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: Horst Thiermann, Dirk Steinritz, Franz Worek, Maria Radtke, Peter Eyer, Florian Eyer, Norbert Felgenhauer, Thomas Zilker
• Journal: Toxicology letters (Toxicol Lett) Vol. 206 Issue 1 Pg. 77-83 (Sep 25 2011) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 21771644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Muscarinic Antagonists
• Pesticides
• Atropine
• Acetylcholinesterase

Topics

• Acetylcholinesterase (blood, metabolism)
• Aged
• Area Under Curve
• Atropine (administration & dosage, blood, therapeutic use)
• Clinical Trials as Topic
• Dose-Response Relationship, Drug
• Erythrocytes (enzymology)
• Female
• Humans
• Male
• Middle Aged
• Muscarinic Antagonists (administration & dosage, blood, therapeutic use)
• Organophosphate Poisoning
• Pesticides (poisoning)
• Poisoning (blood, drug therapy)
• Retrospective Studies
• Stereoisomerism
• Suicide, Attempted
• Treatment Outcome