title: Atropine maintenance dosage in patients with severe organophosphate pesticide poisoning.
abstract: 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(½)=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.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstr. 11, 80937 Munich, Germany. HorstThiermann@bundeswehr.org
authors.forename: Horst
authors.initials: H
authors.lastname: Thiermann
authors.forename: Dirk
authors.initials: D
authors.lastname: Steinritz
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
authors.forename: Maria
authors.initials: M
authors.lastname: Radtke
authors.forename: Peter
authors.initials: P
authors.lastname: Eyer
authors.forename: Florian
authors.initials: F
authors.lastname: Eyer
authors.forename: Norbert
authors.initials: N
authors.lastname: Felgenhauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Zilker
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000368:Aged; D019540:Area Under Curve; D001285:Atropine / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D062025:Organophosphate Poisoning; D010575:Pesticides / Q000506:poisoning*; D011041:Poisoning / Q000097:blood / Q000188:drug therapy; D012189:Retrospective Studies; D013237:Stereoisomerism; D013406:Suicide, Attempted; D016896:Treatment Outcome
chemical_list: D018727:Muscarinic Antagonists; D010575:Pesticides; D001285:Atropine; D000110:Acetylcholinesterase