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Nerve Agents - Prehospital Management

Cinical Overview

Agent Identification

  • Sarin (military designation GB) is a nerve agent that is one of the most toxic of the known chemical warfare agents. It is generally odorless and tasteless. Exposure to sarin can cause death in minutes. A fraction of an ounce (1 to 10 mL) of sarin on the skin can be fatal. Nerve agents are chemically similar to organophosphate pesticides (OP) and exert their effects by interfering with the normal function of the nervous system.
  • Sarin is odorless and is the most volatile nerve agent. 
  • Sarin (GB) can be absorbed into the body by inhalation, ingestion, skin contact, or eye contact. Ingestion is an uncommon route of exposure. Responders should obtain assistance in identifying the chemical(s) from container shapes, placards, labels, shipping papers, and analytical tests. General information on these identification techniques is located in Emergency Response Guidebook.
  • Identification Tools - CHEMM Intelligent Syndromes Tool (CHEMM-IST), WISER, Sarin Chemical Properties.
  • Devices - A limited selection of portable devices for rapid field detection or measurement of sarin is available.
    1. Colorimetric detection systems include the Chemical Agent Detector C2 Kit (vapor, aerosol, liquid), M256A1 Chemical Agent Detector Kit (vapor, liquid), No. 1 Mark 1 Detector Kit (vapor, aerosol), Draeger CDS Kit (vapor, aerosol) or comparable colorimetric detector tube kit.
    2. Some electronic handheld devices are capable of sarin detection and measurement (e.g., the HAZMATCAD Chemical Agent Detector).  Ion mobility spectrometry devices capable of detecting sarin include the SABRE 2000 (particles and vapor).
    3. For additional information see: Guide for the Selection of Chemical Detection Equipment for Emergency First Responders, Guide 100-06, January 2007, 3rd Edition published by the Department of Homeland Security.

Route of Exposure

Exposure to Sarin (GB) can occur by all routes, inhalation, ingestion, and dermal contact.  Liquid Sarin (GB) may produce health effects within minutes. Health effects from mild to moderate exposure may be delayed up to 18 hours; larger exposures may cause death within minutes to hours.

  • 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; bronchorrhea – rapid accumulation of water in the lungs – is one of the most serious effects and can rapidly be fatal. Nerve agent vapors are heavier than air. Odor does not provide adequate warning of detection.
  • Skin/Eye Contact - nerve agent liquids are readily absorbed into 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 and include lacrimation and miosis. Ocular symptoms following remote site (ingestion; skin absorption) systemic exposure may be the last to develop because of the time required for absorbed agent to reach the eye. On the other hand, direct deposition of sarin on the conjunctiva may result in almost immediate ocular symptoms. 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. Prolonged muscarinic receptor activation by Ach (acetylcholine) leads to symptoms characterized by over production of secretions (lacrimation, salivation, bronchial secretions, GI fluid loss, sweating) and smooth muscle activation (diarrhea, urination). This constellation of symptoms is characterized by the mnemonic SLUDGE.

  • Manifestations of nerve agent exposure include:
    • Ocular pinpoint pupils: (highly indicative of nerve agent exposure in a mass casualty situation), eye pain, conjunctivitis, and increased tearing are common (with systemic absorption pinpoint pupils may not occur immediately). Symptoms may occur from local effects secondary to vapor exposure or as a manifestation of systemic absorption.
    • CNS: High dose - seizures, confusion, loss of consciousness, apnea. Other signs and symptoms include; irritability, memory loss, fatigue, memory loss, behavioral and psychological changes.
    • In many instances children may present with only neurological signs and symptoms.
    • Skeletal muscles: Nerve agents stimulate skeletal muscle contraction, producing twitching and fasciculations. This leads to fatigue and flaccid paralysis.
    • Pulmonary: Inhalation of nerve agent vapor causes respiratory tract effects within seconds to minutes, increased, rhinorrhea, and bronchial secretions, chest tightness, wheezing, shortness of breath, and respiratory failure.
    • Cardiovascular: Potentially up to three phases in variable length - transient tachycardia/with or without hypertension (minutes) followed by bradycardia and hypotension. The final phase starts hours to days after exposure with QT interval prolongation and a tendency toward malignant dysrhythmias.
    • Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhea, and involuntary defecation. If GI symptoms occur within one hour of dermal contamination, severe intoxication is present.
    • Other: Runny nose, excessive salivation and sweating, and urination.
  • Link to CHEMM-IST
  • Link to Toxic Syndromes
  • Link to Primary and Secondary Survey

Differential Diagnosis

  • Recognition of potential nerve agent exposure clinical signs and symptoms may be most apparent when multiple patients present with the same syndrome.
  • 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. Onset may be delayed following an exposure route that does not involve direct liquid or vapor deposition on the eye.
  • A mild vapor exposure may mimic a child having allergic rhinitis/conjunctivitis.
  • A mild vapor exposure may present with only visual complaints such as narrowing of the visual field or a sense that everything is going dark.
  • GI symptoms by themselves may be the only presenting signs, and might be expected to present as the initial symptoms following ingestion.
  • Opioid abuse or weaponized opioids can include miosis, apnea, and coma. However, patients should not have significant vomiting and diarrhea. Pulmonary edema, a rare side effect of rapid reversal of the opioid toxidrome with naloxone, should not be mistaken for the bronchorrhea associated with nerve agent exposure.
  • Link to Chemical Hazards Emergency Medical Management Intelligent Syndromes Tool (CHEMM-IST)

Pediatric/Obstetric/Geriatric Vulnerabilities

Pediatric:

Children are more vulnerable to sarin because:

  • Children are likely to have more severe nicotinic effects than adults (weakness, tachycardia, as well as CNS effect (seizures). On the other hand, children tend to have less muscarinic effects than adults (bradycardia, salivation, bronchial secretions, and spasm) potentially making the toxic syndrome more difficult to recognize in a child.
  • Sarin may penetrate the blood brain barrier more easily in children than adults. Children may only exhibit CNS effects.
  • Children exposed to the same levels of sarin as adults may receive a larger dose because they have greater lung surface area: body weight ratios and increased minute volumes: weight ratios.
  • Infants and toddlers do not have the motor skills to escape from the scene of an incident.
  • The high vapor density of gases places the highest concentration close to the ground which is in the breathing zone of children.
  • Children have a higher respiratory rate and inhale a greater volume per minute.
  • Children have smaller diameter airways, anatomic subglottic narrowing, omega shaped epiglottic structure, relatively large tongue size, and less rigid ribs and trachea which make them more vulnerable to pulmonary agent induced pathology such as bronchospasm, copious secretions, and pulmonary edema.
  • Children’s skin is thinner and has more moisture content therefore being more vulnerable to inflammatory effects and to toxin absorption.
  • Children have less fluid reserve, which increases the risk of rapid dehydration following vomiting and diarrhea.

 

Obstetric:

Pregnant women have several unique vulnerabilities when exposed to nuclear, biological, or chemical disaster agents.  The physiologic changes that occur during pregnancy have the potential to alter a pregnant woman’s response to chemical exposures when compared to non-pregnant adults: 

  • Increased blood volumes and the addition of the placental-fetal circulation can result in a dilutional effect, not only of the toxic agents but also of the antidotes administered.
  • Increased tidal volumes may result in increased likelihood of the pregnant victim being exposed to a greater amount of respiratory chemicals in a given unit of time. 
  • Increased renal blood, glomerular filtration, and renal excretion may result (depending on the elimination characteristics of the specific agent) in the victim rapidly excreting not only the noxious agent but also the antidotes that may have been administered.
  • The enlarged pregnant uterus may cause compression of the vena cava (supine hypotension syndrome) when the victim is laid flat on her back either for immobilization or for resuscitation.  This may have implications for fetal well-being if prolonged. 
  • The mother’s safety and well-being should always take priority over any concerns related to potential fetal harm by the toxic agents or by the antidotal treatments. Therefore, any treatments that would be given to a non-pregnant woman should not be withheld because of the pregnancy. 
  • Antidote dosages should be calculated with taking into consideration the increased blood volume in pregnancy.  If this evaluation is inconclusive, use general adult dosing recommendations.  Follow dosing recommendations, but be aware that these may not take into account the physiological changes in pregnancy. 

 

Geriatric:

No systematic human studies that have evaluated the differences in the clinical effects of sarin between older and younger adults are available. Therefore information regarding age differences in responses must be developed from animal experiments or extrapolated from the known differences in the response to pharmaceuticals.  Alterations in both pharmacokinetics and pharmacodynamics as people age contribute to altered responses in older adults. Therefore, older adults could be more vulnerable to sarin due to:

  • Thinner skin which may alter the absorption of poisons following dermal exposure (particularly applicable to vesicants, which may cause more damage in older adults).
  • Increased ratio of body fat to body water which may increase the distribution of fat-soluble poisons.
  • Decreased renal function which may decrease the elimination of some poisons.
  • Decreased serum acetylcholinesterase activity which may alter the effects of nerve agents.
  • Loss of reserve in several key organ systems. Older patents have less cardiovascular, CNS, and pulmonary reserve. Therefore an exposure that may be tolerable in a younger adult could be life-threatening in an older patient.

 

These changes also increase the risk of adverse events from treatment for chemical exposures. Older patients are more likely to develop delirium from anticholinergic medications (e.g., atropine) and from benzodiazepines. Therefore dosing should be slower in cases where immediate reversal of nerve agent effects is not required for stabilization.  Note that since age-related changes are directly related to an individual’s physiological condition, it is impossible to predict the extent of age-related changes in an individual.

Link to Primary and Secondary Survey

Acute Patient Care Guidelines References