Thiermann_2011_Toxicol.Lett_206_77

Although the importance of atropine in therapy of organophosphate (OP) poisoning is generally recognized, its dosing is a matter of debate. A retrospective analysis of atropine dosing was undertaken in 34 patients who had been enrolled in a clinical study assessing obidoxime effectiveness in OP-poisoning. All patients were severely intoxicated (suicidal attempts) and required artificial ventilation. Atropine was administered routinely by intensive care physicians for life-threatening muscarinic symptoms, with the recommendation to favor low dosage. The pharmacological active enantiomere S-hyoscyamine was determined by a radioreceptor assay. When RBC-AChE activity ranged between 10% and 30%, S-hyoscyamine plasma concentrations of approx. 5 nmol L(-)(1) were sufficient. This concentration could be maintained with about 0.005 mg h(-)(1) kg(-)(1) atropine. Only when RBC-AChE was completely inhibited, therapy of cholinergic crisis required atropine doses up to 0.06 mg h(-)(1) kg(-)(1). Elimination half-life of S-hyoscyamine was 1.5 h, showing occasionally a second slow elimination phase with t((1/2))=12 h. Malignant arrhythmias were observed in some 10% of our cases, which occurred late and often in the absence of relevant glandular cholinergic signs, when the S-hyoscyamine concentration was below 2.5 nmol L(-)(1). Arrhythmias mostly resolved on reinstitution of atropine.