Saturday, August 16, 2008

Nuclear, Biologic, & Chemical Agents; Weapons of Mass Destruction

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INTRODUCTION

In the past, injuries resulting from nuclear, biologic, and chemical attack were largely dealt with only in the military sector. Society as a whole, and specifically the civilian medical community, felt it unlikely that such weapons would be used against civilian populations. Recent changes in the global political environment have forced changes in this thinking. Many smaller nations, some of which are judged unstable, are attempting to develop weapons of mass destruction. Likewise, many terrorist organizations are now actively attempting to purchase or develop such weapons. In addition to the risk of an overt attack, other sources of exposure could come from accidents involving many nuclear, biologic, and chemical agents stored in facilities throughout the United States. An accident at any of these facilities could result in a large number of civilian casualties. 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.


NUCLEAR WEAPONS

Several incidents in recent history, both military and civilian, have resulted in radiation injuries. The most notable, and in fact the only war-time use, involved the detonation of nuclear weapons over Hiroshima and Nagasaki, Japan. Unfortunately, many terrorist organizations have attempted to obtain nuclear weapons. A terrorist attack 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

Radiation-induced injury occurs when various types of ionizing radiation interact with body tissues. Radiation exposure may be external or internal. Internal contamination can occur via wound contamination or via inhalation or ingestion of contaminated particles. Four types of radioactive particles may cause damage:

1. Alpha particles—Alpha particles are large particles that are stopped by the epidermis. They cause no significant external damage. Internal contamination may cause local tissue injury.

2. Beta particles—Beta particles are small particles that can penetrate the superficial skin and cause mild burnlike injuries.

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

4. Neutrons—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

A. Symptoms and Signs
The symptoms and signs of radiation exposure occur in 3 phases: prodromal, latent, and symptomatic.

1. 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 more rapidly and last longer.

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

3. Symptomatic phase—Symptoms will depend largely on the body system affected, which will depend on the radiation dose. At doses of 0.7-4 gray (Gy),1 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. If an explosive device was used to disperse radioactive material, patients may also have thermal and blast injuries.

1The gray, a unit of measure for the dose of ionizing radiation, is equal to 1 J/kg of tissue. One gray is equal to 100 rad.

B. Laboratory and X-ray Findings
Obtain a complete blood count (CBC) 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. Despite aggressive medical care, radiation exposures above 10 Gy are usually fatal.

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.

Goans RE et al: Early dose assessment in criticality accidents. Health Phys 2001;81(4):446. [PMID: 11569639] (Describes techniques for estimating the severity of radiation exposure.)

Military Medical Operations Office, Armed Forces Radiobiology Research Institute: Medical Management of Radiological Casualties, 1st ed. Military Medical Operations Office, Armed Forces Radiobiology Research Institute, 1999. (Produced by the U.S. Army, this text provides general information regarding all aspects of radiologic injuries.)


BIOLOGIC WEAPONS

Many agents can be used as biologic weapons. The most likely pathogens are presented here. Biologic agents can be classified as bacterial agents (anthrax, plague, tularemia, brucellosis, Q fever, glanders), viral agents (smallpox, hemorrhagic fever, encephalitis), and biologic toxins (botulinum, ricin, T-2 mycotoxins, staphylococcal enterotoxin B). 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 the attack most likely occurred several days prior to patient presentation. Aerosol release of infectious material is the most common form of biologic attack.

BACTERIAL AGENTS

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. The spore form of anthrax causes infection. Clinically the disease occurs in 3 forms: inhalational anthrax, gastrointestinal anthrax, and cutaneous anthrax.

Clinical Findings

A. Symptoms and Signs
1. Inhalational anthrax—Inhalation anthrax is the form of disease most likely expected after a terrorist attack. After spores are inhaled, a variable incubation period occurs, usually lasting 1-7 days. Prolonged 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.

2. 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, diarrhea (bloody), and the development of an acute abdomen with sepsis. Mortality rates for gastrointestinal anthrax are in excess of 50%.

3. Cutaneous anthrax—Cutaneous anthrax is the most common naturally occurring form of the disease. Cutaneous anthrax 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.

4. 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%.

B. 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. Notify laboratory personnel of a possible anthrax exposure. Often Bacillus spp. are thought to be the contaminant and are not pursued further. Confirmatory enzyme-linked immunoassay (ELISA) and polymerase chain reaction (PCR) tests are available at some national reference laboratories. Chest X-ray may also be useful. Patients with inhalational anthrax will display a wide mediastinum on chest x-ray. No infiltrate is typically observed.

Treatment & Prophylaxis

Because anthrax has a rapid and fulminant course, do not delay treatment while awaiting confirmatory tests. Institute empiric therapy when the diagnosis is considered. Delaying treatment for even hours may significantly increase mortality.

A. 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.

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

C. 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).

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 3 clinical forms: bubonic plague, septicemic plague, and pneumonic plague.

Clinical Findings

A. Symptoms and Signs
1. 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. Bubo size 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%.

2. 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%.

3. 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.

B. Laboratory and X-ray Findings
Y pestis can be identified by several different staining techniques. Routine Gram stain may reveal the organism. Y pestis also has a characteristic bipolar staining pattern with Wright, Giemsa, and Wayson stains. Routine 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 & Prophylaxis

Plague has a rapid disease progression, and any delay in treatment will cause significant increases in mortality. Institute treatment on empiric grounds, and do not delay treatment while awaiting confirmatory tests.

A. Antibiotics
Streptomycin is the drug of choice for the treatment of plague. Gentamicin may also be used and is thought to have equal efficacy (see Table 3-1). Alternative antibiotics include doxycycline, ciprofloxacin, and chloramphenicol.

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

C. 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. Antibiotic choices are the same as for treatment.

Infection Control

Pneumonic plague can be spread from person to person by aerosol droplets. Use droplet precautions, and either the patient or 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.

3. 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 palaearctica is 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

A. 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.

1. 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.

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

3. 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.

4. Oropharyngeal tularemia—After inoculation of the pharynx, an exudative pharyngotonsillitis will develop with cervical lymphadenopathy.

5. 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.

6. 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%.

B. 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 to bronchopneumonia. Pleural effusions are often present.

Treatment & Prophylaxis

A. 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.

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

C. 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).

4. Brucellosis

Brucellae are small aerobic, gram-negative, pleomorphic coccobacilli. Many Brucella spp. occur naturally; however, only 4 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

A. 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-Barre syndrome. Patients may also develop anemia, thrombocytopenia, or neutropenia. Central nervous system and cardiac involvement, although infrequent, accounts 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 biological weapon stems from the prolonged disease course and significant morbidity.

B. 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 & Prophylaxis

A. Antibiotics
Because of the high rate of treatment failure, single drug therapy is no longer 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. Regardless of the antibiotics chosen, combination drug therapy should be used. In patients with serious infections, a 3-drug parenteral regimen is the norm.

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

C. Prophylaxis
No human vaccine against Brucella spp. currently exists. Some authors 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).

5. 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

A. 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 manifest 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%.

B. 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 & Prophylaxis

A. 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.

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

C. 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).

6. Glanders & Melioidosis

Glanders and melioidosis are similar diseases caused by related bacteria. The causal agent of glanders is Burkholderia mallei; the causal agent of melioidosis is Burkholderia pseudomallei. Both organisms are gram-negative bacilli. Glanders and melioidosis occur naturally. Glanders is a rare disease in humans; horses and other domesticated animals are often infected. Melioidosis occurs more commonly in humans and is endemic to Southeast Asia. Infection with either organism occurs via contact with open wounds or mucous membranes or by inhalation.

Clinical Findings

A. Symptoms and Signs
Both glanders and melioidosis can cause multiple clinical syndromes.

1. Localized disease—A localized disease may be seen and typically occurs after wound contamination or mucous membrane exposure. With wound contamination, patients develop a small ulcer with associated cellulitis. Regional lymphadenopathy or lymphangitis is also common. If mucous membrane exposure occurs, patients develop a bloody purulent discharge from the infected area (eyes, nose, or mouth). If secondary systemic infection occurs, a pustular rash similar to smallpox may develop.

2. Pulmonary disease—A pulmonary form of disease may also be seen. Pulmonary disease may occur after inhalation of aerosols or after hematogenous spread. An incubation period of 1-2 weeks occurs initially. Symptoms of pulmonary disease, including fever, chills, cough, chest pain, and dyspnea, develop eventually.

3. Septicemic disease—The most severe form of infection is the septicemic form. Patients present with nonspecific symptoms and signs of fever, chills, malaise, myalgias, photophobia, rigors, diffuse body abscesses, pustular rash, and headache. This condition is usually fatal; death occurs in 7-10 days.

B. Laboratory and X-ray Findings
Both organisms can be identified by routine Gram stain and culture. Special staining with methylene blue or Wright stain may facilitate diagnosis. Growth may be enhanced by the addition of meat nutrient agar or glucose to the growth media. Specialized agglutination and complement fixation tests may also be used. If pulmonary involvement is suspected, chest x-ray may demonstrate lung abscesses, miliary nodules, or pneumonia.

Treatment & Prophylaxis

A. Antibiotics
Both glanders and melioidosis respond to various antibiotics. Appropriate antibiotic choices include amoxicillin-clavulanate, tetracycline, trimethoprim-sulfamethoxazole, rifampin, ciprofloxacin, and ceftazidime (see Table 3-1). Various combinations of antibiotics have been recommended depending on the type and severity of infection.

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

C. Prophylaxis
According to some authorities, a course of trimethoprim-sulfamethoxazole may prevent the onset of disease.

Infection Control

Person-to-person spread of the disease is uncommon but can occur with improper handling of body fluids. Standard precautions are sufficient during patient care activities (see Table 3-2).

VIRAL AGENTS

1. Smallpox

Smallpox is a disease caused by the variola virus. The variola virus is a DNA virus of the genus orthopoxvirus. It occurs in 2 strains: the more severe variola major and a milder form, variola minor. Smallpox was essentially eradicated 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. Concern now exists that the Russian stockpile may have been compromised.

Clinical Findings

A. 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. Unlike chickenpox, 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.

B. Laboratory and X-ray Findings
Analysis of pustular fluid will yield virus particles. All samples should be sealed in 2 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 & Prophylaxis

A. Specific Therapy
Currently there is no specific therapy for smallpox. Treatment is essentially supportive care. Many investigational drugs are currently under study. Strict patient isolation, preferably in the 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.

B. Prophylaxis
Data indicate that vaccination within 4 days of smallpox exposure may lessen subsequent illness. Because of the risk of possible terrorist attack, some authorities are recommending a preemptive initiation of smallpox vaccination. This would be problematic for several reasons. First, the current supply of smallpox vaccine is inadequate to protect a large populace. Second, many complications were known to occur with smallpox vaccination. Postvaccinial encephalitis occurred in approximately 1 in 300,000 vaccinations and was fatal in 25% of patients. Immunocompromised patients may develop a condition known as progressive vaccinia. In this condition, the initial inoculation site failed to heal, became necrotic, and necrosis spread to adjacent tissues. This complication was often fatal. In some patients with eczema, a condition known as eczema vaccinatum could occur. Here, vaccinial lesions would occur in areas previously involved with eczema. Fortunately, the eruption was usually self-limited. In some patients, a secondary generalized vaccinia could develop. In others, inadvertent autoinoculation of eyes, mouth, or other areas occurred. Many of these complications could be treated with vaccinia immune globulin. Unfortunately, vaccinia immune globulin is also in short supply.

Cidofovir has also displayed some efficacy in preventing smallpox infection if given within 48 hours. There is no evidence to suggest that cidofovir is more effective than vaccine. Further, cidofovir is associated with significant renal toxicity.

Individuals vaccinated prior to 1972 are likely no longer protected, given that immunity lapses over a 5- to 10-year period.

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.

2. Hemorrhagic Fever

Viral hemorrhagic fever represents a clinical syndrome caused by several RNA viruses. These viruses exist in 4 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 them potential biological weapons.

Clinical Findings

A. 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.

B. 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 & Prophylaxis

A. 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 intravenously as an initial dose, followed by 16 mg/kg intravenously every 6 hours for 4 days and then 8 mg/kg intravenously 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.

B. 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.

C. 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 body fluids. 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.

3. 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 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

A. 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.

B. 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 & Prophylaxis

A. 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.

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

C. 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 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

1. 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 7 antigenic types, designated types A through G. Once absorbed, toxin will bind to motor neurons and prevent the release of acetylcholine, causing a flaccid muscle paralysis. Natural infection occurs in 3 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

A. 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.

B. 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 & Prophylaxis

A. 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 3 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 through G). Because some patients may develop allergic reactions to the antitoxin, a test dose is recommended.

B. 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.

C. 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.

2. Ricin

Ricin is a polypeptide toxin that causes cell death by inhibiting protein synthesis. Ricin 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

A. 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.

B. 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 & Prophylaxis

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

A. Parenteral Exposure
With parenteral exposure, treatment is largely supportive.

B. 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.

C. 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.

D. 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).

3. 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 in 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 though the skin.

Clinical Findings

A. 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 be 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.

B. 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 & Prophylaxis

A. 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.

B. 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).

4. 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

A. 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.

B. 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 & Prophylaxis

A. 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.

B. 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).



CHEMICAL WEAPONS

Like radiation and biologic agents, many chemicals can be developed into weapons of mass destruction. Chemical weapons are particularly attractive to rogue governments and terrorist organizations because of their low cost, stability, and ease of production. In fact, chemical agents have already been used by terrorist organizations. The terrorist group Aum Shinrikyo released sarin gas in a Japan subway in 1995. Chemical agents can be delivered as liquids, vapors, or as components of explosive devices. Chemical agents 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 developed by the Germans prior to World War II. An agent known as 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. The G agents are more volatile than VX; as a result, the G agents form a vapor more readily.

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. The stimulation of these receptors causes the clinical syndromes consistent with nerve agent toxicity. Toxicity can occur either from skin contact or from vapor exposure. Given their increased volatility, the G agents are more prone to cause vapor exposure.

Clinical Findings

A. Symptoms and Signs
1. 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.

2. 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:

a. 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.

b. 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.

c. 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.

B. 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

A. Specific Therapy
The treatment of nerve agent toxicity involves the use of 3 primary medications. The first, atropine, is an anticholinergic medication used to counteract the hyperstimulation of peripheral muscarinic receptors. Atropine (1-2 mg intravenously; 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 intravenously 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.

B. 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 Chemical Decontamination, below.

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

A. 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.

B. 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

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

B. 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.

C. 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.

D. 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 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.

1. 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

A. 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.

B. 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

A. 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 Chemical Decontamination, below.

B. 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, or 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 Chemical Decontamination, below.

2. 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

A. 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.

B. Laboratory and X-ray Findings
No specific test for lewisite exposure is currently available.

Treatment

A. 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.

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

C. Specific Therapy
British anti-lewisite (dimercaprol), 2-3 mg/kg every 4 hours, is a compound that can be given intramuscularly to decrease the effects of lewisite exposure.

Decontamination

As noted above, the 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 Chemical Decontamination, below.

CYANIDE AGENTS

Historically, cyanide was classified as a blood agent. This classification is somewhat inappropriate because many other chemical agents exert their effects after being distributed within the vascular system. Nevertheless, this classification is still used occasionally. Once cyanide is absorbed, it distributes rapidly throughout the body. It 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

A. 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.

B. 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

A. 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 2 characteristics are the basis of the cyanide antidote kit. The kit contains 3 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 non-anemic 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.

B. 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 of toxin and chemical deactivation of toxin. The physical removal of toxin is usually the most effective means of decontamination in the acute setting. 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.

Prehospital Emergency Medical Services

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INTRODUCTION

1This chapter is a revision of the chapter by Charles E. Saunders, MD, FACEP, & Thomas Hearne, PhD, from the 4th edition.

The delivery of effective, organized, prehospital emergency medical services (EMS) is a development that dates to the 1960s in the United States. Although there were ambulance providers and even some local systems, there was no national approach to prehospital care until publication of the 1966 White Paper entitled "Accidental Death and Disability—The Neglected Disease of Modern Society" (National Academy of Sciences, National Research Council).

When medical emergencies are reported, trained medical personnel arrive on the scene to provide emergency care within 6-10 minutes. The skills of these personnel range from basic first aid techniques and cardiopulmonary resuscitation (CPR) to advanced life support (ALS) techniques, including defibrillation, endotracheal intubation, and the use of emergency medications. Radio communications permit ongoing discussion of patient status and treatment between emergency medical personnel at the scene and the supervising physician at the base hospital. Air ambulances (fixed-wing aircraft or helicopters staffed with medically trained flight crews) can rapidly evacuate and transport patients from a remote emergency scene to a regional medical center.

COMPONENTS OF THE EMERGENCY MEDICAL SERVICES SYSTEM

Modern EMS systems consist of several major components: (1) professional field personnel trained to provide specific levels or types of care, (2) a comprehensive emergency communications network, (3) hospital emergency department physicians and nurses who supervise the treatment provided by EMS field personnel, (4) hospitals categorized according to their relationship with EMS field personnel and according to the level of care they can provide, and (5) EMS administrative officials who manage and coordinate the elements of the system.

Professional EMS Field Personnel

The health professionals and first responders who provide prehospital care are trained to carry out specific levels of care, ranging from basic first aid and CPR provided by first responders, through basic life support (BLS) given by emergency medical technicians (EMTs), to the ALS provided by advanced EMTs (paramedics). These personnel provide care only as extensions or agents of physicians and are not independently licensed to provide medical care. The care they deliver is authorized by standing orders (written authorization to administer certain treatments without prior attempt at base contact by radio) or protocols from physician directors or by orders transmitted by radio from supervisory physicians at the base hospital to EMS personnel at the scene. A critical element in the development of EMS since 1970 has been the recognition that personnel without prior medical training can be prepared through relatively short courses to provide effective prehospital care. The designations, levels of training, and skills of EMS personnel are now largely standardized according to United States Department of Transportation (DOT) curriculum and formal categories established in 1983 by the National Registry of Emergency Medical Technicians. The curriculum is regularly reviewed and updated to reflect changes in medicine and in the prehospital environment. The latest iteration released by the DOT was in 1998, with some modifications in 2000. Types of EMS field personnel and their training are described below and summarized in Table 2-1.

A. First Responders
First responders may include law enforcement officers, rescue squad members, firefighters, or volunteer EMS personnel. First-responder courses usually consist of about 40 hours of classroom instruction and clinical training in basic first aid and CPR. First responders are equipped with basic emergency care equipment (eg, bandages, dressings, tape, blanket and pillow, upper and lower extremity splint sets). Oxygen equipment and a self-refilling bag-valve-mask combination (eg, Ambu bag) are optional. First responders also carry basic tools to help them reach and extricate trapped individuals. Increasingly, first responders are being trained and equipped to perform defibrillation using automated external defibrillators (AEDs).

B. Emergency Medical Technicians (EMTs)
The National Registry of Emergency Medical Technicians currently recognizes 3 formal grades of EMTs according to the typical number of hours of training given, the breadth of skills covered, and the range of procedures authorized: EMT-A (basic), EMT-I (intermediate), and EMT-P (advanced, paramedic). Designations and levels of training may vary from state to state. Emergency physicians should be familiar with regional variations and deviations from the National Registry guidelines.

1. EMT-A—Basic EMTs constitute the essential workforce of EMS systems throughout the United States. Most state laws require at least one certified EMT on board ambulance vehicles that transport patients.

The basic EMT course requires at least 81 hours of training standardized by the DOT. Basic classes frequently exceed this minimum by up to 140 hours. Students learn basic principles of patient care, how to identify signs and symptoms central to patient assessment and diagnosis, and how to provide treatment in specific emergencies. The use of AEDs is now standard curriculum for EMTs in most regions. Optional modules for EMTs include advanced airway management, intravenous access, and assisting patients with self-administration of medications. Additionally, some states allow administration of medications, including epinephrine in anaphylaxis and aspirin in suspected cardiac chest pain.

2. EMT-I—The intermediate EMT is trained to provide a level of advanced care in areas that are underserved by paramedics. The scope of practice has evolved since 1990 to incorporate many advanced cardiac life support procedures, including cardiac monitoring, treatment of arrhythmias, defibrillation, and advanced airway management with either endotracheal intubation or an alternative airway.

3. EMT-P—Advanced EMTs (paramedics) receive over 1000 hours of training in ALS techniques. Their skills include the basic EMT procedures as well as intravenous cannulation, invasive airway management (including endotracheal intubation), recognition of cardiac dysrhythmias, defibrillation, and the use of specific emergency medications. In addition to extensive classroom training, EMT-P personnel also complete clinical training and a field internship with experienced paramedic teams.

Paramedics operate under standing orders and treatment protocols developed by a physician medical director that are usually broader and more advanced than those guiding basic EMTs. These protocols determine the type and level of care administered at the emergency site. Physicians who provide on-line medical supervision of paramedics (by radio and telemetry) from base hospitals may permit paramedics to deviate from established protocols or to provide treatment not specifically covered in standing orders.

Special Qualifications

Additional training is available at all levels of providers for specific care settings. At the first responder level, a Winter Emergency Care course has been developed for the National Ski Patrol to address special situations that occur in ski areas. Similarly there are Wilderness modules at all levels of training that provide additional training for care provided in a remote setting with anticipated long evacuations and transportation. EMT-Tactical courses train EMTs and paramedics to function in a tactical law enforcement situation in which they may support or be part of a police special tactics teams. Finally, Paramedic-Critical Care training enables the advanced provider to provide care to critically injured or ill patients who are being transferred from one facility to another.

Types of EMS Systems

EMS systems can be delivered in various ways. There are 2 basic forms of EMS response: a single-response system and a layered-response (or tiered-response) system. In a single-response system, there is only one grade of EMS unit, and the closest available unit is dispatched to any nearby emergency. In a layered-response system, 2 or more grades of EMS personnel respond hierarchically (eg, first responder, then EMT-A, then EMT-P) as needed. Layered-response systems usually provide for an EMT-A response for all less severe reported medical emergencies, reserving an EMT-P response for severe or life-threatening incidents (Table 2-2).

Communications Network

The communications network is important in tying together the components of an EMS system. A dispatcher at a communications center receives a telephone request from a caller at the site of the emergency and dispatches mobile EMS personnel via the radio network. Dispatchers may use a call triaging system (eg, Priority Medical Dispatching) to assign resources to a call. In many areas of the United States, an easily remembered emergency telephone number (9-1-1) provides the public with rapid access to the communications center. Many systems offer an "enhanced 9-1-1" service that provides immediate callback and location information to the dispatcher.

Communications between the EMS unit and medical facilities varies from region to region. For many BLS transports, contact with the base station or receiving facility is not required. In the event of an ALS transport, contact must be made with a medical facility. In some areas, the facility is called a base station hospital, which provides on-line direction and supervision for an entire EMS region. Information called into the base station hospital is then relayed to the receiving facility. In other areas, the receiving facility is called directly.

Hospital Facilities & Staffing

EMS systems typically include hospitals with a variety of treatment capabilities, ranging from local community hospitals with a limited emergency department staffing to large teaching hospitals in urban areas with emergency physicians, surgeons, anesthesiologists, and surgical teams available 24 hours a day. Hospital facilities are frequently classified according to their relationship to EMS mobile units and their ability to provide definitive care.

A. Base Station Hospitals
Physicians or specially trained nurses with physician backup in the emergency department of the base station hospital provide EMS units with on-line medical supervision during treatment. EMS units may be housed at the base station hospital, but this may not be necessary or feasible because the units are usually strategically deployed in the hospital's service area. In many EMS systems, the base station hospital may also be the one most capable of providing definitive follow-up care.

B. Receiving Hospitals
Receiving hospitals are facilities to which patients may be transported. For each patient, the receiving hospital is selected according to its proximity; its capability to provide definitive care; and the preference of the patient, family members, or family physician, as long as transport to the hospital does not draw the EMS unit away from its primary service area.

C. Hospitals Categorized by Capability
Hospitals may be categorized by their ability to provide acute care as determined by the availability of physicians, nurse, allied health personnel, and other hospital resources (eg, operating rooms, laboratory, blood bank). Many categorization schemes exist. The Joint Commission on Accreditation of Healthcare Organizations has established 4 levels of emergency service:

1. Level I—This service offers emergency care 24 hours a day with at least one physician experienced in emergency care on duty in the emergency care area. In addition, there must be in-house physician coverage by residents at the senior level or higher for the medical, surgical, orthopedic, obstetric-gynecologic, pediatric, and anesthesiologic services.

2. Level II—This service offers emergency care 24 hours a day with at least one physician experienced in emergency care on duty in the emergency care area. Specialty consultation should be available within 30 minutes.

3. Level III—This service offers emergency care 24 hours a day with at least one physician on duty in the emergency care area available within 30 minutes through a medical staff call roster.

4. Level IV—This service is capable of performing a triage function and can administer life-saving first aid until transportation to the nearest appropriate facility is available.

D. Hospitals Categorized by Areas of Care
Hospitals can also be categorized by special areas of care (eg, trauma, burns, neonatal intensive care), especially where regionalization of services in these areas is practiced. The American College of Surgeons, for example, has established the following categorization of trauma facilities:

1. Level I—This designates a full-service trauma center that can provide optimal care of the trauma patient. One or more experienced emergency physicians, a general surgeon, anesthesiology services, laboratory, blood bank, and an operating room team must be available in-house 24 hours a day. All surgical subspecialty services should be immediately available on call. A commitment to education and research in trauma must also be demonstrated.

2. Level II—This trauma center is similar to a level I center but does not necessarily include a commitment to education or research. Occasionally patients with the most severe injuries or those needing highly specialized care may be transferred from a level II center to a level I center.

3. Level III—This trauma center does not have all of the resources available at a level I or level II center but may represent the highest level available in a given community. Usually, initial stabilization and life-saving procedures are performed and the patient is then transferred to a level I or level II center.

EMS Administration

EMS systems may be administered through a variety of organizations, including local health departments, public safety agencies such as police or fire departments, hospitals, or privately owned provider agencies. Often several of these agencies operate EMS systems in the same area, and these agencies are coordinated through an EMS regional council, which interacts with hospitals, public safety agencies, and physician medical directors; sets operational standards; and monitors performance (quality assurance).

Operation of the EMS System

One way to visualize the interplay between various components of the EMS system is to review the sequence of events surrounding a typical emergency medical incident. There are 4 major phases: (1) report of the emergency and activation of the EMS system, (2) dispatch of appropriate prehospital units, (3) medical evaluation and field treatment by EMS personnel, and (4) transport of the patient to the appropriate hospital.

A. Report of the Emergency
In many areas of the United States, a single, easily remembered telephone number (9-1-1) can now be used to request emergency help from the police and fire departments and to activate the EMS system.

B. Dispatch
Dispatchers receive the emergency call, interview the caller to determine the type and severity of the emergency, and dispatch the appropriate type of emergency medical response. In systems with heavy call volumes, calls may be priority ranked and then dispatched in order of urgency of need and resource availability. In some systems, dispatchers offer advice to callers to assist patients pending the arrival of emergency units (prearrival instructions). Algorithms may be employed to guide the dispatcher in decision making (Figure 2-1). Dispatchers in layered-response emergency medical systems frequently follow specific protocols in determining which type of EMS unit to dispatch (ie, ALS, BLS, first responder; see Table 2-2). Dispatchers may also be trained to provide CPR instructions by telephone to callers. Dispatch centers may also monitor hospital availability, manage the status and geographic deployment of EMS vehicles, and through computer-aided dispatch perform EMS management information and quality assurance functions.

C. Medical Evaluation and Treatment
Most EMS systems in urban and suburban areas are capable of responding within a few minutes of receiving an emergency call. First responders can frequently arrive at the scene within 3-6 minutes, and paramedics within 5-10 minutes of receiving the call. Survival following time-sensitive medical emergencies such as cardiac arrest is closely correlated with unit response time, especially when basic EMTs have been trained in defibrillation. In layered-response systems, paramedics are held in reserve for such critical or life-threatening incidents, where their advanced skills may provide definitive or stabilizing care to patients. Many systems have advanced-level first responders, such as engine companies manned with paramedics. These responders can provide the same interventions as ambulance-based paramedics but lack the means to transport patients. These assets can be additional resources in the single complex patient or in the multiple-patient incident.

Upon arrival at the emergency scene, EMS personnel undertake patient assessment and examination. EMT-paramedics in most cases are authorized by standing orders to proceed with patient care. Following patient evaluation and treatment, the EMS unit contacts the supervising emergency medical physician (or, in some states, a nurse) at the base station hospital by radio or telephone to describe the patient's condition and any treatment undertaken. The physician may give specific instructions for further treatment at the scene or request transport to the hospital for care.

D. Transport
The mode of transport (ground or air, with or without sirens or lights) depends on availability, stability of the patient's condition, transport time and distance, risks, and the like. Hospital destination decisions are often guided by local protocols, with critically ill patients directed to the closest, most appropriate facility. For example, a community hospital may be bypassed in favor of the nearest designated trauma center in the case of a severely injured patient. Noncritical cases may be transported to the hospital of the patient's choice.

1. Ground transport—Most patients are transported in surface ambulances. These vehicles vary slightly from state to state in their configuration and on-board equipment, but all follow guidelines set by the DOT. Emergency vehicle operators usually are allowed by local and state laws to violate certain traffic laws while responding to an emergency or carrying a patient in a life-threatening emergency. In the vast majority of cases, however, the patient's life is not in danger and posted speeds and traffic laws should be obeyed. The time gained in using red lights and sirens to get to the hospital is often outweighed by the additional risk of death and disability associated with rapid transport.

In most EMS systems, the responding unit is also the transporting unit. In others, especially layered-response systems, the responding unit may primarily evaluate and stabilize the patient and may summon a lower-level unit to provide transport.

2. Air transport—Some EMS systems and regional trauma hospitals, particularly those serving large outlying rural areas, use helicopters or fixed-wing aircraft with trained medical teams on board as additional resources for prehospital care and transportation. The majority of these aircraft are hospital based, but some are operated by municipal or state governmental agencies. Where these services are unavailable, or when search-and-rescue missions are required, aircraft equipped for medical evacuation may be sent from local military bases, operating within the Military Assistance to Safety and Traffic program.

Air ambulances are usually integrated into the EMS system and are activated according to certain locally established criteria. The decision to transport a patient by air requires careful consideration of the risks and benefits of air versus ground transport (see below).

Medical Supervision

A. On-Line Medical Direction
On-line medical direction is the direction given by radio to EMS personnel at the scene while care is being provided. It is usually given by emergency physicians or nurses at the base station hospital or receiving hospital. In most systems, the use of standing orders is allowed (Figure 2-2). This approach allows treatment to begin as soon as possible. Systems that have changed over from on-line medical control to standing orders have not shown a decrement in medical care but have shown an increase in EMS provider morale.

Even in systems that operate nearly exclusively by standing orders, some exceptions may require on-line direction. These may include cessation of CPR in a nonviable patient or the administration of restricted medications such as narcotics or paralytics. Systems that employ standing orders require effective monitoring, training, and quality assurance mechanisms.

B. Off-Line Medical Direction
Off-line medical direction is the overall direction of the activities of EMS personnel. It includes establishing protocols and standing orders, ensuring adequate training and skills, reviewing patient care records and voice tapes retrospectively, and reviewing performance and outcome data. Off-line medical direction is usually provided by a physician experienced in emergency services or by an agency in which physicians play an active role.

Performance Evaluation

System performance evaluation has many aspects, including the evaluation of input resources and operating guidelines (eg, protocol validation, personnel review, training assessment), evaluation of the process of delivering care in the field (eg, response times, service volume, treatment audits for adherence to protocols), and evaluation of the outcome of prehospital care (eg, complications, complaints, success in the performance of procedures, and patient survival). Outcome data are the most difficult to obtain.

PREHOSPITAL SKILLS & TECHNIQUES

Field Assessment

EMTs responding to a call usually have certain dispatch information, including the location, the nature of the complaint, and the number of patients. Upon arrival, they must quickly determine the presence of hazards to themselves and the patient, ascertain the probable mechanism of injury, and identify other patients, if any. Support can be summoned for hazard suppression or additional medical assistance. Patients who are conscious and in minimal distress may be able to provide historical information. Information may also be obtained from witnesses or family members.

Patients who are very ill may require that interventions be performed simultaneously with assessment. Interventions aimed at stabilizing airway, breathing, or circulation (the ABCs) will take precedence over secondary assessment. The receiving physician should expect that, if the patient is seriously ill or injured, only life-saving measures may be performed prior to arrival. In the more stable patient, a more thorough primary and secondary survey should be performed.

Field Treatment

A. Airway Control
Methods of airway control depend on the EMT's level of skill and certification. Initial steps to provide an airway include positioning the jaw and suctioning secretions (taking care in the trauma victim not to hyperextend the neck). Should this fail to achieve and maintain airway patency, the basic EMT can insert an oral or nasal airway. Ventilation may be assisted by a bag-valve-mask.

EMTs and paramedics may establish alternative airways, depending on local protocol. The Combitube, a dual lumen tube designed to be placed blindly, can be used to ventilate the patient regardless of whether the tube is placed in the esophagus or the trachea. The laryngeal mask airway (LMA) is designed to be placed without laryngoscopy. It has an inflatable cuff that sits over the glottis. This allows for ventilation while minimizing gastric insufflation and aspiration. It is not as secure an airway as the endotracheal tube. An improvement on the original LMA is the LMA-Fastrach, which allows for an endotracheal tube to be passed through the LMA. Both the Combitube and the LMA have been implemented successfully in the prehospital setting.

Endotracheal intubation is the preferred method of airway control in patients with inadequate ventilation. Typically the success rate for prehospital intubation is greater than 90%. However, two recent papers have questioned the value of intubation in the field. A randomized trial involving pediatric intubation found that patients did as well with bag-valve-mask ventilation as they did with intubation. Another study found that over 25% of adult intubations in the prehospital setting were misplaced. When intubation is performed in the field it is suggested that end-tidal CO2 detection and an esophageal detector device be used in addition to more conventional means of confirming location. After the tube is confirmed in the correct location, the risk of dislodgement should be minimized by using a commercial endotracheal tube holder and by securing the patient in a cervical collar and to a long spinal board.

B. Emergency Cardiac Care
1. Cardiopulmonary resuscitation—The probability of survival for victims of sudden cardiac arrest is inversely related to the elapsed time before an effective cardiac rhythm is reestablished. CPR is a temporizing measure that, when initiated within 4-6 minutes, increases the chances of survival. In most systems, a paramedic unit cannot routinely reach the scene within this period. Many systems provide first responders with AEDs. AEDs have been successfully deployed with police and fire first responders. In addition, public access defibrillators provide AEDs to the public at busy venues such as sporting arenas and airports.

2. Defibrillation—Ventricular fibrillation is the initial rhythm encountered in many victims of sudden death. The sooner defibrillation is performed, the higher the survival rate. AEDs (Laerdal Heartstart 2000, others) can recognize ventricular fibrillation (or tachycardia) and deliver a countershock. The rescuer need not be able to recognize dysrhythmias but must be able to recognize cardiac arrest and operate the device. AEDs have enabled nonparamedic first responders to provide rapid defibrillation and have consequently improved survival rates.

3. Electrocardiography—In the treatment of acute coronary syndromes, the prehospital 12-lead electrocardiogram (ECG) significantly shortens the time from arrival in the emergency department to administration of thrombolytic therapy ("door to drug time"). Prehospital fibrinolytic therapy has had mixed results. In European trials, where prehospital care is typically provided by physician-staffed ambulances, 6-month and 1-year survival rates have increased. However, trials in the United States with paramedic-staffed units has not shown a significant improvement over 12-lead ECG in the field with hospital-administered fibrinolytics.

C. Invasive Procedures
1. Venous catheterization—(See Chapter 6.) The use of intravenous techniques by EMS field personnel is usually limited to cannulation of peripheral veins of the upper extremities. In most EMS systems, the procedure can be initiated under standing order by intermediate or paramedic EMTs. Basic EMTs who have had special training in intravenous techniques and fluid therapy may also initiate intravenous lines. Studies have demonstrated that skilled paramedics in the field are able to start an intravenous line in approximately 3 minutes and achieve a success rate greater than 90%. However, when transport times are short (ie, 10 minutes or less), venous catheterization is usually unnecessary because the volume of fluid infused or the medications administered during such a short period are unlikely to be life saving. Further, in penetrating trauma to the thorax, fluid boluses may be detrimental by disrupting the clotting process. In addition, field placement of intravenous lines may increase the chances of infection. Needlestick injuries, which may occur during venous cannulation under adverse circumstances, such as in the back of a moving ambulance, are an increasing concern. Intraosseous needles may be placed by paramedics in the event that vascular access cannot be obtained in the pediatric patient.

2. Needle thoracostomy—Chest decompression for suspected tension pneumothorax may occasionally be life saving and is performed by paramedics in some systems. A 14- or 16-gauge catheter-clad needle is inserted into the second intercostal space along the midclavicular line immediately above the subjacent rib using sterile technique. The catheter is sealed with a Heimlich valve or a latex glove with the fingertip removed. (The open fingertip of the glove is secured around the catheter, allowing air to escape but preventing its reentry.)

3. Cricothyrotomy—(See Chapter 6.) Emergency entry to the airway may be life saving in cases of supraglottic airway obstruction or laryngeal trauma. Cricothyrotomy may be performed by paramedics in some EMS systems, usually after approval by the base physician via radio. Cricothyrotomy may be performed using a surgical, needle, or Seldinger technique. Because the procedure can be unexpectedly difficult, it should be performed as a last resort and only by properly trained personnel.

D. Medications
Medications are a contentious area in the prehospital realm. Because of the lack of clinical trials, it is difficult to state what interventions are of benefit. The emergency physician should know what medications are available to their EMS providers and under what indications they may be used.

1. Advanced cardiac life support—Most drugs for advanced cardiac life support are stocked on most ALS ambulances. Consistently, epinephrine, atropine, lidocaine, sodium bicarbonate, and adenosine are stocked. In addition, nitroglycerin, aspirin, and morphine are available for treatment of acute coronary syndromes. Amiodarone often is not used because of the ongoing debate about its effectiveness and because of cost issues. Some systems do not stock diltiazem because patients with a tachydysrhythmia that requires rate control are relatively stable. Fibrinolytics are rarely used because of their cost, the staffing needed to administer and monitor them, and the minimal benefit shown in prehospital use. Other medications such as labetalol, magnesium, procainamide, and calcium chloride are typically stocked at the discretion of the agency's medical director.

2. Pulmonary—Albuterol should be available to all ALS EMS agencies. Ipratropium has been shown to be beneficial to patients with moderate to severe asthma and to those with chronic obstructive pulmonary disease. In addition to sublingual nitroglycerin, furosemide is typically stocked for treatment of pulmonary edema.

3. Other drugs—Benzodiazepines are typically stocked for treatment of seizures, anxiolysis, and sedation. The use of prehospital benzodiazepines is beneficial to patients presenting with recurrent seizures. Agents stocked include diazepam, lorazepam, and midazolam.

Glucose, in the form of 50% dextrose in water (D50W) and oral glucose solution (occasionally D25W or D10W for pediatric patients), is stocked for treating hypoglycemia.

E. Extrication
Extrication is the process of removing a patient from a condition of entrapment, usually from a motor vehicle. It requires considerable skill and experience. Often, special tools are necessary, such as heavy bolt and metal cutters or large, powered spreading devices (eg, Jaws of Life, Hurst Tool). In most EMS systems, when there is a report of a trapped victim, a fire rescue team is dispatched in addition to the EMS unit to clear fire hazards, wash away spilled gasoline, and provide additional heavy equipment and personnel.

As soon as the patient is accessible with minimal risk to emergency workers, the primary survey should be initiated while further efforts to free the patient continue. Once the patient is immobilized in place, emergency resuscitation can begin.

F. Immobilization and Splinting
1. Immobilization—Victims of trauma may have injuries to the spine or extremities, which, if manipulated, can lead to spinal cord or limb damage. Upon reaching a trauma victim, the rescue team must stabilize the patient's cervical spine. Manual stabilization is maintained throughout extrication. A cervical collar is applied as soon as practicable. Spine boards are sometimes difficult to maneuver in closed spaces, but alternative devices are available, such as the Kendrick Extrication Device (KED). In a hemodynamically unstable patient, rapid extrication onto a long spine board can be accomplished by multiple rescuers manually supporting the spine without the aid of a KED. Immobilization is not considered complete until the patient is secured to the spine board with straps, the patient's head is secured to the spine board with tape across the forehead and beneath the chin, and a cervical collar and lateral neck rolls or head immobilization device are in place.

If endotracheal control intubation is necessary, the cervical spine should remain immobilized while the procedure is performed. Should vomiting occur, the patient may be logrolled to face sideways while one rescuer maintains cervical spine traction.

2. Splinting—(See Chapters 28 and 29.) In general, extremities should be placed in an anatomic position, especially if pulses cannot be felt below a suspected fracture. If the patient protests or if resistance is felt, extremities should remain in a position of comfort. Reduction of fracture dislocations at a joint should be attempted only if vascular compromise is impending, the duration of transport is long, and the rescuer is experienced in the technique. This usually requires the base physician's approval.

A pillow, rolled-up blanket, or other material may often serve as a simple splint. Specific splinting devices include cardboard splints, inflatable air splints, the MAST (military antishock trousers) garment, and traction splints. If inflatable devices are used, care must be taken to monitor distal perfusion, because a compartment syndrome may occur with swelling of the extremity or changes in atmospheric pressure (eg, during air transport). Traction splints are used primarily with fractures of the femur.

G. Protocols and Standing Orders
Protocols are guidelines designed to assist the EMT in performing tasks in a complete and orderly fashion (Figure 2-3). Because situations vary widely and protocols cannot anticipate every variable, they are not meant to be absolute and must be accompanied by training, judgment, and experience. Each EMS system tailors its protocol to the training and skill of its EMTs and the needs of the local medical community.

Standing orders are express authorizations for the performance of a specific task or procedure. Under the standing order, an EMT may be authorized to perform a task or procedure without first obtaining verbal authorization by radio. Standing orders are useful when radio contact is impractical or would delay life-saving intervention (eg, CPR, defibrillation). Standing orders usually contain a clear list of circumstances under which the authorization applies (indications) and detailed instructions on the manner in which the procedure should be performed. They are signed by the physician medical director, who shares legal responsibility for the outcome.

H. Communications
1. Equipment and frequencies—EMS units communicate with receiving hospitals by various methods. Three main radio systems exist: the HEAR network (in the 150-MHz range), the COR system (400 MHz), and the 800-MHz truncated system. The HEAR system is the oldest and has largely been replaced in urban areas by 800-MHz systems, which provide multiple frequencies for providers. In addition, cellular phones and landline telephones are used frequently for communications. Communication is simplex. Signals pass in only one direction at a time, and neither party can simultaneously speak and be heard. In rural areas, communication may be direct, via radio, without a relay station or ground lines.

2. Communication technique—Radio communication must provide information in a concise, precise, and easily understood manner. To facilitate speed and understanding, a common format is followed, with slight variations depending on the community. However, no one should hesitate to ask for clarification, because misunderstandings may prove fatal.

a. The initial contact—The caller always names the party being called first, followed by the caller's own identification:

"Central Hospital, this is medic 19, how do you copy?"

b. The initial response—The initial response confirms the contact in the same manner:

"Medic 19, Central Hospital, receiving you loud and clear, over."

c. The report—The caller gives a concise, orderly report containing pertinent history, physical findings, destination, estimated time of arrival (ETA), and any necessary request for instructions. It should be as brief as possible:

"Central Hospital, medic 19 en route to your location, ETA 8 minutes, with a 20-year old male victim of multiple, small-caliber gunshot wounds to the left chest, right flank, and right thigh. Patient is lethargic; blood pressure 80, pulse 140, respirations 46. Breath sounds absent over the left chest, abdomen soft. We have an ET tube in place, 2 IVs with lactated Ringer's wide open, and MAST garment inflated. Requesting permission for needle decompression of the left chest."

d. The report acknowledgment—This acknowledgment is kept brief; only essential queries should be made:

"Medic 19, have you checked ET tube position?"

"That's affirmative. Withdrawn 2 centimeters without improvement."

"Okay, medic 19; needle thoracostomy, left chest, is approved. Will stand by for update."

e. The sign-off—After receiving an order, the field personnel should repeat it to demonstrate that it was received accurately before signing off:

"Central Hospital, understand needle thoracostomy, left chest, is approved. Stand by."

3. 10-Codes—"Ten codes" are phrases represented by 2 numbers, the first being 10. In many areas, these are used to ensure precise communication and to add some measure of privacy to the conversation. Unfortunately, few EMS personnel have all of the possible 120 codes memorized. The result is often more confusion rather than less. Because mistakes may be dangerous, the codes should not be used unless thoroughly understood by all parties.

4. Telemetry—Receiving hospitals and ambulances may have equipment designed for the transmission of electrocardiographic traces (telemetry). This equipment is seldom used, however, because well-trained paramedics have shown the ability to interpret unstable rhythms (eg, ventricular fibrillation, ventricular tachycardia, bradycardia, and asystole) with acceptable precision, and more complex rhythms (eg, supraventricular tachycardia) rarely require treatment that cannot be postponed until arrival at the hospital. As indicated above, the prehospital 12-lead ECG has shortened the door to drug time in patients with acute coronary syndromes.

I. Air Transport
1. Indications—As noted above, the benefits to the patient must outweigh the risks inherent in this mode of transport. Aeromedical transport is most advantageous when great distances must be covered rapidly, when ground transport is unavailable or impeded by geographic obstacles or dense traffic, or when specialized care (eg, trauma resuscitation) is needed at the scene or en route. Emergency medical helicopters serving rural areas often provide a higher level of care and more skilled procedures (eg, intubation, needle thoracostomy, cricothyrotomy) than are provided by localized services using basic EMTs. However, air transport is hazardous, and helicopters operating at night and in inclement weather have crashed.

2. Requesting service—Helicopters equipped for medical evacuation can be requested, through the EMS communications network, from an area hospital that offers such services or from a local military base that participates in the Military Assistance to Safety and Traffic program.

3. Patient preparation—Before departure, stabilize the patient on a spine board and immobilize the patient as clinically indicated. Secure airway tubes and intravenous catheters.

4. Anticipated physiologic consequences of air transport

a. Hypoxia—Atmospheric pressure decreases with increasing altitude, as does the partial pressure of oxygen. Patients with existing heart or lung disease may suffer adverse consequences. Supplemental oxygen is required.

b. Expansion of trapped gas—The volume of trapped gas increases with decreasing barometric pressure. Thus, as altitude increases, air may expand in endotracheal tube cuffs, air splints, MAST garments, the bowel lumen, the stomach, pneumothorax, abscess cavities, and the bottles and tubing of intravenous infusion apparatus. These compartments must be monitored frequently and vented as necessary. Intravenous flow rates should be adjusted accordingly.

c. Motion, noise, and vibration—These may cause patient discomfort. Forward acceleration with the patient's head forward may cause transient hypotension. This may be prevented by positioning the patient with feet forward.

5. Helicopter safety

a. Site selection and lighting—A helicopter landing site should be level, approximately 100 feet square, and free of obstacles (eg, trees, wires) to approach and departure. It should also be clear of loose debris. The site should be secure from bystanders. At night, the site should be well lighted (eg, with vehicle headlights), but lights should never be directed upward toward the approaching helicopter, because they might interfere with the pilot's vision.

b. Approaching a helicopter—While the rotor blades are turning, approach the aircraft only from the front and only after prompting by the pilot. Avoid the tail rotor. Approach in a crouched position. Do not run. Never approach from uphill.

Lower tall objects such as poles associated with intravenous infusion apparatus. Secure sheets, hats, and loose clothing. Extinguish all smoking material.