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CHAPTER 2 - CONTINUED

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SECTION V. NERVE AGENT PYRIDOSTIGMINE PRETREATMENT

2-17. Purpose

a.    This section prescribes the use of nerve agent pyridostigmine pretreatment as an adjunct to the MARK I. Studies in many different types of animals indicate that when pyridostigmine is used in conjunction with the MARK I (para 2-10 and app E), the survivability of nerve agent poisoned casualties may be enhanced. Also covered in this section are the individual, unit, and command responsibilities for the pretreatment regimen.

b.    Animal data suggest that any potential benefits that may be derived from use of this pretreatment regimen will be realized only in nerve agent poisoned casualties who have been treated with the Mark I at the time of nerve agent exposure, and who have taken their pretreatment medication within 8 hours prior to nerve agent exposure.

c.    Minimal detrimental effects are expected at the recommended dosages. Adverse effects and contraindications are described in paragraph 2-22 below.

2-18. The Nerve Agent Pyridostigmine Pretreatment Tablet Set

a.    The Nerve Agent Pyridostigmine Pretreatment (NAPP) Tablet Set (fig 2-2) contains the pretreatment medication to be taken within 8 hours prior to exposure to nerve agents at which time the MARK I is used. The NAPP consists of a blister pack containing 21 tablets. Each tablet consists of 30-mg pyridostigmine bromide. Each blister pack (NAPP) contains enough tablets for 7 days (1 taken every 8 hours).

Figure 2-2. Nerve Agent Pyridostigmine Pretreatment Tablet Set.

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b.    Service members are initially issued one NAPP when the chemical protective ensemble is expected to be opened for use. They are responsible for carrying the NAPP and safeguarding it against loss. Service members will secure the blister pack in the sleeve or breast pocket of the chemical protective ensemble (or in another part of the ensemble, as directed by local standing operating procedure (SOP)).

NOTE: In conjunction with the NAPP, service members should be issued an additional M291 Skin Decontaminating Kit (fig E-1). The M291 kit will be carried in the protective mask carrier or as specified in unit SOP.

c.    Orders to start taking the NAPP will be issued by the proper authority within the chain of command.

d.    Resupply will be provided by combat, combat support, and combat service support units.

2-19. Effects of Pyridostigmine Bromide

a.    Pyridostigmine bromide protects an enzyme (known as acetylcholinesterase) in the body from the action of nerve agents. Muscles function as a result of nerve impulses and the release of specific chemical substances. A chemical transmitter, acetylcholine, acts at the neuromuscular junction (where the nerve interfaces with the muscle) (fig 2-3). When a nerve impulse reaches the neuromuscular junction, acetylcholine is released, thereby causing the muscle to contract. The enzyme, acetylcholinesterase, stops the action of acetylcholine on the muscle after the muscle has contracted. Nerve agents block the acetylcholinesterase; there is an accumulation of excessive acetylcholine at the neuromuscular junction resulting in nerve agent poisoning and its accompanying symptoms. Pyridostigmine protects acetylcholinesterase against nerve agents, thus preventing the accumulation of excessive acetylcholine when the MARK I is administrated.

b.    Pyridostigmine is not a "true" pretreatment. A true pretreatment would, by itself, provide some protection against chemical agents. Pyridostigmine is an antidote enhancer. Though NOT providing protection by itself, pyridostigmine significantly ENHANCES the efficacy of the MARK I within 1 to 3 hours after taking the first tablet. Maximal benefit develops with time and is reached when a tablet is taken every 8 hours.

Figure 2-3. Schematic neuromuscular junction (not to scale).

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2-20. Principles in the Use of the Nerve Agent Pyridostigmine Pretreatment Tablet Set

a.    To be maximally effective, one pyridostigmine bromide tablet should be taken every 8 hours on a continuous basis prior to exposure to a nerve agent until all 21 tablets in the blister pack have been taken, or the individual has been directed to discontinue taking the medication. If pyridostigmine is to be continued, another blister pack of the medication must be issued. This regimen maintains an effective blood level of the medication. If a tablet is not taken every 8 hours, the beneficial effect of pyridostigmine as a pretreatment significantly diminishes after 8 hours from the last tablet.

b.    The use of the pyridostigmine pretreatment medication does not change the administration of MARK I.

NOTE: Do not attempt to give a NAPP tablet to a casualty with nerve agent symptoms.

c.    At times a commander may have to make a decision to defer administration of the NAPP on schedule. Examples of this would be when service members:

(1)    Have experienced sleep deprivation. The commander would have to decide whether the service members should be allowed to sleep or be awakened to take the pretreatment.

(2)    Are in a contaminated environment. The commander would have to decide whether or not to delay administration of the medication until the unit is safely out of the contaminated area (para d below). In any case, the benefits versus the risks should be carefully weighed before a decision is reached.

d.    When the order to take pyridostigmine has been given, it should be taken as directed (para 2-21). As long as the environment is contaminated, it is desirable to continue the pretreatment. The pretreatment should continue regardless of MOPP level since the protective posture could be breached at any time. Command guidelines should be developed for situations such as:

(1)    Providing collective protection or rest and relief shelters so that personnel can remove their protective mask and take the tablets, or relocate small groups to an uncontaminated area, if possible.

(2)    Taking the tablets while in MOPP 4 would be hazardous. (Examples: Troops are operating at night without lights or are in a chemical agent vapor environment.) In either case it would be more appropriate to delay taking the medication for a few hours until the tablets can be taken in a less hazardous environment.

e.    The NAPP should not be taken during pregnancy.

2-21. Administration of PyridostigminePretreatment in an Uncontaminated Environment

One 30-mg tablet is to be taken by mouth, with sufficient water to assist in swallowing the medication, every 8 hours as directed by your commander. If a dose is missed, do not make it up. Do not take 2 tablets at once because of a missed dose - merely start again with 1 tablet every 8 hours. Taking 2 tablets at once could result in adverse side effects. Taking more than 1 tablet at a time DOES NOT provide additional protection - in fact, it may be more hazardous if there is exposure to a nerve agent.

a.    When the order to take pyridostigmine pretreatment has been given, it should be taken as directed, even though the protective mask is worn.

b.    During hours of darkness while in an uncontaminated environment, the NAPP will be administered using the above schedule.

2-22. Signs and Symptoms of Pyridostigmine Bromide Overdose, Adverse Reactions, and Contraindications

Although no detrimental effects are expected at the recommended dosage, depending on the length of time and the amount of medication taken, as well as individual physiologic variations, some individuals may have contraindications for taking pyridostigmine bromide while others may experience adverse reactions.

a.    Signs and symptoms of overdose, adverse reactions, or side effects are:

(1)   Abdominal cramps.
(2)   Nausea and vomiting.
(3)   Diarrhea.
(4)  Blurring of vision, miosis.
(5)   Increased bronchial secretions.
(6)   Cardiac arrhythmias, hypertension.
(7)   Weakness, muscle cramps, and muscular twitching.
(8)   Skin rash.

b.    Since pyridostigmine bromide may increase bronchial secretions and aggravate bronchiolar constriction, caution should be used in its administration to personnel with bronchial asthma.

c.    Pyridostigmine bromide may cause urinary obstruction.

d.    Additional contraindications include hyperthyroidism, sensitivity to bromide, peptic ulcer disease, and low serum acetylcholinesterase.

e.    If any of the above signs/symptoms occur, the service member should consult unit medical personnel as soon as possible.

2-23. Emergency Medical Treatment for Pyridostigmine Adverse Side Effects, Allergic Reactions, and Overdose

Ordinarily, discontinuing pyridostigmine should be adequate to alleviate the signs and symptoms of adverse side effects, allergic reactions, and overdose. Pyridostigmine may persist in the blood for as long as 24 hours; however, after the blood level peaks in about 4 hours, the effects of the medication diminish gradually.

a.    Emergency treatment for an overdose of pyridostigmine requires the administration of atropine in adequate doses to overcome the cholinergic crisis. Initially, the 2-mg atropine autoinjector found in the MARK I kit should be used. In most cases, this will be sufficient. Further administration of atropine may be necessary to control the cholinergic effects of pyridostigmine. If additional atropine is required, 2 mg should be administered by medical personnel every 15 to 20 minutes, thereby permitting the previous injection of atropine to exert its anticholinergic effect prior to the next injection.

b.    SEVERE cases may require assisted ventilation because of weakness, but would be unusual when the pretreatment medication was administered every 8 hours as directed.

c.    When stabilized, the patient should be evacuated for further observation and treatment.

2-24. Responsibilities

a.    The corps/division/wing commander will:

(1)    Decide whether to begin, continue, or discontinue the administration of NAPP based on the threat. The intelligence officer, chemical officer, and the surgeon act as advisors to the commander in making his decision if a chemical nerve agent threat exists (for example, the enemy having nerve agents in the combat zone or the probability of their use). After 3 days of self-administration of NAPP by the service member, combat conditions should be reevaluated by the commander and his staff to determinate whether to continue the medication or not. However, orders to discontinue the pretreatment CAN and SHOULD be made at any time, depending on the situation. If the pretreatment is to be continued, then a second blister pack must be ordered while the service member completes the administration of the 7 days (21 tablets) and is issued the second pack on the 7th day. Administration of the medication beyond 14 days is not recommended without a thorough evaluation of the situation and recommendation of the medical authority. However, the magnitude of the threat may outweigh any possible adverse side effects and indicate continuance of the pretreatment.

(2)    Train the service members to faithfully take the NAPP as directed to enhance their survivability if they are exposed to a nerve agent. Service members must be trained to take the NAPP during the day, at night, and while in MOPP 4, should these procedures become necessary.

(3)    Issue unit SOPs for the retention and decontamination of the NAPP blister pack during personnel decontamination and overgarment exchange.

b.    Units will:

(1)   Obtain the supplies of NAPP through medical supply channels.

(2)   Maintain at least a 2-week supply of NAPP per member of the unit. One NAPP is issued to each member of the unit. An additional week's supply of NAPP for each individual in the unit will be maintained in the unit area. Authorized quantities will be commensurate with the latest doctrine for its use.

(3)   Store the NAPP for individual issue and request replacements as the items are issued, or as they exceed their labeled shelf life. The NAPP should be stored (refrigerated) in temperatures ranging from 35 ° to 46°F (2° to 8°C). If the medication is removed from refrigeration for a total of 6 months, it should be assumed that it has lost its potency and should not be used.

(4)    Issue the NAPP to the service members at the time the chemical protective ensemble is expected to be opened for use.

c.    Unit medical personnel will:

(1)    Recognize the signs and symptoms of pyridostigmine overdose, adverse reactions, and side effects (para 2-22 above) for determining, on an individual basis, whether or not a service member is to continue the NAPP based on any adverse reaction to the medication.

(2)    Advise the commander if any serious problems occur.

d.   The individual service member will:

(1)    Take the NAPP as directed and in accordance with the provisions of paragraph 2-20 above.

(2)    Secure the NAPP against loss.