Agency for Toxic Substances and Disease Registry 
Case Studies in Environmental Medicine (CSEM) 

Cholinesterase Inhibitors
Including Insecticides and Chemical Warfare Nerve Agents
Part 4: The Cholinergic Toxidrome
Section 11: Management of the Cholinergic Toxidrome
Antidote Stocking (Optional Reading)

Learning Objectives (Optional Reading)

Upon completion of this section, you should be able to

• Identify what antidotes should be stocked for the treatment of patients, or mass casualties involving cholinesterase inhibitor poisoning.
• Describe what local agencies to contact for information about accessing the Strategic National Stockpile.

Misconception

Hospitals have adequate stocks of antidotes to treat most cases of cholinesterase inhibitor toxicity.

Reality

Repeated studies have reported that many hospitals lack sufficient antidote stores to treat even one severe case of cholinesterase inhibitor poisoning, much less enough for a multiple casualty event or terrorist attack.

Inadequacies in Antidote Stocking (Optional Reading)

2-PAM

Numerous studies have documented the failure of hospitals to stock enough 2-PAM to treat one patient, much less to handle a mass casualty event. (Parker, Dart et al. 1990; Chyka and Conner 1994; Dart, Stark et al. 1996; Woolf and Chrisanthus 1997; Teresi and King 1999; Treat, Williams et al. 2001; Kaji and Lewis 2004)

Atropine

Currently, data on hospital stocking of atropine are lacking. However, even one severe case of toxicity from an organophosphorus compound can require the amounts of atropine that would exceed the stores in most communities. [The highest reported dosage requirement was for 3,600 mg in a 24 hour period for a suicidal ingestion, with a total dose of 30,730 mg over the patient’s 35 days of treatment. (LeBlanc, Bensen et al. 1986)]

The need to assess hospital stores of antidotes

Because inadequacies in hospital stocking of antidotes appear to be widespread, community disaster planners need to inventory local/regional stocks and ensure they are adequate.

Atropine from Bulk Powder (Optional Reading)

Because of the high doses required for some cases of organophosphate poisoning, and because of the potential for mass casualty incidents involving insecticides and nerve agents, rapid access to large amounts of atropine may be critical. To address this problem, protocols have been developed for the reconstitution of high-concentration atropine from bulk powder.

Time required and cost

Using such an approach, a single pharmacist can reconstitute one hundred 6 mg syringes of atropine within about a half-hour, at a cost of as little as $11 (versus $5,000 for prefilled syringes).

Storage characteristics

Even when stored at up to 45°C (113°F) 87% of the atropine sulfate reconstituted from bulk power was still undegraded, pathogen-free, and without tropic acid (an expected degradation product) after 8 weeks. (Geller, Lopez et al. 2003; Kozak, Siegel et al. 2003)

Note: Few studies have been carried out to assess how many hospitals keep adequate stocks of atropine on hand for cholinesterase poisoning. One survey in a major metropolitan area in the year 2000 found that while 1,213.237 grams were available city-wide, only 1 of 21 area hospitals had a 3 g supply of the antidote on hand. (Keim, Pesik et al. 2003) Another study of 38 hospitals reported that atropine was one of the “conspicuously under stocked items,” although the actual amounts of the antidote stocked were not given. (Skolfield, Lambert et al. 1997)

Mixing Protocol (Optional Reading)

Protocol for preparing 100 6 mg/3 ml syringes of atropine from bulk powder.

balance scale

atropine sulfate monohydrate powder

10 ml sterile water vial

10 ml syringe

0.2 µm filter (B. Braun PFS 3000)

18 gauge needle for transfer

1 L normal saline IV solution bag

3 ml syringes and needles

syringe batch system (or male-to-male adapter and 60 ml syringes)

syringe labels

alcohol swabs

Weigh out 2 g of atropine sulfate monohydrate powder

Dilute the atropine in 10 ml of sterile water

Remove 50 ml from 1 L bag of normal saline

Instill atropine from (step 2) into 1 L bag of normal saline using 0.2 µm filter

Print labels

Connect 1 L bag of diluted atropine (from step 4) to syringe-batching system

Set up (program-calibrate) syringe pump of syringe batching system

Compound and label syringes of atropine solution

Time required using commercial syringe batching system: 29 min.

Connect 60 ml syringe and fill it from 1 L bag of diluted atropine (from step 4) via male-to-male connecter

With solution in 60 ml syringe, fill 3 ml syringes and label

Time required using manual batching procedure: 34 min.

Modified from: Kozak RJ, Siegel S, Kuzma J. Rapid atropine synthesis for the treatment of massive nerve agent exposure. Annals of Emergency Medicine. May 2003; 41:685-688.

Support Available from the CDC Strategic National Stockpile (Optional Reading)

The Centers for Disease Control and Prevention (CDC) maintains the Strategic National Stockpile (SNS), which contains large quantities of medicines and medical supplies that can be used in a public health emergency large enough to deplete local supplies.

Once Federal and local authorities agree that the Stockpile is needed, it can be delivered to any state in the U.S. or its territories within 12 hours. Each state is then responsible for receiving and distributing stockpile contents to the local communities that need them.

Stockpile contents relevant to cholinesterase inhibitor poisoning include:

• 2-PAM.
• Atropine.
• Diazepam.
• Mechanical ventilators are also available (but within 24-36 hours or less).

The SNS is also fielding local ChemPacks (each containing medications for 1,000 victims) in each state, which do not require Federal authorization for their release.

To find out how to request supplies from ChemPacks or the Strategic National Stockpile, contact your local (or state) emergency management or public health agency.

Key Points

• Stockpiles of antidotes and ventilators are an important aspect of planning for disasters involving cholinesterase inhibitors (e.g., terrorist attacks with nerve agents).
• One of these antidotes, atropine, can be rapidly and economically constituted from bulk powder.
• Contact your public health or emergency management agency for information on accessing the Strategic National Stockpile.