main categories of chemical weapons include
nerveagents such as sarin and VX, blister agents such as
nitrogen and sulfur mustards, and pulmonaryagents such
as phosgene and chlorine (Table 1).4–6 The classification of
cyanide as a blood agent originated from the perception
Table 1—Categories of chemical weapons4–6
Keim © 2006 Prehospital and Disaster Medicine
Blood agents
•Hydrogen Cyanide
•Cyanogen Chloride
Nerve agents
•Tabun
•Sarin
•Soman
•VX
Vesicants
•Lewsite
•Nitrogen and sulfur mustards
Pulmonary agents
•Phosgene
•Chlorine
Prehospital and Disaster Medicine http://pdm.medicine.wisc.edu Vol. 21, No. 2
58 Terrorism Involving Cyanide
laced Kool-Aid in 1978 in Jonestown among Reverend Jim
Jones’ followers; and the frequent use of cyanide-laced
pharmaceuticals as weapons in incidents including the
1982 Tylenol murders of seven Chicagoans, the 1986
Excedrin murders of two people in Washington, and the
2003 Vanilla Coke murder of a Maryland teenager. While
not planned necessarilyby terrorists as a source of cyanide
poisoning, smoke caused by a fire from an explosion or
conflagration constitutes another potentially important
source of cyanide in a terrorist attack.
As these examples of planned or actual use of cyanide as a
weapon a weapon suggest, the use of cyanide as a weapon does
not require specialized skills or knowledge. The lack of
requirements for specialized training or expertise both increas-
es the number of possible candidates who can successfully
implement cyanide attacks, and helps contain the expense
involved in planning and implementing these attacks.
Cyanide also is an attractive weapon for terrorists
because of the lack of availability of effective means of
managing acute cyanide toxicity, particularly involving
multiple victims. Moderate-to-severe poisoning requires
the prompt use of specific antidotes to prevent death.
Given the rapid lethality of cyanide, effective management
of a cyanide disaster involving multiple victims would
requirethe rapid disseminationof large quantities of anti-
dote and its nearly immediate administration. These
requirements cannot be met in the current healthcare envi-
ronment, in whichmany hospitals and emergency vehicles
fail to stock the antidote or do not stock a sufficient num-
ber of antidote kits for a multiple-casualtydisaster.12–14
This point is illustrated by the results of a 21-hospital sur-
vey assessing preparedness for chemical terrorist attacks in
amajor US citybetween 1996 and 2000—a time during
which the federal government markedly increased spend-
ing on bioterrorism preparedness with the passage of the
1996 Nunn-Lugar-Domenici Defense Against Weapons
of Mass Destruction Act (WMD Act).14 The results show
that preparedness for a cyanide emergency was inadequate
in both 1996 and 2000. In 1996, the number of cyanide
antidote kits across the 21 hospitals was 276. In 2000, the
number was 35. Moreover, in 1996, two of the 21 hospitals
met the minimum preparedness criterion of at least 50
cyanide antidote kits in inventory. In 2000, none of the
hospitals met this criterion.
The rapid administration of antidote as required in a
terrorist incident also is hindered by the difficulty in diag-
nosing acute cyanide poisoning. Signs and symptoms of
cyanide poisoning are general, nonspecific, manifestations
of oxygen deprivation (Figure 1), and none definitively
indicate the presence of cyanide poisoning. Furthermore,
no blood test or other diagnostic is available that can rapid-
ly return results within the time required for effective inter-
vention.9The inability to confirm a diagnosis of cyanide
poisoning rapidly at the disaster scene necessitates treat-
ment of the basis of a presumptive diagnosis if treatment is
to be administered in time to be effective. Administration
of antidote based onapresumptivediagnosis of cyanide
poisoning is problematic because the Cyanide Antidote
Package (also known as the Cyanide Antidote Kit (CAK),
the Pasadena Kit, the Taylor Kit, and the Lilly Kit), the
only cyanide antidote currently marketed in the United
States, can cause potentiallylife-threatening toxicities.15–17
The risks of administering the CAK in the prehospital set-
ting may outweigh the benefits in the event that a patient
Figure 1—Cyanide causes progressive tissue hypoxia9
Keim © 2006 Prehospital and Disaster Medicine
marketed in France as Cyanokit® (hydroxocobalamin)
(Figure 2). Hydroxocobalamin, a precursor of vitamin B12,
is present naturally in the body in small amounts.20
Hydroxocobalamin detoxifies cyanide by binding with it to
formcyanocobalamin, which is excreted in urine, without
compromising the oxygen-carrying capacity of the blood or
causing hypotension or other clinically relevant adverse
events.16,20,21 Data onthe pharmacokinetics and the use of
hydroxocobalamin in the prehospital setting are discussed
elsewhere in this supplement.8
Hydroxocobalamin appears to have no major toxicities.8
The most common side effects of hydroxocobalamin
include the discoloration of urine and mucous membranes
and abnormalities in specific colorimetric laboratory tests.
These effects, which arise from the red color of the hydrox-
ocobalamin molecule, are transient (lasting 1–2 days), and
do not appear to reflect clinically meaningful changes.
With this safety profile, hydroxocobalamin could be
administered at disaster scenes so that intervention is not
delayed until hospital care can be provided. Moreover,
hydroxocobalamin need not be reserved for cases of con-
firmed cyanide poisoning, but could be administered in
cases of suspected poisoning. Therefore, hydroxocobalamin
could make morerapid initiation of treatment more feasi-
ble than with the CAK, and thereby, potentially improve
outcomes in a cyanide disaster.The ability to use a cyanide
antidote empirically at the disaster scene could significant-
ly improve the readiness of the United States to respond to
terrorist attacks and other disasters involving cyanide.
Prior to 2001, no plans existed to market hydroxocobal-
amin as an antidote in the United States. As the possibili-
ty of a cyanide attack has become increasingly tangible, and
as healthcare providers and administrators progressively
havebecome moreaware of the nation’s lack of prepared-
ness for a cyanide attack, the need for hydroxocobalamin
has been reevaluated. Although hydroxocobalamin still is
not available domestically, it currently is under develop-
ment for potential introductionas an antidote in the US.
Additionally, new studies to further establish its antidotal
profile are in progress. (Although hydroxocobalamin is cur-
rently approved in the US for the treatment of pernicious
anemia, the 1-mg/ml concentration marketed for this use
is too dilute for use as an antidote. In France, the hydroxo-
cobalamin antidote is available in a 2.5g vial.) The usual
March April 2006 http://pdm.medicine.wisc.edu Prehospital and Disaster Medicine
Keim s59
is treated for cyanide poisoning but does not in fact suffer
from cyanide toxicity.
The CAK includes amyl nitrite administered via a
mechanical ventilation device or by gauze sponge for
inhalationas well as sodium nitrite and sodium thiosulfate,
both of which are administered intravenously. The nitrite
components of the kit form methemoglobin in the process
of neutralizing cyanide. Nitrite-induced methemoglobine-
mia can be toxic because it reduces the ability of the blood
to carry oxygen.1Methemoglobinemia is dangerous, espe-
cially for smoke-inhalation victims, who may have concur-
rent carboxyhemoglobinemia because of exposure to carbon
monoxide. Besides causing methemoglobinemia, the CAK
can cause severe hypotension, leading to shock.17
Administration of the thiosulfate component alone is not a
viable solution for these problems because sodium thiosul-
fate has a slow onset of antidotal action.18 Therefore,it
most often is used in conjunction with other rapidly acting
agents rather than as a single antidote. Because of its safe-
tyliabilities, the CAK seldomis administered outside of
the hospital. In the context of the need for presumptive
diagnosis of acute cyanide poisoning, the potential harm
associated with administration of the CAK renders the
decisionof whether or not to initiate antidotal therapy the
most challenging one in an out-of-hospital triage situation
potentially involving cyanide.19
Adequate Preparedness: An Attainable Goal
Many of the factors that render cyanide appealing to ter-
rorists are difficult to modify to the extent required to
decrease the probability of a cyanide attack. For example,
the relative ease with which cyanide can be used as a
weapon without special training, its versatile means of
deliveryto intended victims, and to a large degree its ready
availability are not significantly manipulable significantly.
On the other hand, the impact of an attack can be mitigat-
ed through preparedness measures designed to minimize
the physical, psychological, and social consequences of
cyanide exposure.
Cyanide preparedness could also be enhanced dramati-
cally in the United States by introduction of a cyanide anti-
dote that is effectively, easily administered, and sufficiently
safeto be given in the prehospital setting for presumptive
cases of cyanide poisoning.1Suchan antidote is currently
Figure 2—Characteristics of the cyanide antidote hydroxocobalamin
Keim © 2006 Prehospital and Disaster Medicine
Prehospital and Disaster Medicine http://pdm.medicine.wisc.edu Vol. 21, No. 2
s60 Terrorism Involving Cyanide
improve the capability to recognize and respond to chemi-
cal injuries arising from causes other than terrorism.
Conclusions
Although the nation remains ill-equipped to manage a
cyanide disaster, significant progress is being realized in
some aspects of preparedness. Advances in antidote thera-
py may provide an intervention that can be administered in
the prehospital setting for presumptive cases of cyanide
poisoning. Additional progress is required in the areas of
ensuring local and regional availability of antidotal treat-
ment and supportive interventions, educating emergency
health care providers about cyanide poisoning and its man-
agement, and raising public awareness of the potential for
acyanide attack and how to respond.
Acknowledgments
The author thanks Jane Saiers, PhD for assistance with
writing this manuscript. All work on this manuscript was
supported in part by EMD Pharmaceuticals, an affiliate of
Merck KGaA and the US developer of the cyanide anti-
dote hydroxocobalamin (Cyanokit®)
dose in France is 5g (2 vials) administered intravenously.
Successful preparedness for a cyanide attack involves
stockpiling sufficient quantities of antidote to respond in
the event of an attack involving multiple victims. Should
hydroxocobalamin be made available in the United States,
stocking practices must be reassessed, and means of ensur-
ing rapid distribution and adequate regional and local sup-
ply will need to be developed.
According to a 2000 task force comprising members of
the United States Centers for Disease Control and
Prevention, law enforcement personnel, and intelligence
defense agencies, stockpiling chemical antidotes is one of
five major activities that local, state, and federal public
health organizations should undertake to enhance pre-
paredness for chemical attacks (Table 2).2For the United
States to be prepared for a chemical attack involving
cyanide, public health organizations must develop action
plans for and allocate resources to each of these five pre-
paredness activities. Because enhancing preparedness for
chemical attacks involves the same skills and resources that
managing non-terrorism-related chemical accidents does,
improving readiness for chemical terrorism should also
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-Enhance epidemiologic capacity for detecting and responding to chemical attacks
-Enhance awareness of chemical terrorism among emergency medical service personnel, police officers, firefighters, physicians,
and nurses
-Stockpile chemical antidotes
-Develop and provide bioassays for detection and diagnosis of chemical injuries
-Prepare educational materials to inform the public during and after a chemical attack
Table 2—Improving preparedness for chemical attacks2Keim © 2006 Prehospital and Disaster Medicine
... [1][2][3][4][5][7][8] The NIH Strategic Plan and Research Agenda for Medical Countermeasures specifies that ingested cyanide is a leading threatunique from inhaled and intravenous cyanide-because of the potentially higher cyanide dose, accessibility, delayed kinetics of absorption, and vulnerability of food and water suppl ies. 5,6,9,12,15,16,23,28,29 When ingested, cyanide salts are exposed to the acidic environment of the stomach and form hydrogen cyanide, which gets absorbed and can cause systemic toxicity. Events over the past 2 decades have revealed the interest of various terrorist network groups in using cyanide in attacks. ...
... Events over the past 2 decades have revealed the interest of various terrorist network groups in using cyanide in attacks. 1,5,6,9,[11][12][13][17][18][19][20]23,[27][28][29] According to the Centers for Disease Control and Prevention, the potential LD 50 for oral KCN exposure is 1.8 to 7.3 mg/kg, but this figure is not well defined and is extrapolated from case report studies. Furthermore, the LD 50 for oral cyanide in swine is not well established, and dosing regimens must be based on previous studies performed mostly on small to moderate-sized animals. ...
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Cyanide is a readily available and potentially lethal substance. Oral exposure can result in larger doses, compared withother routes. Currently, there are no antidotes specific for use in the treatment of oral cyanide poisoning, and studies cannotbe done in humans. We report on a new large animal model of oral cyanide toxicity to evaluate potential antidotes. Six femaleswine (Sus scrofa; weight, 45 to 55 kg) were anesthetized, intubated, and instrumented. Animals received a KCN bolusof either 5 or 8 mg/kg delivered via orogastric tube. Time to apnea was recorded; parameters monitored included heart rate,respiratory rate, blood pressure, pulse oximetry, end-tidal CO2, arterial blood gasses, and lactate concentrations. The Welcht test was used to calculate confidence intervals, mean, and standard deviation, and a Kaplan-Meier survival curve was usedto compare survival between the 2 groups. At baseline, all animals in both groups were similar. Animals in the 5-mg/kg grouphad a more rapid time to apnea (5.1 ± 2.1 min), longer time to death (48.5 ± 38.1 min), and a greater rate of survival than the8-mg/kg group (apnea, 10.6 ± 10.7 min; death, 26.1 ± 5.8 min). All animals displayed signs of toxicity (acidemia, hyperlactatemia,hypotension, apnea). We here report a large animal (swine) model of oral cyanide poisoning with dose-dependent effects in regard to time to death and survival rate. This model likely will be valuable for the development of medical countermeasures for oral cyanide poisoning.
... Experience with mass chemical exposure incidents suggests that first responders and emergency department receivers should know the basic characteristics of chemical agent toxidromes, identification and recognition of the hazards, required mitigation measures for safety and protection in addition to integration and coordination with involved organizations [24][25][26][27]. ...
... A multidisciplinary and coordinated response is required to alleviate the mortality and morbidity among cases and conserve the healthcare system as well as the community [1,27,57]. Knowledge of the physical and chemical properties of the chemical substances were also tested in this domain using around 66% of the items to understand the concept of nature of chemical substance (gas, liquid) and its effect on mitigation and preventive measures during the response phase [24,25,27]. ...
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Background Mass chemical exposure emergencies are infrequent but can cause injury, illness, or loss of life for large numbers of victims. These emergencies can stretch and challenge the available resources of healthcare systems within the community. Political unrest in the Middle East, including chemical terrorist attacks against civilians in Syria and increasing chemical industry accidents, have highlighted the lack of hospital preparedness for chemical incidents in the region. This study aimed to evaluate the effectiveness of a course designed to empower frontline healthcare providers involved in mass casualty incidents with the basic knowledge and essential operational skills for mass chemical exposure incidents in Saudi Arabia. Methods A mixed-methods approach was used to develop a blended learning, simulation enhanced, competency-based course for major chemical incidents for front line healthcare providers. The course was designed by experts from different disciplines (disaster medicine, poisoning / toxicology, and Hazard Material Threat - HAZMAT team) in four stages. The course was piloted over five days at the Officers Club of the Ministry of Interior (Riyadh, Saudi Arabia). The 41 participants were from different government health discipline sectors in the country. Pre- and post-tests were used to assess learner knowledge while debriefing sessions after the decontamination triage session and simulation-enhanced exercises were used for team performance assessment. Results The overall knowledge scores were significantly higher in the post-test (69.47%) than the pre-test (46.3%). All four knowledge domains also had significant differences between pre- and post-test results. There were no differences in the pre and post-test scores for healthcare providers from the different health disciplines. A one-year post-event survey demonstrated that participants were satisfied with their knowledge retention. Interestingly, 38.3% had the opportunity to put this knowledge into practice in relation to mass chemical exposure incidents. Conclusion Delivering a foundation level competency-based blended learning course with enhanced simulation training in major chemical incidents for front line healthcare providers may improve their knowledge and skills in response to such incidents. This in turn can improve the level of national preparedness and staff availability and make a crucial difference in reducing the health impacts among victims.
Chapter
Chemical warfare agents are toxic compounds designed for military use or derived from industrial products. A third group includes biological toxins resembling typical chemical warfare agents in their mode of action. Chemical agents are traditionally classified into nerve agents exhibiting anticholinesterase activity, vesicants (blistering or skin-damaging agents), pulmonary or lung-damaging agents, and the so-called blood agents. While this general classification is based on their main toxic activity, additional features including the onset and nature of early manifestations of exposure can facilitate the identification of the causative agent in the case of a chemical attack and prompt emergency measures for the prevention of further injury and institution of appropriate therapy. This chapter presents the various types of chemical warfare agents, describing each one the mechanism and clinical symptoms of toxicity.
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Мета. Виділити групу високотоксичних хімічних речовин, які за останні десятиліття найчастіше використовуються в умисних кримінальних та суїцидальних інцидентах, диверсійних і терористичних актах, обіг, зберігання, використання та утилізацію яких потрібно особливо прискіпливо контролювати правоохоронним органам. У даній частині статті йдеться про сполуки миш’яку та ціаніди. Матеріали та методи. Аналітичний огляд наукових публікацій виконаний з використанням реферативних баз даних наукових бібліотек Pub Med, Medline і текстових баз даних наукових видавництв Elsevier, Pub Med, Central, BMJ group та інших VIP-баз даних. Використано методи системного, порівняльного та контент-аналізу. Результати та висновки. Проаналізовано наукові публікації, в яких йдеться про високотоксичні сполуки миш’яку та ціаніди, які становлять загрозу життю і здоров’ю людини. Останнім часом, зокрема понад чверть сторіччя, вони стали справжньою зброєю в руках злочинців, кримінальних елементів і терористів у всьому світі. Не можна замовчувати й суїцидальні інциденти, які також мають місце поряд з умисними кримінальними, терористичними та диверсійними актами. На основі аналізу токсичності, клінічних та морфологічних проявів інтоксикації цих хімічних речовин, враховуючи різні шляхи надходження до організму, обґрунтовано необхідність внесення їх до Переліку особливо небезпечних хімічних речовин, обіг яких, зберігання, використання та утилізація потребують більш жорсткого контролю з боку правоохоронних органів. Ключові слова: сполуки миш’яку, ціаніди, ризик для здоров’я, гострі отруєння.
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The Aim of the Research. To identify a group of highly toxic chemicals which over the past decades are most often used in deliberate criminal and suicidal incidents, sabotage, and terrorist act; the handling, storage, use and disposal of which must be especially carefully monitored by law enforcement agencies. In this part of the article arsenic compounds and cyanide are considered. Materials and Methods. An analytical review of scientific publications was carried out using the abstract databases of scientific libraries Pub Med, Medline and text databases of scientific publishing houses Elsevier, Pub Med, Central, BMJ group as well as other VIP databases. Methods of systemic, comparative, and content analysis were used. Results and Conclusions. Scientific publications that contain information on highly toxic arsenic compounds and cyanides, which pose a threat to human life and health, were analyzed. Recently, in particular for more than a quarter of a century, they have become a real weapon in the hands of criminals, delinquents, and terrorists all over the world. Suicidal incidents, which also take place along with intentional criminal, terrorist, and sabotage acts, should not be concealed. Based on the analysis of the toxicity, clinical and morphological expression of intoxication when exposed to these chemicals, considering various routes of entry into the body, the need to include them in the List of hazardous highly toxic chemicals, the handling, storage, use, and disposal of which require stricter control of law enforcement agencies, is justified. Key Words: arsenic compounds, cyanide, health risk, acute poisoning.
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CN- and Hg2+ ions are harmful to both the environment and human health, even at trace levels. Thus, alternative methods for their detection and quantification are highly desirable given that the traditional monitoring systems are expensive and require qualified personnel. Optical chemosensors (probes) have revolutionized the sensing of different species due to their high specificity and sensitivity, corresponding with their modular design. They have also been used in aqueous media and different pH ranges, facilitating their applications in various samples. The design of molecular probes is based on organic dyes, where the key species are N-heterocyclic compounds (NHCs) due to their proven photophysical properties, biocompatibility, and synthetic versatility, which favor diverse applications. Accordingly, this review aims to provide an overview of the reports from 2016 to 2021, in which fluorescent probes based on five- and six-membered N-heterocycles are used for the detection of CN- and Hg2+ ions.
Article
Background Cyanide (CN) is a metabolic poison that is capable of intoxicating individuals through accidental or intentional means. With high concentration exposures, death can occur in minutes. In cases of mass casualty exposures, there is a need for a rapid-acting countermeasure capable of being administered in a short period of time in a pre-hospital setting to treat victims. Objective These studies evaluate the safety and efficacy of a novel aqueous formulation of dimethyl trisulfide (DMTS) as an intramuscular (IM) CN countermeasure using non-anesthetized rodent models. Methods Non-anesthetized rodents (mice and rats) were exposed to hydrogen cyanide (HCN) or potassium cyanide (KCN) along with immediate IM 10% DMTS treatment or vehicle treatment. Survival and other parameters, such as the time to recovery and assessment of clinical toxic signs (e.g., gasping, loss of righting reflex, convulsions, etc.), were quantified to determine the effectiveness of 10% DMTS treatment (12.5, 25, 75 mg/kg IM) compared to vehicle control treatment. A rat KCN delayed-treatment model with a 15-minute treatment delay was also utilized to simulate a real-life exposure/treatment scenario with 10% DMTS treatment. The stability of the 10% DMTS formulation was also assessed. Results A 25 mg/kg IM dose of 10% DMTS exhibits potent efficacy against subcutaneous (SC) KCN challenge in both mice and rats and inhalational HCN exposure in mice. 10% DMTS treatment also shortens the time to recovery in rats using a delayed-treatment model. Conclusion IM treatment with 10% DMTS improves survival and clinical outcomes in non-anesthetized rodent models of acute CN toxicity. Additionally, the use of an SC KCN delayed-treatment model in rats is advised to assess the performance of a candidate CN countermeasure in a more realistic exposure/treatment scenario.
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This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editors-in-Chief as the authors were unable to provide documentation of approval for the interinstitutional assurance /vertebrate animal section of the paper by the relevant authority, Public Health Service (PHS) Office of Laboratory Animal Welfare (OLAW) in the time that was provided.
Article
Cyanides are highly toxic compounds that have been used as weapons of terrorism throughout history. Cyanide (CN) is acutely toxic by all routes of administration; however, inhalation is the main exposure route. To adequately test effective countermeasures against inhalational CN threats, robust and well-characterized animal models are needed. This paper describes the initial development of a hydrogen cyanide (HCN) exposure swine model for documenting the physiological effects and toxicological profile during and after HCN inhalation exposure. Animals were implanted with telemetry transmitters for heart rate (HR), blood pressure, and electrocardiogram monitoring, and vascular access ports for serial blood collections. Nine female swine were exposed to HCN concentrations of 500 ± 6 ppm while breathing parameters were monitored real-time. Inhaled HCN doses ranged from 2.02 to 2.83 mg/kg. Clinical signs included vocalization, agitation, salivation, respiratory distress and apnea. After HCN exposure initiation, systemic arterial pressure fell dramatically with a concomitant increase in HR. Blood samples were collected to determine CN blood levels using LC-MS/MS and blood gas analysis. In summary, the developed HCN inhalation swine model permitted documentation of the physiological effects associated with CN poisoning. This model could be used to evaluate potential CN medical countermeasures in the event of a public health emergency stemming from inhalational CN threats.
Chapter
Cyanide exposure can cause rapid death. The most common cause of cyanide toxicity is inhaled cyanide (hydrogen cyanide) from structure fires [1, 2]. While fortunately less common, the most interesting cause of cyanide toxicity come from suicidal and homicidal acts. There are as many deaths each year in the United States as from cardiac glycosides, beta blockers alone, or organophosphates [3]. The largest threat of cyanide toxicity is actually the result of terrorism and war [4]. Recent events have highlighted the need for preparedness against possible chemical terrorist attacks. Cyanide also creates an occupational hazard in industries such as electroplating, metal extraction, pest control, and oil field work. Several treatments are available to treat cyanide toxicity, and clinical practice guidelines are available [1, 5, 6]. The availability of antidotal therapy also is subject to impact from both market and regulatory forces [7, 8].
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A 78 year old man was found comatose, apneic, and asystolic after closed-space smoke inhalation. He was successfully resuscitated to pulse and blood pressure at the scene. A cyanide component to the poisoning was suspected and two 300 mg doses of sodium nitrite were administered, resulting in significant hypotension. Although high methemoglobin levels were not induced, when added to simultaneously obtained carboxyhemoglobin levels, the total amount of non-oxygen transporting hemoglobin remained nearly constant for about 4-1/2 hours before hyperbaric oxygen (HBO) therapy could be administered. The patient later died in multi-organ system failure. Admission whole blood cyanide level was only 0.34 mcg/mL. These sodium nitrite adverse effects can be avoided by slow intravenous infusion and by administering only recommended doses. In smoke inhalation victims with suspected cyanide poisoning, sodium thiosulfate should be administered first, and sodium nitrite withheld until after the patient is receiving HBO therapy. When available, hydroxocobalamin (which neither induces methemoglobinemia nor causes hypotension) may be the specific cyanide antidote of choice for victims of smoke inhalation.
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Cyanide poisoning causes a high incidence of severe symptomatology and fatality. There are numerous sources of potential cyanide exposure. Without the history of cyanide exposure, diagnosis is often difficult. Treatment with supportive measures and available specific and efficacious antidotes frequently allows survival. The toxicology of cyanide, including sources, clinical features, diagnosis, and treatment, is reviewed.
Article
Objective. —To determine whether antidotes for poisoning and overdose are available in hospitals that provide emergency department care.Design. —Written survey of hospital pharmacy directors, each of whom reported the amount currently in stock of 8 different antidotes: antivenin (Crotalidae) polyvalent, cyanide kit, deferoxamine mesylate, digoxin immune Fab, ethanol, naloxone hydrochloride, pralidoxime chloride, and pyridoxine hydrochloride.Participants. —Pharmacy directors of all hospitals with emergency departments in Colorado, Montana, and Nevada.Main Outcome Measures. —Proportions of hospitals with insufficient stocking of each antidote, defined as complete lack of the antidote or an amount inadequate to initiate treatment of 1 seriously poisoned 70-kg patient.Results. —Questionnaires were mailed to 137 hospital pharmacy directors and 108 (79%) responded. Only 1 (0.9%) of the 108 hospitals stocked all 8 antidotes in adequate amounts. The rate of insufficient stocking for individual antidotes ranged from 2% (for naloxone) to 98% (for digoxin immune Fab). In a multiple regression analysis, smaller hospital size and lack of a formal review of antidote stocking were independent predictors of the number of antidotes stocked insufficiently.Conclusions. —Insufficient stocking of antidotes is a widespread problem in Colorado, Montana, and Nevada. Although these states are served by a certified regional poison center, potentially lifesaving antidotes are frequently not available when and where they might be needed to treat a single poisoned patient.
Article
Smoke is a heterogeneous mixture of particulate matter (carbon particles coated with acids, aldehydes, and acroleins) and heated gases. The gases can be generally classified as irritants, such as hydrochloric acid, sulfur dioxide, oxides of nitrogen, and ammonia; as asphyxiants, such as carbon dioxide; and as cellular toxins, such as carbon monoxide, hydrogen sulfide, and hydrogen cyanide. The composition of the smoke from a given fire depends on the materials burned, the rate of pyrolysis, the absolute temperature, and the oxygen supply. The composition can vary remarkably between samples obtained only a few feet apart. It is therefore quite difficult . . .
Article
The antidotal activities of aquocobalamineacetate and sodium thiosulfate were tested in guinea pigs and cats. The animals were attached to artificial respirators throughout the experiment and were poisoned with a continuous infusion of sodium cyanide solution (4.1 μMol/kg · min NaCN). The rate of action of each antidote was determined from the time taken for the HCN exhalation to drop below the level of 100 nMol/kg · min in guinea pigs, and to values below 25 nMol/kg · min in cats; the detoxifying capacity of each antidote was determined from the time taken for the HCN exhalation to rise above the said values and the time interval for normal function of heart activity to be restored. Aquocobalamine was characterized by its rapid rate of reaction in both the animal species; its detoxifying capacity showed, however, according to our expectations, variations corresponding to the applied doses. The combination of the antidotes aquocobalamine (100 mg/kg) and thiosulfate (500 mg/kg) proved to possess high rate of reaction and a large detoxifying capacity in guinea pigs. Similar results were obtained in cats with antidote doses of 200 mg/kg aquocobalamine combined with 500 mg/kg thiosulfate. The slow rate of reaction and large detoxifying capacity of thiosulfate were confirmed in our experiments. Its combination with aquocobalamine showed no undesirable change in its antidotal action providing a time interval of 1 min was maintained between the 2 injections.
Article
This article has no abstract; the first 100 words appear below. Smoke is a heterogeneous mixture of particulate matter (carbon particles coated with acids, aldehydes, and acroleins) and heated gases. The gases can be generally classified as irritants, such as hydrochloric acid, sulfur dioxide, oxides of nitrogen, and ammonia; as asphyxiants, such as carbon dioxide; and as cellular toxins, such as carbon monoxide, hydrogen sulfide, and hydrogen cyanide. The composition of the smoke from a given fire depends on the materials burned, the rate of pyrolysis, the absolute temperature, and the oxygen supply. The composition can vary remarkably between samples obtained only a few feet apart. It is therefore quite difficult . . . Kenneth Kulig, M.D., F.A.C.E.P. University of Colorado Health Sciences Center Denver, CO 80262
Article
To determine whether antidotes for poisoning and overdose are available in hospitals that provide emergency department care. Written survey of hospital pharmacy directors, each of whom reported the amount currently in stock of 8 different antidotes: antivenin (Crotalidae) polyvalent, cyanide kit, deferoxamine mesylate, digoxin immune Fab, ethanol, naloxone hydrochloride, pralidoxime chloride, and pyridoxine hydrochloride. Pharmacy directors of all hospitals with emergency departments in Colorado, Montana, and Nevada. Proportions of hospitals with insufficient stocking of each antidote, defined as complete lack of the antidote or an amount inadequate to initiate treatment of 1 seriously poisoned 70-kg patient. Questionnaires were mailed to 137 hospital pharmacy directors and 108 (79%) responded. Only 1 (0.9%) of the 108 hospitals stocked all 8 antidotes in adequate amounts. The rate of insufficient stocking for individual antidotes ranged from 2% (for naloxone) to 98% (for digoxin immune Fab). In a multiple regression analysis, smaller hospital size and lack of a formal review of antidote stocking were independent predictors of the number of antidotes stocked insufficiently. Insufficient stocking of antidotes is a widespread problem in Colorado, Montana, and Nevada. Although these states are served by a certified regional poison center, potentially lifesaving antidotes are frequently not available when and where they might be needed to treat a single poisoned patient.
Article
We wanted to estimate the current antidote supply in Alabama hospitals, establish if certain antidotes were stocked more than others, and identify certain parameters (eg, treatment level of care, licensed bed size, or county population) as predictors for the current antidote supply. We faxed surveys to treatment level I/II hospitals and a random sample of treatment level III hospitals. Antidote supply was reported for digoxin immune Fab, pyridoxine, ethanol, pralidoxime, antivenin (Crotalidae), deferoxamine, cyanide, naloxone, and fomepizole. Of treatment level I/II and level III hospitals surveyed, 28 (100%) and 20 (71.4%) responded, respectively. None (0%) of the hospitals surveyed had adequate stocking for all nine antidotes. The results illustrate the common practice of understocking poison antidotes. Hospitals must reevaluate their current antidote inventories for meeting the needs of acutely poisoned patients. Policy containing specific guidelines must be developed and uniformly adopted as standard of practice.