Information on medical and health effects, symptoms and tests for Nerve Agents



Intelligent kill: The dirty art of secret assassination

By Mohammad I. Aslam
Last updated: Monday, 18 June 2012 at 5:48 pm


State-sponsored foreign assassinations of military, religious, ideological and political figures are an ugly reality of world history.
By means of sudden, irregular or secret attack, there is even a common euphemism in international law which bluntly describes the practice: targeted killing.
According to a UN special report on the subject, targeted killings are “premeditated acts of lethal force employed by states in times of peace or during armed conflict to eliminate specific individuals outside their custody”.
And it works something like this.
A state deems a certain individual wanted or a danger to its national security. After ruling out any feasible attempt to bring them to their own jurisdiction, usually because they are based in a third country, it deems itself responsible with silencing them by whatever means necessary.
The operational dynamics are then conducted under the auspices of one of two possible dimensions.
Either to eliminate the target under a fog of plausible deniability, in order for the state authorities to wash their hands clean of any discreditable action in a foreign land, and by extension any prosecution should its agents be captured; or to have blatant disregard to the norms of international law by reference to domestic constitutions that empower them to act under the guise of self-defence – in order to protect themselves from imminent threats of attack.
The use of targeted killing has become quite common in the aftermath of 9/11. U.S. Predator drones strikes against Al Qaeda targets in Pakistan and the Yemen, Israeli airstrikes against Palestinian leaders in the occupied territories and Russian targeting of Chechen separatists in the Caucasus — are just a few recent examples.
But the covert practice of this art has always been a lot murkier.
In 1942, formerly secret memos now reveal how the British Special Operations Executive (SOE) secretly trained Czechoslovakian volunteers to assassinate Reinhard Heydrich, one of the most feared men in Nazi Germany, in a daring ambush on his motorcade.
Alternatively, the main security services of the Third Reich, the RSHA, had in place its own clandestine unit which planned to target Allied soldiers with poisoned coffee, chocolate and cigarettes; as part of a ruthless terrorist campaign.
During the Cold War, the Soviet Union’s equivalent of the CIA, the KGB, poisoned two of its dissidents abroad, once by firing a tiny Ricin-infested pellet from a specially designed umbrella into the target’s leg; and on another occasion by a spray gun firing a jet of poison gas from a crushed cyanide ampoule.
But even when the intended targets happen to miraculously survive a surreptitiously planned death, the devil that’s in the detail can be just as intriguing.
The CIA attempted to kill Cuban dictator Fidel Castro on numerous occasions by utilizing everything from exploding cigars, mafia contractors and femmes fatales — albeit without success.
On another occasion, the CIA unsuccessfully attempted to kill the Republic of Congo’s first Prime Minister, Patrice Lumumba, using a tube of doctored toothpaste which would have left him dead, apparently of Polio.
In 2004, Ukrainian opposition leader Victor Yushenko was poisoned with TCDD, the most toxic form of Polychlorinated Dibenzodioxins, otherwise known as Dioxins, by what is largely suspected were pro-Russian individuals within the state’s security apparatus.
Although many of the shrewd techniques that have been secretly used in the murder of dissidents and enemies abroad have long been acknowledged in the post-cold war era, many practices may still be eluding us by virtue of remaining shrouded in anonymity, even to this day.
But generally speaking, secret state-sponsored targeted killings are still synonymous with booby-trapped car bombs, sniper hits, exploding cell phones and even small arms fire.
In recent years, however, the art of these smart assassinations – designed in the most part to make a person’s death look somewhat natural – have now been refined by the most unthinkable of materials.
And you don’t have to look beyond what happened to Alexander Litvenenko, a former officer in Russia’s internal security force, FSB, and critic of Vladimir Putin’s rule, in London on November 2006.
After meeting what he ostensibly thought were two former KGB officers for tea in a hotel bar, within hours he was hospitalized with mysterious symptoms including progressively severe hair loss, vomiting and diarrhea for three weeks — before he ultimately succumbed to his horrible death.
His post-mortem finally furnished us with details. He was poisoned it turns out, with tiny a nuclear substance, the radioactive isotope, Polonium-210. Its acute radiation syndrome that he ingested virtually meant he had no chance of survival.
The UK authorities were able to piece together trails of the material as left by the culprits, incidentally right back to Russia itself, where almost all the world’s polonium is produced.
The logic of administering such toxic materials was in fact deliberate. Polonium-210 is something which is normally undetectable; as a rare radioactive isotope it emits alpha particles, not the common gamma radiation that standard radiological equipment would detect in hospitals.
The accused culprits may have underestimated the determination of the British authorities to uncover the whole plot, but simultaneously the incident also told us something; the Russians were not going to play by the old rules – they were going to rewrite them.
It would be wrong to assume, however, that biological poisons, chemical agents and nuclear materials are the only things used in smart killings. In fact, the use of materials designed for rudimentary medical procedures have also taken on a new course.
Israel’s Mossad, long considered the most effective intelligence agency in the world per magnitude, and no stranger to the world of targeted killing in foreign countries, has two shiny examples.
In September 1997, Mossad agents sprayed Hamas Leader Khaled Meshal with the poison Levofentanyl – a modified version of the widely-used painkiller Fentany – by using a small camera which served as a trajectory. Although the agents were later apprehended, and eventually exchanged the antidote (following lengthy behind-the-scenes negotiations before it was eventually given to the victim), the audacity of the materials they used spoke volumes: it was designed not to leave any visible or tell-tale signs of harm on the target’s body.
In January 2010, Hamas military commander Mohammad Al Mabhouh was found dead in his Dubai hotel room in what initially appeared to be death by natural causes.
However, upon thorough investigation, not only were 26 suspects (believed to have emanated from Israel) fingered, but the circumstances surrounding his death also soon transpired.
Al Mabhouh was injected in his leg with Succinylcholine, a quick-acting, depolarizing paralytic muscle relaxant. It causes almost instant loss of motor skills, but does not induce loss of consciousness or anesthesia. He was then apparently suffocated — ostensibly to quicken the pace of his death.
In his bestselling book, Gordon Thomas, author of Gideon Spies: The Secret History of the Mossad, gives a chilling and detailed account of how the Mossad uses Biochemists and genetic scientists in order to develop lethal cocktails as bottled agents of death.
This includes the development of nerve agents, choking agents, blood agents, and blister agents – including Tuban (virtually odorless and invisible when dispensed in aerosol or vapor form), Soman (the last of the Nazi nerve gasses to be discovered which also has a slightly fruity odour and is invincible in vapour format), blister agents (which include chlorine, phosgene and diphosgene, and smell of new-mown grass) and blood agents (including those with a cyanide base).
The point to extrapolate is clear. States that employ the practice of smart assassination techniques see them as effective strategies that are justified. They don’t need to admit to carrying them out, but we know they are happening.
An obvious concern raised here is that their almost pathological unwillingness to answer questions about the consequences of resorting to such assassinations – or covert targeted killings – will result in the practice becoming more widespread.
The arbitrary stretching of legal justifications for such assassinations, premised on what an individual country recognizes as self-defence, indirectly renders them to be bound by no limits — and by extension may serve as encouragement for other nations to follow suit, if they interpret their national security considerations being failed by international treaty and cooperation.
Just last month, British Police warned two outspoken Rwandan dissidents of threats to their lives by the Rwandan government, which could come in ‘any form’ or by ‘unconventional means’.
Perhaps this is all just a worrying reflection of international pusillanimity. But the truth is that fear does not grow unless it’s fed. Even if we sigh with relief, or at the very least with muted approval, at the targeted killing of Osama Bin Laden and his associates; it also raises the question of whether or not such actions are any less morally culpable than Russia daring to kill those it designates as traitors so mercilessly in Central London.
The greatest failure may have been the failure to face the truth.
Either way, it will take more than occasional public condemnation, the mewing of pitiful apologies by impotent politicians and the visionary words of empty treaties to finally bring to fruition the unequivocal call for ending this decades-long practice.


Nerve Agents Guide
NOTE:
The Occupational Safety and Health Act (OSH Act) requires employers to comply with hazard-specific safety and health standards. In addition, pursuant to Section 5(a)(1) of the OSH Act, employers must provide their employees with a workplace free from recognized hazards likely to cause death or serious physical harm. Emergency Preparedness Guides do not and cannot enlarge or diminish an employer's obligations under the OSH Act.
Emergency Preparedness Guides are based on presently available information, as well as current occupational safety and health provisions and standards. The procedures and practices discussed in Emergency Preparedness Guides may need to be modified when additional, relevant information becomes available or when OSH Act standards are promulgated or modified.
Because of recent terrorist events many workers have expressed concern about the possibility of a terrorist attack involving nerve agents. In 1995, twelve people were killed when the nerve agent sarin was released in the Tokyo subway system. The following frequently asked questions will help workers understand what nerve agents are and how they may affect their health and safety.
General Information
What are nerve agents?
Nerve agents are highly toxic chemicals called "organophosphates" that poison the nervous system and disrupt bodily functions which are vital to an individual’s survival. They were originally produced in a search for insecticides, but because of their toxicity, they were evaluated for military use.
What are the different forms of nerve agents and their properties?
Nerve agents, depending on their purity, are clear and colorless or slightly colored liquids and may have no odor or a faint, sweetish smell. They evaporate at various rates and are denser than air, so they accumulate in low areas. Nerve agents include tabun(GA), sarin(GB), soman(GD), and VX.
Why are we concerned about nerve agents as a terrorist’s weapon?
There are large stockpiles of nerve agents which, if obtained by terrorists, could be released using bombs, explosives, spray tanks, or rockets.
How long will aerosolized nerve agents persist in the environment?
The "G" agents tend to be volatile liquids which do not persist in the environment very long. The "VX" tends to be highly persistent and thus non-volatile. When compared to the "G" agents, "VX" is much more lethal and persistent. See the following table for more information:
Types and Characteristics Chemical Agents


PERSISTENCE
PERSISTENCE

ENTRANCE

TYPE OF AGENT
SYMBOL
SUMMER
WINTER
RATE OF ACTION
VAPOR/AEROSOL
LIQUID
NERVE
GA, GB, GD
10 min-24 hr
2 hr-3 days
Very Quick
Eyes, Lungs
Eyes, Skin, Mouth
*ARMY FIELD MANUAL NO. 8-10-7. Health Service Support in a Nuclear, Biological, and Chemical Environment.
Health Effects
How do nerve agents affect people?
Nerve agents are highly toxic and rapidly affect exposed individuals. Nerve agents enter the body primarily through the respiratory tract, although they may be absorbed through the eyes or skin. In the liquid state, nerve agents are hazardous via skin or eye contact and through ingestion. Generally, all nerve agents are highly toxic and fast acting.
When a person is exposed to a nerve agent, the nerve agent, upon entering the body, inhibits the normal actions of acetylcholinesterase; a chemical within the body whose normal function it is to break down the chemical acetylcholine. Acetylcholine causes muscular contraction. What nerve agents do to acetylcholinesterase is inhibit it from breaking down acetylcholine which in turn causes violent muscle spasms.
What are the symptoms of nerve agent poisoning?
When an individual is exposed to low amounts of a nerve agent (as a gas or aerosol) the initial symptoms are a runny nose, contraction of the pupils, deterioration of visual accommodation, headache, slurred speech, nausea, hallucinations, pronounced chest pains, and an increase in the production of saliva. At higher doses, these symptoms are more pronounced. Coughing and breathing problems also begin to occur. The individual then may begin to go into convulsions possibly progressing to coma or death. At even higher doses, an exposed individual would almost immediately go into convulsions and die from suffocation because of the simultaneous shut-down of the nervous and respiratory systems.
See the following links for more information on health effects:
Sarin (GB). CDC Emergency Preparedness and Response, (2003, April 3). This page includes links Fact Sheets, an Emergency Response Card, Medical Management Guidelines, and FAQ's about Sarin.
VX. CDC Emergency Preparedness and Response, (2003, April 3). This page includes links to Fact Sheets, an Emergency Response Card, Medical Management Guidelines, and FAQ's about VX.
Tabun (GA). CDC Emergency Preparedness and Response, (2003, March 13). This page includes links Fact Sheets, an Emergency Response Card, Medical Management Guidelines, and FAQ's about Tabun.
Soman (GD). CDC Emergency Preparedness and Response, (2003, March 13). This page includes links Fact Sheets, an Emergency Response Card, Medical Management Guidelines, and FAQ's about Soman.
Controls
How do I protect myself from nerve agents?
If you are exposed to a nerve agent attack, move away from the impacted area quickly without passing through the contaminated area. It may be necessary to "shelter-in-place" if you can’t get out of a building or if the nearest place with clean air is indoors.M
If available, a good way to protect yourself from nerve agents is to wear appropriate chemical protective clothing and respiratory protection. However, protective equipment does not always work against nerve agents. The effectiveness is determined by the materials of construction, the type and level of exposure, and duration of exposure.
What does it mean to "shelter in place?"
"Shelter in place" means to go indoors, close up the building, and wait for the danger to pass. If you are advised to shelter in place, close all doors and windows; turn off fans, air conditioners, and forced-air heating units that bring in fresh air from the outside; only recirculate air that is already in the building; move to an inner room or basement; and keep your radio turned to the emergency response network or local news to find out what else you need to do.
What should I do if I have been exposed to a nerve agent?
If you have been exposed to a nerve agent, remove all clothing immediately and wash with copious amounts of soap and water. Seek emergency medical attention.
Is there any treatment for persons exposed to nerve agents?
Because nerve act rapidly, treatment must begin immediately after exposure or death may occur. A general antidote to nerve agents is a combination of atropine and a reactivator. Atropine protects against the excess of acetylcoline formed during nerve agent poisoning. The reactivator's job is to restore acetylcholinesterase to its normal functions. The degree of difficulty in combating the nerve agent depends greatly on the quantity and type of nerve agent.
Health care professionals use an auto-injector to inject a mixture of atropine and the reactivator into patients exposed to nerve agents. The auto-injector consists of the two active components which are injected into an exposed individual through the use of a very long needle. The auto-injector is usually injected into an individual's thigh or another area where the antidote can reach the heart relatively quickly.
Is there a medical test to show whether I've been exposed to nerve agents GA, GB, GD, or VX?
Yes, medical tests can determine whether you have been exposed to nerve agents. There are tests to measure degradation products of nerve agents in the urine, but these are not generally useful. A different kind of test measures the levels of a substance called cholinesterase in the blood. If these levels are less than half what they should be, and you were exposed to nerve gases, you may experience symptoms of poisoning. Cholinesterase levels in the blood can remain low for months after you have been exposed to nerve agents. Measurement of cholinesterase levels in blood is not specific for exposure to nerve agents.
Has the federal government made recommendations to protect worker health?
OSHA has not set occupational exposure levels for exposure to nerve agents. However, other government departments and agencies have published existing and proposed standards.
Guidefor the Selection of Chemical Agent and Toxic Industrial Material DetectionEquipment for Emergency First Responders (PDF). National Institute of Justice Guide 100-00 (Volume II), (2000, June). This guide for emergency first responders provides information about detecting chemical agents and toxic industrial materials and selecting equipment for different applications.
Guide for theSelection of Personal Protection Equipment for Emergency First Responders (PDF). National Institute of Justice Guide 102-00 (Volume I), (2002, November).
Acute ExposureGuideline Levels (AEGLs) Chemical List. U.S. Environmental Protection Agency (EPA). Use the name for the AEGL chemical or its corresponding CAS number to find AEGL information on this web site.
MedicalManagement Guidelines (MMGs) for Nerve Agents: Tabun (GA); Sarin (GB); Soman(GD); and VX. Agency for Toxic Substances and Disease Registry (ATSDR), (2004, May 24).
Training Products. U.S. Army Medical Research Institute of Chemical Defense, Chemical Casualty Care Division.
First Responders
How should first responders prepare for a release of nerve agents?
First responders should consider the possible impact of a release and potential exposure to nerve agents and address this in their health and safety plan (HASP). The safety and health plan should include guidelines such as: monitoring, detection, awareness training, personal protective equipment, decontamination, and medical surveillance of acutely exposed workers.
What equipment can first responders use to detect if a nerve agent is present?
The military has a number of devices to detect nerve agent vapor and liquid. The most portable of the vapor detectors are the M256A1 card or ticket and the Chemical Agent Monitor (CAM). The most simple liquid detectors are the M8 and M9 papers. Direct reading instruments that are available include specialized gas chromatographs (minicams) and ion mobility spectrometers such as the APD 2000. Since some of these detectors cannot adequately detect the agents at safe airborne levels, users should be trained in regards to the use and limitations of the detectors. Listed below is a table of military detection and monitoring equipment:
Military Detection and Monitoring Equipment
Equipment
Agent
Sensitivity
Time
Cost
Operations/Maintenance/Limits
Notes
M-8 Paper
Nerve-G
Nerve-VX
Mustard-H Liquids only
100-µ drops
100-µ drops
100-µ drops
<=30 sec
$1 per book of 25 sheets
Disposable/
hand-held
Dry, undamaged paper has indefinite shelf life
Chemical agent detector paper; 25 sheets/book and 50 booklets/box; potential for false positives.
M-9 Paper
Nerve-G
Nerve-VX
Mustard-H Liquids only
100-µ drops
100-µ drops
100-µ drops
<=20 sec
$5 per 10-m roll
Disposable/
hand-held 3-year shelf life
Carcinogen
Adhesive-backed dispenser roll or books.
M-18A2
Detector Kit
Nerve-GB
Nerve-VX
Mustard-H, HN, HD, HT
Lewisite-L, ED, MD
Phosgene-CG
Blood-AC Liquid,
vapor, aerosol
0.1 mg/m3
0.1 mg/m3
0.5 mg/m3
10.0 mg/m3
12.0 mg/m3
8.0 mg/m3
2—3 min
$360
Disposable tubes Hand-held
25 tests per kit; Detector tubes, detector tickets, and M-8.
M-256A1
Detector Kit
Nerve-G and VX
Mustard-HD
Lewisite-L
Phosgene oxime-CX
Blood-AC, CK Vapor or liquid
0.005 mg/m3
0.02 mg/m3
2.0 mg/m3
9.0 mg/m3
3.0 mg/m3
8.0 mg/m3
15 min Series is longer AC--25 min
$140
Disposable/
Hand-held 5-year shelf life
Each kit contains 12 disposable plastic sampler-detectors and M-8 paper.
M-272
Water Test Kit
Nerve-G and VX
Mustard-HD
Lewisite
Hydrogen cyanide
0.02 mg/l
2.0 mg/l
2.0 mg/l
20.0 mg/l
7 min
7 min
7 min
6 min
$189
Portable/
lightweight 5-year shelf life USN, USMC
Used to test raw or treated water; Type I and II detector tubes, eel enzyme detector tickets; Kit conducts 25 tests for each agent.
CAM Chemical Agent Monitor
Nerve-GA, GB, VX
Blister-HD and HN Vapor only
0.03 mg/m3
0.1 mg/m3
30 sec
<=1 min
$7,500
Hand-held/portable battery operated 6—8 hours continuous use. Maintenance required.
Radioactive source. False alarms to perfume, exhaust paint, additives to diesel fuel.
ICAM
Improved Chemical Agent Detector
Nerve-G and V
Mustard-HD
0.03 mg/m3
0.1 mg/m3
10 sec
10 sec
$7,500
4.5 pounds
Minimal training
Alarm only;
False positives common.
ICAM-APD
Improved Chemical Agent Detector--Advanced Point Detector
Nerve-G
Nerve-V
Mustard-H
Lewisite-L
0.1 mg/m3
0.04 mg/m3
2.0 mg/m3
2.0 mg/m3
30 sec
30 sec
10 sec
10 sec
$15,000
12 pounds including batteries
Low maintenance
Minimal training
Audible and visual alarm.
ICAD
Miniature Chemical Agent Detector
Nerve-G
Mustard-HD
Lewisite-C
Cyanide-AC, CK
Phosgene-CG
0.2—0.5 mg/m3
10 mg/m3
10 mg/m3
50 mg/m3
25 mg/m3
2 min
(30 sec for high levels)
2 min
15 sec
$2,800
8 oz pocket-mounted 4 months service
No maintenance
Minimal training
Audible and visual alarm;
Marines;
No radioactivity.
M-90 D1A
Chemical Agent Detector
Nerve-G, V
Mustard
Lewisite
Blood Vapor only
0.02 mg/m3
0.2 mg/m3
0.8 mg/m3
N/A
10 sec
10 sec
80 sec
$16,000
15 lb. with battery
Radioactive source exempt from licensing. Minimal training
Ion mobility spectroscopy and metal conductivity technology can monitor up to 30 chemicals in parallel. Alarm only.
M-8A1 Alarm
Automatic Chemical Agent Alarm
Nerve-GA, GB, GD
Nerve-VX
Mustard-HD Vapor only
0.2 mg/m3
0.4 mg/m3
10 mg/m3
<=2 min
<=2 min
<=2 min
$2,555
Vehicle battery operated
Maintenance required
Radioactive source (license required);
Automatic unattended operation;
Remote placement.
MM-1
Mobile Mass Spectrometry Gas Chromatograph
20—30 CWA Vapor
<10 mg/m2 of surface area
<=45 sec
$300,000 military
$100,000 civilian
Heater volatizes surface contaminants.
German "Fuchs" (FOX Recon System/Vehicle)
RSCAAL M-21
Nerve-G
Mustard-H
Lewisite-L Vapor
90 mg/m3
2,300 mg/m3
500 mg/m3

$110,000
Line-of-sight dependent 10 year shelf life 2-person portable tripod
Passive infrared energy detector 3 miles; Visual/
audible warning from 400 meters
SAW
Mini-CAD
Nerve-GB
Nerve-GD
Mustard-HD Vapor
1.0 mg/m3
0.12 mg/m3
0.6 mg/m3
1 min
1 min
1 min
1 pound
No calibration
$5,500
Minimal training
Field use
Alarm only;
False alarms from gasoline vapor, glass cleaner.
ACADA
(XM22)
Nerve-G
Mustard-HD
Lewisite Vapor
0.1 mg/m3
2 mg/m3
--
30 sec
30 sec
--
$8,000
Vehicle mounted, battery powered
Radioactive source (license required) Minimal training
Audible alarm;
Bargraph display--low, high, very high.
Field Mini-CAMs
Nerve-G, V
Mustard-H
Lewisite-L
<0.0001 mg/m3
<0.003 mg/m3
<0.003 mg/m3
<5 min
<5 min
<5 min
$34,000
Designed for field industry monitoring (10 lb.) 8 hours training 24 hour/7 day operations
Plug-in modules increase versatility;
Threshold lower than AEL.
Viking
Spectratrak GC/MS
Nerve-G, V
Mustard-HD
Many others
<0.0001 mg/m3
<0.003 mg/m3
<10 min
<10 min
$100,000
Field use, but 85 pounds
Needs 120v AC, helium 40 hours training
Lab quality analysis;
Library of 62,000 chemical signatures.
HP 6890 GC
with flame photometric detector
Nerve-G, V
Mustard-HD
Many others
<0.0001 mg/m3
<0.0006 mg/m3
<10 min
<10 min
$50,000
Not designed for field use
Gas, air, 220v AC 40 hours training
State-of-
the-art gas chromatograph;
Used by CWC treaty lab.
Reference from National Research Council’s Chemical and Biological Terrorism: Research and Development to Improve Civilian Medical Response.
What personal protective equipment (PPE) should first responders use?
When an active release is occurring, or the release has stopped but there is no information about the duration of the release or the airborne concentration of nerve agents, don level A protection. The requirement of OSHA’s Hazardous Waste Operations and Emergency Response (HAZWOPER) standard (29 CFR 1910.120(q)) provides additional information for responding to hazardous substance releases including nerve agents.

For additional information see CBRNPersonal Protective Equipment Selection Matrix for Emergency Responders - NerveAgents.
Healthcare Workers
How should healthcare workers prepare to respond to a nerve agent release?
Healthcare facilities should have a health and safety plan in place that addresses the possibility of receiving patients exposed to nerve agents from a terrorism event. The document "OSHABest Practices for Hospital-Based First Receivers of Victims" contains practical information developing a emergency management plan and includes victim decontamination, personal protective equipment, and employee training.
How do I decontaminate a patient?
Healthcare professionals should don appropriate gloves and respiratory protection and then remove contaminated clothing from victim and thoroughly wash exposed areas with soap and water. Healthcare professionals should also wash hands after removing any protective gloves and any other potentially exposed body surfaces.

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http://www.fas.org/nuke/guide/usa/doctrine/dod/fm8-9/3ch2.htm

CHAPTER 2

NERVE AGENTS

SECTION I - GENERAL

201. Introduction.

The nerve agents (NA) are a group of particularly toxic chemical warfare agents. They were developed just before and during World War II and are related chemically to the organophosphorus insecticides. The principle agents in this group are: GA (Tabun), GB (Sarin), GD (Soman), GF and VX (methylphosphonothioic acid). (In some countries the "V" agents are known as "A" agents.)

202. Physical and Chemical Properties.

a. Nerve agents are organophosphorus esters. The "G" agents tend to be non-persistent whereas the "V" agents are persistent. Some "G" agents may be thickened with various substances in order to increase their persistence, and therefore the total amount penetrating intact skin. The physical properties are given in Table 2-I.
b. It may be seen that at room temperature GB is a comparatively volatile liquid and therefore non-persistent. GD is also significantly volatile, as is GA though to a lesser extent. VX is a relatively non-volatile liquid and therefore persistent. It is regarded as presenting little vapour hazard to people exposed to it. In the pure state nerve agents are colorless and mobile liquids. In an impure state nerve agents may be encountered as yellowish to brown liquids. Some nerve agents have a faint fruity odour.
c. In general, nerve agents are moderately soluble in water with slow hydrolysis, highly soluble in lipids, rapidly inactivated by strong alkalis and chlorinating compounds.

203. Detection.

Nerve agents may be detected by a variety of means. Single and three colour detector papers are available for individual issue to detect liquid nerve agent. Area detectors are also available as are monitoring devices for local contamination and water testing kits.

204. Protection.

a. To prevent inhalation of an incapacitating or lethal dose it is essential that the breath is held and the respirator put on at the first warning of the presence, or suspected presence, of a nerve agent.
b. Normal clothing is penetrated by these agents whether contact is with liquid or vapour and specialised clothing including a respirator, nuclear, biological, and chemical (NBC) suit, gloves and overboots are required for protection when liquid agent is present. The respirator protects the eyes, mouth and respiratory tract against nerve agent spray vapour and aerosol. Nerve agent vapour in field concentrations is absorbed through the skin very slowly, if at all, so that where a vapour hazard exists alone, the respirator may provide adequate protection without the use of an NBC suit.

205. Decontamination.

a. The importance of early decontamination can not be over emphasised. Decontamination of the skin should be accomplished quickly if it is to be fully effective. Liquid agent may be removed by fullers' earth or chemically inactivated by the use of reactive decontaminants. Decontamination personnel should use a respirator and full protective equipment whilst decontamination is performed.
b. Once a casualty has been decontaminated, or the agent fully absorbed, no further risk of contamination exists. The casualty's body fluids, urine or faeces do not present a chemical warfare (CW) hazard.

206. Mechanism of Action.

a. Absorption. Nerve agents may be absorbed through any body surface. When dispersed as a spray or an aerosol, droplets can be absorbed through the skin, eyes and respiratory tract. When dispersed as a vapour at expected field concentrations, the vapour is primarily absorbed through the respiratory tract. If enough agent is absorbed, local effects are followed by generalised systemic effects. The rapidity with which effects occur is directly related to the amount of agent absorbed in a given period of time.
b. Inhibition by Agents.
(1) The effects of the nerve agents are mainly due to their ability to inhibit acetylcholinesterase throughout the body. Since the normal function of this enzyme is to hydrolyse acetylcholine wherever it is released, such inhibition results in the accumulation of excessive concentrations of acetylcholine at its various sites of action. These sites include the endings of the parasympathetic nerves to the smooth muscle of the iris, ciliary body, bronchial tree, gastrointestinal tract, bladder and blood vessels; to the salivary glands and secretory glands of the gastrointestinal tract and respiratory tract; and to the cardiac muscle and endings of sympathetic nerves to the sweat glands.
(2) The accumulation of acetylcholine at these sites results in characteristic muscarinic signs and symptoms. The accumulation of acetylcholine at the endings of motor nerves to voluntary muscles and in some autonomic ganglia results in nicotinic signs and symptoms.
(3) The accumulation of excessive acetylcholine in the brain and spinal cord results in characteristic central nervous system symptoms. (See Table 2-II.)
(4) The inhibition of cholinesterase enzymes throughout the body by nerve agents may be irreversible and its effects prolonged.
(5) Treatment with oximes should begin promptly.
(6) Until the tissue cholinesterase enzymes are restored to normal activity, there is a period of increased susceptibility to the effects of another exposure to any nerve agent. The period of increased susceptibility occurs during the enzyme regeneration phase which could last from weeks to months, depending on the severity of the initial exposure. During this period the effects of repeated exposures are cumulative.
c. Location of Acetylcholinesterase. Acetylcholinesterase is found associated with the post-junctional membrane at the neuromuscular junction and in the cell bodies and processes of cholinergic neurons. The concentration is particularly high in some central nervous system neurons. The location of acetylcholinesterase in autonomic ganglia is less well understood than that at the neuromuscular junction. Acetylcholinesterase is also found at sites where, as yet, no functional role has been identified: the musculotendinous junction, red blood cells, platelets and the placenta.
d. Further Information. Further information on the action of nerve agents on acetylcholinesterase is given in Annex A.

207. Pathology.

Aside from the decrease in the activity of cholinesterase enzymes throughout the body (which may be detected by chemical methods or by special staining), no specific lesions are detectable by ordinary gross examination. At post-mortem examination there is usually capillary dilation, hyperaemia and oedema of the lungs; there may be similar changes in the brain and the remaining organs. Neuropathological changes have been reported in animals following severe intoxication. During the acute phase these include damage within the central nervous system and at the neuromuscular endplate. Later on, following severe exposure to some nerve agent, lesions to the peripheral motor nerves may be identified.

SECTION II - EFFECTS OF NERVE AGENTS

208. Signs and Symptoms.

a. The order in which signs and symptoms appear and their relative severity depend on the route of exposure and whether the casualty has been exposed to liquid agent or vapour.
b. The signs and symptoms following exposure to nerve agents are given in Table 2-III.
c. The local effects of vapour and liquid exposure are described followed by a description of the systemic effects which occur after significant absorption of agent via any route.

209. Effects of Nerve Agent Vapour.

a. Absorption. The lungs and the eyes absorb nerve agents rapidly. Changes occur in the smooth muscle of the eye, resulting in miosis and in the smooth muscle and secretory glands of the bronchi, producing bronchial constriction and excessive secretions in the upper and lower airways. In high vapour concentrations, the nerve agent is carried from the lungs throughout the circulatory system; widespread systemic effects may appear in less than 1 minute.
b. Local Ocular Effects.
(1) These effects begin within seconds or minutes after exposure, before there is any evidence of systemic absorption. The earliest ocular effect which follows minimal symptomatic exposure to vapour is miosis. This is an invariable sign of ocular exposure to enough vapour to produce symptoms. It is also the last ocular manifestation to disappear. The pupillary constriction may be different in each eye. Within a few minutes after the onset of exposure, there also occurs redness of the eyes due to conjunctival hyperaemia, and a sensation of pressure with heaviness in and behind the eyes. Usually vision is not grossly impaired, although there may be a slight dimness especially in the peripheral fields or when in dim or artificial light.
(2) Exposure to a level of a nerve agent vapour slightly above the minimal symptomatic dose results in miosis, pain in and behind the eyes attributable to ciliary spasm, especially on focusing, some difficulty of accommodation and frontal headache. The pain becomes worse when the casualty tries to focus the eyes or looks at a bright light. Some twitching of the eyelids may occur. Occasionally there is nausea and vomiting which, in the absence of systemic absorption, may be due to a reflex initiated by the ocular effects. These local effects may result in moderate discomfort and some loss of efficiency but may not necessarily produce casualties.
(3) Following minimal symptomatic exposure, the miosis lasts from 24 to 72 hours. After exposure to at least the minimal symptomatic dose, miosis is well established within half an hour. Miosis remains marked during the first day after exposure and then diminishes gradually over 2 to 3 days after moderate exposure but may persist for as long as 14 days after severe exposure. The conjunctival erythema, eye pain, and headache may last from 2 to 15 days depending on the dose.
c. Local Respiratory Effects. Following minimal exposure, the earliest effects on the respiratory tract are a watery nasal discharge, nasal hyperaemia, sensation of tightness in the chest and occasionally prolonged wheezing expiration suggestive of bronchoconstriction or increased bronchial secretion. The rhinorrhoea usually lasts for several hours after minimal exposure and for about 1 day after more severe exposure. The respiratory symptoms are usually intermittent for several hours duration after mild exposure and may last for 1 or 2 days after more severe exposure.

210. Effects of Liquid Nerve Agent.

a. Local Ocular Effects. The local ocular effects are similar to the effects of nerve agent vapour. If the concentration of the liquid nerve agent contaminating the eye is high, the effects will be instantaneous and marked; and, if the exposure of the two eyes is unequal, the local manifestations may be unequal. Hyperaemia may occur but there is no immediate local inflammatory reaction such as may occur following ocular exposure to more irritating substances (for example, Lewisite).
b. Local Skin Effects. Following cutaneous exposure, there is localised sweating at and near the site of exposure and localised muscular twitching and fasciculation. However, these may not be noticed causing the skin absorption to go undetected until systemic symptoms begin.
c. Local Gastrointestinal Effects. Following the ingestion of substances containing a nerve agent, which is essentially tasteless, the initial symptoms include abdominal cramps, vomiting and diarrhoea.

211. Systemic Effects of Nerve Agent Poisoning.

a. The sequence of symptoms varies with the route of exposure. While respiratory symptoms are generally the first to appear after inhalation of nerve agent vapour, gastrointestinal symptoms are usually the first after ingestion. Following comparable degrees of exposure, respiratory manifestations are most severe after inhalation, and gastrointestinal symptoms may be most severe after ingestion. Otherwise, the systemic manifestations are, in general, similar after any exposure to nerve agent poisoning by any route. If local ocular exposure has not occurred, the ocular manifestations (including miosis) initially may be absent.
b. The time course of effects following exposure to nerve agents are given in Table 2-IV.
c. The systemic effects may be considered to be nicotinic, muscarinic or by an action at receptors within the central nervous system. The predominance of muscarinic, nicotinic or central nervous system effects will influence the amount of atropine, oxime or anticonvulsant which must be given as therapy. These effects will be considered separately.

212. Muscarinic Effects of Nerve Agent Poisoning.

a. Tightness in the chest is an early local symptom of respiratory exposure. This symptom progressively increases as the nerve agent is absorbed into the systemic circulation, whatever the route of exposure. After moderate or severe exposure, excessive bronchial and upper airway secretions occur and may become very profuse, causing coughing, airway obstruction and respiratory distress. Audible wheezing may occur, with prolonged expiration and difficulty in moving air into and out of the lungs, due to the increased bronchial secretion or to bronchoconstriction, or both. Some pain may occur in the lower thorax and salivation increases.
b. Bronchial secretion and salivation may be so profuse that watery secretions run out of the sides of the mouth. The secretions may be thick and tenacious. If postural drainage or suction is not employed, these secretions may add to the airway obstruction. Laryngeal spasm and collapse of the hypopharyngeal musculature may also obstruct the airway. The casualty may gasp for breath, froth at the mouth, and become cyanotic.
c. If the upper airway becomes obstructed by secretions, laryngeal spasm or hypopharyngeal musculature collapse, or if the bronchial tree becomes obstructed by secretions or bronchoconstriction, little ventilation may occur despite respiratory movements. As hypoxaemia and cyanosis increase, the casualty will fall exhausted and become unconscious.
d. Following inhalation of nerve agent vapour, the respiratory manifestations predominate over the other muscarinic effects: they are likely to be most severe in older casualties and in those with a history of respiratory disease, particularly bronchial asthma. However, if the exposure is not so overwhelming as to cause death within a few minutes, other muscarinic effects appear. These include sweating, anorexia, nausea and epigastric and substernal tightness with heartburn and eructation. If absorption of nerve agent has been great enough (whether due to a single large exposure or to repeated smaller exposures), there may follow abdominal cramps, increased peristalsis, vomiting, diarrhoea, tenesmus, increased lachrymation and urinary frequency. Cardiovascular effects are a bradycardia, hypotension and cardiac arrhythmias. The casualty perspires profusely, may have involuntary defecation and urination and may go into cardiorespiratory arrest followed by death.

213. Nicotinic Effects.

a. With the appearance of moderate muscarinic systemic effects, the casualty begins to have increased fatiguability and mild generalised weakness which is increased by exertion.
b. This is followed by involuntary muscular twitching, scattered muscular fasciculations and occasional muscle cramps. The skin may be pale due to vasoconstriction and blood pressure moderately elevated (transitory) together with a tachycardia, resulting from cholinergic stimulation of sympathetic ganglia and possibly from the release of epinephrine. If the exposure has been severe, the muscarinic cardiovascular symptoms will dominate and the fascicular twitching (which usually appear first in the eyelids and in the facial and calf muscles) becomes generalised. Many rippling movements are seen under the skin and twitching movements appear in all parts of the body. This is followed by severe generalised muscular weakness, including the muscles of respiration. The respiratory movements become more laboured, shallow and rapid; then they become slow and finally intermittent. Later, respiratory muscle weakness may become profound and contribute to the respiratory depression. Central respiratory depression may be a major cause of respiratory failure.

214. Central Nervous System Effects.

a. In mild exposures, the systemic manifestations of nerve agent poisoning usually include tension, anxiety, jitteriness, restlessness, emotional lability, and giddiness. There may be insomnia or excessive dreaming, occasionally with nightmares.
b. If the exposure is more marked, the following symptoms may be evident: headache, tremor, drowsiness, difficulty in concentration, impairment of memory with slow recall of recent events, and slowing of reactions. In some casualties there is apathy, withdrawal and depression. With the appearance of moderate symptoms, abnormalities of the electroencephalogram occur, characterised by irregularities in rhythm, variations in potential, and intermittent bursts of abnormally slow waves of elevated voltage similar to those seen in patients with epilepsy. These abnormal waves become more marked after one or more minutes of hyperventilation which, if prolonged, may occasionally precipitate a generalised convulsion.
c. If absorption of nerve agent has been great enough, the casualty becomes confused and ataxic. The casualty may have changes in speech, consisting of slurring, difficulty in forming words, and multiple repetition of the last syllable. The casualty may then become comatose, reflexes may disappear and respiration may become Cheyne-Stokes in character. Finally, generalised convulsions may ensue.
d. With the appearance of severe central nervous system symptoms, central respiratory depression will occur (adding to the respiratory embarrassment that may already be present) and may progress to respiratory arrest. However, after severe exposure the casualty may lose consciousness and convulse within a minute without other obvious symptoms. Death is usually due to respiratory arrest and anoxia, and requires prompt initiation of assisted ventilation to prevent death. Depression of the circulatory centres may also occur, resulting in a marked reduction in heart rate with a fall of blood pressure some time before death.

215. Cumulative Effects of Repeated Exposure.

a. Daily exposure to concentrations of a nerve agent insufficient to produce symptoms following a single exposure may result in the onset of symptoms after several days. Continued daily exposure may be followed by increasingly severe effects.
b. After symptoms subside, increased susceptibility may persist for up to 3 months. The degree of exposure required to produce recurrence of symptoms and the severity of these symptoms depend on the dose received and the time interval since the last exposure. Increased susceptibility is not limited to the particular nerve agent initially absorbed.

216. Cause of Death.

a. In the absence of treatment, death is caused by anoxia resulting from airway obstruction, weakness of the muscles of respiration and central depression of respiration.
b. Airway obstruction is due to pharyngeal muscular collapse, upper airway and bronchial secretions, bronchial constriction and occasionally laryngospasm and paralysis of the respiratory muscles.
c. Respiration is shallow, laboured, and rapid and the casualty may gasp and struggle for air. Cyanosis increases. Finally, respiration becomes slow and then ceases. Unconsciousness ensues. The blood pressure (which may have been transitorily elevated) falls. Cardiac rhythm may become irregular and death may ensue.
d. If assisted ventilation is initiated via cricothyroidotomy or endotracheal tube and airway secretions are removed by postural drainage and suction and diminished by the administration of atropine, the individual may survive several lethal doses of a nerve agent. However, if the exposure has been overwhelming, amounting to many times the lethal dose, death may occur despite treatment as a result of respiratory arrest and cardiac arrhythmia.
e. When overwhelming doses of the agent are absorbed quickly, death occurs rapidly without orderly progression of symptoms.

SECTION III - TREATMENT OF NERVE AGENT POISONING

217. Diagnosis and Therapy of Nerve Agent Poisoning.

a. Symptoms. Nerve agent poisoning may be identified from the characteristic signs and symptoms. If exposure to vapour has occurred, the pupils will be very small, usually pin-pointed. If exposure has been cutaneous or has followed ingestion of a nerve agent in contaminated food or water, the pupils may be normal or, in the presence of severe systemic symptoms, slightly to moderately reduced in size. In this event, the other manifestations of nerve agent poisoning must be relied on to establish the diagnosis. No other known chemical agent produces muscular twitching and fasciculations, rapidly developing pin-point pupils, or the characteristic train of muscarinic, nicotinic and central nervous system manifestations.
b. Symptom Differentiation. It is important that individual service members know the following MILD and SEVERE signs and symptoms of nerve agent poisoning. Service members who have most or all of the symptoms listed below must IMMEDIATELY receive first aid (self-aid or buddy aid respectively).
c. MILD Poisoning (Self-Aid). Casualties with MILD symptoms may experience most or all of the following:
(1) Unexplained runny nose.
(2) Unexplained sudden headache.
(3) Sudden drooling.
(4) Difficulty in seeing (dimness of vision and miosis).
(5) Tightness in the chest or difficulty in breathing.
(6) Localised sweating and muscular twitching in the area of the contaminated skin.
(7) Stomach cramps.
(8) Nausea.
(9) Bradycardia or tachycardia.
d. MODERATE Poisoning. Casualties with MODERATE poisoning will experience an increase in the severity of most or all of the MILD symptoms. Especially prominent will be an increase in fatigue, weakness and muscle fasciculations. The progress of symptoms from mild to moderate indicates either inadequate treatment or continuing exposure to agent.
e. SEVERE Symptoms (Buddy Aid). Casualties with SEVERE symptoms may experience most or all of the MILD symptoms, plus most or all of the following:
(1) Strange or confused behaviour.
(2) Wheezing, dyspnoea (severe difficulty in breathing), and coughing.
(3) Severely pin-pointed pupils.
(4) Red eyes with tearing.
(5) Vomiting.
(6) Severe muscular twitching and general weakness.
(7) Involuntary urination and defecation.
(8) Convulsions.
(9) Unconsciousness.
(10) Respiratory failure.
(11) Bradycardia.
f. Aid for Severe Cases. Casualties with severe symptoms will not be able to treat themselves and must receive prompt buddy aid and follow-on medical treatment if they are to survive.

218. Treatment.

The lethal effects of nerve agent poisoning may be combated by a combination of pretreatment and post exposure therapy.

219. Pretreatment.

a. Poisoning by nerve agents which form rapidly aging complexes (for example Soman) may be particularly difficult to treat. These difficulties have been solved, in part, by the use of carbamates as pretreatment. The terms pretreatment or prophylaxis should perhaps be defined as used in this context:
(1) Pretreatment: the administration of drugs in advance of poisoning designed to increase the efficacy of treatment administered post-poisoning.
(2) Prophylaxis: the administration of drugs in advance of the poisoning designed to make post-poisoning therapy unnecessary.
b. The terms are to an extent interchangeable and as, in cases of severe poisoning, postpoisoning therapy is nearly always needed, the term pretreatment will be used here.
c. Carbamate anticholinesterases, e.g., pyridostigmine, may be used as pretreatment against nerve agent poisoning by virtue of their capacity to bind acetylcholinesterase reversibly, preventing the organophosphate (OP) binding to the enzyme. The term reversible is here used comparatively: the carbamate-acetylcholinesterase complex breaks down fairly rapidly, while organophosphate-acetylcholinesterase complexes break down very slowly. The aged soman-acetylcholinesterase complex breaks down virtually not at all.
d. When carbamates are used as pretreatments, carbamoylation of acetylcholinesterase prevents phosphorylation, but later the carbamate-acetylcholinesterase complex dissociates, freeing active enzyme. Current pretreatment regimes bind 30-40% of available red blood cell acetylcholinesterase, thereby allowing the carbamate to protect some of the acetylcholinesterase against attack by nerve agent.
e. The carbamate pyridostigmine, given in a dose of 30 mg every 8 hours, is used as a pretreatment. In conjunction with post exposure therapy, good protection against lethality is obtained within 2 hours of the first dose, but is not optimal until the third dose.
f. Pyridostigmine pretreatment should be stopped upon developing symptoms of nerve agent poisoning following a chemical warfare attack and post exposure therapy started.
g. Pyridostigmine tablets were taken over a 4 to 5 day period by large numbers of troops during the Gulf War of 1991.
(1) The effects of pyridostigmine were examined in several studies including one uncontrolled study of 42,000 troops when, following the recommended dose regime, under the stress of combat conditions, gastrointestinal intestinal changes including increased flatus, loose stools, abdominal cramps and nausea were noted by approximately half the population. Other reported effects were urinary urgency, headache, rhinorrhoea, diaphoresis and tingling of the extremities. These effects were considered tolerable. They did not noticeably interfere with performance of the full range of demanding physical and mental tasks required of service personnel.
(2) Symptoms due to pyridostigmine may be ameliorated by taking the tablets with food.
(3) Pyridostigmine pretreatment was discontinued on medical advice in less than 0.1% of individuals, generally because of intolerable nausea and diarrhoea.
h. When taken in excess of the recommended dosage, symptoms of carbamate poisoning will occur. These include diarrhoea, gastrointestinal cramps, tight chest, nausea, rhinorrhoea, headache and miosis.
i. Good compliance is required if optimal protection is to be obtained. The importance of pyridostigmine pretreatment should therefore be stressed during training.

220. Post-Exposure Therapy.

The main principles of therapy for nerve agent poisoning are early treatment, assisted ventilation, bronchial suction, muscarinic cholinergic blockade (atropine), enzyme reactivation (oximes) and anticonvulsants (benzodiazepines).

221. Emergency Field Therapy.

a. Self Aid (or Buddy Aid).
(1) This comprises first aid measures which the soldier can apply to help him or herself. The rapid action of nerve agents call for immediate self treatment. Unexplained nasal secretion, salivation, tightness of the chest, shortness of breath, constriction of pupils, muscular twitching, or nausea and abdominal cramps call for the immediate intramuscular injection of 2 mg of atropine, combined if possible with oxime. From 1 to 3 automatic injection devices, each containing 2 mg atropine or mixture of atropine, oxime and/or anticonvulsant, are carried by each individual.
(2) One device should be administered immediately when the symptoms and/or signs of nerve agent poisoning appear. This may be done by the casualty or by a buddy; the injection being given perpendicularly through the clothing into the lateral aspect of the middle of the thigh. Further devices, up to a total of 3, should be administered by the casualty or by his or her buddy during the following 30 minutes if the symptoms and/or signs of poisoning fail to resolve.
(3) The timing of these further injections and whether they are given at one time or separately may depend on the casualty's condition and on instructions promulgated by individual nations.
(4) NOTE: If automatic injectors are used in the absence of exposure to agent, the following signs and symptoms may be seen: Dry mouth, dry skin, fast pulse (>90 beats per minute), dilated pupils, retention of urine and central nervous system disturbance. Susceptibility to heat exhaustion or heat stroke is increased, particularly in closed spaces or while wearing protective clothing.
b. First Aid by Trained Personnel.
(1) This comprises the emergency actions undertaken to restore or maintain vital bodily functions in a casualty. Wherever the casualty is not masked the respirator must be adjusted for him or her by the nearest available person. Attention should be given to decontamination at the earliest possible moment and any skin contamination must be removed with a personal decontamination kit.
(2) After nerve agent poisoning, the administration of atropine is repeated at intervals until signs of atropinization (dry mouth and skin and tachycardia >90 per minute) are achieved. Miosis from vapour exposure is not relieved by systemic atropine.
(3) Mild atropinization should be maintained for at least 24 hours by intramuscular injection of 1-2 mg of atropine at intervals of 1/2 to 4 hours, as required. The danger of ventricular arrhythmias arising from atropinization while the casualty is anoxic must be remembered.
(4) Assisted ventilation is required for severely poisoned individuals as they will have:
(a) Marked bronchoconstriction;
(b) Copious secretions in the trachea and bronchi;
(c) Paralysis of the respiratory muscles; and
(d) Central respiratory depression, hypoxia, and convulsions.
c. Resuscitation.
(1) Positive pressure resuscitation should be given but the pressure necessary to overcome the bronchoconstriction may be more than 65 cm of water so that incubation if possible is highly desirable. In an uncontaminated atmosphere assisted ventilation may be done by the standard mouth-to-mouth method after decontamination of the casualty's face and mouth. In a contaminated atmosphere ventilation may be given by a portable resuscitator with NBC filter attached. Both the casualty and the resuscitator should be decontaminated.
(2) In a well equipped medical facility, mechanical resuscitation of the positive pressure type may be used with endotracheal incubation or tracheostomy-artificial respiration must be continued until the casualty is breathing normally or the medical personnel have pronounced the casualty dead. Due to the production of copious secretions, regular suction will be required.

222. Pharmacological Treatment of Nerve Agent Poisoning.

a. The pharmacological treatment of nerve agent poisoning involves the use of:
(1) Anticholinergics to antagonise the muscarinic effects (atropine).
(2) Oximes to reactivate inhibited enzyme.
(3) Anticonvulsants to prevent CNS damage.
b. The effects of drugs used in nerve agent poisoning are described below.

223. Atropine.

a. Atropine sulphate remains an essential drug in the treatment of nerve agent poisoning. It acts by blocking the effects of acetylcholine at muscarinic receptors and so produces relief from many of the symptoms previously listed. If given in large doses, some therapeutic effects are also produced within the central nervous system although atropine does not readily penetrate the blood brain barrier and central muscarinic receptors are thought not to be identical with those in the periphery. It is thought to counteract the respiratory depression in the medulla oblongata.
b. Urgent treatment with atropine in cases of nerve agent poisoning is essential. After the emergency field treatment, atropinisation should be maintained for at least 24 hours by intramuscular injection or slow intravenous infusion of 1 to 2 mg of atropine per hour as required. The dose should be repeated at intervals until signs of successful atropinisation are noted. Intervals of 5 to 15 minutes seem reasonable, but severe poisoning may require higher doses (4 mg to 6 mg per hour or more). Signs of successful atropinisation include the drying up of bronchial, salivary and skin secretions and an increase in heart rate to greater than 90 beats per minute.
c. The effect of atropine in drying bronchial secretions may make the removal of mucus more difficult so suction is likely to be necessary. In excessive doses, atropine may render the ischaemic myocardium more liable to arrhythmias and electrocardiogram (ECG) monitoring should be undertaken in all patients if possible.
d. Atropine overdosage may produce euphoria, hallucinations, anxiety, and delirium and close observation of patients is necessary. Bladder dysfunction may necessitate catheterisation.
e. By inhibition of sweat production, atropine increases heat stress and in warm or hot weather care must be taken to avoid hyperthermia.
f. Atropine given parenterally has comparatively little effect on nerve agent induced miosis. The local application of cycloplegics (atropine eye drops) to the eye reduces both the degree of rniosis, eye pain and headache. However, expert opinion on the value of atropine containing eye drops in the management of nerve agent induced miosis remains divided. It is believed by some that problems of accommodation may be made worse by the application of the drops and that, overall, little benefit may be produced.
g. If atropine is administered in the absence of nerve agent poisoning, the following effects may be noted: dryness of the mouth and pharynx, decreased sweating, slight flushing and tachycardia, some hesitancy of micturition, slightly dilated pupils, mild drowsiness, slowness of memory and recall and blurring of near vision. After 2mg these symptoms should not interfere with ordinary activity except in the occasional person, in hot environments or at high work rates. Higher doses, or repeated doses, will produce more marked symptoms which will usually not be totally incapacitating except in warm environments or high work rates. The effects of atropine are fairly prolonged, lasting 3 to 5 hours after one or two injections of 2mg and 12 to 24 hours after marked over-atropinisation.

224. Oximes.

a. Oximes.
(1) While atropine blocks the muscarinic effects of nerve agent poisoning it has little effect upon the nicotinic actions of the agent at the skeletal neuromuscular junction and at the autonomic ganglia.
(2) Amelioration of the effects of nerve agents at these sites and also at muscarinic sites can, however, be obtained by reactivation of the inhibited acetylcholinesterase by means of oximes. Oximes, therefore, relieve the clinically important symptom of skeletal neuromuscular blockade. However, they penetrate into the central nervous system poorly, and the simultaneous administration of atropine is therefore still required.
b. Enzyme Reactivation.
(1) The relative potency of different oximes in reactivating acetylcholinesterase inhibited by some nerve agents is given in Table 2-V.
(2) Dosing schemes for the clinical intravenous use of currently available oximes, as applied in poisoning of humans by organophosphate insecticides, are shown in Table 2-VI. Under field conditions similar doses can be given intramuscularly, but care should be taken to avoid accidental intra-arterial injection. The dose rates given could form the base for the determination of national dosing procedures which should include emergency field treatment.
(3) An alternative method of administering oxime is as a continuous infusion. On the basis of a theoretical therapeutic plasma concentration of 4mg.1-1, the loading dose and maintenance dose for intravenous use can be calculated for different oximes using data obtained in healthy human volunteers (Table 2-VII). Data from human organophosphorus insecticide poisoning suggest that these dose rates are also applicable in patients.
(4) Clinical experience in human poisoning by organophosphorus insecticide shows that oxime treatment should be continued for some hours after reactivation has been obtained and the patient has recovered. If no enzyme reactivation has been obtained after a 24 to 48 hour period of treatment and the patient has not recovered, then it should be accepted that the enzyme inhibition is resistant to reactivation by the particular oxime and administration should be stopped. There is only limited experience with human poisoning with organophosphorus nerve agents, but animal data suggest that the clinically relevant persistence of nerve agent in the body will probably be shorter than for insecticides. It may be suggested therefore, that oxime treatment should be continued until the recovery of the patient, with a probable maximum duration of 24 to 48 hours.
c. Oxime Induced Side Effects. The rapid injection of pralidoxime 2 (PAM Cl or P2S) can produce drowsiness, headache, disturbance of vision, nausea, dizziness, tachycardia and an increase in blood pressure, hyperventilation and muscular weakness. Obidoxime produces hypotension, a menthol-like sensation and a warm feeling in the face. On intramuscular injection, it can produce a dull pain at the site of injection; after multiple dosing, hepatic dysfunction can be observed. HI6 (a type of oximide) produces similar effects.

225. Anticonvulsants.

a. Atropine protects only partially against convulsions and the resulting brain damage in severe poisoning. Complementary treatment, including anticonvulsants, should be applied as necessary.
b. It has been shown in experimental soman poisoning that diazepam antagonises the convulsive action of soman and that addition of diazepam to the basic treatment regime greatly improves morbidity and mortality, independent of its anticonvulsive effect. Diazepam is the drug of choice and should be injected intramuscularly as a 10 mg dose initially and further doses should be given frequently enough to control convulsions. This may require injections at intervals ranging from a few minutes to several hours.

226. Supportive Care.

Although pre and post exposure therapy will protect against lethality, casualties may still be incapacitated. A patient severely poisoned by an anticholinesterase is a critical medical emergency and may require intensive care for days or weeks. Assisted ventilation may be needed for many hours or days and the patient may be comatose for hours or days and brain damage may result from periods of hypoxia. General supportive care such as IV feeding, restoring electrolyte balance, treatment of shock and control of convulsions is needed. Therapy to control infection, should this occur, should be on the usual lines. Special care should betaken using muscle relaxants in patients poisoned by nerve agents.

 


http://www.bt.cdc.gov/agent/nerve/tsd.asp

TOXIC SYNDROME DESCRIPTION
Nerve Agent and Organophosphate Pesticide Poisoning
The purpose of this document is to enable health care workers and public health officials to recognize an unknown or suspected exposure to a nerve agent or an organophosphate (OP) pesticide. Nerve agents are chemical warfare agents that have the same mechanism of action as OP organophosphate pesticides insecticides. They are potent inhibitors of acetylcholinesterase . Inhibition of acetylcholinesterase leads , thereby leading to an accumulation of acetylcholine in the central and peripheral nervous system. Excess acetylcholine produces a predictable cholinergic syndrome consisting of copious respiratory and oral secretions, diarrhea and vomiting, sweating, altered mental status, autonomic instability, and generalized weakness that can progress to paralysis and respiratory arrest.
The amount and route of exposure to the nerve agent or OP pesticide, the type of nerve agent or pesticide, and the premorbid condition of the person exposed person will contribute to the time of onset and the severity of illness. For example, inhalation of a nerve agent or an OP pesticide leads to a quicker onset of poisoning with more severe symptoms when compared to with dermal exposure s, given the same amount of agent.
Signs and symptoms
The following is a more comprehensive list of signs and symptoms that may be encountered in a person exposed to a nerve agent or OP pesticide. Signs and symptoms are not listed in order of presentation or specificity. Also, partial presentations (an absence of some of the following signs/symptoms) do not necessarily imply less severe disease.
Central nervous system signs and symptoms
Miosis (unilateral or bilateral)
Headache
Restlessness
Convulsions
Loss of consciousness
Coma
Respiratory signs and symptoms
Rhinorrhea (perfuse watery runny nose)
Bronchorrhea (excessive bronchial secretions)
Wheezing
Dyspnea (shortness of breath)
Chest tightness
Hyperpnea (increased respiratory rate/depth) - early (increased respiratory rate/depth)
Bradypnea (decreased respiratory rate) - late (decreased respiratory rate)
Cardiovascular signs resulting from blood loss
Tachycardia (increased heart rate) - early (increased heart rate)
Hypertension (high blood pressure) - early (high blood pressure)
Bradycardia (decreased heart rate) - late (decreased heart rate)
Hypotension (low blood pressure) - late (low blood pressure)
Arrhythmias Dysrhythmias (prolonged QT on EKG, ventricular tachycardia)
Gastrointestinal signs and symptoms
Abdominal pain
Nausea & and vomiting
Diarrhea
Urinary incontinence, frequency
Musculoskeletal signs and symptoms
Weakness (may progress to paralysis)
Fasciculations (local or generalized)
Skin and mucous membrane signs and symptoms
Profuse sweating (local or generalized)
Lacrimation (tear formation)
Conjunctival injection
Laboratory finding suggestive of nerve agent poisoning
Decreased plasma or red blood cell (RBC) cholinesterase activity.
Limitations
Wide normal range for enzyme activity makes interpretation difficult without a baseline measurement.
Cholinesterase activity correlates poorly with severity of local effects after vapor exposures.
Plasma or RBC cholinesterase may be disproportionately inhibited depending on the particular nerve agent, amount of exposure and time interval since exposure.
Interpreting cholinesterase activity
Plasma cholinesterase
usually declines faster than RBC cholinesterase ;
is easier to assay than RBC cholinesterase ;
regenerates faster than RBC cholinesterase ;
may have a day-to-day variation in enzyme activity may be as high as 20% ;
is less specific than RBC cholinesterase ; and
can show false depression from liver disease, malnutrition, pregnancy, genetic deficiency, or drugs ( e.g., codeine, morphine, cocaine, succinylcholine) .
Red blood cell cholinesterase
is a better reflection of CNS cholinesterase activity ;
is more specific test than plasma cholinesterase ;
may have a day-to-day variation in enzyme activity may be as high as 10% ; and
can show false depression from antimalarial therapy , or pernicious anemia
Differential diagnosis
Carbamate insecticides
Medicinal carbamates (eg, pyridostigmine, neostigmine, physostigmine)
Cholinomimetic compounds (eg, pilocarpine, methacholine, bethanechol)
Nicotine alkaloids (eg, nicotine, coniine)
Muscarine-containing mushrooms
Neuromuscular blocking drugs (eg, atracurim, vecuronium)
Note: The actual clinical manifestations of an exposure to a nerve agent or an organophosphate pesticide may be more variable than the syndrome described in this document.
This toxic syndrome description is based on CDC’s best current information.
It may be updated as new information becomes available.


*Nerve Agents*
By BrainNJ
Introduction:
The nerve agents (NA) are a group of particularly toxic chemical warfare agents. They were developed just before and during World War II and are related chemically to the organophosphorus insecticides. The principle agents in this group are: GA (Tabun), GB (Sarin), GD (Soman), GF and VX
Physical and Chemical Properties:
1. Nerve agents are organophosphorus esters. The "G" agents tend to be non-persistent whereas the "V" agents are persistent. Some "G" agents may be thickened with various substances in order to increase their persistence, and therefore the total amount penetrating intact skin.
2. It may be seen that at room temperature GB is a comparatively volatile liquid and therefore non-persistent. GD is also significantly volatile, as is GA though to a lesser extent. VX is a relatively non-volatile liquid and therefore persistent. It is regarded as presenting little vapor hazard to people exposed to it. In the pure state nerve agents are colorless and mobile liquids. In an impure state nerve agents may be encountered as yellowish to brown liquids. Some nerve agents have a faint fruity odor.
3. In general, nerve agents are moderately soluble in water with slow hydrolysis, highly soluble in lipids, rapidly inactivated by strong alkalis and chlorinating compounds.
Protection:
1. To prevent inhalation of an incapacitating or lethal dose it is essential that the breath is held and the respirator put on at the first warning of the presence, or suspected presence, of a nerve agent.
2. These agents penetrate normal clothing whether contact is with liquid or vapor and specialized clothing including a respirator, nuclear, biological, and chemical (NBC) suit, gloves and overboots are required for protection when liquid agent is present. The respirator protects the eyes, mouth and respiratory tract against nerve agent spray vapor and aerosol. Nerve agent vapor in field concentrations is absorbed through the skin very slowly, if at all, so that where a vapor hazard exists alone, the respirator may provide adequate protection without the use of an NBC suit. 
Decontamination
1. The importance of early decontamination cannot be over emphasized. Decontamination of the skin should be accomplished quickly if it is to be fully effective. Liquid agent may be removed by fullers' earth or chemically inactivated by the use of reactive decontaminants. Decontamination personnel should use a respirator and full protective equipment whilst decontamination is performed.
2. Once a casualty has been decontaminated, or the agent fully absorbed, no further risk of contamination exists. The casualty's body fluids, urine or feces do not present a chemical warfare (CW) hazard.
Mechanism of Action
1. Absorption. Nerve agents may be absorbed through any body surface. When dispersed as a spray or an aerosol, droplets can be absorbed through the skin, eyes and respiratory tract. When dispersed as a vapor at expected field concentrations, the vapor is primarily absorbed through the respiratory tract. If enough agent is absorbed, local effects are followed by generalized systemic effects. The rapidity with which effects occur is directly related to the amount of agent absorbed in a given period of time.
2. Inhibition by Agents.
a. The effects of the nerve agents are mainly due to their ability to inhibit acetyl-cholinesterase throughout the body. Since the normal function of this enzyme is to hydrolyse acetylcholine wherever it is released, such inhibition results in the accumulation of excessive concentrations of acetylcholine at its various sites of action. These sites include the endings of the parasympathetic nerves to the smooth muscle of the iris, ciliary body, bronchial tree, gastrointestinal tract, bladder and blood vessels; to the salivary glands and secretory glands of the gastrointestinal tract and respiratory tract; and to the cardiac muscle and endings of sympathetic nerves to the sweat glands. The accumulation of acetylcholine at these sites results in characteristic muscarinic signs and symptoms.
b. The accumulation of acetylcholine at the endings of motor nerves to voluntary muscles and in some autonomic ganglia results in nicotinic signs and symptoms.
c. The accumulation of excessive acetylcholine in the brain and spinal cord results in characteristic central nervous system symptoms
d. The inhibition of cholinesterase enzymes throughout the body by nerve agents may be irreversible and its effects prolonged.
e. Treatment with oximes should begin promptly.
f. Until the tissue cholinesterase enzymes are restored to normal activity, there is a period of increased susceptibility to the effects of another exposure to any nerve agent. The period of increased susceptibility occurs during the enzyme regeneration phase, which could last from weeks to months, depending on the severity of the initial exposure. During this period the effects of repeated exposures are cumulative.
3. Location of Acetylcholinesterase. Acetylcholinesterase is found associated with the post-junctional membrane at the neuromuscular junction and in the cell bodies and processes of cholinergic neurons. The concentration is particularly high in some central nervous system neurons. The location of acetylcholinesterase in autonomic ganglia is less well understood than that at the neuromuscular junction. Acetylcholinesterase is also found at sites where, as yet, no functional role has been identified: the musculotendinous junction, red blood cells, platelets and the placenta.
Signs and Symptoms
1. The order in which signs and symptoms appear and their relative severity depend on the route of exposure and whether the casualty has been exposed to liquid agent or vapor.
2. The signs and symptoms following exposure to nerve agents are given in Table 1.

Table 1
1. The local effects of vapor and liquid exposure are described followed by a description of the systemic effects, which occur after significant absorption of agent via any route.
Diagnosis and Therapy of Nerve Agent Poisoning:
1. Symptoms. Nerve agent poisoning may be identified from the characteristic signs and symptoms. If exposure to vapor has occurred, the pupils will be very small, usually pin-pointed. If exposure has been cutaneous or has followed ingestion of a nerve agent in contaminated food or water, the pupils may be normal or, in the presence of severe systemic symptoms, slightly to moderately reduced in size. In this event, the other manifestations of nerve agent poisoning must be relied on to establish the diagnosis. No other known chemical agent produces muscular twitching and fasciculations, rapidly developing pinpoint pupils, or the characteristic train of muscarinic, nicotinic and central nervous system manifestations.
2. Symptom Differentiation. It is important that individual service members know the following MILD and SEVERE signs and symptoms of nerve agent poisoning. Service members who have most or all of the symptoms listed below must IMMEDIATELY receive first aid (self-aid or buddy aid respectively).
3. MILD Poisoning (Self-Aid). Casualties with MILD symptoms may experience most or all of the following:
a. Unexplained runny nose.
b. Unexplained sudden headache.
c. Sudden drooling.
d. Difficulty in seeing (dimness of vision and miosis).
e. Tightness in the chest or difficulty in breathing.
f. Localized sweating and muscular twitching in the area of the contaminated skin.
g. Stomach cramps.
h. Nausea.
i. Bradycardia or tachycardia
4. MODERATE Poisoning. Casualties with MODERATE poisoning will experience an increase in the severity of most or all of the MILD symptoms. Especially prominent will be an increase in fatigue, weakness and muscle fasciculations. The progress of symptoms from mild to moderate indicates either inadequate treatment or continuing exposure to agent.
5. SEVERE Symptoms (Buddy Aid). Casualties with SEVERE symptoms may experience most or all of the MILD symptoms, plus most or all of the following:
a. Strange or confused behavior.
b. Wheezing, dyspnoea (severe difficulty in breathing), and coughing.
c. Severely pin-pointed pupils.
d. Red eyes with tearing.
e. Vomiting.
f. Severe muscular twitching and general weakness.
g. Involuntary urination and defecation.
h. Convulsions.
i. Unconsciousness.
j. Respiratory failure.
k. Bradycardia.
6. Aid for Severe Cases. Casualties with severe symptoms will not be able to treat themselves and must receive prompt buddy aid and follow-on medical treatment if they are to survive.
Treatment:
The lethal effects of nerve agent poisoning may be combated by a combination of pretreatment and post exposure therapy.
1. Pretreatment:
a. Poisoning by nerve agents that form rapidly aging complexes (for example Soman) may be particularly difficult to treat. These difficulties have been solved, in part, by the use of carbamates as pretreatment. The terms pretreatment or prophylaxis should perhaps be defined as used in this context:
1. Pretreatment: the administration of drugs in advance of poisoning designed to increase the efficacy of treatment administered post-poisoning.
2. Prophylaxis: the administration of drugs in advance of the poisoning designed to make post-poisoning therapy unnecessary.
b. The terms are to an extent interchangeable and as, in cases of severe poisoning, post-poisoning therapy is nearly always needed, the term pretreatment will be used here.
c. Carbamate anticholinesterases, e.g., pyridostigmine, may be used as pretreatments against nerve agent poisoning by virtue of their capacity to bind acetylcholinesterase reversibly, preventing the organophosphate (OP) binding to the enzyme. The term reversible is here used comparatively: the carbamate-acetylcholinesterase complex breaks down fairly rapidly, while organophosphate-acetylcholinesterase complexes break down very slowly. The aged soman-acetylcholinesterase complex breaks down virtually not at all.
d. When carbamates are used as pretreatments, carbamoylation of acetylcholinesterase prevents phosphorylation, but later the carbamate-acetylcholinesterase complex dissociates, freeing active enzyme. Current pretreatment regimes bind 30-40% of available red blood cell acetylcholinesterase, thereby allowing the carbamate to protect some of the acetylcholinesterase against attack by nerve agent.
e. The carbamate pyridostigmine, given in a dose of 30 mg every 8 hours, is used as a pretreatment. In conjunction with post exposure therapy, good protection against lethality is obtained within 2 hours of the first dose, but is not optimal until the third dose.
f. Pyridostigmine pretreatment should be stopped upon developing symptoms of nerve agent poisoning following a chemical warfare attack and post exposure therapy started.
g. Pyridostigmine tablets were taken over a 4 to 5 day period by large numbers of troops during the Gulf War of 1991
1. The effects of pyridostigmine were examined in several studies including one uncontrolled study of 42,000 troops when, following the recommended dose regime, under the stress of combat conditions, gastrointestinal intestinal changes including increased flatus, loose stools, abdominal cramps and nausea were noted by approximately half the population. Other reported effects were urinary urgency, headache, rhinorrhoea, diaphoresis and tingling of the extremities. These effects were considered tolerable. They did not noticeably interfere with performance of the full range of demanding physical and mental tasks required of service personnel.
2. Symptoms due to pyridostigmine may be ameliorated by taking the tablets with food.
3. Pyridostigmine pretreatment was discontinued on medical advice in less than 0.1% of individuals, generally because of intolerable nausea and diarrhoea.
h. When taken in excess of the recommended dosage, symptoms of carbamate poisoning will occur. These include diarrhea, gastrointestinal cramps, tight chest, nausea, rhinorrhoea, headache and miosis.
i. Good compliance is required if optimal protection is to be obtained. The importance of pyridostigmine pretreatment should therefore be stressed during training.
Post-Exposure Therapy:
The main principles of therapy for nerve agent poisoning are early treatment, assisted ventilation, bronchial suction, muscarinic cholinergic blockade (atropine), enzyme reactivation (oximes) and anticonvulsants (benzodiazepines).
Emergency Field Therapy
1. Self Aid (or Buddy Aid)
a. This comprises first aid measures, which the soldier can apply to help him or herself. The rapid action of nerve agents call for immediate self-treatment. Unexplained nasal secretion, salivation, tightness of the chest, shortness of breath, constriction of pupils, muscular twitching, or nausea and abdominal cramps call for the immediate intramuscular injection of 2 mg of atropine, combined if possible with oxime. From 1 to 3 automatic injection devices, each containing 2 mg atropine or mixture of atropine, oxime and/or anticonvulsant, are carried by each individual.
b. One device should be administered immediately when the symptoms and/or signs of nerve agent poisoning appear. This may be done by the casualty or by a buddy; the injection being given perpendicularly through the clothing into the lateral aspect of the middle of the thigh. Further devices, up to a total of 3, should be administered by the casualty or by his or her buddy during the following 30 minutes if the symptoms and/or signs of poisoning fail to resolve.
c. The timing of these further injections and whether they are given at one time or separately may depend on the casualty's condition and on instructions promulgated by individual nations.
d. NOTE: If automatic injectors are used in the absence of exposure to agent, the following signs and symptoms may be seen: Dry mouth, dry skin, fast pulse (>90 beats per minute), dilated pupils, retention of urine and central nervous system disturbance. Susceptibility to heat exhaustion or heat stroke is increased, particularly in closed spaces or while wearing protective clothing.
2. First Aid by Trained Personnel.
a. This comprises the emergency actions undertaken to restore or maintain vital bodily functions in a casualty. Wherever the casualty is not masked the respirator must be adjusted for him or her by the nearest available person. Attention should be given to decontamination at the earliest possible moment and any skin contamination must be removed with a personal decontamination kit.
b. After nerve agent poisoning, the administration of atropine is repeated at intervals until signs of atropinization (dry mouth and skin and tachycardia >90 per minute) are achieved. Miosis from vapor exposure is not relieved by systemic atropine.
c. Mild atropinization should be maintained for at least 24 hours by intramuscular injection of 1-2 mg of atropine at intervals of 1/2 to 4 hours, as required. The danger of ventricular arrhythmias arising from atropinization while the casualty is anoxic must be remembered.
d. Assisted ventilation is required for severely poisoned individuals as they will have:
1. Marked bronchoconstriction;
2. Copious secretions in the trachea and bronchi;
3. Paralysis of the respiratory muscles; and
4. Central respiratory depression, hypoxia, and convulsions.
3. Resuscitation:
a. Positive pressure resuscitation should be given but the pressure necessary to overcome the bronchoconstriction may be more than 65 cm of water so that intubation if possible is highly desirable. In an uncontaminated atmosphere assisted ventilation may be done by the standard mouth-to-mouth method after decontamination of the casualty's face and mouth. In a contaminated atmosphere ventilation may be given by a portable resuscitator with NBC filter attached. Both the casualty and the resuscitator should be decontaminated.
b. In a well equipped medical facility, mechanical resuscitation of the positive pressure type may be used with endotracheal intubation or tracheostomy - artificial respiration must be continued until the casualty is breathing normally or the medical personnel have pronounced the casualty dead. Due to the production of copious secretions, regular suction will be required.
Pharmacological Treatment of Nerve Agent Poisoning:
1. The pharmacological treatment of nerve agent poisoning involves the use of:
a. Anticholinergics to antagonise the muscarinic effects (atropine).
b. Oximes to reactivate inhibited enzyme.
c. Anticonvulsants to prevent CNS damage.
2. The effects of drugs used in nerve agent poisoning are described below
Atropine:
1. Atropine sulphate remains an essential drug in the treatment of nerve agent poisoning. It acts by blocking the effects of acetylcholine at muscarinic receptors and so produces relief from many of the symptoms previously listed. If given in large doses, some therapeutic effects are also produced within the central nervous system although atropine does not readily penetrate the blood brain barrier and central muscarinic receptors are thought not to be identical with those in the periphery. It is thought to counteract the respiratory depression in the medulla oblongata.
2. Urgent treatment with atropine in cases of nerve agent poisoning is essential. After the emergency field treatment, atropinisation should be maintained for at least 24 hours by intramuscular injection or slow intravenous infusion of 1 to 2 mg of atropine per hour as required. The dose should be repeated at intervals until signs of successful atropinisation are noted. Intervals of 5 to 15 minutes seem reasonable, but severe poisoning may require higher doses (4 mg to 6 mg per hour or more). Signs of successful atropinisation include the drying up of bronchial, salivary and skin secretions and an increase in heart rate to greater than 90 beats
per minute.
3. The effect of atropine in drying bronchial secretions may make the removal of mucus more difficult so suction is likely to be necessary. In excessive doses, atropine may render the ischaemic myocardium more liable to arrhythmias and electrocardiogram (ECG) monitoring should be undertaken in all patients if possible.
4. Atropine overdosage may produce euphoria, hallucinations, anxiety, and delirium and close observation of patients is necessary. Bladder dysfunction may necessitate catheterisation.
5. By inhibition of sweat production, atropine increases heat stress and in warm or hot weather care must be taken to avoid hyperthermia.
6. Atropine given parenterally has comparatively little effect on nerve agent induced miosis. The local application of cycloplegics (atropine eye drops) to the eye reduces both the degree of miosis, eye pain and headache. However, expert opinion on the value of atropine containing eye drops in the management of nerve agent induced miosis remains divided. It is believed by some that problems of accommodation may be made worse by the application of the drops and that, overall, little benefit may be produced.
7. If atropine is administered in the absence of nerve agent poisoning, the following effects may be noted: dryness of the mouth and pharynx, decreased sweating, slight flushing and tachycardia, some hesitancy of micturition, slightly dilated pupils, mild drowsiness, slowness of memory and recall and blurring of near vision. After 2mg these symptoms should not interfere with ordinary activity except in the occasional person, in hot environments or at high work rates. Higher doses, or repeated doses, will produce more marked symptoms which will usually not be totally incapacitating except in warm environments or high work rates. The effects of atropine are fairly prolonged, lasting 3 to 5 hours after one or two injections of 2mg and 12 to 24 hours after marked over-atropinisation.
Oximes:
1. Oximes
a. While atropine blocks the muscarinic effects of nerve agent poisoning it has little effect upon the nicotinic actions of the agent at the skeletal neuromuscular junction and at the autonomic ganglia.
b. Amelioration of the effects of nerve agents at these sites and also at muscarinic sites can, however, be obtained by reactivation of the inhibited acetylcholinesterase by means of oximes. Oximes, therefore, relieve the clinically important symptom of skeletal neuromuscular blockade. However, they penetrate into the central nervous system poorly, and the simultaneous administration of atropine is therefore still required.
Anticonvulsants
1. Atropine protects only partially against convulsions and the resulting brain damage in severe poisoning. Complementary treatment, including anticonvulsants, should be applied as necessary.
2. It has been shown in experimental soman poisoning that diazepam antagonises the convulsive action of soman and that addition of diazepam to the basic treatment regime greatly improves morbidity and mortality, independent of its anticonvulsive effect. Diazepam is the drug of choice and should be injected intramuscularly as a 10 mg dose initially and further doses should be given frequently enough to control convulsions. This may require injections at intervals ranging from a few minutes to several hours.
Supportive Care
Although pre and post exposure therapy will protect against lethality, casualties may still be incapacitated. A patient severely poisoned by an anticholinesterase is a critical medical emergency and may require intensive care for days or weeks. Assisted ventilation may be needed for many hours or days and the patient may be comatose for hours or days and brain damage may result from periods of hypoxia. General supportive care such as IV feeding, restoring electrolyte balance, treatment of shock and control of convulsions is needed. Therapy to control infection, should this occur, should be on the usual lines. Special care should be taken using muscle relaxants in patients poisoned by nerve agents.

Definition
Serum cholinesterase is a test that looks at blood levels of certain enzymes (acetylcholinesterase and pseudocholinesterase) that help the nervous system work properly.
Acetylcholinesterase (also known as RBC cholinesterase) and pseudocholinesterase (also known as butyrylcholinesterase or plasma cholinesterase) help break down a chemical that nerves need to send signals.
Acetylcholinesterase is found in nerve tissue and red blood cells. Pseudocholinesterase is found primarily in the liver.
Alternative Names
Acetylcholinesterase; RBC (or erythrocyte) cholinesterase; Pseudocholinesterase; Plasma cholinesterase; Butyrylcholinesterase
How the test is performed
Blood is drawn from a vein, usually from the inside of the elbow or the back of the hand. The site is cleaned with germ-killing medicine (antiseptic). The health care provider wraps an elastic band around the upper arm to apply pressure to the area and make the vein swell with blood.
Next, the health care provider gently inserts a needle into the vein. The blood collects into an airtight vial or tube attached to the needle. The elastic band is removed from your arm.
Once the blood has been collected, the needle is removed, and the puncture site is covered to stop any bleeding.
In infants or young children, a sharp tool called a lancet may be used to puncture the skin and make it bleed. The blood collects into a small glass tube called a pipette, or onto a slide or test strip. A bandage may be placed over the area if there is any bleeding.
How to prepare for the test
No special preparation is necessary for this test.
How the test will feel
When the needle is inserted to draw blood, you may feel moderate pain, or only a prick or stinging sensation. Afterward, there may be some throbbing.
Why the test is performed
This test is done to determine if a person has been exposed to a group of chemicals known as organophosphates, which are used in pesticides. These chemicals turn off cholinesterases. The level of acetylcholinesterase and pseudocholinesterase in your blood can be used to determine your exposure and risk of toxicity.
This test may also be done, although infrequently, to diagnose liver disease. It may also be ordered before a person receives anesthesia with succinylcholine, which may be given before certain procedures or treatments, including electroconvulsivetherapy (ECT).
Normal Values
Typically, normal pseudocholinesterase values range between 8 and 18 units per milliliter (U/mL).
Note: Normal value ranges may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results.
What abnormal results mean
Decreased pseudocholinesterase levels may be due to:
Acute infection
Chronic malnutrition
Heart attack
Liver damage
Metastasis
Obstructive jaundice
Poisoning from organophosphates (chemicals found in some pesticides)
Smaller decreases may be due to:
Pregnancy
Use of birth control pills
What the risks are
There is very little risk involved with having your blood taken. Veins and arteries vary in size from one patient to another and from one side of the body to the other. Taking blood from some people may be more difficult than from others.
Other risks associated with having blood drawn are slight but may include:
Excessive bleeding
Fainting or feeling light-headed
Hematoma (blood accumulating under the skin)
Infection (a slight risk any time the skin is broken
References
Ford MD. Acute poisoning. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier. 2007: chap 111.
Review Date: 6/24/2009
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. Copyright ©2010 A.D.A.M., Inc., as modified by University of California San Francisco. Any duplication or distribution of the information contained herein is strictly prohibited.
Information developed by A.D.A.M., Inc. regarding tests and test results may not directly correspond with information provided by UCSF Medical Center. Please discuss with your doctor any questions or concerns you may have.



http://chemm.nlm.nih.gov/na_hospital_mmg.htm
Acute Management Overview

Agent Identification
Nerve agents (NAs) are the most toxic of the known chemical warfare agents. They are chemically similar to organophosphate pesticides (OPs) and exert their biological effects by inhibiting acetylcholinesterase enzymes.
Nerve agents can cause loss of consciousness and convulsions within seconds and death from respiratory failure within minutes of exposure.
Volatile Nerve Agents (vapor)
Nerve agent vapor is readily absorbed by inhalation and ocular contact and produces rapid local and systemic effects.
G-type agents are clear colorless and tasteless liquids that are soluble in water and most organic solvents.
GB is odorless and is the most volatile nerve agent; however, it evaporates at about the same rate as water. GA has a slightly fruity odor and GD has a slight camphor-like odor (these are not reliable).
Low Volatility Nerve Agents (liquid)
Liquid nerve agent is readily absorbed through the skin; however, effects may be delayed for several minutes to up to 18 hours.
VX is a clear, amber-colored, odorless, oily liquid. It is soluble in water as well as in all other solvents. It is the least volatile nerve agent.
Responders should obtain assistance in identifying the chemical(s) from container shapes, placards, labels, shipping papers, and analytical tests. General information on these identification technicques is located in Emergency Response Guidebook.
Devices - M8, M9 chemical agent detector paper (liquid agents), M18A3 chemical agent detectors (vapor), M256A1 chemical agent detector kit (liquid and vapor), Draeger CDS Kit (vapor and aerosol), Hazmat Smart Strips (qualitative), Chemical Agent Detector C2 Kit (liquid and vapor), Chemical Agent Monitor (CAM) (vapor)
A comprehensive source for the selection of chemical identification equipment is the Guidefor the Selection of Chemical Detection Equipment for Emergency FirstResponders, Guide 100-06, January 2007, 3rd Edition published by the Department of Homeland Security to assist with this process.
Rescuer Protection
Persons whose clothing or skin is contaminated with nerve agent-containing solutions can secondarily contaminate response personnel by direct contact or through off-gassing vapor.
PPE Required - Level A
Nerve Agent Specific Triage
Severe symptoms - these include unconsciousness, convulsions, apnea, and flaccid paralysis.
Mild/ Moderate symptoms - these include localized swelling, muscle fasciculations, nausea and vomiting, weakness, shortness of breath.
Patients who are conscious and have full muscular control will need minimal care.
Patients with a history of possible exposure to vapor only (with no possibility of liquid exposure) who have no signs of exposure by the time they reach the medical facility have not been exposed (because these effects occur within seconds to minutes after exposure). They can be discharged.
Delayed Effects from skin exposure to liquid nerve agent may not develop for up to 18 hours following exposure.
Patients who have inhalation exposure and who complain of chest pain, chest tightness, or cough should be observed and examined periodically for 6 to 12 hours to detect delayed-onset bronchitis, pneumonia, pulmonary edema, or respiratory failure.
Patients exposed to nerve agent vapor that have only miosis and/or mild rhinorrhea when they reach the medical facility do not need to be admitted. All other patients who have had exposure to nerve agent should be hospitalized and observed closely.
Triage for Nerve Agent Casualties
Immediate (1)
Effects - Unconscious, talking but not walking, moderate to severe effects in two or systems more systems (e.g., respiratory, GI, cardiac arrest. muscular, CNS)
Clinical Signs - seizing or postictal, severe respiratory distress, recent cardiac arrest
Delayed (2)
Effects - recovering from agent exposure or antidote
Clinical Signs - diminished secretions, improving respiration
Minimal (3)
Effects - walking and talking
Clinical Signs - pinpoint pupils, runny nose, and mild to moderate difficulty breathing
Expectant (4)
(with limited resources)
Effects - Unconscious
Clinical Signs - Cardiac/respiratory arrest of long duration
Decontamination
Victims whose skin or clothing is contaminated with liquid nerve agent can contaminate rescuers by direct contact or through off-gassing vapor.
Persons whose skin is exposed only to nerve agent vapor pose no risk of secondary contamination; however, clothing and hair can trap vapor.
Route of Exposure
Inhalation - nerve agents are readily absorbed from the respiratory tract. Runny nose and tightness in the throat or chest begin within seconds to minutes after exposure. Nerve agent vapors are heavier than air. Odor does not provide adequate warning of detection.
Skin/Eye Contact - nerve agent liquids are readily absorbed from the skin and eyes. Vapors are not absorbed through the skin except at very high concentrations. Ocular effects may result from both direct contact and systemic absorption. The nature and timing of symptoms following dermal contact with liquid nerve agents depend on exposure dose; effects may be delayed for several hours.
Ingestion - ingestion of nerve agents is expected to be relatively rare compared to inhalation exposure or skin contact; however, they are readily absorbed from the GI tract and are highly toxic.
Clinical Signs and Symptoms
Nerve agents are potent acetylcholinesterase inhibitors causing the same signs and symptoms regardless of the exposure route. However, the initial effects depend on the dose and route of exposure.
Children are much more vulnerable than adults to nerve agent toxicity.
Manifestations of nerve agent exposure include:
Neuromuscular - pinpoint pupils (highly indicative of nerve agent exposure in a mass casualty situation), muscle twitching, confusion, seizures, flaccid paralysis, and coma.
In many instances children present with only neurological signs and symptoms.
Pulmonary - chest tightness, wheezing, shortness of breath, respiratory failure.
Gastrointestinal - nausea, vomiting, abdominal cramps, involuntary defecation.
Other - runny nose, excessive salivation and sweating, and urination.
Link to ToxicSyndromes
Differential Diagnosis
The diagnosis in a severely intoxicated individual is straightforward. The combination of miosis, copious secretions, bronchospasm, generalized muscle fasciculations, and seizures is characteristic.
Look carefully for miosis (if present will be helpful). Miosis may not be present initially following a low volatility nerve agent exposure.
A mild vapor exposure may mimic a child having allergic rhinitis/conjunctivitis.
A mild vapor may present with only visual complaints such as marrowing of the visual field or a sense that everything is getting dark.
GI symptoms by themselves could be confusing and they could be the only presenting signs.
Opiod abuse can include miosis, apnea, seizures etc.
Treatment
Treatment consists of supportive measures and repeated administration of nerve agent specific antidotes.
Nerve agent specific antidotes and supportive treatment may have to be initiated prior to decontamination.




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