Sarin toxicity

In victims of the Tokyo subway sarin attack, endotracheal intubation was not difficult. The Japanese medical literature describes the standard treatment for sarin toxicity as... 

The global standard for the treatment of sarin toxicity is the administration of (1) atropine, (2) an oxime agent like PAM, and (3) diazepam (Medical Letter, 2002). 

One piece of evidence supporting the efficacy of PAM in sarin toxicity has been the clinical benefit associated with PAM in toxicity due to organophosphorous agrochemicals. However, some experts now doubt whether such a benefit really exists. For example, Peter et al (2006), using meta-analytic techniques, reevaluated the effects of oxime therapy in organophosphate poisoning. Not only did they find no beneficial effects, they also reported possible... 

Based on the experience of Iranian physicians who treated sarin toxicity during the Iran-Iraq war (Newmark, 2004), PAM was not available on the front lines and atropine alone was used for treatment. The doses of atropine used were considerably higher than those used in the Tokyo subway sarin attack, or that are generally recommended in the USA (Medical Letter, 2002). The Iranian protocol called for initial administration of 4 mg intravenously. If no atropine effects (improvement in dyspnea or decrease in airway secretions) were seen after 1 to 2 min, 5 mg was then administered intravenously over 5 min while heart rate was monitored. A rise in heart rate of 20 to 30 beats per min was regarded as an atropine effect. In severe cases, 20 mg to 200 mg was given. Regardless of dose, the key to saving lives, in their opinion, was how soon the atropine was administered. 

The results of these studies suggest some long-term effects of sarin toxicity and careful follow-up and observation are indicated in these victims. 

According to inpatient records from St Luke s Hospital, the most common laboratory finding related to sarin toxicity was a decrease in plasma cholinesterase (ChE) levels in 74% of patients. In patients with more severe toxicity, plasma ChE levels tended to be lower, but a more accurate indication of ChE inhibition is measurement of erythrocyte ChE, as erythrocyte ChE (AChE) is considered true ChE and plasma ChE is pseudo ChE . However, erythrocyte ChE is not routinely measured, whereas plasma ChE is included in many clinical chemistry panels thus, it can be used as a simple index for ChE activity. In both the Matsumoto and Tokyo subway sarin attacks, plasma ChE served as a useful index of sarin exposure. In 92% of hospitalized patients, plasma ChE levels returned to normal on the following day. In addition, inpatient records from... 

This chapter has discussed sarin toxicity based on experiences of the attacks in Matsumoto and the Tokyo subway, and also the Iran-Iraq war. This section provides some conclusions drawn from the toxicological issues related to sarin. 

Nakajima, T., Ohta, S., Fukushima, Y., and Yanagisawa, N., Sequelae of sarin toxicity at one and three years after exposure in Matsumoto, Japan., J. Epidemiol., 9 337-43,1999. 

Well-known symptoms of sarin toxicity include miosis, hypersecretions, bradycardia, and fasciculations. However, the mechanism of organophosphate toxicity seems to involve conflicting actions. For example, mydriasis or miosis, and bradycardia or tachycardia may occur. Acute respiratory insufficiency is the most important cause of immediate death. Early symptoms include (i) tachypnea due to increased airway secretions and bronchospasm (a muscarinic effect), (ii) peripheral respiratory muscle paralysis (a nicotinic effect), and (iii) inhibition of respiratory centers (a CNS effect), all of which lead to severe respiratory deficiency. If left untreated at this stage, death will result. Cardiovascular symptoms may include hypertension or hypotension. Various arrhythmias can also occur, and caution is required when the QT interval is prolonged. In particular, if hypoxemia is present, fatal arrhythmias may occur with intravenous administration of atropine... 

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