![Page 1: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/1.jpg)
What neurologists should know about
NERVE AGENTSGrand Rounds
Department of Neurology
University of Cincinnati College of Medicine
18 November 2015
![Page 2: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/2.jpg)
2
Jonathan Newmark, M.D., FAANCOL (ret.), MC, USA
Adjunct Full Professor of Neurology, Uniformed Services University of the Health Sciences
Consultant to the Surgeon General of the Army for Chemical Casualty Care, 2002-2012
MM candidate, composition, College-Conservatory of Music, University of Cincinnati
Special Government Employee, Office of Health Affairs, US Department of Homeland Security
Department of Neurology, School of Medicine, University of Cincinnati
![Page 3: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/3.jpg)
Disclosures
The opinions are my own and not necessarily those of the Army, Department of Defense, nor of the Department of Homeland Security
No disclosures; if I had any, they would be violations of Federal law
3
![Page 4: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/4.jpg)
Resources
National Library of Medicine, Bethesda, Maryland Chemical Hazards Emergency Medical
Management web site: http://chemm.nlm.nih.gov
US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland Chemical Casualty Care Division web site:
http://ccc.apgea.army.mil Medical Management of Chemical-Biological
Casualties course
4
![Page 5: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/5.jpg)
Chemical and Biological Defense for Neurologists
Biological agents: Bacteria
Anthrax (meningitis) Viruses
VEE, other alphaviruses Toxins
Botulinum toxin Chemical agents:
Pulmonary intoxicants Cyanides Sulfur mustard and other vesicating agents Nerve agents
5
![Page 6: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/6.jpg)
6
Nerve agent: DEFINITION
A substance that causes biological effects by inhibiting acetylcholinesterase
Acetylcholinesterase, therefore, is the target of nerve agents
Acetylcholine accumulates
Effects are due to excess acetylcholine
![Page 7: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/7.jpg)
7
NERVE AGENTS
GA (tabun)
GB (sarin)
GD (soman)
GF
VX
![Page 8: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/8.jpg)
8
EXAMPLES OF ANTICHOLINESTERASES
Carbamates Physostigmine (Antilirium) Neostigmine (Prostigmine) Pyridostigmine (Mestinon) Sevin (insecticide)
Organophosphates Malathion Diazinon Nerve agents
Classical nerve agents: GA, GB, GD, VX
![Page 9: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/9.jpg)
9
GA
CHCH33CHCH2 2 OO PP NN
OO
CCNN
CHCH33
CHCH33
![Page 10: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/10.jpg)
10
GB
CHCH33 PP OO CH CH
OO
FF
CHCH33
CHCH33
![Page 11: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/11.jpg)
11
GD
CHCH33 PP OO CH C CH CH C CH33
OO
FF CHCH33 CHCH33
CHCH33
![Page 12: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/12.jpg)
12
VX
PP SS CH CH22CHCH22 NN
OOCHCH33
CHCH33CHCH22OO
CH(CHCH(CH33))22
CH(CHCH(CH33))22
![Page 13: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/13.jpg)
13
HISTORY
First synthesized by Gerhard Schrader, IG Farben,
Germany, 1936-8
Weaponized and stockpiled by Germany in WWII but never
used
Manufactured and stockpiled in quantity by USA, USSR,
Iraq, others
First used on the battlefield by Iraq, 1984-1987
First documented US battlefield casualties, Iraq, 2004
![Page 14: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/14.jpg)
14
![Page 15: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/15.jpg)
15
TERRORIST USE
Matsumoto, 1994
7 deaths
Tokyo, 1995
12 .5 (!) deaths
![Page 16: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/16.jpg)
16
SARIN ATTACK, TOKYO SUBWAY, 1995
![Page 17: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/17.jpg)
Syrian chemical attacks, August 2013
Claims that Bashar al-Assad used nerve agents against rebel-held residential areas
“1400 deaths” – Washington Post
Picture credit: The Guardian, UK
17
![Page 18: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/18.jpg)
18
PHYSICAL PROPERTIES
Clear, colorless liquids (when fresh); not “nerve gas”
Tasteless, most are odorless Freeze/melt <0º C Boil >150º C Volatility GB>GD>GA>GF>>>VX Penetrate skin, clothing
![Page 19: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/19.jpg)
19
TOXICITY
LCt50 LD50
mg-min / m3 mg / 70 kg
GA 400 1,000GB 100 1,700GD 70 50GF 50 30VX 10 10
![Page 20: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/20.jpg)
20
LD50 of VX
![Page 21: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/21.jpg)
21
NERVE AGENT PATHOPHYSIOLOGY
Target: Synaptic acetylcholinesterase (AChE)
Disabling AChE causes toxidrome of overstimulation at all cholinergic synapses
This is a form of cholinergic crisis
![Page 22: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/22.jpg)
22
CHOLINESTERASES: CIRCULATING AND NOT
Blood Acetyl (red cell, erythrocyte, “true”) Butyryl (plasma, pseudo) Easy to measure, not clinically relevant.
Tissue Tissue acetylcholinesterase (at cholinergic
receptor sites) This is the target of nerve agents!
Nerve agents will inhibit ALL of these.
![Page 23: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/23.jpg)
23
PHYSIOLOGY: NORMAL
Electrical impulse goes down nerve
Impulse causes release of neurotransmitter, acetylcholine
ACh stimulates receptor site on organ
Causes organ to act
ACh is destroyed by AChE
No more organ activity
![Page 24: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/24.jpg)
24
![Page 25: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/25.jpg)
25
NEUROTRANSMISSION:NEURON TO NEURON
![Page 26: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/26.jpg)
26
IMPULSE TERMINATION:THE ROLE OF AChE
![Page 27: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/27.jpg)
27
PHYSIOLOGY:NERVE AGENTS
Enzyme (AChE) is inhibited
Does not destroy ACh
Excess ACh continues to stimulate organ
Organ overstimulation
![Page 28: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/28.jpg)
28
EXPOSURE TONERVE AGENT
![Page 29: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/29.jpg)
29
EFFECTS ON STRIATED (SKELETAL) MUSCLE
![Page 30: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/30.jpg)
30
EFFECTS ON SMOOTH AND CARDIAC MUSCLE
![Page 31: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/31.jpg)
31
EFFECTS ON EXOCRINE GLANDS
![Page 32: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/32.jpg)
32
TWO MAJOR TYPES OF CHOLINERGIC RECEPTORS
Muscarinic Smooth muscles Exocrine glands Cranial nerves (vagus)
Nicotinic Skeletal muscles Preganglionic nerves
Both CNS (brain and spinal cord) – roughly 9/1
muscarinic/nicotinic
![Page 33: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/33.jpg)
33
CHOLINERGIC MUSCARINICEFFECTS
Smooth muscles Airways - constrict GI tract - constrict Pupils - constrict
Glands Eyes, nose, mouth, sweat, airways, GI
Heart, bradycardia (vagal)
![Page 34: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/34.jpg)
34
CHOLINERGIC NICOTINICEFFECTS
Skeletal muscles Fasciculations, twitching, fatigue, flaccid
paralysis Note that flaccid paralysis is NEVER the first
sign!
Pre-ganglionic Tachycardia, hypertension
![Page 35: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/35.jpg)
35
CHOLINERGIC NICOTINIC EFFECTS
![Page 36: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/36.jpg)
36
HEART RATE
Muscarinic (vagal) decreases
Nicotinic (ganglionic) increases
May be high, low, or normal
![Page 37: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/37.jpg)
37
CNS
Acutely, large exposure
Loss of consciousness
Seizures
Apnea (central, due to inhibition of brain
center)
Death
![Page 38: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/38.jpg)
38
CNS
Acutely, small exposure: neurobehavioral syndrome May follow any exposure; not dose-dependent Poorly understood; few well-studied patients May last 3-6 weeks (some claim longer) Can be minimal Nonspecific in nature:
Slowness in thinking and decision making Sleep disturbances Poor concentration Emotional problems
NB: This may be indistinguishable from post-traumatic stress disorder (PTSD)
![Page 39: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/39.jpg)
39
VAPOR
Small exposure Eyes: Miosis; injection; dim,
blurred vision; pain; maybe nausea, vomiting (from miosis
alone)
Nose: Rhinorrhea
Mouth: Salivation
Airways: Shortness of breath
![Page 40: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/40.jpg)
40
VAPOR: NOSE AND MOUTH
Runny nose
Worse than cold or hay fever
Leaking faucet
Mouth
Excessive saliva
May run out corners
![Page 41: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/41.jpg)
41
VAPOR:RESPIRATORY TRACT
Small exposure Tight chest
Moderate exposure Severe breathing
difficulty Gasping, irregular
breathing Compounded by
excessive secretions
![Page 42: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/42.jpg)
42
VAPOR:GASTROINTESTINAL
GI symptoms are the earliest symptoms in blood-borne NA exposure Possibly due to large
splanchnic circulation Exposure to a large but not
lethal concentration may cause Nausea, vomiting Pain in abdomen Diarrhea, involuntary
defecation or urination
![Page 43: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/43.jpg)
43
VAPOR: CARDIAC
Each individual has her/his own balance of vagal vs. sympathetic input to heart
Heart rate and blood pressure may increase or decrease
Usually HR increases early, then flattens
Not an indicator of efficacy of treatment! Individuals vary enormously!
![Page 44: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/44.jpg)
44
VAPOR: CNS (BRAIN)
Once nerve agent gets to the brain, symptoms include: Seizures Coma Central apnea (brain doesn’t tell the lungs to
breathe) Flaccid paralysis Death
![Page 45: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/45.jpg)
45
VAPOR
Onset of effects: seconds to minutes
After removal from vapor
Effects do not worsen
May improve
No late-onset effects
![Page 46: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/46.jpg)
46
VAPOR
Large exposure can go through all the preceding stages almost immediately, so first signs and symptoms may be: Loss of consciousness
Seizures
Apnea
Flaccid paralysis
Death
![Page 47: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/47.jpg)
47
LIQUID ON SKIN
Small droplet: local effects Sweating, fasciculations
Medium droplet: systemic effects NOTE: TAKES A LOT LONGER TO GO
SYSTEMIC than does vapor GI will be first system involved
Large droplet: CNS and lungs (also other organs, but those are not life-threatening): Respiratory failure, loss of consciousness, seizures,
apnea, flaccid paralysis, death
![Page 48: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/48.jpg)
48
LIQUID ON SKIN
Onset of effects
Small, medium drop
As long as 18 hours
Large, lethal drop
Usually <30 minutes
Factors affecting this: location on skin,
temperature, moisture
![Page 49: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/49.jpg)
49
LIQUID ON SKIN
Effects may occur despite initial decontamination Effects may worsen
This is a major difference between vapor poisoning and liquid-on-skin poisoning
![Page 50: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/50.jpg)
50
MIOSIS
Almost always after vapor
After liquid on skin:
Small: no
Moderate: maybe
Severe: definitely
![Page 51: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/51.jpg)
51
NORMAL PUPILLARYRESPONSE
![Page 52: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/52.jpg)
52
PINPOINT PUPILS
![Page 53: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/53.jpg)
53
NERVE-AGENT EFFECTS:EYES
3
6
13
20
41
62Day
s af
ter
exp
osu
re
![Page 54: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/54.jpg)
54
MANAGEMENT
ABCs
Drugs
Decontamination
Supportive
Not necessarily in that order
![Page 55: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/55.jpg)
55
MANAGEMENT
Most important
Protect self
Protective gear
Decontaminate casualty
Protect medical facility
Decontaminate casualty
![Page 56: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/56.jpg)
59
SKIN DECONTAMINATION
Early is best, within 1 to 2 minutes Little benefit after 30 minutes
Physical removal is best Forceful flush with water Stick, dirt, cloth, M291
There is a use for MRE bread! Solutions (hypochlorite, etc.)
Detoxify, but only after many minutes
PRINCIPLE: NO KNOWN DECONTAMINANT TRUMPS PHYSICAL REMOVAL ON SKIN!
![Page 57: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/57.jpg)
60
VENTILATION
Possibly less need after pyridostigmine
None forward of battalion aid station
Very high airway resistance until atropine is given
Therefore, give atropine FIRST, then try to ventilate
![Page 58: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/58.jpg)
61
ANTIDOTES
Strategy ONE: Too much acetylcholine
Block excess acetylcholine
Antidote = atropine
Strategy TWO: Enzyme inhibited
Reactivate enzyme
Antidote = oxime (2-PAM Cl)
![Page 59: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/59.jpg)
62
ATROPINE
Cholinergic blocking drug = anticholinergic
Blocks excess acetylcholine
Clinical effects at muscarinic sites Dries secretions
Reduces smooth muscle constriction
This may be lifesaving!
![Page 60: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/60.jpg)
63
ATROPINE AT RECEPTORS
![Page 61: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/61.jpg)
64
ACh AND ATROPINEAT RECEPTORS
![Page 62: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/62.jpg)
65
ATROPINE
Smaller autoinjector (2 mg / 0.7 ml) of Mark I kit
Starting dose 2 mg or 6 mg (1-3 autoinjectors) More: 2 mg every 5 to 10 minutes
Until Secretions drying Ventilation improved
Usual dose in severe casualty: 15 to 20 mg 1000s of mgs in insecticide poisonings due to
lipid solubility of insecticides
![Page 63: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/63.jpg)
66
ATROPINE
Will NOT benefit
Skeletal muscle effects
Miosis, unless used topically
Use will cause blurred vision for 24 hours
![Page 64: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/64.jpg)
67
ACTION OF ATROPINEON SMOOTH MUSCLE
![Page 65: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/65.jpg)
68
EFFECTS OF ATROPINEON EXOCRINE GLANDS
![Page 66: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/66.jpg)
69
STOPPING ATROPINE
Endpoints Reduction in secretions (muscarinic effects) Reduction in chest tightness (muscarinic effects) Patient able to breathe comfortably on his/her own
Do not titrate to Heart rate (variable; not an indicator of severity of
exposure) Miosis (may persist for up to 6 weeks despite
atropine) Twitching or fasciculations (nicotinic effects)
![Page 67: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/67.jpg)
70
OXIMES
React with the complex formed by the combination of nerve agent and AChE
Result of reaction is: Normal, catalytic AChE Nerve agent broken into two harmless
fragments which the body rapidly breaks down
![Page 68: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/68.jpg)
How oxime (2-PAM Cl) works
71
![Page 69: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/69.jpg)
72
OXIMES
Effects at nicotinic sites
Increase skeletal muscle strength
No additional clinical effects at muscarinic
sites
![Page 70: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/70.jpg)
73
OXIMES
Remove agent from enzyme unless aging has occurred
Aging = a reaction in which agent-enzyme bound complex changes
Oximes cannot reactivate enzyme after “aged” Aging T 1/2 = GD 2 min
GB 3 to 4 hours (so we may ignore aging clinically)
Others longer (so we may ignore aging clinically)
![Page 71: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/71.jpg)
74
INTRODUCTION OF 2-PAM ClAFTER AGING
![Page 72: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/72.jpg)
75
OXIMES
Other countries have different ones
United Kingdom: P2S
Germany, much of Europe, Iran: obidoxime (Toxigonin)
Israel: TMB4
Japan: 2-PAM Iodide
Canada: HI-6 (not yet approved by Health Canada)
Next generation American oxime may be MMB-4 (not yet
approved in USA)
![Page 73: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/73.jpg)
76
DOSE OF 2-PAM Cl
Larger autoinjector (600 mg / 2.0 ml) of Mark I kit 1-3 autoinjectors; may give additional 1 autoinjector
after one hour 2000+ mg of 2-PAM Cl may cause severe hypertension
IV: 1 gram slowly (over 20 to 30 min) Repeat in one hour
There is an UPPER BOUND to 2-PAM Cl treatment: no more than 1800 mg IM or 2000 mg IV in one hour
![Page 74: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/74.jpg)
77
MARK I AUTOINJECTOR
Spring-powered injectors
Atropine: 2 mg / 0.7 ml
2-PAM Cl: 600 mg / 2.0 ml
![Page 75: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/75.jpg)
78
ATNAA COMBINED AUTOINJECTOR CONTAINS 2.1 MG ATROPINE AND 600 MG
2-PAM ClThis item is replacing the MARK 1 kit!
![Page 76: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/76.jpg)
79
ATROPINE OPHTHALMICOINTMENT 1%
![Page 77: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/77.jpg)
80
SEIZURES
Without pyridostigmine Not prolonged Anticonvulsant seldom necessary
Prolonged after pyridostigmine (at least in animals) Possible brain damage from prolonged
seizures Anticonvulsant needed (diazepam)
Give diazepam to any severe casualty Dose: 10 mg im (CANA) In a seizing casualty 10 mg won’t be enough.
The combat medic/corpsman carries more. Next generation anticonvulsant = midazolam
![Page 78: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/78.jpg)
81
DIAZEPAM AUTOINJECTOR: CANADIAZEPAM AUTOINJECTOR: CANA
![Page 79: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/79.jpg)
82
ARRHYTHMIAS
Initial, transient from agent, atropine
Terminal after hypoxia
Ventricular fibrillation if atropine given
IV with hypoxia
![Page 80: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/80.jpg)
83
RECOVERY
Severe casualty:
Without complications, conscious, breathing, in 2 to 3 hours
IMPLICATION: A severe nerve agent casualty is a high priority for TREATMENT but is not a high priority for EVACUATION immediately. You should win the clinical battle for the patient’s life at YOUR echelon of care.
![Page 81: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/81.jpg)
CHEMPACK program: COL N and Dr. Susan Cibulsky of DHHS, Glendale, Arizona, 2011
85
![Page 82: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/82.jpg)
107
PYRIDOSTIGMINE:SUMMARY
Pre-exposure or “pretreatment” Not a substitute for post-exposure treatment “Hides” or protects a fraction of AChE
(creates a “reserve force”) Increases the amount of nerve agent a person can
be exposed to and survive; i.e., converts a lethal dose into a potentially survivable dose with antidotes
Causes predictable profiles of side effects Does not interfere with military function
![Page 83: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/83.jpg)
108
PYRIDOSTIGMINE:REGULATORY STATUS
Fully approved for pretreatment for soman ONLY by the Food and Drug Administration FEB 2003
FIRST DRUG EVER APPROVED USING THE ANIMAL RULE!
This means no IND or informed consent is necessary if the commander orders it to be used
Decision to use PB against potential nerve agent attack is driven by intelligence
I advised CENTCOM (7 MAR 03) that if the agent is not known, assume soman is possible and issue and order troops to take PB
![Page 84: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/84.jpg)
109
Upcoming and ongoing developments in nerve agent treatment
Replacement of MARK 1 by ATNAA Midazolam as a substitute for diazepam
(AAS) MMB-4 as a substitute for 2-PAM Cl (INATS) Bioscavengers Post-marketing studies on pyridostigmine Seizure monitor for the field Neuroprotectant for nerve agent poisoning
survivors
![Page 85: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/85.jpg)
Butyrylcholinesterase: a stoichiometric bioscavenger
110
![Page 86: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/86.jpg)
111
![Page 87: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/87.jpg)
112
DR. FREDERICK SIDELL
![Page 88: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/88.jpg)
Resources
National Library of Medicine, Bethesda, Maryland Chemical Hazards Emergency Medical
Management web site: http://chemm.nlm.nih.gov
US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland Chemical Casualty Care Division web site:
http://ccc.apgea.army.mil Medical Management of Chemical-Biological
Casualties course
113
![Page 89: What neurologists should know about NERVE AGENTS Grand Rounds Department of Neurology University of Cincinnati College of Medicine 18 November 2015](https://reader035.vdocuments.site/reader035/viewer/2022062804/5697bf931a28abf838c8f55d/html5/thumbnails/89.jpg)
114
SUMMARYANY QUESTIONS?