Response: Physostigmine May Not Be the Only Option for Treating Anticholinergic Syndrome

We thank Moore PW et al. for their letter to the editor in response to our recent article [1, 2]. They described the use, dosing, effects, and adverse effects of physostigmine as one of the recommended treatments for anticholinergic toxidrome. In the consensus statement that they referenced, physostigmine has been given a class II recommendation for the treatment of moderate to severe peripheral and central anticholinergic symptoms [3]. In other words, it is reasonable to consider using it for anticholinergic toxicity and the benefits generally outweigh the risks. There have been no prospective, randomized controlled trials evaluating physostigmine for the treatment of anticholinergic toxidrome to grant it a class I, standard of care, recommendation. Physostigmine was discovered over 100 years ago, and its use as an antidote has been controversial for many of those years, largely because of concerns about its cholinergic side effects, as Moore PW et al. point out in their letter [2]. The adverse side effects include cardiac arrhythmias, seizures, and potential airway compromise (emesis and bronchorrhea in the setting of altered mental status) [4]. It has been suggested in review articles that physostigmine toxicity (especially in the case of cardiac arrhythmias and seizures) is related to the speed of administration and total dose given [4, 5]. Furthermore, there are concerns for increased risk of cardiac toxicity in patients with ingestions of tricyclic antidepressants or underlying conduction disorders [4, 6]. Physostigmine certainly has a long history of use for the treatment of anticholinergic toxidromes, but it is not a history without adverse events, leading to general hesitancy to use it [4]. Unfortunately, unfamiliarity with the drug and especially the details of its administration are exactly the combination that can precipitate the adverse outcomes related to physostigmine toxicity. In the setting of mild to moderate anticholinergic toxicity, as presented in our original case report, the goal of therapy is to reduce a patient’s tachycardia, hypertension, agitation, and delirium. Historically, physostigmine and benzodiazepines have been the treatments of choice. Dexmedetomidine is a newer drug that provides sedation and reduces heart rate and blood pressure, which is exactly the therapeutic profile desired for these patients. Moreover, dexmedetomidine has a very safe side-effect profile and is easily titrated, with a short half-life, and is now widely used in critical care settings. In other words, it is potentially safer and more familiar (in the ICU setting) than physostigmine. With regard to cost, dexmedetomidine is more expensive, as Moore PW et al. state [2]. However, depending on the patient’s weight, and the number of recurrent doses of hourly physostigmine (as Moore PW et al. recommend), the cost difference between the two drugs may not be as much as proposed. In the setting of an intensive care unit admission, the total cost of therapy from either drug would be a small fraction of the inpatient expense. Finally, with fewer possible adverse effects from dexmedetomidine versus physostigmine, there is the potential for reduced overall cost of the admission due to medication effects and negative outcomes. Further studies would be needed to more fully investigate the cost differences of the two medications. The purpose of our article was to suggest that dexmedetomidine is worth considering for further studies as a treatment option for mild to moderate anticholinergic toxicity based on its pharmacologic profile, growing body of literature for the treatment of alcohol withdrawal syndrome, and our own experience with the medication [1].