Title: 3 ER Cases
13 ER Cases
- Which patient has nerve agent poisoning?
- 9 year-old with miosis, agitation, copious
secretions, uncontrolled urination. HR 120. RR
16/shallow. Sat 83 - 15 year-old with generalized seizure, tongue
fasciculations, absent gag, absent reflexes - 2 year-old old with fussiness/diarrhea
progressing to impaired consciousness, hypotonia
2Nerve Agents in Children
- Josh Rotenberg MD MMS
- Fellow, Pediatric Neurology
- Staff Pediatrician, WRAMC NNMC
- Assistant Professor of Pediatrics, USUHS
3Nerve Agents in Children
- Background Scope of the Problem
- Background The agents
- Diagnosis
- Isolation/Decon
- Treatment
- Pediatric Issues
4Background Scope of the Problem
- CWA in US
- the most important act of terrorism in which CWA
was attempted to use a was the World Trade Center
bombing in 1993. - the explosive used by the terrorists contained
sufficient cyanide to contaminate the entire
structure. - Fortunately, the cyanide was destroyed by the
blast
5Background Scope of the Problem
- Police foil terror plot to use sarin gas in
London (Filed 18/02/2001) - Bin Laden British cell planned gas attack on
European Parliament (Filed 16/09/2001)
6Background Scope of the Problem
- Iran-Iraq war (1984-1988)
- UN confirmed that Iraq used Tabun and other
organophosphorous nerve agents - Sarin and Sulphur mustard used on Kurds in
Northern Iraq - Iraq has weaponized VX - 4 tons
- Gulf-War large, urban civil popualation
threatened for first time since WW1
7Sarin Attacks in Japan
- Matsumoto Japan, June 1994
- 7 died, 58 admitted, 600 injured
- Tokyo Subway March 1995
- Sarin released at several points in the Tokyo
subway - 11 killed, 5,500 injured
- secondary contamination of the house staff in
more than 20
8Background The agents
- Nerve agents include
- Tabun (GA)
- Sarin (GB)
- Soman (GD), and
- VX
9Background The agents
- Originally developed as insectisides
- more powerful than organophosphates
- Tabun is easiest and cheapest to manufacture.
- Described as a starter agent for CW program. Some
consider most likey to be used as terrorist
agent. - Sarin has been used in terrorist attacks
- VX only exists in military stockpiles
10 Background The agents
- Exist as a liquid or a gas
- Liquid is colorless (g-type) amber-colored (VX)
- Gas can be odorless, fruity (tabun) or slight
camphor odor (soman) - Vary in volatility some more persistent than
others - Sarin as volatile as water
- VX very persistent
11Background The agents
- Toxic effects depend on the concentration of the
agent inhaled and the time exposed to the agent. - LD50 - 100 mg/m3 for 1 minute is equivalent to 50
mg/m3 for 2 minutes - Note the vapor density
- Sarin 4.86
- VX 9.2
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13- When would you launch a sarin attack?
14How do nerve agents work?
- Irreversible phosphorylation of cholinesterase
enzymes at acetycholine receptors - Nicotinic
- Muscarinic
- CNS
- Adrenal
15Nerve Agents-Mucosal Absorption
- Nature and onset of signs and symptoms vary by
route of absorption. - Gases may be absorbed through any part of the
respiratory tract mucosa of the nose and mouth
to the alveoli of the lungs. - Aerosol particles
- gt than 5 µm tend to remain in the upper
respiratory tract - lt than 1 µm tend to be breathed in and out again,
although some of these smaller particles may be
retained. - They may also be directly absorbed by the
eye/skin/GI tract
16Nerve Agents - Absorption via Skin
- Agents which penetrate the skin may form
temporary reservoirs so that delayed absorption
may occur (less so, that OPP). - Even the vapor of some agents can penetrate the
intact skin and intoxication may follow. - Wounds/abrasions (even minor injuries caused by
shaving ) present areas which are more permeable
than intact skin. - The penetration of agents through the GI tract or
abrasions may not neccessarily be accompanied by
irritation or damage to the surfaces concerned.
17Neuromuscular Effects
- Twitching
- Weakness
- Paralysis
- Respiratory failure
18Autonomic Nervous System Effects
- Reduced Vision
- Small pupil size
- Drooling
- Sweating
- Diarrhea
- Nausea
- Abdominal pain
- Vomiting
19Eyes -- Miosis
- most common finding
- Matsumoto - 134/219 -2.5 mm or less
- improved with atropine
- Resolved in a month
- Impaired acuity in 124/219
- Blurry vision
- Visual Darkness
- Ocular pain
20Central Nervous System Effects
- Headache
- Convulsions
- Coma
- Respiratory arrest
- Confusion
- Slurred speech
- Depression
- Respiratory depression
21Delayed (Chronic) CNS Effects
- Giddiness, anxiety, jitteriness, restlessness,
emotional lability, excessive dreaming, insomnia,
nightmares, headaches, tremor, withdrawal and
depression, - drowsiness difficulty concentrating, slowness on
recall, confusion, slurred speech, ataxia. - bursts of slow waves of elevated voltage in EEG,
especially on hyperventilation,
22Cause of death
- In the absence of treatment
- anoxia resulting from airway obstruction,
weakness of the muscles of respiration and
central depression of respiration. - Airway obstruction
- due to pharyngeal muscular collapse,
- upper airway and bronchial secretions,
- bronchial constriction and
- occasionally laryngospasm and paralysis of the
respiratory muscles.
23Cause of death
- With adequate pulmonary support/toilet and
atropine, the individual may survive several
lethal doses of a nerve agent. - However, if the exposure has been many times the
lethal dose, death may occur despite treatment as
a result of respiratory arrest and cardiac
arrhythmia. - When overwhelming doses of the agent are absorbed
quickly, death occurs rapidly without orderly
progression of symptoms.
24Other symptoms
- Headache
- cough
- sore throat
- Can persist for weeks
25Differential Diagnosis
- Sudden Mass casualties - no sign of trauma
- ?Suspect airborne toxin
- Hypoxemic, miosis, profuse secretions ? Anti
-Cholinesterase agent - Unconscious, non-hypoxemic ? Cyanide
- venous blood gasses arterialized
- Less acute causes of respiratory problems
- ? Bo-tox - paralysis, absent reflexes
- ? ARDS like picture-anthrax,plague,phosgene
26Diagnosis
- Treatment institute rapidly based on clinical
judgment - Can measure RBC levels of acetycholinesterase
- Assess treatment and recovery.
- Insensitive as a screen
- Matsumoto ChE decreased in 43 of severely
affected - Tokyo decreased in 74 of admiitted
- 4 have genetic low levels
- Have genetic high levels, lose 50, still be nl
- One call to lab, 3 send outs-time is critical
- Clinical presentation is likely to vary in
children.
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28Isolation/Decon
- Decontamination is necessary
- Dogma
- 0.05 bleach- people
- 0.5 household bleach - equipment
- Truth Use what is available
- Good results can be obtained with such widely
differing means as talcum powder, flour, soap and
water, or special decontaminants.
29Isolation/Decon
- Isolation and Decon are necessary in the field
- Hot, Warm, Cold Zone - Triage in hot and cold
zones - Tokyo Most casualties arrive in POV
- First responders may also be early casualties
- Rotate health care workers in hot zone
- 23 health care workers had some sort of
physical disorder, though mild. - symptoms included ocular pain, headache, sore
throat, dyspnea, nausea, dizziness, and nose pain - none was seriously affected
30Triage Tokyo Subway, St. Lukes
- Mild severity
- miosis, rhinorrhea, and mild headache
- Moderate severity
- victims were immobile or complained of moderate
degree dyspnea, vomiting, severe headache or with
neurologic complication like fasciculation - Critical severity
- victims had cardiac or respiratory arrest.
31Treatment
- Atropine, respiratory support (secretion
management) - Antidotes must be given quickly
- But may still be effective if given late, even in
extremis
32Treatment
- Atropine-give liberally to dry secretions
- average total dose in adult 50 mg
- Pralidoxime 1 g over 5-10 min
- Fasciculations, Seizures treated with
benzodiazepines - IM not optimal but acceptable
33Mark 1 - USA/USAF
- Atropine - 2 mg (0.7 ml)
- 2 PAM Cl autoinjector dispenses 600 mg/2 ml
34Prophylaxis
- Pyridostigmine
- Military use only
35Supportive therapy for CWA exposure include
- Pulmonary treatment/toilet
- supplementary oxygen
- bronchodilators
- Fluids, elctrolytes, nutrition
- Hypothermia
- Eye care
- Attention to skin lesions,
- Treatment of complicating infections
36Pediatric considerations/guidance
- Antidotes - Dosages
- Organ System Specific
- Tokyo Subway, 1995
- 16 children
- 5 pregnant women
- Matsumoto, 1994
- age 3-89
- mean 33 y.o.
37Treatments Pediatric Dosage
- Atropine - ACLS protocol
- 0.02 to 0.05 mg/kg to a maximum of 2 mg. May
repeat q 10 minutes to reverse cholinergic
symptoms. - Min dose 0.1 mg
- Max dose - 0.5 mg child 1 mg adolescent
- Should we be liberal
- with atropine?
- ACLS dosing may
- not be sufficient
38Atropine Poisoning in Israeli Children
- n268, 92 of pediatric ERs
- Most cases accidental 7.5 intentional by
parents expecting exposure - doses of 0.01 to 0.17 mg/kg
- no fatalities,seizures
- 0.045 to 0.17 mg/kg - mild effects
39Treatments Pediatric Dosage
- Pralidoxime (US) 2-PAM, Protopam
- 20-50 mg/kg x 1 im/iv/sc. May repeat in 1 hour to
relieve muscle weakness (nicotinic) - Watch for muscle rigidity, laryngospasm,
tachycardia - n.b. others used in Europe and Israel
- Some studies suggest continuous infusion may be
better - no data in kids
40 Treatments Pediatric Dosage
- Diazepam For severe seizures/status epilepticus
- 30d to 5 y 0.05 to 0.3 mg/kg IV to a max of
5mg/dose. May repeat q15-30 minutes - 5 y.o. 0.05 to 0.3 mg/kg IV to a max of 10
mg/dose.
41CNS
- Carbamate and Organophosphate poisoning in young
children -- Pediatric Emerg Care, April 1999 - age 2-8, Median 2.8
- Stupor/Coma 100
- Hypotonia 100
- Miosis 56
- Diarrhea,, Bradycardia, Salivation 25-37
- Pulmonary edema 37
- Predominance of CNS findings in children?
- Immaturity of blood brain vs. developmental
effect on CNS cholinesterase
42Pulmonary
- Increased minute volume and vapor density
increases dose of vapor to children - Smaller airway will be more easily obstructed
- bronchoconstriction and secretions
43Dermatologic
- Skin absorption of liquid may be significant
consideration in infants. - Large surface to volume ratio in children
compared to adults - Fat soluble agents (less than OPP)
- Breaks in skin may permit easier penetration of
agent. - Incidence of atopy is approx 4.
44Dermatologic
- Decontamination - Bleach is a mild to moderate
mucosal irritant. - 0.5 bleach may cause contact dermatittis
- In children can present like prickly heat,
erythema, edema, blistering.
45Environmental Exposure/ Temperature Regulation
- Hypothermia - Patients will be fully disrobed
before decontamination - cold water/bleach solution.
- Adequate cover, clothing, diapers should be
available for parents and children. - Watch for delayed effects with warming
46Feeding
- No information is available regarding breast
feeding. - However, nerve agents are less lipid soluble than
OPP. - Breast feeding mothers should be encouraged to
pump and discard. - Until when? No research done
- Institutions should be ready to support infant
feedings
47Developmental-Triage and care
- Mild and early symptoms may be missed due to a
childs inability to communicate symptoms of pain
and pressure. - Alternatively, a physician might dismiss signs
symptoms such as sleepiness, hypotonia, cramps,
rhinnorhea as typical of other childhood
illnesses and behavior. - What will we do with the mother/infant pairs in
decon? - Unescorted children?
48Long-Term Effects
- CNS Organophospate poisoning literature suggests
chronic CNS (neurocognitive/cerebellar) and PNS
impairment - Carcinogenicity Limited data in animals suggests
no effect. One study suggests genotoxicity in
human lymphocytes - Reproductive Effects Limited data in animals
suggests no effect. - Tokyo - well babies
49Take Home Goodies
- Mass cas no traumaInhalant
- Presentation varies with
- agent, state, absorption, temperature
- Autonomic, CNS, muscular symptoms
- Start treatment based on suspicion
- atropine, respiratory support
- Consider diazepam, pralidoxime
- Pediatric Issues acute and chronic
50AAP Guidelines