Faculty Bibliography

The goal of emergency medicine is to improve health while preventing and treating disease and illness in patients seeking emergency medical care. Improvements in emergency medical care and the delivery of this care can be achieved through credible and meaningful research efforts. Improved delivery of emergency medical care through research requires careful planning and the wise use of limited resources. To achieve this goal, emergency medicine must provide appropriate training of young investigators and attract support for their work. Promotion of multidisciplinary research teams will help the specialty fulfill its goals. The result will be the improvement of emergency medical care which will benefit not only the patients emergency physicians serve but also, ultimately, the nation's health

BACKGROUND: Many authors currently recommend infusing the adult dose (1 g) of pralidoxime over a 15-30 minute period. When administered in this manner, computer simulations predict that plasma pralidoxime concentrations will fall below 4 mg/L as early as one and one half hours after administration. The objective of this study was to assess whether a loading dose followed by a continuous infusion would maintain therapeutic levels longer than the traditional short infusion regimen of pralidoxime if the same total dose was administered. METHODS: Utilizing a randomized, crossover design, healthy volunteers were administered either 16 mg/kg of pralidoxime intravenous over 30 minutes or 4 mg/kg of pralidoxime intravenous over 15 minutes followed by 3.2 mg/kg/h for 3.75 h (for a total dose of 16 mg/kg). Pralidoxime levels were obtained at 0, 10, 20, 30, 60, 120, 180, 240, 300, and 390 minutes and patients were observed for vital sign changes and adverse effects. RESULTS: Seven subjects completed both arms of the study. One subject's data were excluded from pharmacokinetic analysis due to aberrant plasma pralidoxime analysis. The loading dose followed by the continuous infusion maintained therapeutic levels for 257.3 +/- 50.5 minutes whereas the short infusion maintained therapeutic levels for 118.1 +/- 52.1 (p < 0.001). Adverse effects were encountered during the short infusion regimen which did not occur during the continuous infusion. Dizziness or blurred vision occurred in all subjects during the short infusion regimen. Additionally, statistically significant increases in diastolic blood pressure occurred during the short infusion regimen. CONCLUSIONS: The results of this study indicate that a loading dose followed by a continuous infusion of pralidoxime maintains therapeutic concentrations for a longer period of time than the currently recommended short infusion regimen in healthy volunteers

BACKGROUND: Cocaine is metabolized in part by plasma cholinesterase to form ecgonine methyl ester. Decreased plasma cholinesterase activity is associated with enhanced cocaine toxicity in both humans and animals. This study was designed to determine whether the administration of exogenous plasma cholinesterase is protective against cocaine toxicity. METHODS: Using a blinded protocol, female Swiss albino mice were randomized to receive an intraperitoneal injection of either 13.7 mg/kg of purified human plasma cholinesterase dissolved in phosphate buffered saline, or an equal volume of phosphate buffered saline as a control. One hour later, all animals received an intraperitoneal injection of either 100 or 125 mg/kg of cocaine, and the incidence of seizures and death was recorded. In a similar fashion, another group of animals was randomized to receive a human plasma cholinesterase dose of either 13.7 or 27.4 mg/kg, followed by 150 mg/kg of cocaine. RESULTS: Administration of 13.7 mg/kg of human plasma cholinesterase increased plasma cholinesterase activity by a mean of 63 +/- 13 fold, with a Tmax of 90 minutes and a Vd of 85 +/- 13 mL/kg. Cocaine's effects on seizures and death were attenuated by human plasma cholinesterase. A cocaine dose of 150 mg/kg represents an ED100 for seizures and an LD100. At this dose, lethality was reduced to 30% (p < 0.001) and seizures were reduced to 40% (p < 0.001) by administration of 27.4 mg/kg of human plasma cholinesterase. CONCLUSIONS: Pretreatment with purified human plasma cholinesterase protects mice against the convulsive and lethal effects of cocaine