This study provides further evidence of both the safety and efficacy of physostigmine in the treatment of antimuscarinic delirium.

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Purpose The presence of two or more Lisch nodules (melanocytic hamartomas of the iris) is one of seven diagnostic criteria for neurofibromatosis type 1 (NF1), a common monogenic disorder of dysregulated neurocutaneous growth. We investigated the hypothesis that Lisch nodules arise secondary to ultraviolet (UV) radiation exposure from sunlight. Methods We mapped and quantified Lisch nodule burden in the irides of 77 adults with NF1. We also inventoried lifetime sunlight (UV radiation) exposure, determined NF1 neurocutaneous severity, and selectively genotyped two NF1 mutations predictive of severity. Results There was high inter-individual variability in Lisch nodule burden. Lisch nodules were primarily located in the inferior hemifield (half) of the iris, regardless of its color (P = 3.0 × 10−20). Light irides harbored significantly more Lisch nodules than dark irides (P = 4.8 × 10−5). There was no statistically significant correlation of Lisch nodule burden to lifetime sunlight exposure “dose” or NF1 neurocutaneous severity. Conclusions The difference in Lisch nodule burden between the superior and inferior iris hemifields is likely due to the sunlight-shielding effects on the superior half by peri-ocular structures. The difference in Lisch nodule burden between light and dark irides is likely due to the photo-protective effects of pigmentation. The genes underlying the control of iris color may thus be viewed as modifiers of severity of Lisch nodule burden in NF1. Given the role of UV radiation and, presumably, DNA damage in Lisch nodule pathogenesis, “benign tumor of the iris,” not “hamartoma,” may be a better descriptor.

Background: Antimuscarinic delirium is associated with significant morbidity, and its management requires substantial resource allocation, including intubation, restraint, and intensive care unit (ICU) placement. There is controversy over the management of these patients. Physostigmine can rapidly reverse antimuscarinic delirium but has been associated with adverse effects. Objective: This study aims to assess the effect of physostigmine use on resource allocation and adverse events. Methods: This is a retrospective chart review of patients with an antimuscarinic toxidrome at a single hospital approved by the local institutional review board. A blinded abstractor recorded data from patient charts. Whether the patient was given physostigmine, intubated, restrained, or admitting to critical care was recorded. We recorded instances of seizure, vomiting, or bradycardia. The primary aim was to compare frequency of intubation as a function of physostigmine administration. Results: A total of 141 patients were identified. We found no difference between the groups in age, gender, or initial heart rate; 65 (46%) were given physostigmine, 45 (32%) were admitted to the ICU, and 29 (20%) were intubated. Patients who received physostigmine in the first 24 hours were less likely to be intubated and less likely to be admitted to an ICU. The instance of bradycardia (n = 16), vomiting (n = 27), and seizures (n = 7) was limited, and there were no significant differences between the groups. There were no associations noted between physostigmine administration and adverse effects. Conclusion and Relevance: This study demonstrated that physostigmine use is associated with decreased resource utilization (including intubation and ICU placement) without increasing rates of bradycardia, vomiting, or seizures.

Introduction Toxicity related to calcium-channel blockers remains a significant cause of morbidity and mortality. Amlodipineinduced shock is unique in that its mechanism of action is thought to occur in part via the release of nitric oxide (NO) in the peripheral vasculature. Specific therapeutic interventions, including methylene blue (an NO scavenger), have been suggested, but efficacy studies are severely limited. To facilitate a larger porcine study into the effect of various interventions on amlodipine toxicity, we undertook this model development and feasibility study. Methods Intravenous amlodipine was prepared by dissolving commercially obtained amlodipine tablets in dimethylsulfoxide. The concentration of the drug was verified using ultraviolet spectroscopy. We administered this solution to three animals in order to determine a toxic dose, capable of facilitating a two-arm study of amlodipine toxicity. ResultsThe first pig died rapidly after the bolus infusion. The second pig developed mild toxicity, but the dissolution of the plastic tubing by the solvent and subsequent leakage limited the interpretability of the result. The third animal developed expected toxicity with an infusion rate between 2.0 and 5.5 mg/kg/h. Conclusion This study demonstrates a potentially repeatable model of amlodipine-induced toxic shock using intravenous administration of amlodipine and several methodological considerations for researchers undertaking similar work.