729 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 52 Biological, Chemical, and Radiological Attacks in Pregnancy Shawn P. Stallings & C. David Adair Division of Maternal - Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee College of Medicine, Chattanooga, TN, USA Introduction It is an unfortunate reality that in many parts of the world there is an ongoing threat of terrorism against target groups that fre- quently include pregnant women. In addition to the concerns about injuries due to conventional weapons and explosions, there is now the potential for attacks using chemical and/or biological agents, as exemplifi ed by the the release of Sarin gas in a Tokyo subway system in 1995, and the anthrax - contaminated letters mailed in 2001. Pregnant women represent a unique population that differs from the populace at large both in terms of susceptibility to certain agents and in the management of any exposures. Transport and triage of the patient, and her long - term management in the face of continued pregnancy must be anticipated and planned for in advance to optimize outcomes. This chapter aims to address some of the special concerns of mass casualty management for pregnant women and to review some of the potential biological, chemical, or radioactive agents that might be involved in an intentional event. Clinical v ignette “ A 22 year - old primigravida at 30 weeks of gestation presented to her local hospital for evaluation due to fever, chills, cough, and malaise. The initial work - up revealed a temperature of 39.6 ° C, but at the time she had stable respiratory status. Her chest radiograph revealed a prominent pattern of diffuse infi ltration without evi- dence of consolidation. After evaluation by the patient ’ s midwife and obstetrician, she was placed on antibiotics for suspected com- munity - acquired pneumonia or viral pneumonia and admitted to the antepartum - postpartum fl oor. Fetal testing was reassuring. On the second day following admission she complained of severe headache and backache, and she developed frequent emesis. The following day her condition worsened, ultimately requiring oxygen supplementation to maintain her arterial oxygen saturation (S p O 2 ) above 93%. At this time a maculopapular rash was noticed over most of her body and this was thought to be pregnancy related. Due to her headache and change in status, laboratory blood tests were repeated and showed an elevation in her liver enzymes, along with a falling platelet count. Despite meticulous intravenous hydration in response to the emesis, her urine output began to decline. The patient began to report uterine contractions, and was found to be 3 cm dilated with signifi cant effacement. The fetal status, via electronic monitoring showed a change at this point, with a decrease in heart rate variability and intermittent decelerations. Because of the fetal heart rate tracing, the patient was deemed too unstable for immediate transport to a tertiary center and prepara- tions were made for cesarean delivery with a tentative diagnosis of severe pre - eclampsia. At the time of the surgical skin preparation, the patient ’ s maculopapular rash was noted to have progressed to a vesicular form. The infant was delivered, failed to respond ade- quately to resuscitation and was pronounced dead in the delivery room. By this time, the medical team suspected a contagious infec- tion, possibly varicella, and isolation measures were instituted. The patient was later transferred to a tertiary care facility for intensive care support. ” In the above anecdote, a young, previously unvaccinated patient presented with an unknown exposure to what was later proven to be smallpox. At most community hospitals and birth- ing centers, the initial care providers are generally not emergency medicine or infectious disease personnel and recognition of con- tagious conditions may be delayed. The admission of such a patient to the antepartum/postpartum wing may inadvertently expose a large number of susceptible patients and staff. Under most circumstances, the personnel are not to be faulted. The presentation of a biological threat may be subtle and unexpected, Chapter 52 730 patients who are en route [1] . For example, knowledge of the approximate gestational age of any pregnant women involved will allow the providers to transport women with viable fetuses to hospitals where fetal monitoring is available and to triage those fi rst and early second trimester patients to hospitals or facilities where there may not be fetal monitoring equipment. In a major bioterrorism event, it is important to have protocols that help in the rapid identifi cation of victims who have been exposed and who are showing symptoms, versus those who are exposed but as yet asymptomatic. Asymptomatic patients may require different interventions, such as prophylaxis, and quaran- tine, rather than active therapy. Pregnant women represent a unique population because of their predisposition to go into labor in times of stress. For this reason the treatment of preterm labor and a plan to deal with large numbers of potentially infected or affected preterm babies should be kept in mind when design- ing any master plan for population dense areas. Local hospitals, along with regional tertiary care centers, will need to have a plan in place for the triage of victims near the site of contact with the harmful substance, or for containment of persons who may have been contaminated and are at risk of spreading the agent to others. In the case of pregnant women, those requiring intensive care and those with preterm fetuses will likely need to be transferred to a tertiary care center. The master plan should always include a back - up plan to deal with the possibility of failed communication lines or transportation modes. Labor and delivery unit managers should be prepared to provide fetal monitoring to multiple patients in isolated or inten- sive care unit settings. Such monitoring, of course, must be accompanied by preparation of equipment and personnel to take care of any emergent deliveries that may become necessary. While some patients may require only evaluation, others will require a longer stay, which may strain both the physical resources at the hospital and the personnel involved in their care. Back - up plans for relief personnel may involve rotating duty for regular staff, part - time staff, or even volunteer personnel with known labor and delivery experience. Identifying such individuals in advance facilitates the rapid response to an acute event. Finally, it should always be borne in mind that attacks frequently do not occur in isolation, and coordinated second or third attacks might occur in rapid succession, generating new waves of victims. Review of s elected a gents The following review deals with a selcted group of agents which could be encountered in the setting of an intentional attack. This list is, of course, not exhaustive. Injuries from conventional weapons that involve blast injury or penetrating trauma from bullets or shrapnel are managed as described in the chapter on trauma in pregnancy, and are not covered here. The agents for intentional attack may be separated into three basic categories: biological, chemical, and radiological. and thus the necessary isolation precautions and treatment may be delayed. It is clear that, as in so many other situations, a high index of suspicion, adequate training, and general preparedness are the only protection against uncommon occurrences. General p reparation The specifi c needs of the pregnant patient are often lost among the basic humanitarian concerns of such disasters as the Indian Ocean Tsunami in 2004 and the fl ooding of the Gulf Coast after Hurricanes Katrina and Rita in 2005. While it is clearly impracti- cal to focus on a specifi c subgroup of people in a disaster it is worthwhile having the issues faced by pregnant survivors in mind when preparing for dealing with evacuation and treatment on a massive scale. Some of these specifi c needs will be discussed below. One of the major differences between a chemical and/or bio- logical intentional attack and a natural disaster is that in the former, there is a pressing need to contain the spread of potent contaminants and highly contagious and lethal organisms. A second major difference relates to the temporal relationship between the injury and the time of the event. With a natural disaster, traumatic and other immediate injury is generally limited to the time around the event, whereas with chemical and biological agents, some of the worst effects may only become apparent days to weeks after the inciting event. A major legislative step was taken by the United States gov- ernment in 1996 with the “ Defense Against Weapons of Mass Destruction Act ” [1] . The bill highlighted the contemporary lack of preparedness of emergency medical systems for large - scale intentional destructive events, and included a mandate for funding and training fi rst - responders to serve the general popu- lation in such events. While most patients will likely be encoun- tered fi rst by emergency services personnel and physicians, obstetric providers should be ready to participate or advise in the care of pregnant patients. In cases of natural disaster or industrial accident, management of resources will be run by a state or local law enforcement head, fi re chief, or the person in charge of emergency services. Within the USA, in the the event of a terrorist attack, the Federal Bureau of Investigation (FBI) will take control of the disaster site from a security and investi- gation standpoint and the Federal Emergency Management Agency (FEMA) will be charged with the mobilization of federal resources to deal with the aftermath [2] . Most other countries have similar federal or national structures in place to cope with such events. Problems that may be anticipated include diffi culties in com- munication, differences in command structure and coordination, and the logistics of allocation of both personnel and physical resources [1] . Coordination between emergency fi rst responders and hospital - based medical personnel is important, and back - up communication systems are vital. Reliable information from the scene of the event is critical for planning for the disposition of Biological, Chemical, and Radiological Attacks in Pregnancy 731 rare, but has been raised as a concern for bioterrorism because of its high mortality rate and ease of dissemination [6] . The spores of B. anthracis are stable for many years, are resis- tant to sunlight, heat and disinfectants, and can be dispersed as a dry or moist aerosol cloud. It is reported that weaponized spores may be disseminated throughout an entire building even after delivery within a sealed envelope [4] . As an example of the deadly nature of the spores, it was reported from the former Soviet Union that an outbreak near one of their weapons facilities in 1979 resulted in 77 cases of inhalational anthrax with 66 deaths (85% mortality) [4] . In the fall of 2001, 22 cases of anthrax infec- tion occurred following delivery of spores through the United States Postal Service. Eleven of the cases were inhalational, with fi ve deaths occurring in that group, while the rest of the cases were cutaneous [4,6] . The knowledge that strains of B. anthracis have been modifi ed and may potentially be released creates a whole new outlook in public health policies. It is estimated that more than 30 000 potentially exposed persons were placed on postexposure prophylaxis during the US outbreak of 2001 [4] . The direct and indirect costs of handling even as limited a con- tamination as the 2001 mailed attacks are undoubtedly high. The spores germinate in an environment rich in amino acids, nucleic acids and glucose, such as in mammalian tissues or blood. The bacteria then multiply rapidly and will only form spores again when the nutrients are depleted, such as when contami- nated body fl uids are discharged and encounter ambient air. The vegetative bacteria do not survive long in ambient conditions, but the spores may remain stable for many years. Inhalational anthrax begins when inhaled spore particles 1 – 5 microns in size enter alveolar spaces and are ingested by macro- phages. Spores that survive and are not lysed may travel to the mediastinal lymphatic tissue where they germinate and multiply. The incubation period varies. Most often incubation occurs during 1 – 7 days, but can be delayed as many as 43 days [4 – 6] . The replicating B. anthracis produces toxins that will continue to cause cell damage even after living bacteria are eradicated with antibiotics [6] . This ongoing damage results in hemorrhagic lymphadenitis, hemorrhagic mediastinitis, necrosis, and pleural effusions. The patient may present initially with fever, cough, dyspnea, and malaise. An initial chest radiograph may be abnor- mal with widened mediastinum, infi ltrates, and effusion. The more fulminant cases progress rapidly with a continued rise in fever, worsening dyspnea, chest pain, and respiratory failure. Blood culture will usually show the characteristic colony forma- tion, but communication with the laboratory is important when B. anthracis is suspected since colonies may be mistaken for con- taminant normal fl ora [5,6] . Hemorrhagic meningitis is also a frequent occurrence in such patients and the organism may be identifi ed readily in the cerebrospinal fl uid. Cutaneous anthrax occurs following deposition of the spores in cuts or abrasion of the skin. Following germination in the skin, toxin production will cause local edema and necrosis. A vesicle typically forms which then dries to form a black eschar. Antibiotic therapy will not alter the course of skin destruction and eschar Biological a gents Biological agents have received the most attention from the news media as potential weapons of terrorism. In describing some of the concerning agents, Dr Gregory Moran has noted: “ The ideal agent for biological terrorism (BT) would be capable of produc- ing illness in a large percentage of those exposed, would be dis- seminated easily to expose many people (e.g. by way of aerosol), would remain stable and infectious despite environmental exposure, and would be available to terrorists for production in adequate amounts. Fortunately, few agents have all of these characteristics ” [3] . The Centers for Disease Control and Prevention (CDC) have designated three different categories for agents that are potential threats for bioterrorism. Category A agents include those that are easily disseminated and which have high morbidity and mortality rates or, alterna- tively, have great potential to cause widespread panic or dis- ruption. These agents include anthrax, smallpox, plague, botulism, and viral hemorrhagic fevers [4,5] . Category B agents include those considered easy to disseminate but which do not cause such widespread injury. These agents include ricin, threats to food safety such as E. coli O157:H7, typhus and Q fever. Category C agents include pathogens that have not historically been used for acts of terrorism or mass destruction, but whose high morbidity and mortality rate make them potential targets for deliberate engineering to allow widespread dissemination. Such agents could include various tick - borne hemorrhagic viruses and tick - borne encephalitides (see Table 52.1 ) [3 – 5] . Anthrax Anthrax arises from infection with the Gram - positive, spore - forming bacterium Bacillus anthracis . Humans acquire naturally occurring disease from contact with infected animals or contami- nated animal products. The disease more commonly infects her- bivores which ingest the spores from the soil. Animal vaccination is a common practice and has decreased animal mortality from the disease [6] . There are three manifestations of the illnesses in humans depending on the route of contact: cutaneous, inhala- tional, and gastrointestinal. The cutaneous form is the most common naturally occurring disease, although outbreaks of gas- trointestinal anthrax are occasionally reported due to consump- tion of undercooked, contaminated meat. Inhalational anthrax is Table 52.1 Examples of CDC category A , B , and C biological agents [3 – 5] . Category A Category B Category C Inhalational anthrax Coxiella burnetti (Q fever) Hantavirus Smallpox Ricin toxin Tickborne hemorrhagic fever Pneumonic plague Salmonella species Tickborne encephalitis viruses Viral hemorrhagic fevers E. coli O157:H7 Yellow fever Botulism Chapter 52 732 during pregnancy, but the potential benefi ts may outweigh the risk associated with systemic disease in the event of a large - scale exposure. Experience from the military vaccination program sug- gests no adverse effect on pregnancy outcomes for women vac- cinated prior to becoming pregnant [9] . Smallpox Younger generations know very little of the devastation of small- pox infection, as a result of widespread vaccination and aggressive disease control measures. Ironically, this extraordinary medical accomplishment has left the vast majority of the world ’ s popula- tion susceptible to the potential reintroduction of this disease. Initial dissemination may be diffi cult, but the number of second- ary contacts and ease of transmission to secondary victims make this agent attractive to groups seeking to induce massive societal disruption. Smallpox is caused by the DNA virus variola. It is easily trans- mitted from person to person by respiratory droplets. In addition, the virus may remain stable on fomites for up to 1 week [4] . The virus replicates in respiratory epithelium and then migrates to regional lymph nodes. An initial viremia, accompanied by mild fever and malaise, will lead to introduction of the virions into a variety of tissues, resulting in localized infection of the kidneys, lungs, intestines, skin, and lymphoid tissues. After an incubation period of 7 – 17 days, a second viremia occurs with high fever, headache, backache, rigors, and vomiting. A rash is usually appar- ent within 48 hours of this new phase. The rash is initially maculopapular, but changes soon to a vesicular eruption. The characteristic smallpox appearance is reached when the vesicles become pustules. Viral shedding may occur from the time of the rash until the lesions have crusted and separated. Death may occur in this phase due to overwhelming viremia and organ failure [4] . From historical series of pregnant women affected by smallpox it is known that there may be very high rates of prematurity and fetal loss [10] . In addition, pregnant women appear more suscep- tible to the disease, with historical case - fatality rates as high as 61% among unvaccinated individuals, and mortality rates of 27% even among vaccinated pregnant women. This compares with com- monly reported mortality rates in non - pregnant adults of 3% when vaccinated and 30% among unvaccinated patients [5,10] . Pregnant women more commonly develop the hemorrhagic form of the disease in comparison with non - pregnant women and men [7,10] . The hemorrhagic form of smallpox is characterized by fever, back- ache, abdominal pain, and a diffuse red rash. Historically, sponta- neous epistaxis, ecchymoses, and bleeding into various organs led to rapid death in such patients. The case - fatality rate among women with hemorrhagic smallpox was 100% in one series. Congenital smallpox among liveborn infants has been described in as many as 9 – 60%, with a very high mortality rate [7,10] . An infected patient should be isolated in a negative - pressure room. In the setting of large numbers of infected individuals, quarantine and separate physical facilities may be needed. Airborne and contact precautions must be used. All discarded laundry or waste should be placed in biohazard bags and auto- resolution. Systemic spread may be possible, and if untreated the mortality is reported to be as high as 20% [4,6] . Gastrointestinal anthrax may be contracted from ingestion of contaminated meat. Spores may germinate in either the upper or lower intestinal tract. Ulcer formation in the mouth or esophagus may lead to regional lymphadenitis. In the lower tract, infection of the terminal ileum or cecum may lead to nausea, vomiting, abdominal pain, and bloody diarrhea. In both cases, death may occur due to systemic illness, and mortality as high as 25 – 60% has been reported. [4 – 6] . There is little specifi c information available on anthrax infection during pregnancy [7] . It is important to remember that casual contact or respiratory droplets from coughing or sneezing do not spread anthrax. While person - to - person respiratory transmission does not occur, care should be exercised when caring for patients with non - intact skin from cutaneous anthrax [5] . Treatment of anthrax is by combina- tion therapy that usually includes ciprofl oxacin and doxycycline, and may also include clindamycin, rifampin, vancomycin, or chloramphenicol [6] . The recommendations for appropriate antibiotic therapy are the same for pregnant women or children as for non - pregnant adults. One should check with an infectious disease consultant or the CDC website for the latest recom- mended drug combination. Supportive therapy is also usually required for severe cases. Prophylactic antimicrobial therapy is not needed unless law enforcement and public health offi cials document an actual expo- sure. It is recommended that the primary care women ’ s health providers do not initiate therapy unless directed to do so by the appropriate public health offi cials [8] . Screening may be per- formed by way of nasal swab, but due to potential error, postex- posure prophylaxis is recommended only after a confi rmed exposure or high - risk encounter [8] . Adult exposure prophylaxis is typically given with ciprofl oxa- cin 500 mg orally every 12 hours for 60 days or doxycycline 100 mg orally every 12 hours for 60 days [4 – 6,8] . The recom- mendation is the same for pregnant and lactating women. The potential morbidity and mortality from anthrax are felt to out- weigh the historical concerns regarding these medications [8] . If the anthrax isolate in a current case is found to be sensitive to penicillin, the pregnant or lactating patient should be switched to amoxicillin 500 mg orally three times a day for the remainder of the prophylaxis period [8] . Vaccination against anthrax is available. The vaccine, called anthrax vaccine adsorbed (AVA), is a cell - free product given in a 6 - dose series over 18 months [6] . While there has been signifi cant media coverage of concerns over side effects of the vaccine fol- lowing the US military ’ s mandated vaccination of active - duty and reserve - duty personnel, AVA is thought to be acceptably safe [6] . Due to the potential for spores to remain dormant in tissues for prolonged periods despite antibiotic prophylaxis, there has been interest in the use of AVA for postexposure prophylaxis in con- junction with antibiotics [6,7] . The vaccine should theoretically be safe for use during pregnancy due to a lack of active organism. No published experience is available on the use of the vaccine Biological, Chemical, and Radiological Attacks in Pregnancy 733 organism can also be ingested from a contaminated food source. The gastrointestinal form of the disease also follows a rapid course, with the buboes developing in mesenteric drainage sites. Persons infected by the inhalational route may not develop the typical buboes but may progress rapidly to septicemia. The diagnosis is made by a sputum Gram stain showing Gram - negative coccobacilli with bipolar “ safety pin ” staining. Chest X - ray may show consolidating lobar pneumonia. Further tests include an IgM enzyme immunoassay, antigen detection, and PCR [5] . These tests are available typically through state health departments and CDC. This approach requires a high index of suspicion and the ordering of the requisite tests early enough to involve state organizations in containment. Patients with sus- pected bubonic plague should be separated from other patients, preferably under negative - pressure conditions, and body fl uid precautions should be followed until at least 3 days of appropriate antibiotics have been completed [4] . Patients who are suspected of being septic, or having respiratory symptoms, or are diagnosed with pneumonic plague should be maintained under respiratory droplet precautions including negative pressure isolation until the completion of 4 days of antibiotic therapy [4] . Standard therapy is 10 days of intravenous antibiotic, which may be switched to oral therapy when there are positive signs of improved condition. For non - pregnant adults the recommended treatment is streptomycin 1 mg intramuscularly twice a day or gentamicin 5 mg/kg IM or IV every 24 hours. Other choices include chloramphenicol or fl uoroquinolones. For patients with suspected meningitis, chloramphenicol (50 – 75 mg/kg per day) is considered mandatory because of its superior penetration of the CNS [4,5] . It is thought that the major determinant of the outcome of mother and child is the timing of antibiotic administration [6] . Historically, plague acquired during pregnancy led to nearly uni- versal fetal loss and could be especially severe in pregnant women [7] . Gentamicin should be substituted for streptomycin in the case of pregnancy. Chloramphenicol should be used with caution in pregnant women due to potential adverse effects on fetus and newborn. Doxycycline and ciprofl oxacin have also been consid- ered as alternative regimens and use in this situation should rep- resent the choice between the benefi t of treating the infection versus any potential risks of the medication to the fetus [7] . Empiric treatment of the newborn following delivery of an infected mother should also be considered. In the event of a bioterrorist attack, it is thought that postexposure prophylaxis is necessary to prevent rapid spread of the disease. A decision regarding whether or not to place pregnant patients on the rec- ommended prophylaxis of doxycycline 100 mg twice a day would need to be made based on the risk of exposure and the anticipated spread of the disease [7] . Timely treatment with the appropriate antibiotics is very important in affecting the outcome in preg- nancy. Untreated, the mortality from plague is estimated to be close to 100%. Even in treated cases, pneumonic plague is highly lethal with up to 50 – 60% mortality despite appropriate antibiotic therapy. Given the small risk to the fetus of doxycycline use in claved prior to disposal [4] . A certain number of hospital person- nel may need to be vaccinated in advance in order to provide care in the event of a deliberate infection. The United States govern- ment made an attempt at vaccinating a core group of staff at hospitals all over the country in 2002, but the program met with limited success due to concerns about adverse reactions to the vaccine. Again, for obstetric units, planning to care for multiple pregnant, infectious victims will be challenging. Hospitals with maternity services should anticipate the need to designate obstet- ric and neonatal physicians and nurses for a team response. Although Cidofovir has been tried with success against other pox viruses and has been reported to have in vitro activity against variola, it cannot yet be recommended as treatment for smallpox [5] . The principles of managing an outbreak of smallpox will be isolation and supportive care of infected patients and postexpo- sure vaccination for contacts. Vaccination against smallpox is by inoculation of the related orthopoxvirus, vaccinia. Vaccination is moderately effective at aborting or attenuating the disease if given within 4 days of an exposure [5] . Complications from widespread vaccination with vaccinia in the past included localized dermal reactions, vaccinia gangrenosa (with local extensive skin necrosis at the site of inoculation), eczema vaccinatum (a superinfection of eczema with the vaccinia virus), progressive vaccinia, and post- vaccinial encephalitis [10] . While pregnant mothers may be vac- cinated, there is a low risk of a potentially fatal fetal infection from the vaccinia virus. Therefore, routine vaccination of preg- nant women in non - emergent settings is not recommended. In the event of an actual bioterrorism event, a pregnant woman at risk for exposure must weigh the relatively small risk of an adverse effect from the vaccine, against the devastating outcome associ- ated with smallpox infection in pregnancy [10] . Plague Plague has held a special place in world history with multiple pandemics leading to the deaths of millions of people. The bacil- lus, Yersinia pestis , is generally transmitted to humans from a rodent host by way of a fl ea vector. However, direct host - to - host transmission may occur by way of an infectious aerosol from affected individuals. This makes the disease extremely contagious. The disease is rapidly fatal in the absence of appropriate antibiotic treatment [4] . There have been attempts in the past to weaponize plague; however, most such attempts have met with limited success. Still, it is thought that plague represents a bioterrorism threat by way of an aerosol or inhalational route. Typical bubonic plague is acquired from the bite of a fl ea, which regurgitates the Y. pestis from its foregut. The organisms rapidly multiply and spread to regional lymph nodes within 1 – 8 days. The infection of lymph nodes creates a characteristic bubo, which is a large tender area of infl ammation within the regional lymph node. Once this occurs, the patient may become septic within several days. Some patients will develop pneumonia and begin to shed the Yersinia organisms in their cough droplets. Victims will typically develop a productive cough with blood - tinged sputum within 24 hours of the onset of symptoms [4] . The Chapter 52 734 320 mg with sulfamethoxazole 1600 mg daily for the duration of the pregnancy. Chronic infection is more common in women who develop the acute infection during pregnancy. This is thought to be related to the relatively immunocompromized state of pregnancy. The use of the trimethoprim/sulfamethoxazole during pregnancy reduces the frequency of abortion, and decreases the number of women with identifi able Coxiella in the placenta at birth [12] . Such treated patients are still at risk for preterm delivery and low birth weight. Prolonged therapy should be instituted after delivery, and the recommended postpartum regimen is doxycycline 100 mg twice daily and hydroxychloro- quine 600 mg daily for 1 year following the pregnancy. For women who are appropriately treated, future pregnancies seem to be unaffected. Similarly, women who acquire and resolve the acute infection prior to becoming pregnant do not show any adverse pregnancy effects [12] . Breastfeeding is not recom- mended for women with acute Q fever. Ricin Ricin is a potent toxin easily derived from the beans of the castor plant ( Ricinus communis ). The history of ricin ’ s use as a lethal agent goes back several years and crosses many political lines. Recently, this toxin received extensive media attention as an agent of terrorism following the arrest of six persons in Manchester, England, in December of 2002, who allegedly produced the toxin in an apartment for use in a potential attack. The discovery of powdered ricin in the mailroom serving US Senate Majority Leader Bill Frist ’ s offi ce in February 2004 resulted in renewed fears regarding vulnerability to an attack with this toxin. The potential for ricin to be a weapon of mass destruction rests in the ease with which it can be produced, its stability, and its relatively easy route of dissemination with low risk of detection. The amount of ricin necessary to produce effects is also very small. The protein is derived in the processing of castor beans, the oil from which is used in a number of diverse industrial settings, including the manufacture of brake and hydraulic fl uid [13] . The waste mash, or aqueous phase of the oil production, contains 5 – 10% ricin, which can then be isolated using chromatography. The toxins RCL III and RCL IV are relatively small dimeric pro- teins consisting of an “ A ” and “ B ” chain. After entry into the cell by binding to the cell surface glycoproteins, the toxin inhibits the 60S ribosomal subunit preventing continued protein synthesis. The interruption of protein synthesis eventually leads to cell death [13] . In the event of inhalational exposure, symptoms are related to irritation of the lungs. Respiratory symptoms will begin usually 4 – 8 hours after the exposure. Early symptoms can include fever, chest tightness, cough and dyspnea. Within 1 – 2 days, severe infl ammation of the respiratory tract, cell death, and the develop- ment of acute respiratory distress syndrome may be expected. The only treatment is respiratory support with mechanical ven- tilation. [3,5] . There has been concern that ricin may be used to contaminate the water or food supply. In the event of a gastroin- testinal exposure, necrosis of the gastrointestinal epithelium as pregnancy and the very high morbidity and mortality of the disease itself, most would agree that, if indicated, the prophylactic antibiotics should be given. Viral h emorrhagic f evers Extremely infectious body fl uids also raise the potential for wide- spread transmission of some of the most feared tropical hemor- rhagic viruses, such as Ebola or Marburg. These viruses could conceivably mutate to spread by inhalational routes that would allow wider dissemination. One documented outbreak of Ebola Zaire virus killed 9 out of 10 infected victims [11] . With no known cure or vaccine, intensive support and isolation are the only available responses, and any widespread infection would likely overload our current medical system. One has only to read an account of these viruses [11] to appreciate that advance prepa- ration and containment may be our best approach. Q f e v e r Q fever is caused by an intracellular bacterium, Coxiella burnetii . This agent may be considered for use in bioterrorism because of the ease with which it causes infection [5] . Most immunocompe- tent persons have a self - limited infection without serious long - term complications, although chronic infection and endocarditis may occur in a small proportion of infected individuals and this can be debilitating. An intentional release of Q fever would most likely cause social disruption and psychological effects rather than mass casualties. The organism has long been known for its asso- ciation with infection leading to abortion in animals. More recent information suggests that there is a similar effect on fetal loss in humans as well. Q fever is generally obtained through inhalation of Coxiella organisms. The organisms are carried in body fl uids such as the amniotic fl uid of farm animals. The incubation period is between 2 and 14 days. The clinical manifestations are similar to other non - specifi c viral illnesses with fever, chills and headache. The patient may also experience malaise, anorexia and weight loss. More serious complications include neurologic symptoms in at least 23% of acute cases [5] . The diagnosis is generally made on the basis of the clinical complaints along with the presence of patchy infi ltrates seen on chest X - ray and a history consistent with exposure. Serology for Coxiella IgG and IgM may be useful, with antibodies appearing during the second week of the illness. The typical treatment for a non - pregnant adult is doxycycline twice a day for 5 – 7 days. Fluoroquinolones can also be used. The disease is not thought to be contagious from person to person [5] . While Q fever has long been known to cause low birth weight and abortion in farm animals, more recent data from France suggest that there is also a signifi cant effect on human pregnancy [12] . Acute infection during the fi rst trimester leads to a very high rate of abortion in untreated patients. Acute infection in the second or third trimester is less commonly associated with fetal loss but can be associated with low birth weight and premature delivery [12] . The recommended treatment is trimethoprim Biological, Chemical, and Radiological Attacks in Pregnancy 735 agents are usually clear and colorless and may be disseminated as either a vapor or liquid. Exposure may occur through skin absorption, inhalation, or gastrointestinal ingestion. Patients who have had signifi cant exposure or who are present- ing with obvious symptoms should be treated with atropine and pralidoxime (2 - PAM) [14,15] . Atropine is commonly given as a 1 - mg intramuscular or intravenous dose and is sometimes avail- able for self - administration via an auto - injector. The patient should be reevaluated every 3 – 5 minutes, and repeat doses may be given (up to 6 mg total) until secretions decrease and ventila- tion improves. Pralidoxime, which reactivates the acetylcholines- terase at the nicotinic receptor, can also be given as a 600 – 1000 mg intramuscular injection or as a slow intravenous infusion [14,15] . In the event of severe respiratory compromise, intubation and mechanical ventilation may be required. Severely affected victims should be given a benzodiazepine (diazepam, lorazepam, or mid- azolam) to raise the seizure threshold and help prevent secondary anoxic brain injury [15] . Successfully treated patients will begin to recover within a few hours, but neurological symptoms may last for weeks. There is little information on the fetal effects of such an expo- sure. The fetus will be particularly susceptible to any respiratory depression or anoxia in the mother. Theoretically, these com- pounds may be able to reach the fetal brain with resultant behav- ioral depression likely, and this may alter fetal biophysical and non - stress testing. Ultimately, fetal survival will depend on expe- ditious care of the mother. Vesicants and p ulmonary a gents Vesicants, such as mustard gas and Lewisite, are easily absorbed through the skin and mucous membranes [15] . The damage may not be evident until hours after the exposure. Damage is caused by cross - linking and methylation of DNA. Blisters may form on the skin in the early stages. Skin sloughing will later place the patient at risk for secondary infection. Similarly, damage to lung tissues results in a chemical pneumonia that may also lead to secondary infection. Mortality is generally low from an acute attack, but the number of people affected may be high, and because of the high morbidity associated with these agents caring for these victims, will consume signifi cant medical resources [14,15] . In a similar vein, pulmonary agents, such as phosgene and chlorine, lead to respiratory tract injury within hours, with damage to the alveolar – capillary membrane and subsequent pul- monary edema. Victims of phosgene usually require mechanical ventilation and careful management of fl uid balance, but survival beyond 48 hours suggests that recovery is likely [14,15] . Radiation Public concern over radiation exposure has been elevated by worries about the safety of nuclear power facilities, the transport and disposal of nuclear waste, and the threatened use of radiation contaminated weapons – so - called “ dirty bombs ” . Much is known about the consequences of inadvertent exposure. Damage well as damage to spleen, liver and kidneys may occur. Symptoms might manifest as abdominal cramps and nausea, as well as high - output gastrointestinal fl uid loss. Ricin is thought to be much less toxic when ingested rather than inhaled, although a large gastro- intestinal exposure could lead to enough necrotic multiorgan damage to produce hemorrhage and hypovolemic shock [3,5] . The diagnosis can be confi rmed by ELISA testing. Patients should be treated with decontamination including removal of garments and cleansing of the body with soap and water. Outside of contact with residual, undetected toxin remaining on the victim, there is thought to be little secondary risk to emergency department personnel; however, universal contact precautions should be observed. There is no direct antidote to the toxin, although gastric decontamination with charcoal may be benefi - cial in some cases [3,5] . Supportive care is the main approach to management. In the case of exposure during pregnancy, the molecular weight of the toxin makes it unlikely to cross the pla- cental barrier. The outcome for the baby will depend on maternal response to supportive care. Toxins or c hemicals There are several compounds that may represent mass risk either as the result of a deliberate act (e.g. release of a nerve gas in the Tokyo subway system in 1995), or as a result of an industrial accident. Chemical weapons may be classifi ed either by their lethality or by their ability to persist in the environment [14] . Lethal agents are classifi ed into four categories: nerve agents or anticholinesterases, vesicants or blistering agents, choking or pul- monary agents, and cyanogens or “ blood ” agents [15] . For the most part, care of the pregnant patient will differ little from that in the non - pregnant patient, especially prior to fetal viability. As in trauma situations, the health and survival of the fetus depend most upon the mother ’ s condition, as a result of both the imme- diate and the prolonged supportive care. Whenever a chemical threat is suspected, the medical team should wear protective equipment including rubber boots and impermeable suits. Decontamination of the victims is a high pri- ority, and patients should be moved to a well - ventilated setting for safe disposal of clothing and decontamination of the skin [14] . Dilute sodium hypochlorite solution is preferred to water, and the eyes should be irrigated with large amounts of water or normal saline [14] . Nerve a gents – a cetylcholinesterase i nhibitors Organophosphorus compounds such as tabun, sarin, soman, and VX primarily act through the inhibition of acetylcholinesterase at synapses and neuromuscular junctions [14,15] . Tyrylcholinesterase in plasma, and acetylcholinesterase in the red blood cell, are also inhibited by these agents. The result is an excess of acetylcholine leading to bronchial hypersecretion and bronchoconstriction, mental status changes, nausea, vomiting, and muscle fascicula- tions and weakness [15] . A large exposure may be rapidly fatal with loss of consciousness, seizures, and apnea from respiratory muscle paralysis and central nervous system depression. The Chapter 52 736 tual recovery [18] . Severe organ dysfunction may be present, including low white blood cell counts leading to immunodefi - ciency. A gastrointestinal syndrome also may occur with loss of the cells lining the small and large intestines, leading to water and electrolyte loss through vomiting, diarrhea and impaired absorp- tion. The patient may also demonstrate confusion and disorienta- tion resulting from the dramatic changes of dehydration and electrolyte imbalance. Such mental status changes, including periods of unconsciousness, are a poor prognostic sign [18] . Full recovery is possible and may occur over a prolonged period of time, from several weeks to 2 years. The initial management of a large radiation exposure includes treating traumatic injuries (fractures, lacerations) as they would normally be managed. In addition, care should be taken to remove external contaminants. The history should focus on the details of the source of exposure including the type of radiation, the proximity to the source, and the duration of the exposure [18] . A careful medical history should be obtained and, in preg- nant women, an estimate of the gestational age and a summary of the pregnancy history should be included. Diagnosis of ARS may be aided by following the complete blood count every 4 – 6 hours. A signifi cant drop in the absolute lymphocyte count and platelet count may aid in timing the exposure. Suspected expo- sures less than 2 Gy may not require hospitalization. Prospective evaluation of the white blood cell count and the cell differential count over the course of the next few days may be appropriate. Nausea and vomiting might not be present in the early phase for someone with less than 7.5 Gy of exposure (see Table 52.2 ) [16,18] . For more severe ARS with a known higher exposed dose, sup- portive care should be the rule. Careful history and physical examination is imperative. Nausea and vomiting can be initially managed with selective serotonin 5HT 3 receptor antagonists [18] . Admission to hospital will be necessary. The anticipated drop in blood cell counts merits prophylactic use of antiviral prophylaxis and possibly neutropenic precautions. Management should be performed in conjunction with a hematologist or others knowl- edgeable in radiation illness. Potassium iodide has been considered as a means of protecting thyroid function in the event of an acute population exposure to radiation [19] . This becomes useful primarily in the event of can range from skin reddening to cancer induction and death. Particularly relevant to pregnancy is the fact that fetuses and children (in whom there is ongoing rapid cell division) are more susceptible to the subtle effects of radiation exposure than are adults [16,17] . Damage is also cumulative, with increasing or repetitive exposures resulting in more severe damage [16] . “ Dirty bombs ” are typically intended to spread radiation in such a way as to make large areas uninhabitable. Depending on the source, the amount of radiation released from such a weapon is unlikely to cause severe forms of acute radiation syndrome [16] . According to the United Nations ’ report of Iraq ’ s testing of dirty bombs in 1987, the Iraqis deemed that radiation levels achieved were too low to cause signifi cant damage and the project was abandoned. In a modern context, such weapons would likely be used to disrupt routines and generate fear in the general public. Management of the initial exposure to radiation revolves around limiting the amount of time near the source, increasing the distance from the source, and use of physical barriers, such as glass or concrete to shield an individual from exposure [16] . In the event of an exposure, it is recommended that exposed individuals leave the area on foot (as opposed to using cars or public transportation that may harbor contaminated dusts), and to make use of barriers by entering buildings. Clothes should be removed and bagged for later disposal. A shower may remove contaminated dust or debris from the skin [16] . These principles of contamination must also be considered for the patient present- ing to the hospital or clinic for evaluation. Radiation exposure can result in signifi cant dysfunction to many organs. Depending on the dose and duration of exposure, as well as the mechanism of exposure, injuries may range from local (such as a burn) to more widespread injury such as acute radiation syndrome (ARS) [18] . A local injury often involves exposed contact areas like the hands. Patients may present with erythema, blistering, desquamation, and ulceration of the skin. The patient may or may not know when the exposure occurred. For example, handling an unknown metallic object might be the source of exposure. Such injuries generally evolve slowly and the full extent of injury may not be known for several weeks. Conventional wound management may be ineffective [18] . The acute radiation syndrome (ARS) is a quickly developing illness caused by a total body exposure to radiation. It is charac- terized by simultaneous damage to several organ systems from ionizing radiation that caused defi ciency in cell numbers or cell function. Radioactive sources provoking ARS might consist of machines that emit gamma rays, X - rays, or neutrons. There are three phases of ARS [18] . The fi rst is a prodromal phase in which a patient might experience nausea, vomiting and loss of appetite. Generally these symptoms disappear within a day or two and a symptom - free latent period may follow. The length of the latent period may vary depending on the radiation dose. A period of fully expressed illness may then follow with electrolyte imbal- ances, diarrhea, hematologic abnormalities, and even CNS changes. The overt illness results either in death or in slow, even- Table 52.2 Biological effects of total body irradiation [16] . Amount of exposure Effect 50 mGy (5 rads) No detectable injury 1 Gy (100 rads) Nausea and vomiting for 1 – 2 days, temporary drop in new blood cell production 3.5 Gy (350 rads) Nausea and vomiting initially, followed by periods of apparent wellness. At 3 – 4 weeks, may see defi ciencies of white blood cells and platelets > 3.5 Gy May be fatal Biological, Chemical, and Radiological Attacks in Pregnancy 737 members of other relevant hospital departments, such as emer- gency medicine, critical care, and the fi rst - response and transport teams, is essential. Helpful resources and training centers exist, including the Department of Energy - sponsored Radiation Emergency Assistance Center/Training Site (REAC/TS) program in Oak Ridge, Tennessee, and the Department of Homeland Security ’ s Center for Domestic Preparedness in Anniston, Alabama. References 1 Disaster management . In: Holleran RS , ed. Air and Surface Patient Transport: Principles and Practice , 3rd edn. St. Louis : Mosby , 2003 . 2 Bleck TP . Fundamentals of disaster management . In: Farmer JC , Jimenez EJ , Talmor DS , Zimmerman JL , eds. Fundamentals of Disaster Management . Des Plaines, IL : Society of Critical Care Medicine , 2003 : 1 – 8 . 3 Moran GJ . Threats in bioterrorism II: CDC category B and C agents . Emerg Med Clin N Am 2002 ; 20 : 311 – 330 . 4 Darling RG , Catlett CL , Huebner KD , Jarrett DG . Threats in bioter- rorism I: CDC category A agents . Emerg Med Clin N Am 2002 ; 20 : 273 – 309 . 5 Agrawal AG , O ’ Grady NP . Biologic agents and syndromes . In: Farmer JC , Jimenez EJ , Talmor DS , Zimmerman JL , eds. Fundamentals of Disaster Management . Des Plaines, IL : Society of Critical Care Medicine , 2003 : 71 – 93 . 6 Inglesby TV , O ’ Toole T , Henderson DA , Bartlett JG , Ascher MS , Eitzen E , et al. Anthrax as a biological weapon, 2002; updated recom- mendations for management . JAMA 2002 ; 287 ( 17 ): 2236 – 2252 . 7 White SR , Henretig FM , Dukes RG . Medical management of vulner- able populations and co - morbid conditions of victims of bioterror- ism . Emerg Med Clin N Am 2002 ; 20 : 365 – 392 . 8 American College of Obstetricians and Gynecologists . Management of asymptomatic pregnant or lactating women exposed to anthrax. ACOG Committee Opinion No. 268 . Obstet Gynecol 2002 ; 99 : 366 – 368 . 9 Wiesen AR , Littell CT . Relationship between prepregnancy anthrax vaccination and pregnancy and birth outcomes among US army women . JAMA 2002 ; 287 ( 12 ): 1556 – 1560 . 10 Suarez VR , Hankins GDV . Smallpox and pregnancy: from eradicated disease to bioterrorist threat . Obstet Gynecol 2002 ; 100 : 87 – 93 . 1 1 P r e s t o n R . The Hot Zone . New York : Random House , 1994 . 12 Raoult D , Fenollar F , Stein A . Q fever during pregnancy . Arch Intern Med 2002 ; 162 : 701 – 704 . 13 Mirarchi FL . CBRNE – Ricin. Available at www.emedicine.com/ emerg/topic889.htm . 14 Evison D , Hinsley D , Rice P . Chemical weapons . BMJ 2002 ; 324 : 332 – 335 . 15 Lantz G , Talmor DS . Chemical agents and syndromes . In: Farmer JC , Jimenez EJ , Talmor DS , Zimmerman JL , eds. Fundamentals of Disaster Management . Des Plaines, IL : Society of Critical Care Medicine , 2003 : 57 – 70 . 16 Oak Ridge Institute for Science and Education, Radiation Emergency Assistance Center/Training Site . Guidance for Radiation Accident Management. Types of radiation exposure. Available at http://orise. orau.gov/reacts/guide/injury.htm . Retrieved January 7, 2007 . exposure to radioactive iodine, which is typically present early in a nuclear explosion and decays rapidly. Radioactive iodine is potentially taken up by the thyroid gland and leads to destruction of the normal glandular tissue. Potassium iodide salt taken within the fi rst 3 – 4 hours of an event saturates the thyroid gland ’ s iodine uptake mechanism, blocking uptake of the radioactive form. Due to the quick decay of radioactive iodine, only a single dose is usually needed [19] . Because of the relatively greater activity of the thyroid gland in children, potassium iodide is recommended for children as well. Adults should receive one tablet or 130 mg. Children aged 3 – 18 are to receive one half - tablet (65 mg). Children aged 1 – 3 years receive 32 mg, and under 1 year of age, 16 mg is the recommended dose. The adult dose therapy is recommended for pregnant women, as the fetus is also susceptible. Women who are breast- feeding should also be given the usual adult dose, and the child should receive the appropriate dose based on age [19] . Unfortunately, high - dose radiation exposure can have severe effects on the developing fetus. Estimates of the risk of injury from ionizing radiation are based in part on reports from Hiroshima and Nagasaki following the atomic explosions there. Along with other data, a linear relationship has been used to estimate risks to the fetus from smaller exposures. While no direct evidence links exposure to diagnostic medical imaging tests with childhood cancers or birth defects [17,20] , exposures from an intentional event could pose signifi cant fetal risk due to a much higher dose of ionizing radiation. In the case of the pre - implantation embryo, the most likely outcomes are either no detectable effect or complete loss of the embryo [17,20] . For example, an exposure of 10,000 millirads (mrads) is associated with a 2% risk of death for the pre - implan- tation embryo [20] . In the fi rst trimester, the threshold for detect- ing an increased risk of birth defects, such as brain malformation or injury to the mid - face, teeth or genitalia, is 5000 – 25 000 mrad. Microcephaly, developmental delay, and cognitive impairment can occur with large exposures, (greater than 12 000 – 20 000 mrad) particularly between 8 and 15 weeks [17,20] . Developmental delay and impairment may occur later in the gestation, but at doses that would induce ARS in the mother. The expected risk of mental impairment in the fetus exposed to 100 rad (1 Gy) is approximately 40%, while the risk climbs to 60% with 150 rad of ionizing radiation [17] . Summary Most new information on these described agents will likely come in the form of case reports from isolated exposures or events. Basic science research must continue to discover the complex microbiology of some of these agents, particularly as it is altered by pregnancy. The most critical immediate need is for systems preparation. A written, well - instructed triage and management plan, including back - up plans for communication and personnel, is a necessary fi rst step. Collaboration between obstetricians and Chapter 52 738 drome. Available at http://orise.orau.gov/reacts/guide/syndrome. htm . Retrieved January 7, 2007 . 19 Centers for Disease Control. Emergency Preparedness and Response . Radiation emergencies: potassium iodide. Available at www.bt.cdc. gov/radiation/ki.asp . 20 Miller JC . Risks from ionizing radiation in pregnancy . Radiology Rounds 2004 ; 2 ( 2 ). 17 American College of Obstetricians and Gynecologists . Guidelines for diagnostic imaging during pregnancy. ACOG Committee Opinion No. 158, 1995 . Available at www.acog.com/publications/commit- tee_opinions/bco158.htm . Retrieved January 1, 2001. 18 Oak Ridge Institute for Science and Education, Radiation Emergency Assistance Center/Training Site . Guidance for Radiation Accident Management. Managing radiation emergencies: acute radiation syn- . hospital departments, such as emer- gency medicine, critical care, and the fi rst - response and transport teams, is essential. Helpful resources and training centers exist, including the Department. Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee College of Medicine, Chattanooga, TN, USA Introduction It is an unfortunate reality that in many parts of the. 729 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy.