Chapter 3. Nuclear, Biologic, & Chemical Agents; Weapons of Mass Destruction

For centuries, military forces have utilized nonconventional weapons using various chemical and biologic agents. During World War I, powerful chemical weapons were developed that affected hundreds of thousands of soldiers. Nuclear weapons were first created during World War II with devastating results. Today, thousands of these nuclear, biologic, and chemical weapons of mass destruction are stored in facilities throughout the world. An accident at any of these facilities could result in a large number of civilian casualties. In addition, many terrorist organizations are now actively attempting to purchase, steal, or develop such weapons for their use. As with most mass casualty situations, emergency physicians will be at the forefront of patient care. This chapter attempts to provide specific information regarding the management of nuclear, biologic, and chemical weapons injuries.

A terrorist attack utilizing a nuclear weapon would most likely involve the detonation of a nuclear bomb or the detonation of a conventional explosive that also dispersed radioactive material (so-called dirty bomb).

General Considerations

The detonation of a nuclear weapon results in a much larger blast area and much hotter fireball than that produced by conventional explosives. If victims survive the blast trauma and thermal burns, they are at risk for radiation injuries. There are four types of radioactive particles that may cause damage when they interact with body tissue:

1. Alpha particles are large particles that are stopped by the epidermis and cause no significant external damage. Internal contamination, from the inhalation or ingestion of contaminated particles, may cause local tissue injury.

2. Beta particles are small particles that can penetrate the superficial skin and cause mild-burn-type injuries.

3. Gamma rays are high-energy particles that can enter tissues easily and cause significant damage to multiple body systems.

4. Neutrons are large particles that are typically produced only during nuclear detonation. Like gamma rays, they cause significant tissue injury.

The effect that radiation will have on the body depends on the type of radiation, the amount of exposure, and the body system involved. Tissues that display higher rates of cellular mitosis, such as the gastrointestinal and hematopoietic systems, are more severely affected. At very high radiation doses, neurovascular effects will also be seen. Radiation injury may cause either abnormal cell function or cell death.

Clinical Findings

Symptoms and Signs

The symptoms and signs of radiation exposure occur in three phases: prodromal, latent, and symptomatic.

Prodromal Phase

Patients will develop nonspecific symptoms of nausea, vomiting, weakness, and fatigue. Symptoms generally last no longer than 24–48 hours. With higher radiation exposures, symptoms will occur earlier and last longer.

Latent Period

The latent period duration depends on the dose of radiation and the body system involved (neurologic, several hours; gastrointestinal, 1–7 days; hematopoietic, 2–6 weeks).

Symptomatic Phase

Symptoms will depend largely on the body system affected, which will depend on the radiation dose. At doses of 0.7–4 Gy, the hematopoietic system will begin to manifest signs and symptoms of bone marrow suppression. Because of their long life span, erythrocytes are less severely affected than are the myeloid and platelet cell lines. Neutropenia and thrombocytopenia may be significant and lead to infectious and hemorrhagic complications. At doses of 6–8 Gy, gastrointestinal symptoms develop. Nausea, vomiting, diarrhea (bloody), and severe fluid and electrolyte imbalances will occur. The neurovascular system becomes affected at doses of 20–40 Gy. Symptoms include headache, mental status changes, hypotension, focal neurologic changes, convulsions, and coma. Exposures in this range are uniformly fatal.

Laboratory and X-Ray Findings

Obtain a complete blood count with differential for all patients sustaining a radiation injury. Although symptomatic bone marrow suppression may not be evident for some weeks, a drop of the absolute lymphocyte count of 50% at 24–48 hours is indicative of significant exposure. Monitor electrolytes in patients with gastrointestinal symptoms.

Treatment

In the absence of aggressive medical therapy, the LD50 (the dose of radiation that will kill 50% of those exposed) is approximately 3.5 Gy. Aggressive medical care affords improved survival. Treat all life-threatening injuries associated with blast or thermal effects according to standard advanced trauma life support protocols. Perform surgical procedures early to avoid the electrolyte and hematopoietic effects that will occur. Clean wounds extensively and close them as soon as possible to prevent infection. Treat nausea and vomiting with standard antiemetic medications (prochlorperazine, promethazine, ondansetron). Treat fluid and electrolyte abnormalities with appropriate replacement. Anemia and thrombocytopenia can be treated with transfusion therapy. Leukopenia may be treated with hematopoietic growth factors such as sargramostim and filgrastim. In some instances, bone marrow transplantation may be utilized. Follow neutropenic precautions at absolute neutrophil counts below 500. Some authors recommend prophylactic antibiotics at counts below 100. Use broad-spectrum antibiotics to treat infections. Infection is the most common cause of death in radiation patients.

Decontamination

Remove all contaminated clothing. Change contaminated dressings and splints. Thoroughly clean the patient's skin with soap and water or a 0.5% hypochlorite solution. Hair should be washed and in some instances removed. Eyes may be washed with large amounts of water or sterile saline. All contaminated materials should be bagged if possible and sent for proper disposal.

Disposition

Patients who have been decontaminated and have only mild transient symptoms can be safely discharged. Because of the variable and lengthy latent period involved with this disorder, early admission is not indicated. Patients should be closely monitored and admitted when warranted.

Many agents may be used as biologic weapons. The most likely pathogens are presented here. Biologic agents can be classified as bacterial agents, viral agents, and biologic toxins. A high index of suspicion will be required in order to identify patients who have experienced a biologic attack. A large number of patients with severe febrile illnesses will be the most likely clue. Keep in mind that the attack most likely occurs by aerosol release of infectious material several days prior to patient presentation.

Bacterial Agents

See Table 3–1.

Anthrax

Bacillus anthracis is a gram-positive, sporulating rod. Anthrax infection occurs naturally after contact with contaminated animals or contaminated animal products. A biologic attack would likely involve the aerosol release of anthrax spores. Clinically, the disease occurs in three forms: inhalational, gastrointestinal, and cutaneous.

Clinical Findings

Symptoms and Signs

Inhalational Anthrax

Inhalational anthrax is the form of disease most likely expected after a terrorist attack. After spores are inhaled, an incubation period occurs, usually lasting 1–7 days. However, incubation periods of up to 60 days have been observed. Initially, nonspecific symptoms of fever, cough, headache, chills, vomiting, dyspnea, chest pain, abdominal pain, and weakness occur. This stage may last from a few hours to a few days. Following these nonspecific symptoms, a transient period of improvement may be seen. When the second stage of disease is reached, high fever, diaphoresis, cyanosis, hypotension, lymphadenopathy, shock, and death will occur. Often, death will occur within hours once the second stage is reached. The average time from onset of symptoms to death is 3 days. Once the initial symptoms of inhalational anthrax develop, the overall mortality rate may be as high as 95%. Early diagnosis of anthrax infection and rapid initiation of therapy may improve survival.

Gastrointestinal Anthrax

Gastrointestinal anthrax occurs when spores are ingested into the digestive tract. Two forms of the disease occur: oropharyngeal and abdominal. Oropharyngeal disease occurs when spores are deposited in the upper gastrointestinal tract. An oral or esophageal ulcer develops followed by regional lymphadenopathy and eventual sepsis. In abdominal anthrax, the spores are deposited in the lower gastrointestinal tract. Symptoms include nausea, vomiting, bloody diarrhea, and the development of an acute abdomen with sepsis. Mortality rates for gastrointestinal anthrax are in excess of 50%.

Cutaneous Anthrax

Cutaneous anthrax is the most common naturally occurring form of the disease. It occurs when spores come in contact with open skin lesions. This usually occurs on the arms, hands, and face. Following exposure, a small, often pruritic, papule will develop. Eventually, this papule will turn into a small ulcer over 2 days, then progress to a small vesicle, and ultimately to a painless black eschar with surrounding edema. Then, over a period of 1–2 weeks, the eschar will dry and fall off. Regional lymphadenitis or lymphadenopathy may also occur. In some case, secondary sepsis may develop. Without treatment, cutaneous anthrax has a mortality rate of 20%; however, the mortality rate drops to 1% with treatment.

Anthrax Meningitis

Anthrax meningitis can occur as a complication of any other form of anthrax. Symptoms include headache and meningismus. Anthrax meningitis carries a mortality rate of nearly 100%.

Laboratory and X-Ray Findings

Multiple laboratory studies can be used to identify anthrax. In fulminant cases, the organism may be seen on routine Gram stain. Blood cultures, wound cultures, and nasal cultures may be obtained. Given the lack of an infiltrate, sputum cultures are rarely useful. Often Bacillus spp. are thought to be the contaminant; therefore, notify laboratory personnel of possible anthrax. Confirmatory enzyme-linked immunoassay (ELISA) and polymerase chain reaction (PCR) tests are available at some national reference laboratories. Patients with inhalational anthrax will display a wide mediastinum on chest x-ray without infiltrate.

Treatment and Prophylaxis

Because anthrax has a rapid and fulminant course, do not delay treatment while awaiting confirmatory tests. Delaying empiric treatment for even hours may significantly increase mortality.

Antibiotics

Most naturally occurring strains of anthrax are sensitive to penicillin. Some strains, however, are penicillin resistant. Weapons-grade anthrax is likely to be penicillin resistant. As a result, the first-line therapy is now ciprofloxacin; doxycycline is an acceptable alternative (see Table 3–1). Treatment should continue for 60 days. If cultures were obtained, later sensitivity testing may direct antibiotic use.

Supportive Care

Patients may require intensive medical support such as airway management, hemodynamic support, and various measures to manage multisystem organ failure.

Prophylaxis

Individuals thought to be at high risk for anthrax exposure should receive treatment as though infection has occurred. Later, laboratory analysis may allow discontinuation of therapy. An anthrax vaccination is available and requires injections at 0, 2, and 4 weeks, followed by injections at 6, 12, and 18 months. An annual booster is also required. If a combination of vaccination and antibiotics is used during treatment, the course of antibiotics may be shortened to 30 days.

Infection Control

No data indicate that anthrax is spread via person-to-person contact. Use standard precautions during patient care activities (Table 3–2).

Plague

Yersinia pestis is a nonmotile, gram-negative bacillus. Plague occurs naturally after the bite of an infected arthropod vector. Biologic attack would most likely involve the aerosolized release of Y. pestis. Plague occurs in three clinical forms: bubonic plague, septicemic plague, and pneumonic plague.

Clinical Findings

Symptoms and Signs

Bubonic Plague

Bubonic plague is the most common naturally occurring form of the disease. Infection begins with the bite of a contaminated flea. A latent period then occurs and may last up to 1 week, followed by fevers, chills, and weakness. Eventually, the organism will migrate to the regional lymph nodes where it causes destruction and necrosis. A swollen and tender lymph node called a bubo will develop, which ranges from 1 to 10 cm. Some patients may develop secondary sepsis. Without treatment, bubonic plague has an estimated mortality rate of 50%; however, with antibiotic therapy the mortality rate falls to 10%.

Septicemic Plague

Septicemic plague may occur either as a complication of other forms of plague or as a primary entity. Symptoms include fever, dyspnea, hypotension, and purpuric skin lesions. Gangrene of the nose and extremities may occur, hence the name “black death.” Complications of disseminated intravascular coagulation may also be evident. Without treatment, septicemic plague has an estimated mortality rate of 100%; however, with antibiotic therapy the mortality rate falls to 40%.

Pneumonic Plague

Pneumonic plague may occur either as a complication of other forms of plague or as a primary entity. It is the most likely form of the disease to result from a terrorist attack. A latent period of 1–6 days following exposure is likely. Patients will then develop signs and symptoms of severe pulmonary infection including fever, cough, dyspnea, hypoxia, and sputum production. Gastrointestinal symptoms of nausea, vomiting, and diarrhea may also occur. Pneumonic plague has an estimated mortality rate of 100% if antibiotic therapy is not begun within 24 hours.

Laboratory and X-Ray Findings

Y. pestis can be identified by several different staining techniques, including routine Gram, Wright, Giemsa, and Wayson stains. Blood cultures, sputum cultures, and cultures of lymph node aspirates may be useful. Specialized rapid confirmatory tests are available at some laboratories. In patients with pneumonic plague, chest x-ray will display a patchy or confluent infiltrate.

Treatment and Prophylaxis

Plague has a rapid disease progression, and any delay in empiric treatment will cause significant increases in mortality.

Antibiotics

Streptomycin or gentamicin is the drug of choice for the treatment of plague (see Table 3–1). Alternative antibiotics include doxycycline, ciprofloxacin, and chloramphenicol.

Supportive Care

Patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.

Prophylaxis

Patients in a community experiencing a pneumonic plague epidemic should receive antibiotic therapy if they develop a cough or a fever above 38.5°C (101.2°F). Any person who has been in close contact with an individual with plague should receive a 7-day course of antibiotics.

Infection Control

Pneumonic plague can be spread from person to person by aerosol droplets. Use droplet precautions, and either the patient or the caregivers should wear masks (see Table 3–2). Once the patient has received 48 hours of antibiotics and has improved clinically, standard precautions may be used.

Tularemia

Francisella tularensis is a nonmotile, aerobic, gram-negative coccobacillus. Two strains of tularemia are known to exist. F. tularensis biovar tularensis is considered highly virulent, whereas F. tularensis biovar palaearctiais more benign. Tularemia occurs naturally after the bite of an infected arthropod vector or after exposure to contaminated animal products. Biologic attack would most likely involve the release of aerosolized F. tularensis. Tularemia displays multiple clinical forms including ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, and typhoidal forms. The form of disease depends on the site and type of inoculation.

Clinical Findings

Symptoms and Signs

Patients with any form of tularemia may present with the abrupt onset of fever, chills, headache, malaise, and myalgias. Often a maculopapular rash is seen.

Ulceroglandular Tularemia

Ulceroglandular tularemia usually occurs after handling infected animals or after the bite of an infected arthropod vector. At the inoculation site, a papule will form that will eventually become a pustule and then a tender ulcer. The ulcer may have a yellow exudate and will slowly develop a black base. Regional lymph nodes will become swollen and painful.

Glandular Tularemia

Glandular tularemia displays signs and symptoms similar to ulceroglandular tularemia, except that no ulcer formation is noted.

Oculoglandular Tularemia

After ocular inoculation, a painful conjunctivitis will develop with regional lymphadenopathy. Lymphadenopathy may involve the cervical, submandibular, or preauricular chains. In some cases, ulcerations occur on the palpebral conjunctiva.

Oropharyngeal Tularemia

After inoculation of the pharynx, an exudative pharyngotonsillitis will develop with cervical lymphadenopathy.

Pneumonic Tularemia

Pneumonic tularemia occurs after inhalation of F. tularensis or following secondary spread from other infectious foci. A terrorist attack will most likely cause this form of disease. The findings of pulmonary involvement are variable and include pharyngitis, bronchiolitis, hilar lymphadenitis, and pneumonia. Early in the course of disease, systemic symptoms may predominate over pulmonary symptoms. In some cases, however, pulmonary disease progresses rapidly to pneumonia, pulmonary failure, and death.

Typhoidal Tularemia

In this form of tularemia, systemic signs and symptoms of disease are present without a clear infectious site. Signs and symptoms include fever, chills, headache, malaise, and myalgias.

Any form of tularemia may be complicated by hematogenous spread leading to pneumonia, meningitis, or sepsis. The overall mortality rates for untreated tularemia range from 10% to 30%; however, with antibiotic therapy, mortality rates drop to less than 1%.

Laboratory and X-Ray Findings

F. tularensis requires special growth media. Notify laboratory personnel of a possible tularemia specimen so that proper plating can be performed. Cultures may be obtained from sputum, pharyngeal, or blood specimens. Specialized ELISA and PCR confirmatory tests are also available at some reference laboratories. In the case of pneumonic tularemia, chest x-ray may demonstrate peribronchial infiltrates, bronchopneumonia, or pleural effusions.

Treatment and Prophylaxis

Antibiotics

Streptomycin and gentamicin are considered the drugs of choice for the treatment of tularemia (see Table 3–1). Ciprofloxacin has also displayed efficacy against tularemia. Second-line agents such as tetracycline and chloramphenicol may be used, but these agents are associated with higher rates of treatment failure. A 10-day course of antibiotics should be used. For second-line agents, a 14-day course should be used.

Supportive Care

Rarely, patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.

Prophylaxis

Some data suggest that a 14-day course of antibiotics begun during the incubation period may prevent disease. Antibiotic choices are the same as for treatment. A live attenuated vaccine for tularemia also exists and is often used for at-risk laboratory workers. Vaccination decreases the rate of inhalational tularemia but does not confer complete protection. Given tularemia's short incubation period, and the incomplete protection of the vaccine, postexposure vaccination is not recommended.

Infection Control

Significant person-to-person transmission of tularemia does not occur. Standard precautions are sufficient during patient care activities (see Table 3–2).

Brucellosis

Brucellae are small aerobic, gram-negative, pleomorphic coccobacilli. Many Brucella spp. occur naturally; however, only four species are infectious to humans. Each species typically infects a particular host organism, and human infection follows contact with contaminated animal material. The Brucella spp. that are infectious to humans are B. melitensis (found in goats), B. suis (found in swine), B. abortus (found in cattle), and B. canis (found in dogs). B. suis has been weaponized in the past.

Clinical Findings

Symptoms and Signs

The symptoms and signs of brucellosis are similar whether infection is contracted via oral, inhalational, or percutaneous routes. The usual incubation period following infection is 1–3 weeks. Because Brucella spp. infection can involve multiple body systems, a wide range of clinical findings is typical. Nonspecific symptoms are common and include fever, chills, malaise, and myalgias. Osteoarticular involvement may manifest as joint infections or vertebral osteomyelitis. Respiratory symptoms include cough, dyspnea, and pleuritic chest pain. Cardiovascular complications are numerous and include endocarditis, myocarditis, pericarditis, and mycotic aneurysms. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and hepatitis. Multiple types of genitourinary infections can also occur. Neurologic involvement may cause meningitis, encephalitis, cerebral abscesses, cranial nerve abnormalities, or Guillain–Barré syndrome. Patients may also develop anemia, thrombocytopenia, or neutropenia. Central nervous system and cardiac involvement, although infrequent, account for most fatalities. Brucella spp. are not known for their lethality, and infection has an estimated mortality rate of less than 2%. Its interest as a biologic weapon stems from the prolonged disease course and significant morbidity.

Laboratory and X-Ray Findings

Brucella spp. will grow on standard culture media. Because of their slow growth, cultures may need to be maintained for at least 6 weeks. Specialized biphasic culture techniques may improve isolation. A more common diagnostic modality is a serum tube agglutination test. ELISA and PCR studies are available at some reference laboratories. If vertebral involvement is suspected, spinal x-rays, magnetic resonance imaging, computed tomography scanning, or bone scintigraphy may be helpful.

Treatment and Prophylaxis

Antibiotics

Because of the high rate of treatment failure, single-drug therapy is not recommended. A prolonged course of multiple antibiotics is now considered to be the standard of care. The most common regimen involves the use of rifampin and doxycycline given for a 6-week period (see Table 3–1). Other antibiotics that have displayed efficacy against Brucella spp. include gentamicin, streptomycin, trimethoprim–sulfamethoxazole, and ofloxacin. In patients with serious infections, a three-drug parenteral regimen is the norm.

Supportive Care

Rarely, patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.

Prophylaxis

No human vaccine against Brucella spp. currently exists. Some physicians recommend a 3- to 6-week course of antibiotics following a high-risk exposure such as a biologic attack.

Infection Control

Person-to-person spread of brucellosis is thought to be uncommon. Standard precautions are sufficient during patient care activities (see Table 3–2).

Q Fever

Q fever is caused by a rickettsial organism known as Coxiella burnetii. C. burnetii has a worldwide distribution and occurs naturally in many domesticated animals (dogs, cats, sheep, goats, cattle). The organism is shed in feces, urine, milk, and placental material. Much like anthrax, C. burnetii produces a sporelike form. Humans become infected by inhaling contaminated aerosols.

Clinical Findings

Symptoms and Signs

After infection, a typical incubation period ranges from 5 to 30 days. The symptoms and signs of Q fever are nonspecific and may occur acutely or have an indolent course. Typical symptoms and signs include fever, chills, malaise, myalgias, headache, and anorexia. If cough occurs, it tends to occur late in the disease process and may or may not be associated with pneumonia. Various cardiac manifestations may occur and include endocarditis, myocarditis, and pericarditis. Gastrointestinal findings are common and include nausea, vomiting, diarrhea, and hepatitis. A nonspecific maculopapular rash may develop. Although not as common, various neurologic symptoms may also occur.

In some patients, Q fever may become a chronic condition. Chronic Q fever is typically manifested as endocarditis and tends to affect previously diseased cardiac valves. Although Q fever can be debilitating, it is usually not fatal. Mortality rates are generally less than 2.5%.

Laboratory and X-Ray Findings

C. burnetii is difficult to grow in culture and sputum analysis is equally futile. Several serologic tests are available and include indirect fluorescent antibody staining, ELISA, and complement fixation. These tests often must be conducted at specialized reference laboratories. Elevated liver enzymes are also common in C. burnetii infection.

Treatment and Prophylaxis

Antibiotics

Most cases of C. burnetii infection will resolve without antibiotic therapy. Regardless, antibiotics are recommended because treatment will lower the rate of complications. A 7-day course of either doxycycline or tetracycline is usually sufficient (see Table 3–1). Fluoroquinolones are an acceptable alternative.

Supportive Care

Rarely, patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.

Prophylaxis

Prophylactic antibiotics should be started 8–12 days after initial exposure. Antibiotics are ineffective if started sooner. A 7-day course of either doxycycline or tetracycline is usually sufficient. Fluoroquinolones are an acceptable alternative. An investigational vaccine exists but is not yet available to the general public.

Infection Control

Person-to-person spread of the disease is unlikely. Standard precautions are sufficient while engaging in patient care activities (see Table 3–2).

Viral Agents

Smallpox

Smallpox is a disease caused by the variola virus, which is a DNA virus of the genus Orthopoxvirus. It occurs in two strains: the more severe variola major and a milder form, variola minor. Smallpox was essentially eradicated worldwide by an aggressive treatment and vaccination campaign conducted by the World Health Organization. The last naturally occurring case was in Somalia in 1977. Two stockpiles of the virus remain, one in the Centers for Disease Control and Prevention in Atlanta and the other in the Institute of Virus Preparations in Moscow.

Clinical Findings

Symptoms and Signs

Disease begins with inhalation of the variola virus. After an initial exposure, a 7- to 17-day incubation period begins, during which the virus replicates in the lymph nodes, bone marrow, and spleen. A secondary viremia then develops leading to high fever, malaise, headache, backache, and in some cases delirium. After approximately 2 days, a characteristic rash will develop. The rash begins on the extremities and moves to the trunk. The palms and soles are not spared. The rash follows a typical progression beginning as macules, then papules, and eventually becoming pustular. Eventually, lesions will form scabs that separate, leaving small scars. The rash appears similar to chickenpox, except that all the lesions in smallpox will be in similar stages of development. In unvaccinated individuals, mortality rates associated with variola major are approximately 30%. Variola minor has a similar progression to variola major, but toxicity and rash are not as severe. In unvaccinated individuals, the mortality rates associated with variola minor are approximately 1%. In 10% of cases, a variant form of rash will develop. A hemorrhagic rash displaying petechiae and frank skin hemorrhage may occur. This variant of smallpox carries a mortality rate of nearly 100%. Likewise, a malignant form exists in which the pustules remain soft and velvety to the touch.

Laboratory and X-Ray Findings

Analysis of pustular fluid will yield virus particles. All samples should be sealed in two airtight containers. Variola can easily be recognized via electron microscopy. The virus itself can be grown in cell cultures or on chorioallantoic egg membranes. Further characterization of strains can be accomplished via biologic assays. PCR analysis is available at some reference laboratories.

Treatment and Prophylaxis

Specific Therapy

Currently there is no specific therapy for smallpox other than supportive care. Many investigational drugs are currently under study. Strict patient isolation, preferably at home, should be used. Any person having close contact with infected patients should be either quarantined or monitored for signs of infection. Antibiotics may be used if secondary bacterial infection occurs.

Prophylaxis

Smallpox vaccination is very effective at preventing the disease and gives immunity for 5–10 years. Universal smallpox immunization of the general population was discontinued over 30 years ago when smallpox was eradicated. Because of the risk of possible terrorist attack, there has recently been a preemptive initiation of smallpox vaccination for selected health care workers. However, the smallpox vaccine has several rare complications. Postvaccinal encephalitis occurs in approximately 1 in 300,000 vaccinations and is fatal in 25% of patients. Immunocompromised patients who are vaccinated may develop a condition known as progressive vaccinia, which is often fatal. In this condition, the initial inoculation site failed to heal, became necrotic, and necrosis spread to adjacent tissues. In some patients with eczema, a postvaccination condition known as eczema vaccinatum may occur. Here, vaccinial lesions occur in areas previously involved with eczema. Fortunately, the eruptions are usually self-limited. In some patients, a secondary generalized vaccinia could develop. In others, inadvertent autoinoculation of eyes, mouth, or other areas may occur. Many of these complications are treated with vaccinia immune globulin. Data indicate that vaccination within 4 days of smallpox exposure may lessen subsequent illness. Cidofovir has also displayed some efficacy in preventing smallpox infection if given within 48 hours. However, cidofovir is not more effective than the vaccine and is associated with significant renal toxicity.

Infection Control

Smallpox is highly infectious. Infection is spread by aerosol droplets. It is generally thought that each index case will subsequently infect 10–20 secondary individuals. The period of infectivity begins with the onset of rash and ends when all scabs separate. Use airborne precautions during patient care activities (see Table 3–2). Any material in contact with patients should be either autoclaved or washed in a bleach solution.

Hemorrhagic Fever

Viral hemorrhagic fever represents a clinical syndrome caused by several RNA viruses. These viruses exist in four different families: the Arenaviridae, the Filoviridae, the Flaviviridae, and the Bunyaviridae. Numerous viruses in each family may cause slightly different forms of hemorrhagic fever. The different forms of hemorrhagic fever are often named by their geographic origin (Table 3–3). Human infection occurs after contact with infected animals or infected arthropod vectors. Many of these viruses are also highly infectious in the aerosol form. This characteristic makes these viruses potential biologic weapons.

Clinical Findings

Symptoms and Signs

Several clinical aspects of hemorrhagic fever are unique to the individual forms (Table 3–3). Many symptoms and signs, however, are common to all types of hemorrhagic fever. Alterations in the vascular bed and increased vascular permeability lead to the dominant features of this disease. Early symptoms and signs include fever, conjunctival injection, mild hypotension, prostration, facial flushing, vomiting, diarrhea, and petechial hemorrhages. Eventually some patients may develop shock and mucous membrane hemorrhage. In some instances, evidence of hepatic, pulmonary, and neurologic involvement will be present. Secondary bacterial infection is also common.

Laboratory and X-Ray Findings

A number of nonspecific laboratory abnormalities may be seen, including leukopenia, thrombocytopenia, proteinuria, hematuria, and elevated liver enzymes. Definitive diagnosis is possible with various rapid enzyme immunoassays and with viral culture.

Treatment and Prophylaxis

Specific Therapy

Ribavirin is a nucleoside analog that has been shown to improve mortality in some forms of hemorrhagic fever. Dosing is as follows: 30 mg/kg IV as an initial dose, followed by 16 mg/kg IV every 6 hours for 4 days, and then 8 mg/kg IV every 8 hours for 6 days. Ribavirin is usually most effective if begun within 7 days. Unfortunately, ribavirin is thought to be ineffective against the filoviruses and the flaviviruses. Convalescent plasma containing neutralizing antibodies is also effective in some cases.

Supportive Care

Intravenous lines and other invasive procedures should be limited. Use fluid resuscitation with caution. Because of increases in vascular permeability, peripheral edema and pulmonary edema are frequent complications of volume replacement. If frank disseminated intravascular coagulopathy develops, consider heparin therapy.

Prophylaxis

A vaccine against yellow fever is currently available. Many other investigational vaccines exist but are not currently available to the general public. Protocols also exist for the use of ribavirin in high-risk exposures.

Infection Control

The causal agents of hemorrhagic fever are highly infectious. Use caution when using sharps or when coming into contact with the body fluids of the patients. Some forms are spread via aerosol, and patients with significant cough should be placed under airborne precautions. All laboratory specimens should be double sealed in airtight containers.

Viral Encephalitis

Much like viral hemorrhagic fever, viral encephalitis represents a clinical syndrome caused by numerous viruses. Of the pathogens that cause viral encephalitis, members of the family Togaviridae are thought to have the potential as biologic weapons. The family Togaviridae includes the eastern equine encephalitis (EEE) virus, western equine encephalitis (WEE) virus, and Venezuelan equine encephalitis (VEE) virus. VEE virus has been weaponized in the past. In nature, these viruses are spread by infected arthropod vectors and they infect humans as well as equines. They are also infectious in aerosol form, hence their utility as biologic weapons.

Clinical Findings

Symptoms and Signs

Nearly all forms of infection will cause nonspecific symptoms and signs of fever, chills, malaise, myalgias, sore throat, vomiting, and headache. A large number of associated equine deaths may lead one to suspect equine encephalitis. The degree to which encephalitis develops depends on the pathogen involved. Although nearly all cases of VEE are symptomatic, encephalitis occurs in less than 5% of cases. If encephalitis does develop, and the patient recovers, residual neurologic sequelae usually do not occur. Without encephalitis, VEE has an expected mortality rate of less than 1%. Although uncommon, if encephalitis develops, the mortality rate increases to approximately 20%. In contrast, EEE tends to progress to neurologic involvement. Encephalitis is usually severe and residual neurologic findings are common. With EEE, mortality rates range from 50% to 75%. WEE displays an intermediate degree of severity, with an overall estimated mortality rate of approximately 10%. If encephalitis develops, confusion, obtundation, seizures, ataxia, cranial nerve palsies, and coma may occur.

Laboratory and X-Ray Findings

Although nonspecific, leukopenia and lymphopenia are common. In cases of encephalitis, cerebral spinal fluid analysis will display a lymphocytic pleocytosis. A number of serologic studies such as ELISA, complement fixation, and hemagglutination inhibition may aid diagnosis. Although time consuming, the gold standard test for VEE involves viral isolation following inoculation of cell cultures of suckling mice. Additional specialized tests may be available only at regional reference laboratories.

Treatment and Prophylaxis

Specific Therapy

Unfortunately, no specific treatment for equine encephalitis exists. Supportive care is all that can be offered. Headache may be treated with typical analgesics. Seizures are treated with typical anticonvulsant medications.

Supportive Care

Patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.

Prophylaxis

An investigational vaccine against VEE virus exists. It does not provide protection against all strains of VEE virus, and some patients will not display an effective antibody response. In 20% of the patients receiving the vaccine, fever, malaise, and myalgias may develop.

Infection Control

Infection is not spread by person-to-person contact. Standard precautions are sufficient during patient care activities. To limit the spread of disease, patient exposure to arthropod vectors should be prevented.

Biologic Toxins

See Table 3–4.

Botulinum Toxin

Botulism is caused by a protein toxin produced by Clostridium botulinum. C. botulinum is a gram-positive, spore-forming, obligate anaerobe found naturally in the soil. Many authorities consider botulinum toxin to be among the most potent naturally occurring poisons. The toxin occurs in seven antigenic types, designated types A–G. Once absorbed, toxin will bind to motor neurons and prevent the release of acetylcholine, causing a flaccid muscle paralysis. Natural infection occurs in three forms: wound botulism, foodborne botulism, and intestinal botulism. Wound botulism occurs after C. botulinum contaminates an open wound, subsequently producing toxin. Foodborne botulism occurs after ingesting food already contaminated by the toxin. Intestinal botulism, typically seen in infants, occurs after ingesting food contaminated by C. botulinum, which in turn produces toxin. Although not occurring naturally, botulism can also be caused by inhalation of the toxin. This is the form of botulism that will likely occur following biologic attack. Contamination of food or water supplies also represents a possible terrorist threat. Food contamination, however, is unlikely to induce the large numbers of affected persons that would be seen following aerosol exposure. Water contamination would be difficult because current purification techniques are effective in neutralizing botulinum toxin.

Clinical Findings

Symptoms and Signs

After initial exposure, an incubation period ranging from 12 to 80 hours will occur. The duration of the incubation period depends on the type and amount of exposure. After the incubation period, a flaccid symmetric muscle paralysis will affect the bulbar musculature. Patients often display ptosis, diplopia, dysphagia, dysarthria, and dysphonia. Dilated, poorly reactive pupils are common. Eventually the paralysis will extend to the lower muscle groups, leading to paralysis. Airway compromise is common and patients may lose respiratory function.

If foodborne exposure is involved, gastrointestinal symptoms such as nausea, vomiting, and diarrhea may occur. Botulism does not cause altered sensorium, sensory changes, or fever.

Laboratory and X-Ray Findings

A mouse bioassay is the definitive test for botulism. Specimens for evaluation may be obtained from suspected food, blood, gastric contents, or possibly stool. This type of diagnostic testing is not widely available, and specimens may need to be sent to specialized laboratories. In addition to laboratory studies, electromyograms may display patterns consistent with botulism.

Treatment and Prophylaxis

Specific Therapy

A botulinum antitoxin can be obtained from many state health departments or from the Centers for Disease Control and Prevention. Antitoxin therapy is most effective when given early in the disease course. It acts by binding free toxin but will not restore nerve terminals that have already been compromised. The civilian antitoxin is effective in neutralizing the three most common types of botulinum toxin found to affect humans (types A, B, and E). If other forms of toxin are utilized, an investigational heptavalent antitoxin may be available from the military. The military antitoxin is effective against all types of toxin (types A–G). Because some patients may develop allergic reactions to the antitoxin, a test dose is recommended.

Supportive Care

Patients may require intensive medical support such as airway management and ventilator support. Parenteral or tube feedings may be required. Treat secondary bacterial infections with antibiotics. Avoid clindamycin and aminoglycoside antibiotics because they may worsen neurologic blockade.

Prophylaxis

Some evidence suggests that initiation of antitoxin prior to the onset of symptoms may prevent disease. Unfortunately, large amounts of the antitoxin are not available. A more prudent course of action would be to institute antitoxin therapy at the first signs of illness.

Infection Control

Person-to-person transmission of botulism does not occur. Standard precautions are sufficient during patient care activities (see Table 3–2). If food is suspected of being contaminated, thorough cooking will neutralize the toxin.

Ricin

Ricin is a polypeptide toxin that causes cell death by inhibiting protein synthesis. It occurs naturally as a component of the castor bean from the castor plant, Ricinus communis. Accidental ricin toxicity has occurred following ingestion of castor beans. Although ricin is less toxic than many other potential biologic agents, it is inexpensive, easy to produce, and can be aerosolized. These characteristics make it a potential biologic weapon. Ricin may be delivered by parenteral injection, ingestion, or inhalation. Ingestion and inhalation are the likely modes of biologic attack.

Clinical Findings

Symptoms and Signs

The signs and symptoms of ricin intoxication depend on the type and amount of exposure. Parenteral exposure causes necrosis of local tissues and regional lymph nodes. As the toxin spreads, visceral organs become involved, manifested as a moderate to severe gastroenteritis. Parenteral exposure is an unlikely means of biologic attack. If ricin is ingested, symptoms of gastrointestinal exposure will occur and may include nausea, vomiting, hematemesis, bloody diarrhea, melena, or visceral organ necrosis. If death occurs following parenteral or gastrointestinal exposure, it is usually secondary to circulatory collapse.

The most likely means of biologic attack involve aerosol exposure. Inhalation of ricin is manifested by direct pulmonary toxicity. Between 4 and 8 hours after exposure, the patient may develop fever, cough, chest pain, and dyspnea. Findings consistent with an aerosol exposure include bronchitis, bronchiolitis, interstitial pneumonia, and acute respiratory distress syndrome. If death occurs, it is usually secondary to respiratory failure and generally will occur within 36–72 hours.

Laboratory and X-Ray Findings

Various laboratory tests, including ELISA, PCR, and immunohistochemical staining, may aid in the diagnosis of ricin toxicity. In the event of pulmonary involvement, chest x-ray may display bilateral infiltrates or noncardiogenic pulmonary edema.

Treatment and Prophylaxis

The treatment of ricin toxicity depends largely on the mode of exposure.

Parenteral Exposure

With parenteral exposure, treatment is largely supportive.

Gastrointestinal Exposure

The treatment of gastrointestinal exposure primarily involves the elimination of toxin. This can be accomplished by vigorous gastric lavage and by the use of cathartics such as magnesium citrate or whole bowel irrigation. Activated charcoal may be considered. Correct electrolyte abnormalities and maintain adequate volume status. Treat secondary bacterial infections with appropriate antibiotics.

Pulmonary Exposure

With pulmonary exposure, treatment involves providing adequate ventilatory support. Patients may require oxygen, intubation, and ventilator management. Treat secondary bacterial infections with appropriate antibiotics.

Prophylaxis

Ricin vaccines are under development.

Infection Control

Ricin intoxication is not spread by person-to-person contact. Standard precautions are sufficient during patient care activities (see Table 3–2).

T-2 Mycotoxins

Like penicillin, mycotoxins are a diverse group of compounds produced by fungi for environmental protection. These compounds are frequently toxic to many animal species including humans. The T-2 mycotoxins are a particular group of compounds produced by fungi of the genus Fusarium. Although the actions of the T-2 mycotoxins are not completely understood, they are known to inhibit DNA and protein synthesis. They are most toxic to rapidly dividing cell lines.

Many properties of these compounds make them attractive as biologic weapons. Specifically, they are resistant to destruction by ultraviolet radiation and are heat stabile. T-2 mycotoxins confer toxicity after ingestion, inhalation, or dermal exposure. Unlike most other biologic agents, they can be absorbed directly through the skin.

Clinical Findings

Symptoms and Signs

With T-2 mycotoxin exposure, contamination via dermal, gastrointestinal, and pulmonary routes may occur simultaneously. The earliest symptoms and signs may begin within minutes to hours. Dermal exposure may manifest as skin pain, erythema, blistering, and skin necrosis. Toxin exposure to the eyes and upper airway may cause ocular pain, redness, tearing, sneezing, rhinorrhea, oral pain, blood-tinged mucus, and epistaxis. Patients with pulmonary involvement will display chest pain, cough, and dyspnea. Signs and symptoms of gastrointestinal toxicity include abdominal pain, nausea, vomiting, and a bloody diarrhea. With systemic toxicity, patients may develop weakness, dizziness, and ataxia. Similar to radiation exposure, these toxins may also cause bone marrow suppression resulting in thrombocytopenia and neutropenia.

Laboratory and X-Ray Findings

Two primary forms of laboratory testing may be used to identify T-2 mycotoxins. First, antigen detection can be performed on urine samples. The metabolites of the T-2 mycotoxins are eliminated primarily in the urine and feces. These metabolites are detectable in the urine up to 1 month after exposure. Second, mass spectrometric evaluation can be conducted on various body fluids. Appropriate samples include nasal secretions, pulmonary secretions, urine, blood, and stomach contents.

Treatment and Prophylaxis

Specific Therapy

The treatment of T-2 mycotoxin poisoning is essentially supportive care. Remove all contaminated clothing and wash the patient's skin with large amounts of soap and water. Treat dermal burns with standard therapy. Treat secondary bacterial infections with appropriate antibiotics. Ocular involvement requires irrigation with water or sterile saline. Activated charcoal may aid in gastrointestinal decontamination. Patients with pulmonary involvement may require advanced respiratory techniques such as intubation or ventilatory support.

Prophylaxis

Vaccines against the T-2 mycotoxins are under study. The early use of soap and water may prevent skin toxicity.

Infection Control

The T-2 mycotoxins are dispersed as an oily liquid. Contact with this liquid may cause cross-contamination. Therefore, remove all contaminated clothing and wash the patient's skin with soap and water. Standard precautions are sufficient during patient care activities (see Table 3–2).

Staphylococcal Enterotoxin B

Staphylococcal aureus produces a number of exotoxins that produce disease in humans. One such exotoxin, staphylococcal enterotoxin B (SEB), is a causal agent of the gastrointestinal symptoms seen in staphylococcal food poisoning. It is a heat-stabile toxin that belongs to a group of compounds known as super antigens. These compounds have the ability to activate certain cells in the immune system, causing a severe inflammatory response. This response causes injury to various host tissues. Aside from injury caused by SEB in natural infections, it can be aerosolized, making it a potential biologic weapon. Biologic attack could involve deliberate contamination of foodstuffs, although a more likely scenario would involve an aerosol release.

Clinical Findings

Symptoms and Signs

After exposure to SEB, a variable incubation period occurs, ranging from 4 to 10 hours for gastrointestinal exposure and from 3 to 12 hours for inhalational exposure. Regardless of the type of exposure, nonspecific symptoms and signs will develop and include fever, chills, headache, malaise, and myalgias. If the exposure occurred via the gastrointestinal route, then patients will also develop nausea, vomiting, and diarrhea. Conversely, if the exposure occurred via an inhalational route, the patient will also develop chest pain, cough, and dyspnea. Death is rare but in severe cases may occur from respiratory failure. Patients generally recover from symptoms after 1–2 weeks.

Laboratory and X-Ray Findings

The presence of SEB can be confirmed by identifying specific antigens via ELISA testing. Obtain serum and urine samples. Urine samples are more productive because toxin tends to accumulate in the urine. In the case of aerosol exposure, respiratory and nasal swabs may also demonstrate toxin if samples are obtained within 1 day of exposure. With inhalational exposure, the chest x-ray is usually normal but in severe cases may demonstrate pulmonary edema.

Treatment and Prophylaxis

Specific Therapy

The treatment of SEB exposure is largely supportive. Correct electrolyte abnormalities and maintain volume status. If pulmonary edema develops, patients may benefit from diuretic therapy and in some cases may require intubation and ventilatory support. Steroids may be given to lessen the inflammatory response, but this approach is controversial. Treat secondary bacterial infections with appropriate antibiotics.

Prophylaxis

Vaccines against SEB are under study.

Infection Control

Person-to-person transmission of toxin is not a hazard. Standard precautions are sufficient during patient care activities (see Table 3–2).

Like radiation and biologic agents, many chemicals can be developed into weapons of mass destruction (Table 3–5). Chemical weapons are particularly attractive to rogue governments and terrorist organizations because of their low cost, stability, and ease of production. In fact, a chemical nerve agent was already used by a terrorist organization. Aum Shinrikyo released sarin in the Tokyo subway in 1995. Chemical agents can be delivered as liquids, vapors, or components of explosive devices. They are generally categorized as nerve agents, pulmonary agents, vesicants, and cyanide agents.

Nerve Agents

The nerve agents are a diverse group of compounds that were first developed by the Germans prior to World War II. GA (tabun) was the first nerve agent produced, followed by several others including GB (sarin), GD (soman), GF, and VX. Each of these agents has different physical characteristics, of which volatility is the most critical. These agents are classified as organophosphates and induce toxicity by binding to and inhibiting various forms of the acetylcholine esterase enzyme. This causes increased levels of acetylcholine, leading to hyperstimulation of both central and peripheral muscarinic and nicotinic receptors. Toxicity can occur either from skin contact or from inhalation of vapor.

Clinical Findings

Symptoms and Signs

Latent Period

When nerve agent exposure occurs as a vapor, there is generally no significant latent period and symptoms will develop within minutes. Likewise, the clinical effects of vapor exposure do not tend to progress over time. In contrast, liquid contamination may have a significant latent period depending on the amount of skin exposure. With small exposures, latent periods of up to 18 hours may be seen. Further, with liquid contact, symptoms and signs may progress over a period of time.

Clinical Syndromes

The findings that will develop following nerve agent poisoning depend on the amount and type of exposure. As the degree of exposure increases, so does the severity of symptoms. The general clinical syndromes of nerve agent toxicity are as follows:

Central Nervous System

The effects on the central nervous system may range from mild to severe depending on the degree of exposure. Mild symptoms and signs include mood swings, difficulty concentrating, poor judgment, and sleep disturbances. With more significant exposures, coma, convulsions, and apnea may occur.

Peripheral Nicotinic Stimulation

The symptoms and signs of peripheral nicotinic receptor stimulation are manifest primarily as alterations in skeletal muscle functioning. The degree of involvement depends on the degree of exposure. Initially muscle fasciculations or weakness will occur and may eventually progress to paralysis.

Peripheral Muscarinic Stimulation

The symptoms and signs of peripheral muscarinic receptor stimulation are manifest primarily as increased exocrine gland and smooth muscle activity. Typical symptoms and signs of exocrine gland stimulation include rhinorrhea, salivation, sweating, increased gastrointestinal secretions, and increased pulmonary secretions. Increased pulmonary secretions may be severe enough to compromise the patient's airway. Increased smooth muscle activity will cause vomiting, diarrhea, increased urination, and abdominal pain.

Laboratory and X-Ray Findings

Acetylcholine esterase exists in various tissues within the body. Two important subpopulations of acetylcholine esterase are the plasma cholinesterase and the erythrocyte cholinesterase. Decreased activity within either population may indicate nerve agent exposure. Of the two forms, the erythrocyte cholinesterase is the more sensitive indicator of exposure.

Treatment

Specific Therapy

The treatment of nerve agent toxicity involves the use of three primary medications. The first, atropine, is an anticholinergic medication used to counteract the hyperstimulation of peripheral muscarinic receptors. Atropine (1–2 mg IV; if no effect, double dose every 5 minutes until secretions dry) should generally be given until secretions begin to dry. Atropine will not prevent central nervous system or nicotinic toxicity. In contrast, pralidoxime chloride (2-PAM), 1–2 g IV given over 15–30 minutes, ameliorates nicotinic toxicity by breaking the bond formed between the nerve agent and the esterase enzyme. The nerve agent–esterase bond may be broken as long as the compound has not aged, a process by which the bond becomes irreversible. For most of the nerve agents, the aging process is not clinically significant. One notable exception is GD (soman), which ages after only 2 minutes and is refractory to 2-PAM therapy. Finally, a common complication of severe intoxication is seizure activity. Seizures may be treated with benzodiazepines.

Supportive Care

Patients may require intensive medical support such as airway management and ventilatory support. Frequent suctioning of secretions may also be required.

Decontamination

For more specific information on decontamination, see the section “Chemical Decontamination.”

Pulmonary Agents

Many different chemicals can be classified as pulmonary or lung agents. All have a similar mechanism of toxicity, producing delayed onset of pulmonary edema. Of these agents, carbonyl chloride (phosgene) has been the most studied. Because phosgene is the prototypical lung agent, most of the discussion here relates to phosgene; however, the principles of management can be applied to all lung agents. As a military agent, phosgene was first used during World War I and today can be found in numerous industrial applications. Because of its high volatility, phosgene forms a gas readily, often with the faint scent of freshly cut hay. It is not absorbed through the skin, but when inhaled, it causes toxicity. After inhalation, phosgene is deposited in the peripheral airways, where it undergoes acetylation reactions. Subsequent damage to the alveolar-capillary membrane will occur, resulting in pulmonary edema. Phosgene may also interact with mucous membranes, causing local irritation.

Clinical Findings

Symptoms and Signs

As noted previously, the primary effect of phosgene involves lung toxicity, although with some exposures, patients may have transient irritation to the eyes, nose, and mouth. In some cases, rhinorrhea and oral secretions may be significant. Patients may also complain of mild chest discomfort and cough secondary to bronchial irritation. In significant exposures, early death may occur secondary to laryngeal spasm. Despite these early effects, most of the toxicity of phosgene exposure is delayed. After inhalation, a variable latent period of up to 24 hours will ensue. The length of the latent period depends on the dose of phosgene delivered and will be shorter with higher exposures. Eventually the patient may develop symptoms and signs consistent with pulmonary edema, including dyspnea, hypoxia, chest pain, and cough. In some cases, pulmonary edema may be severe enough to cause hypotension. The degree to which each patient is affected depends on the severity of exposure. In severe exposures, death may occur.

Laboratory and X-Ray Findings

No clinical test exists for the diagnosis of phosgene exposure. Appropriate studies such as arterial blood gas measurements and chest x-ray should be used to manage pulmonary edema. Hemoconcentration secondary to pulmonary edema may also be evident.

Treatment

Bed Rest

Any activity, even walking, may increase the severity of pulmonary edema. As a result, discourage patients from any physical activity.

Upper Respiratory Symptoms

In some cases, upper airway secretions may be significant. Nasal, oral, or bronchial secretions should be suctioned, if needed. If bronchospasm develops, it may be treated with intravenous steroids and inhaled bronchodilators. Treat secondary bacterial infections with appropriate antibiotics.

Lower Airway Symptoms

If pulmonary edema develops, it should be managed with standard medical interventions including supplemental oxygen, intubation, and ventilator management. Positive end-expiratory pressure is a useful ventilator adjunct. Treat secondary bacterial infection with antibiotics.

Hypotension

Secondary hypotension may develop in the event of severe pulmonary edema. Treatment of hypotension is problematic, given the increased permeability of the alveolar-capillary membrane. Supplemental crystalloid or colloid solutions can be used but they may worsen pulmonary edema. Vasopressor agents such as dopamine may also be used.

Decontamination

No specific decontamination is required except removing the patient from the phosgene gas.

Vesicants

Vesicants are a group of related compounds known to cause skin lesions, primarily blisters. Despite their predilection for skin involvement, multiple systemic effects are also seen. Although multiple agents may be used as vesicants, sulfur mustard and lewisite are the most common.

Sulfur Mustard

Sulfur mustard (mustard) was first used as a chemical weapon during World War I. Mustard is a lipophilic compound that is readily absorbed through intact skin. It causes significant dermal toxicity and after systemic absorption will affect various body systems. Exposure can occur after contact with mustard vapor or liquid. At different ambient temperatures, mustard may exist in either form. It displays a characteristic odor of garlic or mustard, hence its name. The exact mechanism of mustard toxicity is not known but appears to involve DNA alkylation. Mustard also displays mild cholinergic activity. After systemic absorption, cell lines undergoing active mitosis are affected the most.

Clinical Findings

Symptoms and Signs

The symptoms and signs of mustard toxicity depend on the dose and mechanism of exposure. Unfortunately, initial mustard exposure is not symptomatic, and the patient may be unaware of contamination. Given the initial lack of symptoms, patients may not decontaminate, thus increasing toxicity. Depending on the dose, the latent period after exposure may range from 2 to 48 hours. In mild exposures, patients may display only mild dermal injury; in severe exposures, death may occur within hours. The specific symptoms and signs of mustard toxicity depend on the body areas exposed and the degree of systemic absorption. As noted, the skin is typically affected and will display areas of erythema, burning, and blister formation. The blisters may become large and express a clear to straw-colored fluid. The fluid does not contain mustard agent.

The eyes are one of the organs most sensitive to mustard exposure and may develop symptoms and signs first. Following ocular exposure, ocular pain, photophobia, conjunctivitis, and blepharospasm may occur. The superficial layers of the cornea may be denuded, leading to corneal clouding with visual changes.

With injury to the respiratory tree, patients may develop oronasal burning, rhinorrhea, sore throat, or epistaxis. In more severe exposures, findings of cough, dyspnea, mucous membrane necrosis, airway muscular damage, pulmonary edema, and respiratory failure may be seen. Symptoms and signs of gastrointestinal exposure may result either from the direct toxicity of mustard exposure or from mustard's cholinergic affects. Nausea, vomiting, diarrhea, and constipation are common findings.

Severe mustard exposure may also affect the central nervous system; mental status changes and seizure activity are the most common findings. Given mustard's interference with DNA activity, delayed findings of bone marrow suppression may also occur.

Laboratory and X-Ray Findings

With exposure to mustard, an early leukocytosis is typical. If bone marrow suppression develops, later findings of anemia, leukopenia, and thrombocytopenia may be seen. If wound or pulmonary secretions become more purulent, a secondary bacterial infection should be suspected and Gram stain and culture obtained. Gastrointestinal symptoms may require electrolyte monitoring. The primary metabolite of mustard agent thiodiglycol may be detected in the urine in contaminated patients. Such specialized testing usually can be conducted only at reference or military laboratories. In the event of pulmonary involvement, chest x-ray may demonstrate a focal or diffuse pneumonitis and occasionally pulmonary edema.

Treatment

Decontamination

The most critical aspect in the treatment of mustard toxicity is removal of the chemical agent. This is problematic given the initial lack of symptoms. Even delayed decontamination, however, may lessen subsequent toxicity. Washing contaminated areas with either large amounts of soapy water or 0.5% hypochlorite solution is the preferred method of decontamination. For more specific information on decontamination, see the section “Chemical Decontamination.”

Specific Therapy

With skin injuries, leave small blisters intact and unroof larger lesions. Clean unroofed areas frequently and cover them with antibiotic cream (Polysporin, silver sulfadiazine). Treat other irritated areas of skin with systemic analgesics or topical lotions. With ocular exposure, use topical antibiotics to prevent secondary bacterial infections. Topical anticholinergics may prevent the discomfort of ciliary spasm. With pulmonary involvement, treat associated cough with typical antitussive medications. Treat episodes of bronchospasm with systemic steroids and inhaled bronchodilators. Treat secondary bacterial infection with appropriate antibiotics. Supplemental oxygen, intubation, or ventilator management may be required in some patients. Typical gastrointestinal antispasmodics may ameliorate the symptoms of gastrointestinal exposure. Bone marrow transplant, growth factor utilization, and factor replacement are alternatives for the treatment of bone marrow suppression.

Decontamination

As noted above, toxin can be removed by washing contaminated surfaces with large amounts of soapy water or 0.5% hypochlorite solution. For more specific information on decontamination, see the section “Chemical Decontamination.”

Lewisite

Much like sulfur mustard, exposure to lewisite causes injury to contaminated body surfaces and may lead to systemic symptoms. Unlike mustard, however, lewisite exposure causes symptoms and signs without a significant latent period. Lewisite is a volatile agent with the odor of geraniums. Its exact mechanism of action is unknown, but it is thought that the arsenic component of lewisite may inhibit various enzymes.

Clinical Findings

Symptoms and Signs

As noted above, the symptoms and signs of lewisite exposure begin without a significant latent period. Even though findings of exposure begin early, it may take several hours for symptoms to fully develop. The severity of clinical findings depends on the degree and method of exposure. Shortly after skin exposure, an area of dead skin will develop that will subsequently blister. These lesions may take up to 18 hours to fully develop. Skin necrosis may also be evident. Symptoms and signs of ocular exposure are similar to those associated with mustard toxicity and include conjunctivitis, iritis, edema, ocular pain, and corneal injury. If pulmonary toxicity develops, findings of cough, dyspnea, and pulmonary edema may occur. Lewisite causes increases in vascular permeability that may lead to third spacing of fluid with subsequent hypotension. In some cases, gastrointestinal, renal, and liver involvement may be seen.

Laboratory and X-Ray Findings

No specific test for lewisite exposure is currently available.

Treatment

Decontamination

As with mustard exposure, the cornerstone of treatment involves early decontamination. Compared with mustard exposure, decontamination is usually more successful with lewisite exposure, given the early onset of symptoms. Standard washing with soap and water or 0.5% hypochlorite solution is sufficient.

Supportive Care

Patients may require intensive medical support such as airway management, hemodynamic support, and various measures to manage multisystem organ failure.

Specific Therapy

British antilewisite (dimercaprol), 2–3 mg/kg every 4 hours, is a compound that can be given IM to decrease the effects of lewisite exposure.

Cyanide Agents

Cyanide has a high affinity for trivalent iron compounds and will bond to the cytochrome a3 complex within the mitochondria. The cytochrome a3–cyanide bond effectively blocks aerobic cellular respiration, and anaerobic metabolism ensues. Cyanide exposure most often occurs naturally after inhalation of smoke from burning synthetic materials. In a biologic attack, cyanide exposure would likely follow an aerosol release. Cyanide gas is known to exhibit the scent of bitter almonds.

Clinical Findings

Symptoms and Signs

After inhalation of cyanide gas, the cytochrome a3 enzyme is effectively blocked. Because cells can no longer utilize oxygen, they will convert to anaerobic metabolism, leading to a lactic acidosis. This inability to utilize oxygen effectively smothers the patient. Tachycardia, hypertension, and tachypnea will be seen initially. As symptoms and signs progress, anxiety, mental status changes, coma, seizures, cardiac arrest, and death will occur. Because cyanide does not alter oxygen–hemoglobin saturation, cyanosis will not develop. In fact, the inability to utilize oxygen increases the venous oxygen saturation, leading to a cherry red appearance to the skin. It generally takes 6–8 minutes for death to occur following cyanide exposure.

Laboratory and X-Ray Findings

An elevated blood cyanide concentration confirms the diagnosis. Given the short time interval to death, such testing is not useful in the acute setting but may later confirm the diagnosis. Two rapid tests, an elevated venous blood oxygen saturation and an increased lactic acid level, are characteristic of cyanide poisoning.

Treatment

Specific Therapy

In addition to cyanide's affinity for certain iron compounds, it also has a high affinity for sulfhydryl groups and for the methemoglobin complex. These two characteristics are the basis of the cyanide antidote kit. The kit contains three components: amyl nitrite (used if no vascular access is available), sodium nitrite, and sodium thiosulfate. First, the patient is given a nitrite compound (inhalation of an amyl nitrate ampule or sodium nitrite), which will cause the formation of methemoglobin. The dose of sodium nitrite is based on the patient's weight and hemoglobin concentration although 300 mg IV is the usual dose for nonanemic adults. Given the high affinity of methemoglobin for cyanide, it will preferentially bind the compound and help to remove it from the cytochrome a3 complex. Second, the patient is given sodium thiosulfate (typically 12.5 g IV for an adult), which interacts with cyanide, forming thiocyanate. Thiocyanate is then excreted in the urine.

Recently, hydroxocobalamin (a form of vitamin B12) was approved to treat cyanide poisoning. A 5-mg IV injection will bind circulating and cellular cyanide molecules to form cyanocobalamin that is then excreted in the urine within a few minutes. A second 5-mg dose can be given if necessary.

Supportive Measures

Severe lactic acidosis may be treated with bicarbonate administration. Seizures may be treated with benzodiazepines. In many cases, patients require intubation and ventilator support.

Decontamination

The only effective mode of decontamination involves removing the patient from the cyanide gas.

Chemical Decontamination

Because of the risk of cross-contamination to health care workers, the need for patient decontamination should be emphasized. All patients suspected of experiencing a chemical weapons attack should be decontaminated as soon as possible. Optimally, patient decontamination should be conducted in the field. Often this is not practical and a decontamination station should be established in a secure location adjacent to the health care facility. All persons conducting decontamination duties should be provided adequate protective clothing and should receive specialized training.

Decontamination involves physical removal and chemical deactivation of toxin. Remove all clothing, jewelry, dressings, and splints. Wash the patient with copious amounts of soap and water. Avoid vigorous scrubbing because this may facilitate toxin absorption. After physical removal of toxin, any remaining toxin can be chemically deactivated. This may take some time and thus is considered secondary to physical removal of toxin. The most common neutralizing solution is 0.5% hypochlorite solution, which detoxifies many chemical agents via oxidation reactions. Hypochlorite solution should not be used to decontaminate open peritoneal wounds, open chest wounds, exposed neural tissue, or ocular tissue. Irrigate these areas with copious amounts of normal saline. All contaminated materials should be bagged and sent for proper disposal.