Acetylcholinesterase Inhibitors (Carbamates, Nerve Agents, Organophosphates) Exposure

Table of Contents

Aliases

Acetylcholinesterase inhibitor, ATNAA®, carbamate, Duodote®, insecticide, nerve agent, organophosphate, pesticide, weapons of mass destruction, WMD

Patient Care Goals

  1. Rapid recognition of the signs and symptoms of confirmed or suspected acetylcholinesterase inhibitor (AChEI) agents such as carbamates, nerve agents, or organophosphates exposure followed by expeditious and repeated administration of atropine, the primary antidote
  2. Carbamates and organophosphates are commonly active agents in over-the-counter insecticides
  3. Accidental carbamate exposure rarely requires treatment

Patient Presentation

Inclusion Criteria

  1. DUMBELS is a mnemonic used to describe the signs and symptoms of acetylcholinesterase inhibitor agent poisoning. All patient age groups are included where the signs and symptoms exhibited are consistent with the toxidrome of DUMBELS
    1. Diarrhea
    2. Urination
    3. Miosis/Muscle weakness
    4. Bronchospasm/Bronchorrhea/Bradycardia (the killer B’s)
    5. Emesis
    6. Lacrimation
    7. Salivation/Sweating

Exclusion Criteria

No recommendations

Patient Management

  1. Don the appropriate PPE
  2. Remove the patient’s clothing and wash the skin with soap and water
    1. Acetylcholinesterase inhibitor agents can be absorbed through the skin
    2. Contaminated clothing can provide a source of continued exposure to the toxin
  3. Rapidly assess the patient’s respiratory status, mental status, and pupillary status
  4. Administer the antidote immediately for confirmed or suspected acetylcholinesterase inhibitor agent exposure
  5. Administer oxygen as appropriate with a target of achieving 94-98% saturation and provide airway management
  6. Establish intravenous access (if possible)
  7. Apply a cardiac monitor (if available)
  8. The heart rate may be normal, bradycardic, or tachycardic
  9. Clinical improvement should be based upon the drying of secretions and easing of respiratory effort rather than heart rate or pupillary response.
  10. Continuous and ongoing patient reassessment is critical

Assessment

  1. Acetylcholinesterase inhibitor agents are highly toxic chemical agents and can rapidly be fatal
  2. Patients with low-dose chronic exposures may have a more delayed presentation of symptoms
  3. Antidotes (atropine and pralidoxime) are effective if administered before circulation fails
  4. The patient may develop:
    1. Miosis (pinpoint pupils)
    2. Bronchospasm
    3. Bradycardia
    4. Vomiting
    5. Excessive secretions in the form of:
      1. Tearing
      2. Salivation
      3. Rhinorrhea
      4. Diarrhea
      5. Urination
      6. Bronchorrhea
  5. Penetration of an acetylcholinesterase inhibitor agent into the central nervous system (CNS) will cause:
    1. Headache
    2. Confusion
    3. Generalized muscle weakness
    4. Seizures
    5. Lethargy or unresponsiveness
  6. Estimated level of exposure based upon signs and symptoms
    1. Mild
      1. Miosis alone (while this is a primary sign in vapor exposure, it may not be present is all exposures)
      2. Miosis and severe rhinorrhea
    2. Mild to moderate (in addition to symptoms of mild exposure)
      1. Localized swelling
      2. Muscle fasciculations
      3. Nausea and vomiting
      4. Weakness
      5. Shortness of breath
    3. Severe (in addition to symptoms of mild to moderate exposure)
      1. Unconsciousness
      2. Convulsions
      3. Apnea or severe respiratory distress requiring assisted ventilation
      4. Flaccid paralysis
  7. Onset of symptoms can be immediate with an exposure to a large amount of the acetylcholinesterase inhibitor
    1. There is usually an asymptomatic interval of minutes after liquid exposure before these symptoms occur
    2. Effects from vapor exposure occur almost immediately
  8. Signs and symptoms with large acetylcholinesterase inhibitor agent exposures (regardless of route)
    1. Sudden loss of consciousness
    2. Seizures
    3. Copious secretions
    4. Apnea
    5. Death
  9. Obtain an accurate ingestion history (as patient may become unconscious before arrival at ED):
    1. Time of ingestion or exposure
    2. Route of exposure
    3. Quantity of medication or toxin taken (safely collect all possible medications or agents)
    4. Alcohol or other intoxicant taken
    5. Pertinent cardiovascular history or other prescribed medications for underlying disease
  10. The patient can manifest any or all of the signs and symptoms of the toxidrome based on the route of exposure, agent involved, and concentration of the agent:
    1. Vapor exposures will have a direct effect on the eyes and pupils causing miosis
    2. Patients with isolated skin exposures will have normally reactive pupils
    3. Certain acetylcholinesterase inhibitor agents can place the patient at risk for both a vapor and skin exposure 

Treatment and Interventions (see dosing tables below)

  1. Medications:
    1. Atropine
      1. Atropine is the primary antidote for organophosphate, carbamate, or nerve agent exposures, and repeated doses should be administered liberally to patients who exhibit signs and symptoms of exposure or toxicity
      2. Atropine may be provided in multi-dose vials, pre-filled syringes, or auto-injectors
        1. BLS Providers may use auto-injectors
      3. Commercially available atropine auto-injectors include:
        1. Atro-Pen® 1 mg of atropine (dark red container)
        2. Atro-Pen® 2 mg of atropine (green container)
        3. Pediatric Atro-Pen® 0.25 mg of atropine (yellow container)
        4. Pediatric Atro-Pen® 0.5 mg of atropine (blue container)
    2. Pralidoxime chloride (2-PAM)
      1. Pralidoxime chloride is a secondary treatment and should be given concurrently in an effort to reactivate the acetylcholinesterase
      2. Pralidoxime chloride may be provided in a single dose vial, pre-filled syringes, or auto-injectors
      3. Auto-injectors contain 600 mg of pralidoxime chloride
      4. In order to be beneficial to the victim, a dose of pralidoxime chloride should be administered shortly after the nerve agent or organophosphate poisoning as it has minimal clinical effect if administration is delayed
    3. Benzodiazepines
      1. Benzodiazepines are administered as an anticonvulsant for those patients who exhibit seizure activity [see Seizures guideline for doses and routes of administration]
      2. Lorazepam, diazepam, and midazolam are the most frequently used benzodiazepines in the prehospital setting
      3. In the scenario of an acetylcholinesterase inhibitor agent exposure, the administration of diazepam or midazolam is preferable due to their more rapid onset of action
      4. Benzodiazepines may be provided in multi-dose or single-dose vials, pre-filled syringes, or auto-injectors
      5. CANA® (Convulsive Antidote Nerve Agent) is a commercially available auto-injector that contains 10 mg of diazepam
    4. Mark I® Kits
      1. A commercially available kit of nerve agent/organophosphate antidote auto-injectors. These are being phased out and replaced with Duodote by the CDC
      2. A Mark I® kit consists of one auto-injector containing 2 milligrams of atropine and a second auto-injector containing 600 milligrams of pralidoxime chloride
    5. Duodote®
      1. A commercially available auto-injector of nerve agent/organophosphate antidote
      2. Duodote® is one auto-injector that contains 2.1 milligrams of atropine and 600 milligrams of pralidoxime chloride
    6. ATNAA® (Antidote Treatment Nerve Agent Auto-injector)
      1. An auto-injector of nerve agent/organophosphate antidote that is typically in military supplies
      2. ATNAA® is one auto-injector that contains 2.1 milligrams of atropine and 600 milligrams of pralidoxime chloride
      3. ATNAA® may be seen in civilian supplies assets when Duodote® is unavailable or in short supply
    7. CHEMPACK
      1. Federally-owned cache of nerve agent antidotes that is managed by the Centers for Disease Control and Prevention (CDC) and offered to states that voluntarily agree to maintain custody and security of CHEMPACK assets
      2. These are forward-deployed at sites determined by states that are part of the program such as hospitals and EMS centers
      3. Deployment of CHEMPACKs are reserved for events where the nerve agent/organophosphate exposure will deplete the local or regional supply of antidotes
      4. There are two types of CHEMPACK containers:
        1. EMS Containers: CHEMPACK assets for EMS contain a large portion of auto-injectors for rapid administration of antidotes by EMS providers of all levels of licensure/certification – They contain enough antidote to treat roughly 454 patients
        2. Hospital Containers: CHEMPACK assets contain a large portion of multidose vials and powders for reconstitution – they contain enough antidote to treat roughly 1000 patients
  2. Medication Administration:
    1. Atropine in extremely large, and potentially multiple, doses is the antidote for an acetylcholinesterase inhibitor agent poisoning
    2. Atropine should be administered immediately followed by repeated doses until the patient’s secretions resolve
    3. Pralidoxime chloride (2-PAM) is a secondary treatment and, when possible, should be administered concurrently with atropine
    4. The stock of atropine and pralidoxime chloride available to EMS providers is usually not sufficient to fully treat the victim of an acetylcholinesterase inhibitor agent exposure; however, EMS providers should initiate the administration of atropine and, if available, pralidoxime chloride
    5. Seizures should be treated with benzodiazepines. There is some emerging evidence that, for midazolam, the intranasal route of administration may be preferable to the intramuscular route. However, intramuscular absorption may be more clinically efficacious than the intranasal route in the presence of significant rhinorrhea
    6. The patient should be emergently transported to the closest appropriate medical facility as directed by direct medical oversight
  3. Recommended Doses (see dosing tables below) The medication dosing tables that are provided below are based upon the severity of the clinical signs and symptoms exhibited by the patient. There are several imperative factors to note:
    1. For organophosphate or severe acetylcholinesterase inhibitor agent exposure, the required dose of atropine necessary to dry secretions and improve the respiratory status is likely to exceed 20 mg. Atropine should be administered rapidly and repeatedly until the patient’s clinical symptoms diminish. Atropine must be given until the acetylcholinesterase inhibitor agent has been metabolized. It may require up to 2000 mg of atropine over several days to weeks
    2. Since the antidotes in the Mark I® kit are in two separate vials, the atropine auto-injector in the kit can be administered to the patient in the event that Atro-Pen® or generic atropine auto-injectors are not available and/or intravenous atropine is not an immediate option
    3. Due to the fact that Duodote® auto-injectors contain pralidoxime chloride, they should not be used for additional dosing of atropine beyond the recommended administered dose of pralidoxime chloride
    4. All of the medications below can be administered intravenously in the same doses cited for the intramuscular route. However, due to the rapidity of onset of signs, symptoms, and potential death from acetylcholinesterase inhibitor agents, intramuscular administration is highly recommended to eliminate the inherent delay associated with establishing intravenous access
    5. The antidotes can be administered via the intraosseous route. However, due to the rapidity of onset of signs, symptoms, and potential death from acetylcholinesterase inhibitor agents, intramuscular administration remains the preferable due to the inherent delay associated with establishing intraosseous access and the limited use of this route of administration for other medications

 

Notes – Acetylcholinesterase Inhibitors (Carbamates, Nerve Agents, Organophosphates) Exposure