August 26, 2023

In a previous installment of Pharmacy Phriday, we discussed Atropine’s use during bradycardia.  In this edition, we focus on Atropine’s use along with 2-Pam, or Pralidoxime, for organophosphate (OP) poisonings or nerve agent exposures. These two medications serve as antidotes for these specific poisonings and are combined in the DuoDote, which if available to the provider, allows for quicker administration in the case of an exposure.  The other primary medication used in the treatment of these exposures is a benzodiazepine to address resultant seizures.

The listing of the Duo Dote and the associated protocol for nerve agent exposure can be found in the UH protocol under “Appendix #2: Medical Procedures/ Special Procedures/ Nerve Agent Antidote Kit”.  The use of Atropine in OP poisonings can be found in the UH Protocols under the “Adult Medical Emergencies Protocols/ Toxic Ingestion/ Exposure/ Overdose.”

An estimated 3 million or more people worldwide are exposed to organophosphates each year, mainly through exposure to insecticides.  Following an exposure, the enzymes and neurotransmitters of the nervous system are affected causing the signs and symptoms seen.

You may recall that the parasympathetic system releases a neurotransmitter called acetylcholine (ACh) which slows things down. An enzyme involved in the balance between the sympathetic and parasympathetic systems is Acetylcholinesterase (AChE).  AChE breaks down ACh, thus limiting its effects. In an OP or nerve agent poisoning, the AChE enzyme is inhibited from doing its work, letting ACh act unrestricted on nicotinic and muscarinic receptors. To prevent the effects of the ACh, we administer Atropine.  To reactivate the AChE, 2-PAM is administered.

Signs and symptoms of these toxidromes depend on the specific receptors affected in the body and can be recalled using some rather easy to remember acronyms.

SLUDGE (symptoms associated with muscarinic receptors)

Salivation

Lacrimation

Urination

Defecation

GI upset

Emesis

MTWtHF (symptoms associated with nicotinic receptors)

Muscle weakness/paralysis

Tachycardia

Weakness

Hypertension

Fasciculations (muscle twitch)

Of the many signs and symptoms, airway concerns and hypoxia are symptoms of paramount importance in OP poisonings. This is one reason the suggested endpoint for atropine use is dried pulmonary secretions and adequate oxygenation.

Access to these medications and adequate quantities of them are a consideration in these emergencies.  Various benzodiazepines can be found in the UH drug boxes.  Atropine can be found in the drug boxes, but quantities will only be a start in a true OP poisoning. 2-PAM is not provided in the UH drug box and is only found in specific situations and circumstances.

Another source of these medications that exist for the mass casualty incident is the SDS CHEMPACK program.  EMS CHEMPACKS, capable of treating 454 patients, can be accessed through the initiation of the Incident Commander and Medical Control and delivered directly to the scene from strategically located caches.  The CHEMPACKS provide large quantities of Atropine, 2-PAM, and Valium. 

As mentioned above, the Duo Dote does combine two of these medications.  Though not as readily available as they once were, the Duo Dotes may be accessible through special Haz-Mat response teams, some industrial settings, or on rare occasions, on individual squads. 

The Duo Dote can be administered by the EMT in the scenario of a nerve agent exposure.  Up to 3 auto-injectors can be used for one patient depending on the severity of symptoms.  The Duo Dote is not appropriate for pediatric patients under 90 pounds.  Follow this LINK for a demonstration of the use of the auto-injector. 

Be sure to pre-plan for these types of emergencies.  Some suggested topics to discuss may include uses of and storage of organophosphates in your response areas, availability and access to medications, decontamination concerns, proper PPE for responders, and other important details within the algorithms and key points in the protocols as well as local policies and procedures.  

Till the next time, stay safe!

Sincerely,

The UH EMS-I Team

University Hospitals

August 29, 2022

Dear Colleagues,

In the last installment of Pharmacy Phriday, Atropine’s use during bradycardia was reviewed. This edition focuses on Atropine’s use along with 2-Pam, or Pralidoxime, for organophosphate (OP) poisonings or nerve agent exposures. These two antidotes for this specific poisoning are combined in the DuoDote. 

The medications and associated protocol for nerve agent exposure can be found in the UH protocol under “Appendix #2: Medical Procedures/ Special Procedures/ Nerve Agent Antidote Kit”. The use of Atropine in OP poisonings can be found in the UH protocols under the “Adult Medical Emergencies Protocols/ Toxic Ingestion/ Exposure/ Overdose.”

To recap from last week’s article, the parasympathetic system releases acetylcholine (ACh) which slows things down.  It is the chief neurotransmitter of the parasympathetic nervous system.  The review pointed out that Atropine is used in symptomatic bradycardia because it blocks ACh from acting.  

Another enzyme involved in the balance between the sympathetic and parasympathetic systems is Acetylcholinesterase (AChE).  AChE breaks down ACh, thus limiting its effects in the process of maintaining homeostasis.  In an OP or nerve agent poisoning, the AChE enzyme is inhibited from doing its work, letting ACh act unrestricted, resulting in a rapid onset of symptoms.

Special receptors, called muscarinic receptors, are stimulated by Ach, which create symptoms we often associate with an OP or nerve agent poisoning that include Salvation, Lacrimation, Urination, Defecation, GI upset, and Emesis. This is where the mnemonic “SLUDGE” originates. (It is interesting to note that similar actions, signs, and symptoms are the result of poisonings from a natural product, muscarine, found in wild mushrooms.  Among various species of mushrooms, most are not edible due to the toxins they produce.) 

Other receptors involved with the parasympathetic system and affected by OP poisoning and nerve agent exposures include nicotinic receptors.  These receptors are associated with vascular function and muscle movement and exhibit symptoms such as Muscle weakness/paralysis, Tachycardia, Weakness, Hypertension, and Fasciculations (muscle twitch).  This creates a mnemonic based on the days of the week, “MTWtHF”.  The CNS is also affected, causing symptoms that can include mood, behavior, and emotional changes, as well as apnea and seizures, to name a few.

In these emergencies, Atropine is used to block the excessive ACh at the muscarinic receptors but is unfortunately not effective on the other receptors.  The second medication included in a Duo Dote, 2-PAM, is effective on the nicotinic receptors by assisting AChE to reactivate and slow down the run-away ACh. This action will relieve respiratory muscle paralysis and weakness throughout the body.  Benzodiazepines are often used to address CNS symptoms such as seizures.  Of the many signs and symptoms, airway concerns and hypoxia are symptoms of paramount importance in OP poisonings. This is one reason the suggested endpoint for atropine use is dried pulmonary secretions and adequate oxygenation.

Access to these medications and adequate quantities of them are a consideration in these emergencies.  Various benzodiazepines can be found in the UH drug boxes, and Atropine can be found in the drug boxes, but quantities will only be a start in a true OP poisoning. Dosing of Atropine for subsequent doses following an initial dose is 2 mg IV until symptoms are resolved.  2-PAM is not provided in the UH drug box and is only found in specific situations and circumstances.

As mentioned above, the Duo Dote does combine two of these medications.  Though not as readily available as they once were, the Duo Dotes may be accessible through special Haz-Mat response teams, some industrial settings, or in rare occasions, on individual squads.  The EMT can also administer the Duo Dote in the scenario of a nerve agent exposure.  Up to 3 auto-injectors can be used for one patient, depending on the severity of symptoms.  Follow this link for a demonstration on the use of the auto-injector.  https://www.youtube.com/watch?v=WlqMSat0dBA

Another source of these medications that exist for the mass casualty incident is the SDS CHEMPACK program.  EMS CHEMPACKS, capable of treating 454 patients, can be accessed through the initiation of the incident commander and medical control and delivered directly to the scene from strategically located caches.  The CHEMPACKS provide large quantities of Atropine, 2-PAM, and Valium.  There are also hospital CHEMPACKS, but the EMS CHEMPACK contains significantly more pre-filled auto-injectors of nerve agent antidotes and Valium in addition to the multi-dose vials of these medications.  It is rumored that Ohio EMS is currently revamping the CHEMPACK Training Program.  As the information on the new training is forthcoming, we will be sure to mention the details in these CE articles.

Be sure to pre-plan for these types of emergencies.  Some suggested topics to discuss may include:

• uses of and storage of organophosphates in our response areas

• additional resources needed

• availability and access to medications ·       

• decontamination concerns ·        

• proper PPE for responders ·        

• other important details within the algorithms

• key points in the protocols

• local policies and procedures

Till the next time, stay safe!

Sincerely,

The UH EMS-I Team

University Hospitals