Atropine maintenance dosage in patients with severe organophosphate pesticide poisoning

Toxicol Lett. 2011 Sep 25;206(1):77-83. doi: 10.1016/j.toxlet.2011.07.006. Epub 2011 Jul 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Muscarinic Antagonists
  • Pesticides
  • Atropine
  • Acetylcholinesterase