Preparedness against Nerve Agent Terrorism - ACS Symposium

Chapter 23

Preparedness against Nerve Agent Terrorism 1,4

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Tetsu Okumura , Kouichiro Suzuki , Atsuhiro Fukuda , Shinichi Ishimatsu , Shou Miyanoki , Keisuke Kumada , Nobukatsu Takasu , Chiiho Fujii , Akitsugu Kohama , and Shigeaki Hinohara 1

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Downloaded by NORTH CAROLINA STATE UNIV on September 23, 2012 | http://pubs.acs.org Publication Date: December 20, 1999 | doi: 10.1021/bk-2000-0745.ch023

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Emergency Department, St. Luke's International Hospital, Tokyo, Japan Department of Acute Medicine, Kawasaki Medical School, Kurashiki, Japan St. Luke's International Hospital, Tokyo, Japan

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Onthemorning of March 20, 1995 sarin was released in the Tokyo Subway System. As a result, 12 people died and 5500 more were sickened. There had never been such a large-scale act of urban terrorism caused by nerve gas. The most important measure in fighting nerve agent terrorism is preparedness. Public organizations and hospitals must have decontamination facilities. EMTs and the medical staff in hospitals should have personal protective equipment. Hospitals should stock antidotes and public organizations need multi-ventilator systems. Local communities must have protocols for chemical -and-radiation contaminated victims, multi-channel and multi-directional information networks regarding hazardous materials, and must practice repeatedly and regularly. The close follow-up of sarin victims is also extremely very important. As die world has learned, urban terrorism can take many forms: bombing, biological agent attacks, chemical agent attacks, and nuclear weapon attacks. On the meaning of March 20, 1995 the Tokyo Subway System was filled with a noxious substance later identified as a diluted form of the nerve gas, sarin. A total of five subway commuter cars were affected during the Monday morning rush hour. There were 12 fatalities and 5500 more were sickened. From a worldwide historical perspective, there has never been such a large-scale disaster caused by a nerve gas in peacetime. This disaster in Japan was a wake-up call for the rest of die world. The most important measure against urban terrorism using nuclear, biological, or chemical agents is preparedness. Terrorists always have an eye pealed for the weak points of an urban community. In this attack, the lack of preparedness against nerve agents was exposed. This article throws light on what problems existed from die viewpoint of preparedness, and discusses preparedness against nerve agent terrorism. We also believe that 4

Current address: Department of Acute Medicine, Kawasaki Medical School, Kurashiki, Japan. 356

©2000 American Chemical Society

In Natural and Selected Synthetic Toxins; Tu, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999.

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most of the preparation tactics that can be used in an urban terrorism situation are useful for other chemical or nuclear disasters.


Background The attack occurred at approximately 8:00 a.m. According to a traffic white paper, the capacity of subway trains between 8:00 am and 8:40 am reaches more than 200% (passengers cannot read opened newspapers, only magazines). Later police announcements noted the terrorists respectively carried diluted sarin solution in plastic bags into the subway trains and simultaneously stuck the sharpened tip of an umbrella into these bags. There were 12 fatalities and 5500 more persons were sickened. St. Luke's International Hospital, a private 520-bed facility, received the greatest number of victims because it is located within 3 tan of the affected subway stations. Fig. 1 shows the affected Tokyo Subway System and the location of St. Luke's Hospital. When the first emergency call from the Tokyo Metropolitan Ambulance Control Center, which is under the administration of the Tokyo Metropolitan Fire Department came into our Emergency Center at 8:16 a.m., it was reported that there had been a gas explosion at a subway station. We, therefore, started to prepare for burns and carbon monoxide poisoning. At 8:28 a.m. the first patient complaining of eye pain and visual darkness arrived at the emergency départaient on foot from one of the subway stations. The first ambulance arrived at 8:43 a.m. In the first hour about 500 patients including three cardiopulmonary arrest on arrival patients were rushed to the Emergency Center. The directors of the hospital declared a disaster-oriented system, which included canceling of all routine operations and outpatient examinations at 9:20 a.m. More than 100 doctors and 300 nurses and volunteers were mobilized to care for the patients (1). Table 1 shows the time course of events with details. Even in the hospital passageways, the victims were receiving IV infusion. At St. Luke's Hospital, triage was done mainly in the Emergency Center. We divided victims into three categories, mild: ambulatory victims who presented with only eye symptoms, moderate: non-ambulatory victims who presented with other systemic signs and symptoms, and severe: victims needing mechanical ventilation. Mild patients were closely observed with an IV line for several hours in the outpatient department and sent home. Moderate patients were admitted to wards. Severe patients were moved to our ICU. The number of mild cases with only eye symptoms, who were released after a half day observation, was 528. The number of moderate cases with other systemic signs and symptoms, who were admitted, was 107. The number of severe cases requiring intubations and artificial ventilation was 5 (2). Table 2 shows the symptoms of the patients. The most prominent sign was miosis, followed by headache, visual darkness, eye pain, dyspnea, nausea, cough , and throat pain. The most significant change in chemical laboratory data was low plasmal Cholinesterase values. The ability to manage samples reached its limitation. Usually we use a computer system, but the system broke down due to the enormous number of samples. Therefore results had to be reported manually. As for



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O Subway stations where many casualties arose Figure 1. Affected Tokyo Subway System


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Table 1 : Time Course with Information Time


7:55 8:16

Information source

Events The attack occurred simultaneously in a number of locations.

The Tokyo Metropolitan Fire Department

Information

Explosions occurred at subway stations.

8:25

F irst victim came to ER on foot

8:40

F irst ambulance came.

Many people collapsed in the

8:43

First cardiopulmonary arrest patient

subway station.

Victims

There was no explosion.

came by a private veh icle. More than 500 victims rushed to the ER. 9:20 9:40

All routine operations and outpatient examinations were canceled. Cholinesterase level returned: very low. Pralidoxime was started to be given for severe patients.

The Tokyo Metropolitan Fire Department President of Shinshu University Hospital Doctor from the Self Defense

10:30

Cause material is acetonitrile.

Sarin intoxication is suspected. Sarin intoxication is

Forces Hospital.

suspected.

11:00 First press conference was given.

TV news:

Cause material is sarin,

12:00 Doctor conference was held to standardize the triage and treatment

police announcement (There was no direct information from police.)

14:00 Mildly affected patients were sent home. 17:00 Transportation of the admitted patients The Tokyo Metropolitan was rerejected by the Tokyo Metropolitan ^ Department Fire Department. F

Ambulances are not available for the victims' transport to other hospitals until midnight.

18:00 Germany, France, and England offered the dispatch of rescue teams. 20:00 Final reconfirmation of admitted patients' information (name, address, severity, etc)was done. 22:00 The list of the patients w as announced.

SOURCE: Adapted with permission from Reference 1. Copyright 1998.


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Table 2: Patient Signs and Symptoms


Signs and Symptoms

% (number of patients)

Ophthalmological Si/Sx: Miosis: Eye Pain: Visual Darkness: Blurred Vision: Conjunctival Injection: Tearing:

90.5% (568 / 627) 37.5% (235 / 627) 37.6% (236 / 627) 17.9% (112 / 627) 6.7% (42/627) 4.3% (27/627)

Respiratory Si/Sx: Dyspnea: Cough: Chest Oppression: Wheezing:

29.2% (183/627) 18.8%(118/627) 12.0% (75/627) 1.0% (6/627)

Gastrointestinal Si/Sx: Nausea: Vomit:

26.8% (168 / 627) 14.7% (92 / 627)

Neurological Si/Sx: Headache: 50.4% (316/627) Easy Fatigability: 15.2% (95 / 627) Fasciculation: 7.0% (44/627) Extremity's Numbness: 2.9% (18/627) Vertigo & Dizziness: 2.7% (17 / 627) Consciousness Disturbance: 2.4% (15/627)

ENT Si/Sx: Throat Pain: Runny Nose:

18.3% (115/627) 15.2% (95/627)

Psychological Si/Sx: Agitated State:

5.7% (36 / 627)



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other chemical laboratory data, 11 % of the patients had higher than normal CPK values. Blood cell counts indicated leukocytosis. Arterial blood gas assays revealed many cases of respiratory alkalosis with the exception of the cardiopulmonary arrest on arrival patient. Of the 57 cases who had an ECG taken, four cases showed mild QT elongation without the necessity of therapy. Four cases had bradycardia, which responded well to atropine sulfate (2). Fig.2 shows the distribution of plasma Cholinesterase levels. The severity of the condition of patients correlated closely with the plasma Cholinesterase levels. Ninety-six percent of the patients received atropine sulfate for the treatment of miosis. We were careful not to overdose and it was used until the first signs of thirst and tachycardia appeared. After nerve gas became the suspected cause we decontaminated the admitted patients by having them change clothes and shower. Administration of pralidoxime (PAM) was also started within three hours of initial chemical exposure in 95 % of the admitted cases. PAM was especially effective for fasciculation. For convulsion, we used diazepam in eight cases, although its effect was short. For injected conjunctiva, topical steroidal eyedrops were used. Two cases experienced acute stress disorder (ASD). For these severe ASD patients, a mild antidepressant was used (2) and respiratory stabilization was mandatory to the well being of the patients. The duration of a hypoxic state has the most influence on the patient's prognosis. That means that not only hospital care, but also prehospital care is very important. Within two to four days after the Sarin Attack, 95% of the hospitalized patients had recovered and were subsequently discharged with satisfactory relief of their complaints. Decontamination There was nofielddecontamination when the Attack occurred. The Tokyo Metropolitan Fire Department established Haz-Mat Units in 1990. At the time of the attack, 10 units were deployed in several fire stations in Tokyo. These were all dispatched to the affected subway stations. They were mainly engaged in analysis of the cause material. The cause material was analyzed as acetonitrile. Later this analysis was proved to be wrong. Japanese Self Defense Forces carried out decontamination of the affected subway trains and stations, but they did not decontaminate victims. We were unable to satisfactorily decontaminate victims in the hospital , especially mild cases. In part, this was because it took time to determine the cause of the victims' illness and, in part, because we did not have enough space for the victims to shower and change clothes. However, we should be able to recognize some chemical agents and carry out decontamination earlier when we see mass casualties complaining of the same signs and symptoms. In Japan there are very few hospitals with a room specifically for decontamination. There was no room set aside for decontamination in St. Luke's Hospital. Therefore, secondary exposure of the medical staff arose from sarin vapor on the victims' clothing. Many


In Natural and Selected Synthetic Toxins; Tu, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1999. Figure 2. Distribution of Plasma Cholinesterase Levels

plasma Cholinesterase levels on arrival (IU/L: DTNB method)


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cases of secondary exposure were especially noted in poorly ventilated area of the hospital (3). Decontamination; i.e., removal of die cause material, is a very essential concept in chemical disasters. Nerve agents are no exception. Decontamination should be thought a matter to be considered at any stage and site. It should be done either in fields or outside of the hospitals, since if mass casualties arise, some victims without decontamination will come directly to the hospital from the disaster site. Therefore public organizations, such as the armed forces or fire departments, must have some mobile facilities where victims can shower and change clothes. These facilities could be utilized not only for dealing with nerve agents, but also for other chemical disasters and nuclear disasters. Prevention of hospital contamination is also very important. Therefore all hospitals should have decontamination facilities. The decontamination area of a hospital can be located either inside or outside of the hospital. An indoor decontamination area would be ideal, but decontamination outside is simpler and less expensive than equipping an indoor decontamination area (4). A parking lot would be one good candidate. The waste water from showering should be kept separated and should not be allowed to run over the pavement into sewer drains. Protective Equipment The Tokyo Haz-Mat Units used after the Sarin Attack had protective masks, suits, boots, and gloves, but ordinary EMTs had no protection. Without decontamination and protection, 135 of 1,364 EMTs involved in rescue efforts experienced secondary exposure. At St. Luke's Hospital, the medical staff wore usual medical masks and surgical latex gloves after it was recognized the cause material was a nerve agent. But the efficacy of their protection was questionable. Better ventilation of the accommodation room was more effective against the secondary exposure. Vapor sarin from victims' clothes could not be avoided. Protection from nerve agents is also important. Two types of respiratory protection are available: cartridge respirators and supplied air respirators. Cartridge respirators are especially useful for decontamination outside hospitals. They are inexpensive, portable and easy to use and store. However, they must be fit tested, someone must decide which type of cartridge to use based on the materials causing injury to victims, and they cannot be used for long time. Air-powered respirators require no fit testing but need an air supply and hoses. Chemical resistant suits are necessary for decontamination in both prehospital and hospital settings. After this attack, protective clothing has been included in ordinary ambulances, but few hospital in Japan keep any of this clothing. Ordinary latex gloves offer little chemical protection. Cox has recommended nitrile and Viton as materials for the gloves of medical staff who care for chemically contaminated victims. He has also noted, however, that some classes of chemicals rapidly penetrate nitrile. In such cases gloves made of Viton, which is quite bulky though, are indicated (4). Every hospital should prepare such personal protective equipment (PPE).


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Stockpiling of Drugs and Instruments Antidote storage is important for mass casualties of poisonings. Initially, we had stored 100 ampoules of PAM and 1030 ampoules of atropine sulfate. These were sufficient for the initial treatment, but our pharmaceutical department had to make an additional order to wholesale dealers at the early stage. In total, we used 700 ampoules of PAM and 2800 ampoules of atropine sulfate (1). In Japan, organophosphoral poisoning is most common in rural areas. Organophosphates are used for agricultural chemicals. If they are ingested by farmers attempting suicide, these persons will be taken to rural hospitals. In the Tokyo Metropolitan area , where organophosphoral poisoning is rare, few hospitals have sufficient stockpiles of antidotes, especially PAM. PAM was transported from a maker in Osaka to Tokyo by air and super express trains. Fortunately, St. Luke's Hospital happened to have a stockpile of these antidotes because organophosphoral poisoning patients had been admitted just before the attack. Stockpiling of antidotes is troublesome for hospitals, because they must be regularly exchanged for new supplies before their expiration date. This is not cost-beneficial. WHO has divided antidotes into three (A, B, and C) according to the extent of emergency in its guidelines for the Poison Information Centers. Category A includes antidotes which should be given within thirty minutes, category B those which should be given within two hours, and category C those which should be given within six hours. In preparing for possible chemical disasters, every regional mainstay hospital should store antidotes according to WHO's classification and the geographical situation. Every hospital should stock highly emergent antidotes (WHO classification A), for example, CN-kits. Fortunately, the cause material in the Tokyo Attack was "diluted" form of sarin. Therefore, the ratio of victims requiring intratracheal intubation among all the victims was low. But, if sarin had been used in pure form, the circumstances for the victims' treatment would have been greatly changed. In such a situation, an enormous number of intratracheal tubes, bags, and ventilators would have been required. At the early stage, manual bagging can be done in such a situation. A multiple ventilator system would be useful. Such a system has already come on market. Public organizations, such as the armed forces orfiredepartments, must also have such a system. Information Network Initially, we thought that the patients' illness including miosis was cased by some kind of organic phosphorus, which is often included in agricultural chemicals. However, we were puzzled as to why it had happened in the subway. On the day of the Sarin Attack, medical information mainly came to St. Luke's Hospital from three sources (1). Information came first from the president of Shinshu University Hospital, who had experience with treatment of the Matsumoto Sarin Incident victims, via telephone and



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facsimile. Simultaneously, it came from a doctor sent from the Self Defense Forces Hospital. The third source was TV news. It took three hours for the police to announce officially that the material was sarin, but the police did not inform us directly. We also tried to contact the Japan Poison Information Center regarding treatment, but the telephone circuit had already became overloaded due to the enormous number of calls from hospitals. There are only two Poison Information Centerstohandle inqiries from all over the Japan. Information on the cause material and its treatment should be well organized and distributed promptly. The information network ought to be mutidirectional and multi-channel (1). In the public trial for those participating in the Tokyo Subway Sarin Attack it was revealed that the laboratory of the Tokyo Metropolitan Police Department discovered the cause material to be sarin at 9:55 a.m., but an official announcement concerning the cause material was not made on TV until 11:00 a.m. This delay shows the level of the comprehension regarding information on chemical disasters in Japan. Protocols, Training and Exercises Disaster planning exists in Japan, but this is mainly for natural disasters. In the Tokyo Subway Sarin Attack, the concerned organizations acted independently without central coordination. Therefore, no substantial information networking was established among organizations (5). Every community and hospital must include preparations for chemical disasters and nuclear ones in their disaster planning. Cox advocates that it is best to have one protocoltohandle all these situations. Because situations involving radiation or chemical contamination patients will be rare, two different protocols could result in confusion (4). Protocols without training and practice are worthless. Training in decontamination and PPE procedures must be done regularly and repeatedly. In local communities, every concerned organization, including the police, the armed forces, the fire department, Haz-Mat teams, and hospitals, must meet and communicate with each other in disaster drills. The importance of further follow-ups of the victims Learning from experience with past cases is important preparedness for the future. In other words, this is also preparedness for future cases. A lot is unknown about the long term effects of nerve agents. In animals, some literature has described such long-term effects, but there is little information about the effects in humans. No definite conclusions have been made concerning them. And whether initial treatment can change these effects or not is not known. We sent questionnaires to the 660 victims treated at St. Luke's on the day of the attack one years after the attack. Of these, 303 victims replied, and 46% still had some symptoms. Regarding physical symptoms, 18.5% of the victims still complained of eye problems, 11.5% of easy fatigability, and 8.6% of headache. As for psychological symptoms, 12.9% of them complained of fear of subways, 11.6% indicated the fears concerning their escape from the attack (6). A medical check-up was carried out one year after the attack on 133 victims who wanted such a check-up. Since we could find no abnormalities in any



366 cases, can these symptoms be explained completely by post traumatic stress disorder (PTSD) ? We felt the necessity to investigate subtle subclinical neurological changes. Therefore, we carried out a study of subclinical neuropsycobehavioral effects with the Department of Public Health of Tokyo University. Table 3 shows the items. The results were published in journals (7,8, 9). In these studies, it was suggested that a delayed effect on the vestibulocerebellar system was induced by acute sarin poisoning, that females might be more sensitive than males (7), and that asymptomatic sequelae to sarin exposure, rather than PTSD, persist in the higher and visual nervous systems beyond the turnover period of ChE. Sarin may have neurotoxic actions in addition to the inhibitory action on brain ChE (8). Chronic effects on pychomotor performance are supposed to be caused directly by acute sarin poisoning. On the other hand, psychiatric symptoms and fatigue appearedtoresult from PTSD induced by exposure to sarin (9). These studies are number-limited and are preliminary study, but they indicate the necessity for close follow-ups of victims. Fig. 3 shows the residual symptoms two years after the Tokyo Sarin Attack, and two most major symptoms in each category. We sent questionnaires to the victims. Eighty-eight percent still had some symptoms. Fortunately, there were no apparent physical abnormalities except for the victims' eyes. We should continue to study long-term effects of sarin clinically and subclinically. To know the actual conditions of the victims is the first step in making clear the pathogenicity of nerve agents. We believe that new and more effective treatment for victims of nerve agents must be promoted.

Table 3: Examined Items WHO-NCTB: Neuro-Core Test Batteries NES: Neurobehavioral Evaluation System Evoked Potentials VEP: Visual Evoked Potential BAEP: Brainstem Auditory Evoked Potential ERP: Event-Related Potential P300 RR Interval Variability in ECG PB: Postural Balance



Depressive Feeling

Flashbacks

Blurred Vision

Eye Fatigue

Dullness

Easy Fatigability

10

20

30

40

50

60

70

80

90

Figure 3. Residual Symptoms after Two Years (Two Major Symptoms in Each Category)

(0/o)


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References: 1. Okumura, T.; Suzuki, K.; Fukuda, A. et al. The Tokyo Sarin Attack: Disaster Management, Part 2: Hospital Response. Acad Emerg Med. 1998, 5, 618-24. 2. Okumura, T.; Takasu, N.; Ishimatsu, N. et al. Report on 640 Victims on The Tokyo Subway Sarin Attack Annal. Emerg Med. 1996, 28, 129-35. 3. Sanoyama T.; Monden M.; Ohbu S. et al. The investigation of Secondary Exposure at St. Luke's International Hospital. Nihon-Iji-Shinpo. 1995, 3727, 17-9. 4. Cox, R.D. Decontamination and Management of Hazardous Materials Exposure Victims in the Emergency Department Annal. Emerg. Med. 1994, 23, 761-770. 5. Okumura, T.; Suzuki, K.; Fukuda, A. et al. The Tokyo Sarin Attack: Disaster Management, Part 1: Community Emergency Response. Acad Emerg Med. 1998, 5, 613-7. 6. Ishimatsu, S.; Tanaka, K.; Okumura, T. et al. Result of the Follow-up Study of the Tokyo Subway Sarin Atack (1 Year after the Attack) [Abstract]. Kyuukyu-Igakkai-shi. 1996, 7, 567. 7. Yokoyama, K.; Araki, A.; Okumura, T. et al. Preliminary Study on Delayed Vestibulo-cerebellar Dysfunction in Tokyo Subway Sarin Poisoning in Relation to Gender Difference: Frequency Analysis Postural Sway. J. Occup. Environ. Med. 1998, 40,17-21. 8. Murata K.; Araki S.; Okumura, T. et al. Asymptomatic Sequelae to Acute Sarin Poisoning in the Central and Autonomic Nervous System 6 Months after the Tokyo Subway Attack. J. Neurol. 1997, 244, 601-606. 9. Yokoyama, K.; Araki, S.; Okumura, T. et al. Chronic Neurobehavioral Effects of Tokyo Subway Sarin Poisoning in Relation to Posttraumatic Stress Disorder. Arch. Environ. Health 1998, 53, 249-56.


Preparedness against Nerve Agent Terrorism - ACS Symposium

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