電子期刊 |
ISSN:1684-193X
|
Updated
July 26, 2003
|
|
Contents:
Volume 2, Number 1; July, 2003 |
|
Availability of Nerve Gas Antidotes at Emergency Pharmacy
in Taiwan |
Chor-Ming
Lin, MD; Hon-Ping Ma, MD; Tzong-Luen Wang, MD, PhD |
From the Department of Emergency Medicine ( Lin
CM, Ma HP, Wang TL), Shin-Kong Wu Ho-Su Memorial Hospital.
Correspondence to Dr. Tzong-Luen Wang, Department
of Emergency Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, 95
Wen Chang Road, Taipei, Taiwan. E-mail M002183@ms.skh.org.tw
|
Abstract
|
|
|
Incident
chemical attack was one of the devastating man-made disasters. To
investigate the hospital stockpiling for nerve agent antidote, we
studied the safety deposit of atropine as an indicator in 10 emergency
response hospitals in Taipei. Two of them were tertiary medical
center, and the remaining eight secondary referral hospitals. The
average amount of safe deposit was calculated from January 2002
to December 2003 for each hospital. The amount of stockpile in the
two medical centers was higher than that of the other 8 response
hospitals (1650+110 mg v. 230+45 mg, P<0.01).
The average amount of atropine in all hospitals was 380+50
mg. In addition, the average time needed to supply additional antidotes
was 3+1 hours. The capacity of the treatment during attack
was estimated to be 2.6+0.2 persons per hour for each hospital.
Although the stockpile of these hospitals fulfilled the requirements
from Department of Health, they could not afford an adequate capacity
for a sarin event. In conclusion, our study revealed that the hospital
stockpiling of atropine is insufficient for incidental chemical
attack in Taiwan, the increase of hospital stockpile
or the implementation of in situ rapid synthesis method might be
a resolution.
Key words--- Incidental Chemical Attack; Nerve Agents;
Atropine; Hospital Stockpile |
|
|
Introduction
|
|
|
|
In recent years,
the terrorism attacks occurred again and again. 1-4
Attacks by biological, chemical and radiological agents were considered
the most possible and devastating methods for such man-made disasters.4-6
Of chemical weapons, nerve gases such as sarin are well known as
the threatening means. 1,4,7-9
Because of the possible involvement of numerous people, the antidote
atropine may be rapidly depleted. 10,11
The condition remains to be elucidated in Taiwan. Although the Department
of Health requested all the hospitals had three-month safety reserve
for all medical logistics, the real reserve may be not the same
as what is expected. Most of the hospitals maintain zero stockpiles
and have their needs satisfied by certain logistic companies. Although
it allows for the requests provided by the Department of Health,
the situation will be very different when a terrorist attack such
as a sarin event occurs.
To solve the problem, Dr. Kozak ever provided a simple method to
compounding a large volume of injectable atropine from powder with
good results. 11 In addition, there
is a significant cost advantage to using powered atropine as a hospital
stockpile. Before we tested if the method can be applied to our
system, the first issue we have to clarify is the availability of
injectable atropine in the hospitals in Taiwan. We therein underwent
the following investigation to evaluate the availability of atropine
and its corresponding response capacity for a possible chemical
terrorist attack.
|
|
|
Methods |
|
The emergency response hospitals
have to be evaluated annually by the bureau of Health, Taipei City
Government. The amount of safe deposit for medical supply was one
of the checklists. We therein collected the data about the amount
of atropine safe deposits in 10 emergency response hospitals in
Taipei City. Two of them were tertiary medical center, and the remaining
eight secondary referral hospitals. The average amount of safe deposit
was calculated from January 2002 to December 2003 for each hospital.
For the hospitals that maintained zero hospital deposits, we investigated
furthermore the operation of medical supply logistics. The average
time needed from the notice or ordering of the hospitals to the
arrival of medical supply were studied and recorded.
For estimation of the average victims that could be treated in the
first hour, we assumed the average use of intravenous atropine being
2 mg per 5 min or totally 24 mg in the first hour.
|
|
|
|
Results |
|
The
safe deposit for atropine was requested as 100 mg for medical center
and 50 mg for other response hospitals by the definition of the
Department of Health. All of the hospitals in this study could fulfill
the criteria. The amount of stockpile in the two medical centers
was higher than that of the other 8 response hospitals (1650+110
mg v. 230+45 mg, P<0.01). The average amount of atropine in the
hospitals enrolled for investigation was 380+50 mg. In other words,
each hospital could treat 16+2 persons for one hour.
In addition, the average time needed to supply additional antidotes
was 3+1 hours. In consideration of the average stockpiles, the capacity
of the treatment during a nerve agent attack would be 2.6+0.2 persons
per hour for each hospital. Because Taiwan still had no experience
of the chemical attack, the number of possible victims could not
be estimated. However, if we took Tokyo Sarin attack as an example,
the affected person was more than 5,000. If the similar attack occurs
in Taipei where there are 64 emergency response hospitals, the capacity
of treatment will be 1,000 persons totally. The shortage of atropine
will be the problem for such an event.
|
|
|
|
|
|
|
Discussion |
|
|
|
Logistics is usually
one of the critical steps for determining successful disaster relief
and rescue. Effective logistics management ensures that all functions
are executed in a unified time-efficient and cost-effective manner.
According to FEMA, individual logistics functions and associated
subfunctions include: 12 (a) materiel
management including requisitioning, ordering, and sourcing; acquisition;
resource tracking; receipt; storage and handling; security; accountability;
inventory; deployment; issue and distribution; recovery; reutilization;
and disposition; (b) property management including accountability,
inventory, disposal, and record processing; (c) facility management
including facility selection and acquisition, building services,
information systems, communications, fleet management, safety and
health, and physical security; (d) transportation management including
transportation prioritizing, ordering, sourcing, and acquisition;
time-phasing plans; and movement coordination and tracking. In the
viewpoint of chemical disasters, immediate supply of the antidotes
is always the essential step for effective treatment for the victims
exposed to the chemical agents.
Intentional chemical disasters are one of the types of terrorism
in the world. The organophosphate nerve agents tabun (GA), sarin
(GB), soman (GD), and cyclosarin (GF) are among the most toxic chemical
warfare agents known. 1,4,7-9,13,14
Together they comprise the G-series nerve agents, thus named because
German scientists first synthesized them, beginning with GA in 1936.
Sarin was developed in 1938, followed by GD in 1944 and finally
GF in 1949. The only other known nerve agent is O-ethylS-(2-diisopropylaminoethyl)
methylphosphonothioate (VX). Besides decontamination and emergency
care including airway maintenance and circulation support, reversal
of nerve agent toxicity depends on the prompt parenteral administration
of the antidotes such as atropine and pralidoxime. In general, Nerve
agents act by first binding and then irreversibly inactivating acetylcholinesterase,
producing a toxic accumulation of acetylcholine at muscarinic, nicotinic,
and central nervous system synapses.15 At muscarinic receptors,
nerve agents cause miosis and glandular hypersecretion (salivary,
bronchial, lacrimal, bronchoconstriction, vomiting, diarrhea, urinary
and fecal incontinence, bradycardia). At nicotinic receptors, they
cause sweating and initial defasciculation followed by weakness
and flaccid paralysis. At cholinergic receptors of central nervous
system, these agents produce irritability, dizziness, lethargy,
amnesia, ataxia, seizures, coma, and respiratory depression. Nerve
agents also cause tachycardia and hypertension via stimulation of
the adrenal medulla. They also appear to bind nicotinic, cardiac
muscarinic, and glutamate N-methyl-d-aspartate receptors. Nerve
agents also antagonize gamma-aminobutyric acid neurotransmission,
which in part may mediate seizures and neuropathy.
In 1995, sarin attack in Tokyo subway that killed 12 victims and
affected over 5,000 people. 4,7-9
Although the event might be not considered as an intentional
chemical disaster by definition in consideration of the maintenance
of intact society in Japan, it still disclosed the shortcomings
in disaster preparedness. The shortage of the antidote atropine
for such a mass casualty was an example. The antidotes including
atropine are usually deposited in the hospital’s pharmacy. The amount
of the antidotes available at hand is always not sufficient for
a large number of the victims exposed to the nerve gases. In the
United States, disaster response organizations are stockpiling the
antidotes, but still consume much time to make the latter available. 16
The same situation could occur in Taiwan.
Our study demonstrated that the reserve of the antidotes for nerve
agents is low for a mass casualty caused by intentional or accidental
chemical incidents. The possible reason for the above observation
is that most of the hospitals keep zero deposit under the concept
of hospital management. The medical supply companies take over most
of the logistics work for medical institutes. It of course has its
own cost-effective benefits in the usual time, but may sacrifice
the efficiencies during a chemical incident. We think the resolutions
may include two major ways. The first is to establish disaster response
hospitals that are mainly responsible for the management of specific
types of the disasters. This resolution needs full and long-standing
financial support from the government. The other way is to develop
the alternative method to make the antidotes available. For this
purpose, the medical supply companies should have the ability to
keep the antidotes immediately available at any time. Otherwise,
the hospitals have to have the ability to synthesize the antidotes
immediately in situ.
Dr. Kozak provided recently a method of rapid atropine synthesis
in situ. 11 With their method, a large
amount of atropine could be provided in less than 1 hour for emergency
personnel to treat hundreds of victims. On average, 10 to 20 mg
is needed per patient. A single 2-g bottle could therefore be applied
to the treatment of more than 100 victims. As they stated, rescue
personnel could even use the hand-fill method to reconstitute antidote
at the scene of the chemical attack. Although the safety (or quality
control) and the authorization may be two major problems for us
to use the model, the rapid synthesis method is still a good way
in recent situation here. As Dr. Kozak mentioned, several potential
candidates for rapid synthesis include pralidoxime, diazepam, beta-agonists,
and cyanide antidotes.
In conclusion, our study revealed that the hospital stockpiling
of atropine is insufficient for incidental chemical attack in Taiwan
although its amount still fulfilled the requirements defined by
the Department of Health.
|
|
|
References |
|
|
|
1. |
Sidell FR. Chemical
agent terrorism. Ann Emerg Med 1996;28:223-4 |
2. |
Laquer W. Post-modern terrorism.
Foreign Affairs 1996;76:24-36 |
3. |
Bentura S. Chechen leader threatens
Moscow with nuclear terrorism. Agence France Presses English Wire
Service, November 8, 1991 |
4. |
Okumura T, Takasu N, Ishimatsu
S, et al. Report on 640 victims of the Tokyo subway sarin attack.
Ann Emerg Med 1996;28:129-35 |
|
5. |
Carter A, Deutch J, Zelikow
P. Catastophic terrorism–Tackling the new danger. Foreign Affairs
1998;77:80-94 |
|
6. |
Roberts B. Has the taboo been
broken? In Roberts B (ed): Terrorism with Chemical and Biological
Weapons: Calibrating Risks and Responses. Alexandria, VA: Chemical
and Biological Arms Control Institute, 1997:121-40 |
|
7. |
Nozaki H, Hori S, Shinozama
Y, et al. Secondary exposure of medical staff to sarin vapor in
the emergency room. Intensive Care Med 1995;21:1032-35 |
|
8. |
Kon M, Suzuki T, Ishikawa M.
A case of fatal sarin poisoning: management problems. Jap J Disast
Med 1996;1:12-14 |
|
9. |
Suzuki T, Morita H, Ono K, et
al. Sarin poisoning in Tokyo subway. Lancet 1995;345:980 |
|
10. |
Goldsmith MF. Preparing for medical
consequences of terrorism. JAMA 1996;275:1713-4 |
|
11. |
Kozak RJ, Siegel S, Kuzma J.
Rapid atropine synthesis for the treatment of massive nerve agent
exposure. Ann Emerg Med 2003;41:685-8 |
|
12. |
Federal Emergency Management
Agency (FEMA). Logistic Management Support Annex. Available at http://www.uscg.mil/d13/retco/pdf/frplm.pdf/
Accessed on May 31, 2003 |
|
13. |
Brennan RJ, Waeckerle JF, Sharp
TW, et al. Chemical warfare agents: emergency medical and public
health issues. Ann Emerg Med 1999;34:191-204 |
|
14. |
Centers for Disease Control
and Prevention. Biological and chemical terrorism: strategic plan
for preparedness and response. Recommendations of the CDC strategic
planning workgroup. MMWR Morb Mortal Wkly Rep. 2000;49(RR-4):1-14 |
|
15. |
Arnold JL. CBRNE - Nerve Agents,
G-series: Tabun, Sarin, Soman. eMedicine. Available at http://www.emedicine.com/emerg/topic898.htm/
Accessed on May 31, 2003 |
|
16. |
Geller RJ, Lopez GP, Cutler
S, et al. Antidote availability: reformulation of bulk atropine
for nerve agent casualties. Presented at: National Disaster Medical
System Conference; May 1999, Washington, D.C. |
|
|