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3 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

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3 ER Cases

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3 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

Joshua Rotenberg MD MMS, Pediatric Neurology


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Nerve Agents in Children

Josh Rotenberg MD MMS

Fellow, Pediatric Neurology

Staff Pediatrician, WRAMC & NNMC

Assistant Professor of Pediatrics, USUHS

Joshua Rotenberg MD MMS, Pediatric Neurology


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Nerve Agents in Children

  • Background: Scope of the Problem

  • Background: The agents

  • Diagnosis

  • Isolation/Decon

  • Treatment

  • Pediatric Issues

Joshua Rotenberg MD MMS, Pediatric Neurology


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Background: 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

Joshua Rotenberg MD MMS, Pediatric Neurology


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Background: 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)

Joshua Rotenberg MD MMS, Pediatric Neurology


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Background: 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

Joshua Rotenberg MD MMS, Pediatric Neurology


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Sarin 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%

  • Joshua Rotenberg MD MMS, Pediatric Neurology


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    Background: The agents

    • Nerve agents include:

      • Tabun (GA)

      • Sarin (GB)

      • Soman (GD), and

      • VX

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Background: 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”

  • Joshua Rotenberg MD MMS, Pediatric Neurology


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    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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Background: 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

    Joshua Rotenberg MD MMS, Pediatric Neurology



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    Joshua Rotenberg MD MMS, Pediatric Neurology


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    How do nerve agents work?

    • Irreversible phosphorylation of cholinesterase enzymes at acetycholine receptors

      • Nicotinic

      • Muscarinic

      • CNS

      • Adrenal

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Nerve 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

      • > than 5 µm tend to remain in the upper respiratory tract

      • < 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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Nerve 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.

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Neuromuscular Effects

    • Twitching

    • Weakness

    • Paralysis

    • Respiratory failure

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Autonomic Nervous System Effects

    • Reduced Vision

    • Small pupil size

    • Drooling

    • Sweating

    • Diarrhea

    • Nausea

    • Abdominal pain

    • Vomiting

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Eyes -- 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

  • Joshua Rotenberg MD MMS, Pediatric Neurology


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    Central Nervous System Effects

    • Headache

    • Convulsions

    • Coma

    • Respiratory arrest

    • Confusion

    • Slurred speech

    • Depression

    • Respiratory depression

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Delayed (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,

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Cause 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.

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Cause 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.

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Other symptoms

    • Headache

    • cough

    • sore throat

    • Can persist for weeks

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Differential 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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Diagnosis:

    • 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.

    Joshua Rotenberg MD MMS, Pediatric Neurology



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    Isolation/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.

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Isolation/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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Triage: 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.

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Treatment

    • Atropine, respiratory support (secretion management)

    • Antidotes must be given quickly

      • But may still be effective if given late, even in extremis

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Treatment

    • 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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Mark 1 - USA/USAF

    • Atropine - 2 mg (0.7 ml)

    • 2 PAM Cl autoinjector dispenses 600 mg/2 ml

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Prophylaxis

    • Pyridostigmine

    • Military use only

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Supportive 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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Pediatric considerations/guidance

    • Antidotes - Dosages

    • Organ System Specific

    • Tokyo Subway, 1995

      • 16 children

      • 5 pregnant women

    • Matsumoto, 1994

      • age 3-89

      • mean 33 y.o.

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Treatments: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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Atropine Poisoning in Israeli Children

    • n=268, 92% of pediatric ER’s

    • 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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Treatments: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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    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.

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    CNS

    • 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

  • Joshua Rotenberg MD MMS, Pediatric Neurology


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    Pulmonary

    • Increased minute volume and vapor density increases dose of vapor to children

    • Smaller airway will be more easily obstructed

      • bronchoconstriction and secretions

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Dermatologic

    • 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%.

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Dermatologic

    • 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.

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Environmental 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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Feeding

    • 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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Developmental-Triage and care

    • Mild and early symptoms may be missed due to a child’s 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?

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Long-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

    Joshua Rotenberg MD MMS, Pediatric Neurology


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    Take Home Goodies

    • Mass cas + no trauma=Inhalant

    • 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

  • Joshua Rotenberg MD MMS, Pediatric Neurology


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    AAP Guidelines

    Joshua Rotenberg MD MMS, Pediatric Neurology


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