Sarin experiences in Japan: Acute toxicity and long-term effects

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Abstract

Two terrorist attacks with the nerve agent Sarin affected citizens in Matsumoto and Tokyo, Japan in 1994 and 1995, killing 19 and injuring more the 6000. Sarin, a very potent organophosphate nerve agent, inhibits acetylcholinesterase (AchE) activity within the central, peripheral, and autonomic nervous systems. Acute and long-term Sarin effects upon humans were well documented in these two events.

Sarin gas inhalation caused instantaneous death by respiratory arrest in 4 victims in Matsumoto. In Tokyo, two died in station yards and another ten victims died in hospitals within a few hours to 3 months after poisoning.

Six victims with serum ChE below 20% of the lowest normal were resuscitated from cardiopulmonary arrest (CPA) or coma with generalized convulsion. Five recovered completely and one remained in vegetative state due to anoxic brain damage. EEG abnormalities persisted for up to 5 years.

Miosis and copious secretions from the respiratory and GI tracts (muscarinic effects) were common in severely to slightly affected victims. Weakness and twitches of muscles (nicotinic effects) appeared in severely affected victims. Neuropathy and ataxia were observed in small number (less than 10%) of victims, which findings disappeared between 3 days and 3 months. Leukocytosis and high serum CK levels were common. Hyperglycemia, ketonuria, low serum triglyceride, hypopotassemia were observed in severely affected victims, which abnormalities were attributed to damage of the adrenal medulla. Oximes, atropine sulphate, diazepam and ample intravenous infusion were effective treatments. Pralidoxime iodide IV reversed cholinesterase and symptoms quickly even if administered 6 h after exposure.

Post Traumatic Stress Disorder (PTSD) was less than 8% after 5 years. However, psychological symptoms continue in victims of both incidents.

In summary, both potent toxicity and quick recovery from critical ill conditions were prominent features. Conventional therapies proved effective in Sarin incidents in Japan.

Introduction

Terrorists of a cult named “Aum Supreme Truth” attacked citizens with the nerve agent Sarin in 1994 in Matsumoto, and in 1995 in Tokyo, Japan. “Aum Supreme Truth” was founded in 1987 based on Buddhism, Yoga and Taoism. Cult members were predominately from young generations. The cult manufactured nerve agents Sarin and VX and biological weapons for countermeasures to its societal enemies, especially the police and other governmental agencies. The target of Sarin attack in Matsumoto was the district court; in Tokyo, the subway and the National Police Agency at Kasumigaseki-Sarin is an organophosphorous compound (methylphosphonofluoridic acid l-methylethyl ester), developed in 1938 as a chemical weapon. It is a potent cholinesterase inhibitor acting on the brain as well as somatic and autonomic nervous systems. LD50 in vapor form is 100 mg-min/m3.

The first attack occurred in summer at midnight in a residential area. Nearly 600 people were poisoned with 7 deaths and 56 hospitalized victims. In the second attack, Sarin was released in several subway cars on different lines leading to the government office center in Tokyo during a Monday morning rush hour. Twelve deaths and 5,500 exposures occurred.

The clinical states of the dead and injured victims, responses to various therapies, physical and psychological sequelae were recorded in both incidents with follow for up to 10 years. Because these were the first worldwide incidents with mass casualties caused by the nerve agent Sarin, it is important to describe the various aspects of the human toxicity. Because the two incidents occurred in different situations, rescue activities, the commitment of local administrations and follow up activities differed. Therefore, the events and outcomes are described separately.

Section snippets

The Matsumoto incident

At about 10:30 PM, June 27, 1994 in a quiet residential area of Matsumoto. 12 l of 70% Sarin solution were released within 10 min using a heater for evaporation and a motor vehicle's fan for dispensing the gas. Matsumoto is a city of 200,000 located in the central highlands of Japan.

The first emergency call arrived at 11:09 PM from a house located 20 meters from the presumed site of emission. Thereafter, ambulances transported injured people to 6 hospitals until 4:14 AM the 28th of June. Five

The Tokyo subway incident

At about 8:00 AM on Monday, March 20th, 1995, Sarin became airborne after terrorists broke plastic bags containing fluid with 30% Sarin in fully peopled subway cars, all headed to the center of governmental offices. Twelve people died: six within 2 h of exposure and six from 20 to 80 days later. Sarin and its metabolites were detected in many specimens.

Treatment outcomes have also been reported elsewhere [13], [24], [25], [28], [29].

These data and a questionnaire survey to all victims are

Discussion

Because of these 2 incidents, a variety of medical data was gathered on acute and chronic effects of Sarin in humans. Its pathophysiology is discussed elsewhere in this publication.

Inhalation of Sarin gas can cause immediate death. In the Matsumoto incident, 4 dead victims were found in rooms where they lived, even though Sarin gas was expelled in the open air 40 to 60 meters away. Some showed signs of having had generalized convulsions. The primary cause of death was probably respiratory

Future issues and the role of neurologists

Giving the experiences of Sarin incidents in Japan, the following are considered important for preparedness in future.

1. Establishment of treatment.

2. Long-term health checks and follow-up of psychic problems.

Despite low frequency of neurological sequelae, they may last up to 5 years. A team of neurologists, psychiatrists and epidemiologists should be a core of follow up systems. Collaboration with administration and health care personnel is important.

Neurological and medical health checks are

Acknowledgement

We thank Dr. Leon Prockop (University of South Florida) for editing the manuscript.

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