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Although many organisms have been suggested as being capable of use as biological warfare agents, only a few have been studied to the point of being a threat rather than a hazard.[13] Management of deliberate epidemics is the role of specialist physicians, and anesthesiologists are likely to encounter only those agents that have serious pulmonary effects and are likely to require ICU care. The renewed study of epidemic illness is essential, and there are many analogies from normal epidemic outbreaks that are relevant to deliberate biological warfare attacks, particularly by terrorists. In 2004, there was considerable concern about the spread of the new severe acute respiratory syndrome (SARS) virus, which provides a good model about the spread of a new infectious pathogen in a world linked by fast air connections. Whereas previous slower forms of travel allowed the incubation of symptoms before arrival at the destination, air travel does not, and patients may be asymptomatic at the time of their arrival. The lesson for all hospital practitioners is to be aware of the possibility of transmission of infection from distant locations. Recent travel history should be an essential part of the initial patient interrogation process.
Bacillus anthracis, an aerobic, gram-positive, spore-forming, rod-shaped organism, is one of the few listed standard biological warfare agents that has proved to be a hazard and a weaponized threat. The natural reservoir of the disease is spores in the soil, and it is these highly resilient spores that form the basis for its use as a biological warfare agent. During World War II, a whole Scottish island was experimentally contaminated and remained in this condition for more than 40 years.[13] There has been evidence for weaponization of the bacillus by several other countries.
Anthrax exists in cutaneous, gastrointestinal, and pulmonary forms, but the pulmonary form is the major concern of the anesthesiologist and intensivist. In the natural state, pulmonary anthrax is rare, but deliberate release of spores in an aerosol would make the presentation more common.
The physical findings in pulmonary anthrax are nonspecific, but chest radiography may show signs of effusion or pulmonary edema and mediastinal widening. An available immunoassay can detect circulating toxin. The infective dose of anthrax when inhaled is 8000 to 15,000 spores. Spores between 2 and 5 µm in diameter reach the alveoli; spores larger than this size are trapped in the upper airways. After trapping, the spores are removed to the mediastinal and hilar lymph nodes by pulmonary macrophagocytes. After a germination period of 1 to 3 days, large amounts of anthrax toxin are released into the circulation, causing the clinical manifestations of the pulmonary form of the disease. The initial insidious phase, lasting 1 to 4 days, consists of general malaise, fatigue, myalgia, nonproductive cough, and fever. During the next phase of the pulmonary disease, necrotizing hemorrhagic mediastinitis occurs, causing chest discomfort, dyspnea, and stridor. In untreated cases, multiple organ failure follows, which is very refractory to treatment and causes death within 24 to 36 hours. In 50% of cases, hemorrhagic meningitis with coma occurs.
Considerable work has been done on the mechanism of the pathogenesis of anthrax infection and the effects of the toxin, which result from three proteins with a central protective component binding the other two, known as the edema and lethal factors. After transfer to the cytoplasm, edema factor, a calmodulin-dependent adenylcyclase, converts ATP to cyclic AMP,[81] which causes tissue edema and suppression of the oxidative burst associated with polymorphonuclear phagocytosis.[82] Lethal factor is thought to be associated with macrophage expression of tumor necrosis factor and interleukin-1, cytokines that are a fundamental part of the systemic inflammatory response.
Treatment of anthrax infection classically has been founded on the use of benzyl penicillin, but there is evidence of resistance. The current antibiotic recommendation is to use ciprofloxacin (400 mg given every 8 hours), and this was widely used as prophylaxis during the 2001 U.S. terrorist scare. Other approaches may be more appropriate, including 200 mg of doxycycline given intravenously, followed by 100 mg given intravenously every 8 hours or gentamycin, erythromycin, or chloramphenicol ( Table 64-12 ). The recommended antibiotic prophylaxis is 500 mg of ciprofloxacin given every 12 hours or 100 mg of doxycycline mg given orally every 12 hours. This treatment should be started as soon as possible after exposure.[83]
Vaccines have been studied, and the standard Michigan vaccine should be given at 0, 2, and 4 weeks and then at 6, 12, and 18 months, followed by annual boosters. If vaccines are not available, antibiotic prophylaxis should be continued for 60 days. For anesthesiologists, intensivists, and other staff working on the longer-term care of anthrax cases, prophylaxis is important, as is careful filter protection of ventilation and disinfection. When possible, disposable circuits should be used.
Plague was the scourge of the medieval world, and natural outbreaks continued well into the 20th century. It has long been considered as a potential biological warfare agent and was researched extensively by the USSR. The pulmonary form is very serious and requires ICU support. The causative organism, Yersinia pestis, is an anaerobic, gram-negative coccobacillus that is transmitted to humans from fleas carried by rodents or by animal-human or human-human droplet infection.[84] [85] Bubonic, pneumonic, and septicemic forms of plague exist; the latter two are fatal without treatment.
Only about 100 to 5000 organisms constitute an infective dose. The incubation period is 2 to 3 days, after which pneumonia develops with malaise, high fever, myalgia, hemoptysis, and septicemia. The patient may have dyspnea, stridor, and cyanosis. With the worsening condition, intermittent positive-pressure ventilation is required together with aggressive antibiotic treatment. Confirmation of the diagnosis comes from growth of the causative organism in blood, lymph node, or sputum cultures. There is also an enzyme-linked immunosorbent assay (ELISA).
Pneumonic plague has long been recognized as being fatal, but antibiotic treatment reduces the mortality to at least 60%. The first line of treatment is 30 mg/kg of streptomycin given every 12 hours for 10 days. Alternatives are gentamicin and chloramphenicol. There is an inactivated vaccine (Greer vaccine), but its effectiveness is not thought to be high.
Cholera is a widespread natural infection that originated in the Far East and caused several epidemics in Europe through the 19th century. Although the domain of the specialized physician, the profound fluid imbalances caused by the disease make admission of patients to the ICU likely in severe cases. Cholera has been suspected of being weaponized, but it can be spread effectively only by causing mass poisoning through the water supply. Outbreaks occurring in China during World War II were thought to be caused this way.
The infection is localized to the small bowel and causes a major outpouring of fluid and electrolytes. Paradoxically, fluid can still be absorbed, and this is the basis of the use of oral rehydration solutions in mass outbreaks in developing countries.
| Agent | Infective Dose | Incubation Period | Effects (after Inhalation) | Staff Protection | Specific Treatment | Chemoprophylaxis | Vaccine | Mortality if Untreated |
|---|---|---|---|---|---|---|---|---|
| Bacillus anthracis | 8000–15,000 spores | 1–5 days | Mediastinitis, meningitis, MOF | Isolation, vaccination, universal precautions | Ciprofloxacin, 400 mg IV tds; doxycycline, 200 mg IV once, then 100 mg IV tds. Penicillin, 2 MU IV 2 hourly + streptomycin, 30 mg kg-1 IM qds. | Ciprofloxacin, 500 mg PO bd × 4 weeks + vaccinate; doxycycline, 100 mg PO bd × 4 weeks + vaccinate | Michigan at 0, 2, 4 weeks, 6, 12, 18 months, then annually | Pneumonic, 100% |
| Yersinia pestis | 100–500 organisms | 2–3 days | Pneumonia, septicemia, MOF | Isolation, universal precautions | Streptomycin 30 mg kg-1 IM qds × 10 days; doxycycline, 200 mg IV, then 100 mg IV tds × 14 days (chloramphenicol) | Doxycycline, 100 mg PO bd × 7 days; tetracycline, 500 mg PO qds × 7 days | Greer at 1–3 + 3–6 months | Pneumonic, 100% |
| Viral hemor-rhagic fevers | 1–10 organisms | 4–21 days | Coagulopathy, edema, MOF | Isolation, HEPA masks, universal precautions | Ribavirin, 30 mg kg-1 IV once, then 15 mg kg-1 IV qds × 4 days, then 7.5 mg kg-1 IV tds × 6 days (immunoglobulin) | NA |
|
90% (Ebola—Zaire) |
| Viral encephalitides | 10–100 organisms | 2–6 days (VEE) | Encephalitis, convulsions, coma, CNS damage | Universal precautions | Supportive, anticonvulsants | NA | Available for VEE, EEE, and WEE | 75% (EEE) |
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7–14 days (EEE/WEE) |
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| Francisella tularensis | 10–50 organisms | 2–10 days | Pneumonia, pleural effusions | Universal precautions | Streptomycin 30 mg kg-1 IV qds × 10–14 days; gentamicin, 3–5 mg kg-1 IV od | Doxycycline, 100 mg PO bd × 14 days | Live attenuated | 35% |
| Variola | 10–100 organisms | 7–10 days | Rash, secondary pneumonia | Isolation, universal precautions | Cidofovir, 5 mg kg-1 IV once every 2 weeks | Vaccinia immunoglobulin | Wyeth | Unvaccinated 30%, vaccinated 3% |
| Burkholderia mallei | 1–10 organisms | 10–14 days | Septicemia, pneumonia, lymphadenopathy | Universal precautions | Co-amoxiclav, 20 mg kg-1 IV tds | Tetracycline, 500 mg PO qds × 14 days | None | Uncertain: >30% if septicemic |
| Coxiella burnetii | 1–10 organisms | 10–14 days | Myalgia, malaise, fever | Barrier nursing | Doxycycline, 100 mg PO bd × 5–7 days | Doxycycline, 100 mg PO bd 8–12 days after exposure × 5 days | Q vax | <1% |
| Brucella spp. | 10–100 organisms | 5–60 days | Malaise + cough, sacroiliitis, pancytopenia | Barrier nursing | Doxycycline, 100 mg PO bd + rifampicin, 900 mg tds PO for 6 weeks | Doxycycline and rifampicin for 3 weeks | None | <5% |
| Escherichia coli O157.H2 | 10–100 organisms | 1–5 days | Vomiting + diarrhea, renal failure | Barrier nursing | Antibiotics not required | NA | None | <5% |
| CNS, central nervous system; EEE, eastern equine encephalitis; HEPA, high-efficiency particulate air filter; MOF, multiple organ failure; NA, not applicable; VEE, Venezuelan equine encephalitis; WEE, western equine encephalitis. | ||||||||
| Adapted from White SM: Chemical and biological weapons: Implications for anaesthetic and intensive care. Br J Anaesth 89:306, 2002. | ||||||||
The management of cholera is essentially that of fluid and electrolyte replacement. Traditionally, this has been accomplished through the intravenous route, but modern practice is to use oral rehydration solutions containing electrolytes and glucose.[86] Early rehydration in this way avoids the need for admission to intensive care. In the case of a deliberate cholera epidemic, rehydration would be a high priority for mass casualties. Tetracyclines have traditionally been the antibiotic treatment of choice, but resistance has been reported.[86]
Glanders is an equine disease caused by the gram-negative bacillus Burkholderia mallei. It has long been considered to be a potential biological warfare agent in a modified form because the organism is known to be highly infectious in the aerosolized form. Acute and chronic forms can affect humans.[87] The septicemic form appears 10 to 14 days after exposure, making the agent one of long latency. There is a sudden onset of high fever, rigors, and myalgia with cervical lymphadenopathy and splenomegaly, leukopenia, or leukocytosis. In this form, septic shock and multiple organ failure occur, and the fatality rate without treatment is high. After inhalation of the organism, the acute pulmonary form is seen with septicemia, bilateral pneumonia, and pulmonary nodular necrosis. The chest radiograph shows miliary shadowing. The severe acute forms of the disease are most likely to concern intensivists, but there is an oropharyngeal form with ulceration of the septum and turbinates, a blood-stained mucopurulent discharge, and a macropapular or pustular rash similar to that of smallpox. In the chronic form, glanders can produce chronic lymphadenopathy, multiple musculocutaneous abscess formation, and oropharyngeal nodules. The first-line treatment of glanders is an antibiotic combination (amoxicillin-clavulanate and sulfadiazine (30 mg/kg every 8 hours for 3 weeks). Doxycycline, rifampicin, and ciprofloxacin are second-line drugs. No vaccine against glanders exists.
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