American College of Physicians: Internal Medicine — Doctors for Adults ®


The chemical agents every doctor should recognize

While the media have focused on bioterrorism, chemicals pose a more immediate threat

From the May ACP Observer, copyright 2003 by the American College of Physicians.

By Phyllis Maguire

SAN DIEGO—While bioterrorism has received prominent attention since the anthrax attacks of 2001, the nation faces a significant and credible threat in the form of deliberate attacks or industrial accidents involving commonly available chemicals.

At an Annual Session presentation on chemical agents and their possible use in terrorist incidents, Stefanos N. Kales, FACP, said that the prevalence of these chemicals represents both good and bad news.

One down side: Chemicals are widely available. Terrorists could easily attack a known chemical production or transport site, or commandeer a crop sprayer to release chemicals on urban centers.

Even worse, Dr. Kales said, low-tech mechanisms for spreading chemical agents can be deadly. To distribute sarin during the notorious 1995 Tokyo subway attack, for example, terrorists simply poked holes in plastic bags filled with a liquid form of the toxin.

Dr. Kales notes that with chemical poisoning, time is such a critical factor that physicians often have to make empirical diagnoses.

To further complicate matters, he said, the agents act quickly. While symptoms—and damage—from biological agents like smallpox or anthrax can take days or longer to develop, the damage from chemical agents often begins immediately and requires rapid diagnosis and treatment.

The good news? Because many chemical agents are already widely used in industry and agriculture, many communities have formed hazardous materials teams. In addition, many physicians—particularly those working in occupational medicine—have some experience diagnosing and treating exposure to many of these agents.

"When you understand the toxicology of basic syndromes," said Dr. Kales, "you can apply it to both chemical accidents and chemical terrorist attacks."

Lessons learned

Most potentially fatal exposures from chemical episodes would be due to inhalation, said Dr. Kales, who is director of employee health and industrial medicine at the Cambridge Health Alliance in Cambridge, Mass., and assistant professor of occupational medicine at the Harvard School of Public Health. He pointed out that in industry, the number of occupational fatalities from inhalation exposure far outweighs those from chemical ingestions and dermal exposures.

Another important lesson from chemical accidents is the importance of immediate decontamination. Hazardous materials teams and firefighters who respond to chemical incidents try to decontaminate victims at the scene. With widespread exposure, however, immediate on-scene decontamination is not always feasible, and victims might arrive at hospitals on their own.

"One of the best things a hospital can have is outdoor shower facilities" for mass casualty situations, Dr. Kales said. Removing patients' clothes eliminates up to 90% of retained chemical vapors and substances, and soap and water are very effective chemical decontaminants. "It's important that patients are decontaminated before coming inside and contaminating the hospital," he added.

Another must for hospitals are stockpiles of major antidotes, he continued. These include cyanide antidote kits (the nitrate portion can also be used for hydrogen sulfide poisonings); pralidoxime and atropine to treat exposure to nerve agents and other cholinesterase inhibitors, many of which are agricultural insecticides; and diazepam. (While benzodiazepines are the only anticonvulsants that can effectively treat nerve agent victims, you can also use them as universal anticonvulsants for exposure to other chemicals.)

Chemical vs. biological terrorism

When preparing for chemical incidents, physicians need to keep in mind how these episodes would differ from biological attacks.

Perhaps most importantly, Dr. Kales said, the epidemiology of chemical incidents is critically different from biological ones. "With biological terrorism, you'd expect to see patients presenting one by one in disparate sites, with an emerging rare disease or in strange age group presentations," he pointed out.

In a chemical incident, however, "it's going to be a boom or a hiss—and readily evident," he said, with groups of persons in close proximity to the release rapidly affected. "Instead of an epidemic emerging over days or weeks, problems will arise within minutes and hours. You won't have the luxury of time that you would with an exotic infection or biological terrorism."

Your initial assessment of any patient with chemical poisoning should focus on the ABCs: keeping the airway open and maintaining breathing and circulation. Physicians also need to look for markers of poisoning severity: altered mental state, a loss of consciousness and respiratory or cardiovascular insufficiency or instability. (Even when chemicals are suspected, don't neglect basic protocols like administering narcan to victims who are unconscious.)

While recognizing a chemical victim might not be difficult, "the problem is deciding which chemical patients have been exposed to and which treatment you should undertake," Dr. Kales said. "For most of these agents, we don't have real-time tests either for the patient or the environment to tell you which specific chemical has been involved." Because time is such a critical factor, physicians responding to chemical episodes often have to make empirical diagnoses.

To do that, you need to be able to recognize the four basic clinical classes of chemical poisons. They include asphyxiants, cholinesterase inhibitors, pulmonary irritants and vesicants or blistering agents. Dr. Kales outlined symptoms and management protocols for each of the four groups.


When you think of asphyxiants, cyanide is the prototypical agent. This class of chemicals causes primarily cardiovascular and central nervous system manifestations. These symptoms, Dr. Kales said, all reflect tissue hypoxia. High-dose exposures may cause sudden collapse.

"Because many of these agents affect oxygen delivery or cellular aerobic metabolism, you'll often see lactic acidosis and hypotension," he pointed out. "There is also a relative absence of respiratory irritation, no increase in secretions, and the size of the pupils is either normal or dilated."

There are two main categories of asphyxiants, simple and toxic. Simple asphyxiants include nitrogen, methane and carbon dioxide. These agents displace oxygen, producing oxygen deficiency and hypoxia.

Toxic asphyxiants, on the other hand, deny oxygen to tissues by interfering with oxygen delivery or oxygen utilization on the cellular level. They include carbon monoxide, cyanide and hydrogen sulfide. Carbon monoxide is the most common toxic asphyxiant and causes the most fatal workplace poisonings-as well as the most non-drug related home toxic fatalities. (Many patients use carbon monoxide detectors to prevent this. For more information, see "Responding to carbon monoxide detector alarms.")

  • Carbon monoxide. The hallmark of carbon monoxide, Dr. Kales said, is an elevated carboxyhemoglobin level. As a result, you should be suspicious of carboxyhemoglobin levels above 8% in smokers and above 3% in non-smokers.

    (There is no such thing, he claimed, as an "urban range" for carboxyhemoglobin in the United States. Also, "cherry red" skin color is an "extremely unreliable" and late indicator of exposure to these agents, he said.)

    All toxic asphyxiants are "particularly tricky," said Dr. Kales. A patient may exhibit severe signs of hypoxia, "yet if you test the blood gas, the PaO2 is normal unless the patient has developed respiratory failure due to central nervous system depression."

    In these cases, the oxygen saturation on a blood gas will also come up normal. And "if you do pulse oximetry," he explained, "it can't distinguish between carboxyhemoglobin and oxyhemoglobin."

    Dr. Kales pointed out that many small hospitals do not have in-house carboxyhemoglobin testing, but they should. "This is an inexpensive investment for your hospital," he said, "and a very good one."

    He also said that physicians must be extremely cautious with low to moderate carboxyhemoglobin values in patients with likely carbon monoxide exposure. Patients who receive oxygen in the field and/or experience a delay in transport may have a lower carboxyhemoglobin value but still have carbon monoxide poisoning.

    If you're treating patients exposed to carbon monoxide, give 100% normobaric oxygen using a tight-fitting mask or intubation if necessary. Consider hyperbaric oxygen for severe cases. Continue treatment until the carboxyhemoglobin is less than 5%.

    And if you're treating smoke inhalation victims for carbon monoxide with 100% oxygen but seeing no improvement in their acidosis and hypotension, he said, "They may have concomitant cyanide poisoning complicating the carbon monoxide inhalation."

  • Cyanide. For treating suspected cyanide intoxication in smoke inhalation, Dr. Kales recommended using only the thiosulfate component of the cyanide antidote for fire victims. "You can give thiosulfate with impunity because it's relatively non-toxic," he said. "Thiosulfate will help the patient, and it won't produce any further hypoxia to the tissues by inducing methemoglobin." If hyperbaric oxygen is available, nitrite (which induces methemoglobin) can be given to a fire victim if necessary because the hyperbaric oxygen will counteract both carboxyhemoglobin and methemoglobin.

    For other causes of cyanide exposure, give both nitrite and thiosulfate components of the cyanide antidote kit along with 100% oxygen and supportive measures.

Cholinesterase inhibitors

This group includes nerve agents such as sarin, as well as organophosphate pesticides. These agents produce cholinergic excess, smooth muscle constriction, profuse secretions, constricted pupils and visual complaints. Cholinesterase inhibitors can also produce skeletal muscle weakness fasciculations, Dr. Kales said.

This is "the runny nose, crying, drooling, peeing, pooping, vomiting type of poisoning," he said. "Patients who are severely affected have excess secretions from all orifices, as well as diffuse smooth muscle constriction and increased motility."

All of these agents can be absorbed through inhalation, the skin and ingestion, making "decontamination extremely important." Because excess bronchial secretions, bronchial constriction, respiratory muscle weakness and central nervous depression all contribute to respiratory failure, Dr. Kales added, "airway management—including suctioning—is very important."

Organophosphate insecticides, which are available at most hardware stores or agricultural suppliers, cause a slower onset of symptoms compared to nerve agents—but a much longer duration of action. As a result, Dr. Kales said, "these victims may need hundreds or even thousands of milligrams of atropine to manage their poisoning."

Nerve agents, on the other hand, are much more toxic. While they act more quickly, however, symptoms run a much shorter course. "Patients will need significantly less atropine," he said, "but they need to be treated immediately."

Among all the types of chemical poisoning, cholinesterase inhibitor poisoning has the most treatment options. Atropine works against the poison's muscarinic manifestations. Pralidoxime chloride (up to 2 grams for adults) reactivates the acetylcholine enzyme, while benzodiazepines are effective anticonvulsants.

The military now advocates giving diazepam to any victim who has lost consciousness, is post-ictal or has manifestations in two or more organ systems, in addition to those who are experiencing a seizure.

Pulmonary irritants

These agents include chlorine, phosgene and ammonia, all of which are used in industry. While these agents don't cause systemic poisoning, they do produce major respiratory effects that can be fatal.

Irritants' water solubility determines their toxicity and tissue activity. Highly soluble agents—such as ammonia, hydrochloric acid and formaldehyde—and tear gas (which is actually an aerosolized solid) are absorbed primarily by the mucus membranes in the upper respiratory tract, where they produce more immediate symptoms. (Sulfur mustard is also a highly soluble pulmonary irritant, but experts classify it as a blister agent.)

Agents with low solubility, such as phosgene and zinc chloride, penetrate deeper into the lungs and can cause pulmonary edema. An agent with intermediate solubility, such as chlorine, can cause bronchospasm and eye and nose irritation, as well as pulmonary edema.

History is important when triaging for severity. Dr. Kales suggested asking the following questions: What was the poisoning mechanism? Were victims in a confined space? Did they lose consciousness?

"You want to be particularly careful with the upper airway," he added. Victims of high solubility agents could have significant upper respiratory burns.

"Over time, the laryngeal edema can progress, the airway will constrict and the patient will asphyxiate right there," he said. "When patients present with certain upper airway signs like hoarseness, burns or stridor, physicians should definitely directly visualize the airway and prepare for intubation."

Dr. Kales added that the danger of low solubility agents like phosgene, however, is their latency period. Physicians can see these patients early on, triage and dismiss them, he said, when they may in fact be at risk for delayed pulmonary edema.

Treatment for all pulmonary irritants is primarily supportive. Use bronchodilators for bronchospasm, and add steroids if the bronchospasm is severe. Steroids are contraindicated for patients with serious skin burns.

It is unclear, Dr. Kales explained, whether steroids help prevent pulmonary edema brought on by phosgene. "However, a couple of agents such as zinc chloride and nitrogen oxide produce similar problems," he said. "We believe that steroids will reduce the pulmonary fibrosis that can occur several weeks after exposure to these agents."

Do not, however, give diuretics to patients in whom you suspect phosgene or other toxic, non-cardiogenic pulmonary edema. "These patients are physiologically hypovolemic," said Dr. Kales, "so diuretics are contraindicated."

Vesicants, or blister agents

Most commercial and industrial caustics that physicians encounter are simple acids or bases, and are not classified as military "blister" agents. "If we apply enough water, we get rid of the agent and stop the burn," Dr. Kales said.

One special case requiring treatment beyond vigorous irrigation is hydrogen fluoride, which is used in glass etching and some household products such as rust removers.

"Fluoride is the most electromagnetic element in the periodic chart," Dr. Kales explained. "It seeks out calcium and magnesium and wreaks havoc in the deep tissues."

Patients who have sustained large burns or are exposed to high concentrations of hydrofluoric acid are in danger of systemic hypocalcemia and hypomagnesemia. Treat them with an ampule or two of calcium in their IV fluid, and monitor their calcium and magnesium levels and electrocardiogram readings. You can also use certain calcium preparations locally as a direct antagonist and antidote for the burns.

Sulfur mustard is the most notorious military blister agent and has been the most widely used chemical in warfare over the last century. Mustard—which is typically employed to incapacitate and debilitate troops—has caused more military casualties than any other chemical agent.

Although it's often referred to as a gas, mustard is actually an oily, persistent liquid at room temperature. "Unless it's given in high concentrations, victims will experience no symptoms for hours," Dr. Kales pointed out.

Mustard may get off to a slow start, but decontamination has to take place almost immediately. With no symptoms to alert them, however, victims may not know they've been "slimed" unless they're using active detection methods. Mustard becomes a vapor with rising temperature, doing more damage to victims' respiratory systems.

Patients will first feel the effects of mustard on their eyes. Severe effects can include temporary and permanent blindness. Skin effects appear next. "Initially this would produce erythema, then vesiculation and then coalesce into bullae," Dr. Kales said.

Larger exposures affect victims' airways and can later cause systemic effects, including bone marrow suppression.

Significant exposures require specialized ophthalmologic, burn and critical care, and vigilance for infectious complications. "The military is investigating a number of therapies," Dr. Kales noted. "Officials believe that administering nonsteroidal anti-inflammatory drugs early on can reduce systemic effects by reducing inflammation." They are also developing ocular treatments that include combinations of steroids and antibiotics.


Who should you call for help?

If you suspect chemical poisoning, start by calling your local or regional poison center and local health department.

You can also call a federal chemical and biological hotline at 800-424-8802. Clinicians can reach the CDC at 404-639-3311.

The following Web sites list more information on chemical agents and their medical management:


Responding to carbon monoxide detector alarms

Carbon monoxide is the most common cause of workplace and non-drug related home poisoning fatalities, particularly in the Northeast and Midwest. That's because carbon monoxide can be released by faulty heating systems or through buildup from combustion-powered devices used indoors without proper ventilation, such as forklifts or power washers.

As a precaution, many patients outfit their homes with carbon monoxide detectors. What should you do when frantic patients call and say the alarm on their carbon monoxide detectors has gone off?

"Tell patients to open their windows, call 911 and go outside," said Stefanos N. Kales, FACP, director of employee health and industrial medicine at the Cambridge Health Alliance in Cambridge, Mass., and assistant professor of occupational medicine at the Harvard School of Public Health.

While the quality of carbon monoxide detectors keeps improving, Dr. Kales said that false alarms may still occur. Sensors can be tripped by old batteries or by being placed too close to cooking sources or garages. Calling 911 summons the fire department, which typically has reliable, portable carbon monoxide detectors.

If patients have been exposed to carbon monoxide, how rapidly and aggressively should you treat them? It depends in part on how symptomatic they are. You also have to take into account factors like pregnancy and underlying heart disease.

"Carbon monoxide will bind much more actively and have a longer half life in a fetus," Dr. Kales said. "The most prudent thing would be to have these people come in and evaluate them."


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