Critical Care Obstetrics part 75 pdf

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.. This chapt

Critical Care Obstetrics, 5th edition Edited by M Belfort, G Saade,

M Foley, J Phelan and G Dildy © 2010 Blackwell Publishing Ltd.

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,

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

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 disinfecresis-tants, 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 Inhalaconsump-tional anthrax is

Table 52.1 Examples of CDC category A , B , and C biological agents [3 – 5]

Inhalational anthrax Coxiella burnetti (Q fever) Hantavirus

fever Pneumonic plague Salmonella species Tickborne encephalitis

viruses Viral hemorrhagic fevers E coli O157:H7 Yellow fever

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 reintroducpopula-tion of this disease Initial dissemination may be diffi cult, but the number of second-ary contacts and ease of transmission to secondsecond-ary 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

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

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 gastroingastroin-testinal 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 ever

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

immunocompetent 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

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

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 dehydradisorienta-tion 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,

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

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

11 Preston 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

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