Use of a Physostigmine Continuous Infusion for the Treatment of Severe and Recurrent Antimuscarinic Toxicity in a Mixed Drug Overdose

Abstract

Introduction Physostigmine was once a widely used antidote for the treatment of antimuscarinic toxicity. However, reports describing the association of physostigmine with asystole and seizures in severe tricyclic antidepressant poisoning resulted in a decrease in use. Recent literature has demonstrated that physostigmine is a safe and effective antidote for the treatment of antimuscarinic toxicity. There are only two previously published articles regarding the use of physostigmine administered as a continuous intravenous infusion for persistent antimuscarinic toxicity. We present a case of physostigmine continuous infusion for the treatment of antimuscarinic symptoms in a polydrug overdose due to the ingestion of diphenhydramine along with bupropion, citalopram, acetaminophen, and naproxen. Case Presentation A 13-year-old female presented with hyperthermia, myoclonus and rigidity, hallucinations, severe agitation, and antimuscarinic toxicity including inability to sweat after a polydrug overdose. Several doses of lorazepam were administered followed by physostigmine which produced resolution of hallucinations and attenuation of the antimuscarinic symptoms including perspiration, temperature improvement, and decreased agitation. After periods of improvement and recurrence of antimuscarinic effects, a continuous infusion of physostigmine was administered at 2 mg/h and continued for almost 8 h to maintain attenuation of symptoms. GABAergic agents including lorazepam and phenobarbital were used later in the hospital course for presumed symptoms of serotonergic and adrenergic toxicity after resolution of antimuscarinic effects. The patient did not experience any adverse effects of physostigmine administration. Discussion Physostigmine administered as a continuous infusion may be a reasonable treatment option for severe and recurrent symptoms related to antimuscarinic toxicity.

Focus on Over-the-Counter Drugs' Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants

“…Overdose of promethazine is associated with an antimuscarinic delirium, agitation, and neuroleptic malignant syndrome (100, 102,104,133). Scott et al (104) recorded a promethazineinduced delirium treated with physostigmine intravenously, which reversed both central and peripheral anticholinergic effects, similarly to a polydrug overdose due to the ingestion of DPH (94). Chlorpheniramine is used as a cheap sleep aid and/or as an anxiolytic due to its antimuscarinic properties; its abuse has been related to pleasurable feelings, which reinforces the repetitive use and the possibility of developing drug dependence (Table 1).…”

“…DPH misuse was reported in 12 articles, including 10 case reports (17,(89)(90)(91)(92)(93)(94)(95)(96)(97); the remaining two included, respectively, a case series (98) and a retrospective review study (99) (Supplementary Table 1). Apart from the retrospective review study focusing on all Mandrax R (DPH + Methaqualone) abuse cases (n = 67, male) retrieved from the United States (US) Army during January-June 1972, users were here mostly represented by female (F/M, 9/6).…”

“…Apart from the retrospective review study focusing on all Mandrax R (DPH + Methaqualone) abuse cases (n = 67, male) retrieved from the United States (US) Army during January-June 1972, users were here mostly represented by female (F/M, 9/6). A high number of users were adolescents, aged between 13 and 18 years (17,94,(96)(97)(98). Reported psychiatric comorbidities mostly included SUD (17,(89)(90)(91)(92)95), schizophrenia/psychotic symptoms (89,91,92), and mood disorders (17,90,91).…”

“…Continued polydrug overdose (e.g., DH together with bupropion, citalopram, acetaminophen, omeprazole, and naproxen) was recorded(94). DPH recreational use was associated with relaxation, calmness, and sleep improvement(90,92,96,98,99).…”

The Role of Dexmedetomidine in Pediatric Patients Presenting with an Anticholinergic Toxidrome

“…In the latest report by National Poison Data Systems, there are more than 40,000 exposures to antihistamines in children with exposures growing by over 1,000 every year over the last ten years. In 2018, antihistamines were found to be the second most common cause of pharmaceutical death in ages [13][14][15][16][17][18][19]. This is in addition to other medications that cause anticholinergic presentations such as antipsychotics and nonpharmaceutical exposures [1].…”