Hazardous-Materials Antidotes

In recent years, hazmat response has transformed itself from a discipline largely focused on industrial and transportation accidents with small numbers of victims to one that also addresses intentional toxicological exposures. Concurrently, hazmat teams have increased their response and mitigation capabilities, and many have expanded their medical resources as well.

Emergency medical services personnel have several responsibilities at a hazmat scene, including medical care of victims and any affected rescuers and the medical monitoring and rehabilitation of hazmat technicians and other emergency responders. The majority of toxic exposures have no specific antidote (though most victims of hazmat exposure will improve and recover with supportive care). Those antidotes that do exist are frequently unavailable to paramedics in many EMS systems, despite clear-cut indications for their use and the relative ease of administration of most medications. EMS agencies that respond to hazmat incidents, whether or not they are part of a hazmat response team, should consider adding these antidotes to their ALS protocols.

Organophosphate, Nerve Agent and Carbamate Antidotes

The mechanism of toxicity is essentially the same for organophosphates, carbamates and nerve agents. Both organophosphates and nerve agents block the action of acetylcholinesterase, an enzyme responsible for clearing the neurotransmitter acetylcholine from the post-synaptic nerve terminals. The unchecked stimulation of various parts of the nervous system causes signs and symptoms listed in

Figure 1. Collectively these effects may be remembered via the acronym SLUDGE.

Atropine sulfate, a widely available parasympatholytic drug commonly used in ACLS algorithms to treat symptomatic bradycardia, can also be used to treat these symptoms associated with excessive cholinergic stimulation. The dosage of atropine for bradycardia is generally 0.5¡V1.0 mg to a maximum of 0.04 mg/kg in adults. However, use as an antidote for organophosphate or nerve agent exposure requires doses of 2.0¡V6.0 mg or more at a time. A large amount of the drug in repeated doses is often necessary for full resolution of signs and symptoms. Atropine is often given in conjunction with 600¡V1,800 mg pralidoxime chloride, also known as 2-PAM chloride, which liberates acetylcholinesterase and has some anticholinergic effects as well.

The United States military issues atropine sulfate and 2-PAM chloride in auto-injectors as part of the Mark I Nerve Agent Antidote Kit. The Mark I kit is a spring-loaded device that functions like an Epi-Pen and facilitates the rapid administration of antidotes to large numbers of exposed individuals. For this reason, many jurisdictions, especially those involved in the Metropolitan Medical Response System, have chosen to stockpile these kits and/or place them on EMS units for ready accessibility by first responders to treat an initial wave of civilian casualties. A victim of nerve agent poisoning will generally require 1¡V3 Mark I kits for initial resuscitation, depending on the dose, route and duration of exposure and the severity of their signs and symptoms upon first EMS contact. The FDA has also recently approved a pediatric version of the atropine auto-injector, which contains an age-appropriate dose of the drug.

Hydrogen Cyanide and Hydrogen Sulfide Antidotes

Hydrogen cyanide poisoning may be immediately life-threatening or fatal, but treatment may also be initiated in the field. Cyanide is a systemic asphyxiant that impairs oxygen transport and oxygen utilization by cells. Consequently, aerobic respiration is disrupted, cells cannot make energy and a vicious cycle of cell death, tissue death and, ultimately, organ death ensues. Victims of cyanide exposure rapidly develop cellular hypoxia. Death can occur within five minutes if the cyanide dose is sufficient and the disease process is not recognized and treated.

Victims of hydrogen cyanide poisoning are treated with the contents of a cyanide antidote kit, which includes amyl nitrite, sodium nitrite and sodium thiosulfate. Formerly known as the Lilly Kit, these medications are now available in the Pasadena Cyanide Antidote Kit. The Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) requires hospital emergency departments to maintain a cyanide antidote kit, but the high price tag of this kit (several hundred dollars), the paucity of cyanide incidents annually and the lack of local protocols for their use have prevented widespread deployment of cyanide antidotes in the prehospital setting.

The textbook emergency medical treatment for a patient suffering from cyanide poisoning is to administer three drugs sequentially: amyl nitrite, sodium nitrite and sodium thiosulfate. Amyl nitrite, known as poppers among the street-drug crowd, are small pearls that are crushed, held under the patient's nose and inhaled for 30 seconds at a time until both IV access and sodium nitrite become available. A single dose of 300 mg of sodium nitrite is then given intravenously over no less than five minutes, due to its propensity to cause hypotension. Both amyl nitrite and sodium nitrite convert a certain amount of circulating hemoglobin into methemoglobin. The third drug, sodium thiosulfate (12.5 grams in 50 ml), is given intravenously and transforms the remaining cyanide into a less harmful substance until it can be metabolized and excreted. Sodium thiosulfate is the most important of the three antidotes, costs approximately $20 per dose and can be administered as a single agent for cyanide poisoning.

Hydrogen sulfide is often found in sewers and similar confined spaces. It is treated similarly to cyanide poisoning, with the exception of sodium thiosulfate, which is ineffective for these compounds.

Hydrofluoric Acid Antidotes

Hydrogen fluoride is a relatively weak acid, but one that can cause serious injury and death even in very small amounts. Hydrofluoric acid causes a deep chemical burn that secondarily binds calcium ions and causes clinically significant hypocalcemia. The preferred antidote for hydrofluoric acid poisoning is calcium gluconate (not calcium chloride; note that most ambulances carry only calcium chloride). Calcium gluconate exists as both an intravenous preparation and a gel. Administration of calcium at the injury site (and systemically if necessary) binds fluoride ions to create an insoluble salt and supplies additional calcium to counteract potentially life-threatening hyperkalemia, which results from extracellular ion shift. Industrial sites utilizing hydrogen fluoride will often have calcium gluconate gel on hand to treat exposures.

The most common method of administration is topical, using either pre-mixed calcium gluconate gel or one ampule of 10% calcium gluconate mixed into a tube of water-soluble jelly, such as KY or Surgi-Lube. Calcium gluconate can be mixed with normal saline solution as well and used to irrigate the eyes via nasal cannula or the Morgan Lens. In addition, the drug can be given intravenously to treat cardiac effects, which are generally first observed through a prolonged QT interval.

Nitrate and Nitrite Poisoning

Antidotes

Nitrites and nitrates are nitrogen compounds that can be found in household and industrial settings. Amyl nitrite and sodium nitrite are both examples of nitrogen compounds. Such compounds convert hemoglobin to methemoglobin, which lacks oxygen-carrying capacity. While this effect is desirable to a certain extent when treating cyanide poisoning, large amounts of methemoglobin cause chocolate-colored blood and a marked hypoxemia that is harmful to the patient. This phenomenon is known as methemoglobinemia.

The antidote of choice for nitrite and nitrate poisoning is methylene blue. One to two milligrams of the drug per kilogram are given intravenously over the course of 5¡V10 minutes to convert methemoglobin back to its normal state and oxygen-carrying capacity.

Conclusion

There are a variety of antidotes available for treating exposures to hazardous materials in the prehospital setting. The most commonly available and most likely to be beneficial are atropine sulfate, pralidoxime chloride, the cyanide antidote kit, calcium gluconate and methylene blue. The decision to adopt these pharmaceutical interventions should be driven by local hazard assessments and medical protocols. Education of the local medical control committee or service medical director is also desirable in order to make a case for inclusion of these medications in the drug box of an EMS service or regional hazmat response team. ƒÞ

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