Dose-Dependent Response to Cyclodextrin Infusion in a Rat Model of Verapamil Toxicity

Introduction: Sulfobutylether-b-cyclodextrin (SBE-CD) is a pharmaceutical excipient known to bind verapamil. Following intravenous administration, clearance of SBE-CD approximates glomerular filtration rate. We hypothesized that infusion of SBE-CD would increase time to asystole in a rat model of verapamil toxicity in a dose-dependent manner. The objective was to demonstrate the effect of a range of SBE-CD concentrations in a rat model of verapamil toxicity. Methods: Twenty-five Wistar rats were allocated to control or 1 of 4 intervention groups. All received ketamine and diazepam anesthesia followed by verapamil infusion 32 mg/kg/h. The verapamil infusion for the intervention groups was premixed with SBE-CD in a 1:1, 1:2, 1:4, or 1:8 molar ratio (verapamil to SBE-CD). The control group infusion did not contain SBE-CD. Additional saline or water was added to the infusion so that the total volume infused was the same across groups, and the osmolality was maintained as close to physiologic as possible. Heart rate, respiratory rate, and temperature were monitored. The primary endpoint was time to asystole.Results: Verapamil coinfused with SBE-CD in a molar ratio of 1:4 resulted in prolonged time to asystole compared to control (21.2 minutes vs 17.6 minutes, P , 0.05). There were no differences in time to asystole between control and any other intervention group. There was no significant difference in time to apnea between control and any intervention group. We assessed the effect of a range of SBE-CD concentrations and identified 1 concentration that prolonged time to asystole. Mechanismsthat may explain this effect include optimal volume expansion with a hyperosmolar cyclodextrin containing solution, complexation of verapamil within the hydrophobic cyclodextrin pore, and/or complexation within micelle-like aggregates of cyclodextrin. However, mechanistic explanations for the observed findings are speculative at this point. Conclusion: The 1:4 verapamil to SBE-CD concentration was modestly effective with SBE-CD concentrations above and below this range demonstrating nonstatistically significant improvements in time to asystole. [West J Emerg Med. 2012;13(1):63–67.

Dose Dependent Response to Cyclodextrin Infusion in a Rat Model of Verapamil Toxicity

Introduction: Sulfobutylether-b-cyclodextrin (SBE-CD) is a pharmaceutical excipient known to bind verapamil. Following intravenous administration, clearance of SBE-CD approximates glomerular filtration rate. We hypothesized that infusion of SBE-CD would increase time to asystole in a rat model of verapamil toxicity in a dose-dependent manner. The objective was to demonstrate the effect of a range of SBE-CD concentrations in a rat model of verapamil toxicity. Methods: Twenty-five Wistar rats were allocated to control or 1 of 4 intervention groups. All received ketamine and diazepam anesthesia followed by verapamil infusion 32 mg/kg/h. The verapamil infusion for the intervention groups was premixed with SBE-CD in a 1:1, 1:2, 1:4, or 1:8 molar ratio (verapamil to SBE-CD). The control group infusion did not contain SBE-CD. Additional saline or water was added to the infusion so that the total volume infused was the same across groups, and the osmolality was maintained as close to physiologic as possible. Heart rate, respiratory rate, and temperature were monitored. The primary endpoint was time to asystole.Results: Verapamil coinfused with SBE-CD in a molar ratio of 1:4 resulted in prolonged time to asystole compared to control (21.2 minutes vs 17.6 minutes, P , 0.05). There were no differences in time to asystole between control and any other intervention group. There was no significant difference in time to apnea between control and any intervention group. We assessed the effect of a range of SBE-CD concentrations and identified 1 concentration that prolonged time to asystole. Mechanismsthat may explain this effect include optimal volume expansion with a hyperosmolar cyclodextrin containing solution, complexation of verapamil within the hydrophobic cyclodextrin pore, and/or complexation within micelle-like aggregates of cyclodextrin. However, mechanistic explanations for the observed findings are speculative at this point. Conclusion: The 1:4 verapamil to SBE-CD concentration was modestly effective with SBE-CD concentrations above and below this range demonstrating nonstatistically significant improvements in time to asystole. [West J Emerg Med. 2012;13(1):63–67.

Take-home naloxone program implementation: lessons learned from seven Chicago-area hospitals

Despite consensus recommendations from the American College of Emergency Physicians (ACEP), the Centers for Disease Control and Prevention, and the surgeon general to dispense naloxone to discharged ED patients at risk for opioid overdose, there remain numerous logistic, financial, and administrative barriers to implementing take-home naloxone programs at individual hospitals. This article describes the recent collective experience of 7 Chicago-area hospitals in implementing take-home naloxone programs. We highlight key barriers, such as hesitancy from hospital administrators, lack of familiarity with relevant rules and regulations in regard to medication dispensing, and inability to secure a supply of naloxone for dispensing. We also highlight common facilitators of success, such as early identification of a C-suite champion and the formation of a multidisciplinary team of program leaders. Finally, we provide recommendations that will assist emergency departments planning to implement their own take-home naloxone programs and will inform policymakers of specific needs that may facilitate dissemination of naloxone to the public