maximum 10 mg) and atropine (0.0143 mg/ kg, maximum 1 mg) (Feldt-Rasmussen et al., 1985). A maximum decrease of 27 ± 5 percent in ChE was observed 5 minutes after injection, but no decrease in FEV1 was observed during 90 minutes of follow-up. The study demonstrated that the muscarinic effects of PB are completely blocked by atropine.

Gouge and colleagues (1994) reported on pulmonary function changes following PB administration among soldiers during the Gulf War. Ten asthmatics and six healthy normal soldiers received 30 mg PB orally and had a vital capacity measurement and lung exam every 2 hours for 8 hours. No consistent change in VC was observed, but seven of the ten asthmatics reported increased chest tightness 2–6 hours after PB. No respiratory symptoms were reported by the normal controls or by any of the 264 other members of the unit who received a 30-mg PB dose. There was no measurement of airflow obstruction in this clinical study, and the reported symptoms cannot be interpreted. The study was not blinded or controlled (with a placebo), symptoms may have been due to other etiologies (e.g., stress), and may not have been correlated with airflow obstruction.

In summary, there are few studies in normal subjects on the respiratory effects of PB. Respiratory function is of interest because the muscarinic effects of PB overdosage include increased bronchial secretions and possibly smooth muscle contraction, which can increase airflow obstruction. Nicotinic side effects include muscular weakness, which can also impair respiratory function. However, as noted above, the existing clinical studies suggest that mild increases in airflow obstruction may occur within 1–2 hours of PB administration, but the effects are subclinical and rapidly reversible.

Thermoregulation in Healthy Volunteers

Seidman and Epstein (1989) published a review of the existing literature on the thermoregulatory effects of anticholinesterase agents in 1989 (the earliest of the six reviewed studies). Case studies of acute organophosphate poisoning in humans are noteworthy for the frequent finding of severe hyperthermia, which often occurred late (more than 24 hours after initial presentation) and lasted for several days in patients surviving the initial toxicities (reviewed in Seidman and Epstein, 1989). Less commonly, OP-poisoned individuals presented with hypothermia, probably due to a combination of effects including hypothalamic dysregulation, excessive sweating, and muscle paralysis leading to obliteration of the shivering response.

In an investigation of heat stress and PB effects on thermoregulatory indices, eight heat-acclimated healthy young men were subjected to repeated bouts of exercise in a hot–humid environment after receiving four oral doses of either PB or placebo in a double-blind crossover fashion (Seidman and Epstein, 1989). No significant effects of PB could be demonstrated on physiological parameters, including final rectal temperature, amount of heat stored in the body, dry heat exchange, sweat excretion, and sweat efficiency.



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