Do medical toxicologists use physostigmine to treat anticholinergic toxidrome?

February 18, 2015, 2:28 pm

physostigmine★★½☆☆

The Use of Physostigmine by Toxicologists in Anticholinergic Toxicity. Watkins JW et al. J Med Toxicol 2014 Dec 16 [Epub ahead of print]

Abstract

Physostigmine is a carbamate that reversibly inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine (ACh). By so doing, it increases the levels of ACh in synapses, serving as an antidote for drugs and agents causing anticholinergic syndrome. Unlike neostigmine, physostigmine crossed the blood-brain-barrier and has both peripheral and central effects.

Decades ago, physostigmine was routinely used with some frequency to treat overdose with many drugs having anticholinergic actions, including tricyclic antidepressants. Then in 1980, Pentel and Peterson reported 2 patients with seizures and prolonged QRS intervals (120 and 240 msec, respectively) who suffered asystolic arrest after receiving physostigmine. After this report, tricyclic toxicity was generally considered an absolute contraindication for using physostigmine and a cardiac conduction defect (AV block) was considered a relative contraindication. A review of the literature found scant support for these contraindications. However, because of the paper by Pentel and Peterson and the uncertainty surrounding the entire issue, many clinicians avoided use of physostigmine altogether.

The authors of this study retrospectively reviewed over 2 years of data from the Toxicology Investigators Consortium (ToxIC) registry to identify cases that presented with evidence of anticholinergic syndrome. The registry is a database with details reported from a number of institutions of cases cared for by practicing medical toxicologists. The main stated goal was to determine “the rate at which physostigmine was administered to these patients by toxicologists . . .”

The retrospective review identified 815 patients exhibiting anticholinergic toxidromes from January 2012 through March 2014. Among their findings:

  • 28.7% received benzodiazepines alone for treatment
  • 12.4% received physostigmine alone
  • 8.8%  received both physostigmine and benzodiazepine
  • 47.4% received no definitive treatment

The authors did further analysis, calculating odds ratios and confidence intervals, determining for example that patients receiving only physostigmine had a significantly lower rate of intubation compared with those in other treatment groups (1.9 v 8.4%, OR 0.21,CI 0.05 – 0.87.)

I have to say I’m highly skeptical of such statistics when applied willy-nilly to non-randomized patients extracted from clinical databases.Certainly such statistical analysis is easy to apply to such data, but what could it possibly mean.To say that 1.9% of patients treated with physostigmine alone, that’s 1.9% of what. We don’t know — and given the nature of these databases can’t know — exactly who these patients were, why they were intubated, or whether administering physostigmine preventing the rate of intubation from being higher.  the statistics really have no useful meaning. As the authors point out in their discussion of study limitations, association does not prove causation.

Incredibly, the authors analyzed the prevalence of intubation and rhabdomyolysis among the treatment groups, but say nothing about the endpoints of death or asystolic arrest. I would like to think that is because such outcomes did not occur, but the paper is not at all clear on this.

The authors conclude that “the data we currently have appear to support the use of physostigmine for the anticholinergic toxidrome.” Such use, in skilled hands, may very well be safe and effective, but what is presented in this paper does not support that contention at all.

Related posts:

Physostigmine for quetiapine overdose?

Quetiapine and delirium

 

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