Addressing the Need of Cyanide Disaster Preparedness
March 28th, 2017
By Bryant Moeller
Executive Summary:
Cyanide is a metabolic poison that binds and inhibits cytochrome C oxidase in the
mitochondria.1,2 The result of this inhibition is termination of oxidative
phosphorylation and ATP production, which forces cells to use the less efficient
glycolysis pathway for their energy needs.3 Prolonged use of glycolysis causes a
buildup of lactic acid and metabolic acidosis.4 The consequences of acute cyanide
exposure are severe, and result in loss of consciousness, cardio and respiratory
failure, hypoxic brain injury, and dose-dependent death from within minutes to
hours. The oral LD50 of cyanide in humans is about 1.1 mg/kg, or 554 ppm for 10
minutes via the inhalational route.5
Exposure to cyanide can occur in a variety of ways. The most well known cases of
cyanide poisoning are the famous examples of its use in suicide or murder, such as
the Jonestown mass suicide or the Chicago Tylenol murders.6,7 However, in the
United States alone, about 2 billion pounds of cyanide is used annually in industrial
applications such as mining, metallurgy, and the manufacture of many synthetic
materials.8 As a result, an accident during either the transportation or use of
industrial cyanide is a cause for concern. Additionally, nitrates present in many
materials are liberated upon combustion, making cyanide exposure a little-known
threat along with carbon monoxide in smoke inhalation scenarios9. Finally, cyanide
has a well-documented history of use as an agent of war or terror. Cyanide
impregnated mortar rounds were a part of many other weaponized chemicals
employed during World War I,10 and the Aum Shinrikyo cult attempted to use
cyanide gas in an attack on the Tokyo subway system in 1995.11 The widespread
availability, lack of expertise required for deployment, and requirement of specific
antidotes make cyanide a concern for use in terrorism.
In the event of a mass casualty exposure scenario, hasty response of trained medical
professionals and rapid deployment of medical countermeasures are paramount to
saving lives. However, the deployment speed of countermeasures is hindered by the
difficulties of accurately identifying cyanide exposure.12 Compounding this issue is
the problem that clinical confirmation of cyanide exposure using currently available
diagnostic tools can take hours, and results will not be available in the timeline
required for intervention. 13
It is imperative that information detailing how to correctly identify and treat
cyanide exposure is disseminated to emergency responders. This educational
program, which seeks to inform emergency responders about cyanide’s unique
exposure scenarios, symptoms, and both current as well as pipeline treatment
options, has the potential to improve clinical outcomes by enhancing the nations
readiness for disaster preparedness.
Gap 1: There is a need for early responders to accurately diagnose cyanide
exposure.
Due to the fast onset of cyanide toxicity, the timeline required for successful
administration of cyanide antidotes is also accelerated. Rapid and accurate
diagnosis of the causative agent is paramount to starting antidotal therapy in the
timeframe required to reverse toxicity. Most of the time, this diagnosis must be
made without confirmation of available diagnostic tools. As a result, the first
responder must rely on available clues at the scene as well as symptoms of those
affected to make an accurate diagnosis. The difficulty of this task is greater in mass
casualty scenarios such as an industrial accident or terrorist attack, where hundreds
or thousands of lives hang in the balance.
The CNS and heart are the most sensitive tissues to cyanide due to their high oxygen
demand, and this sensitivity is visible in the symptoms following exposure.14–16
Symptoms of acute cyanide exposure are initially tachycardia, hyperventilation,
nausea, and dizziness, followed by bradycardia, respiratory failure, loss of
consciousness, and death as toxicity progresses.17 However, these symptoms are
indicative of generalized oxygen deprivation, and as a result are not specific to
cyanide exposure.
The site of exposure can also help inform first responders and help narrow down
the number of possible toxicants. For industrial accidents, documentation of the
chemical inventories onsite should be able to quickly inform emergency responders
on the way to the incident. Additionally, for smoke inhalation scenarios, cyanide
exposure can be assumed along with carbon monoxide. Lethal cyanide levels have
been found in the blood of many fire victims.18 However, for cases of intentional
poisoning such as murders, suicides, or terrorist attacks, antidotal therapy may
need to be administered when cyanide is only suspected. Large quantities of
antidote may be needed in this situation depending on the number of people
affected.
This scenario highlights the importance of educational programs for first
responders like the one proposed here. This program has potential to increase
knowledge of first responders to accurately recognize cyanide symptoms and
identify exposure scenarios. This will enhance preparedness in mass casualty
scenarios, and can greatly improve disaster readiness to help save lives.
Gap 2: There is a need for early responders to understand which cyanide
antidotes are available.
Emergency response personnel need to have medical countermeasures available to
them in the timeframe required for successful intervention. RTI International
published a rare look into the national cyanide disaster readiness in 2006 that
detailed advanced life support (ALS) preparedness and perceived threat levels in
the United States post September 11, 2001. 19
The results showed that in 76% of standard emergency vehicles, no cyanide
antidote was available. Additionally, 28% of emergency responders ranked cyanide
antidotes as low importance compared to other supplies on the vehicle. One of the
most troubling findings of the report was that 32.1% of providers did not have
access to a large antidote cache as part of a disaster readiness plan, and 31.7 % were
not sure if they had such a cache available.19 Even with the best-trained emergency
responders, disaster readiness suffers if there are no supplies available.
However, access to cyanide antidotes is only part of the preparedness problem.
Another crucial area for disaster readiness is trained medical personnel.19 Only 16%
of ALS personnel in the study had experience using a cyanide antidote kit. The
percent dropped to virtually zero for first responders in rural areas, exposing
another pain point in the chain of successful countermeasure deployment.19
There are currently two FDA approved cyanide antidote therapies in the United
States: hydroxocobalamin, and a cocktail of nitrates and thiosulfate known as the
cyanide antidote kit.8,20–22 The cyanide antidote kit is contraindicated for cases of
smoke inhalation, because the nitrate component of the kit lowers the oxygen
carrying capacity of the blood, which is already diminished in cases of smoke
inhalation. Additionally, both antidotes require IV administration, and getting the IV
line prepared is often the rate-limiting step of medical countermeasure deployment.
Next generation antidotes such as sulfanegen and cobalamin are administered by IM
injection, increasing the number of people who can be treated in a mass casualty
scenario. 13,23–28
The RPI International study makes it clear that there is a need for hands on cyanide
antidote training for emergency responders, which this onsite educational program
can provide. Additionally, it is important for emergency responders to know what
cyanide antidotes are available in their area, which ones are appropriate for
different cyanide exposure scenarios, and finally, what improvements the next
generation of cyanide antidotes offer.
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