Acute myocardial infarction associated with the serotonin syndrome.
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Adult↗
Biomedical subjects
Steven B Bird
Publications and source records attributed to Steven B Bird.
Multiple centrally acting antidotes protect against severe organophosphate toxicity.
BACKGROUND: Accumulation of acetylcholine in the central nervous system is believed to account for the rapid lethality of organophosphate pesticides and chemical nerve agents. Diazepam is known to supplement atropine therapy, but its specific mechanism of action is uncertain. OBJECTIVES: To test four centrally acting agents for early antidotal efficacy in severe dichlorvos poisoning in the murine model. METHODS: The up-and-down method was used to dose four candidate antidotes: diazepam, xylazine, morphine, and ketamine. Antidotes were administered subcutaneously to unsedated adult Sprague-Dawley rats who were pretreated with 3 mg/kg intraperitoneal glycopyrrolate. All animals received 20 mg/kg of dichlorvos subcutaneously 5 minutes later. A blinded observer adjudicated the outcomes of 10-minute mortality and survival time. RESULTS: All animals pretreated with either no antidote (8/8 deaths) or glycopyrrolate alone (8/8) died within 10 minutes of dichlorvos injection. Pretreatment with diazepam (3/9 deaths), or xylazine (3/9), decreased lethality substantially (Fisher p = 0.007; median effective doses, 0.12 mg/kg and 3.0 mg/kg, respectively). Intermediate doses of morphine (3.1 to 5.5 mg/kg) resulted in survival, but higher doses did not, presumably because of excessive respiratory depression (7/11 deaths; p = 0.09). Ketamine (7/8 deaths) was ineffective as an antidote. Survival times also were prolonged in the diazepam and xylazine groups (log-rank p < 0.001) and, to a lesser degree, the morphine group (p = 0.07). CONCLUSIONS: Doses of diazepam, xylazine, and morphine below those used for deep sedation protect against severe dichlorvos poisoning, implying that several distinct central mechanisms are each sufficient to avert lethality. These findings suggest new possibilities for prophylaxis or therapy.
Animals↗
House officer procedure documentation using a Personal Digital Assistant: a longitudinal study.
BACKGROUND: Personal Digital Assistants (PDAs) have been integrated into daily practice for many emergency physicians and house officers. Few objective data exist that quantify the effect of PDAs on documentation. The objective of this study was to determine whether use of a PDA would improve emergency medicine house officer documentation of procedures and patient resuscitations. METHODS: Twelve first-year Emergency Medicine (EM) residents were provided a Palm V (Palm, Inc., Santa Clara, California, USA) PDA. A customizable patient procedure and encounter program was constructed and loaded into each PDA. Residents were instructed to enter information on patients who had any of 20 procedures performed, were deemed clinically unstable, or on whom follow-up was obtained. These data were downloaded to the residency coordinator's desktop computer on a weekly basis for 36 months. The mean number of procedures and encounters performed per resident over a three year period were then compared with those of 12 historical controls from a previous residency class that had recorded the same information using a handwritten card system for 36 months. Means of both groups were compared a two-tailed Student's t test with a Bonferroni correction for multiple comparisons. One hundred randomly selected entries from both the PDA and handwritten groups were reviewed for completeness. Another group of 11 residents who had used both handwritten and PDA procedure logs for one year each were asked to complete a questionnaire regarding their satisfaction with the PDA system. RESULTS: Mean documentation of three procedures significantly increased in the PDA vs handwritten groups: conscious sedation 24.0 vs 0.03 (p = 0.001); thoracentesis 3.0 vs 0.0 (p = 0.001); and ED ultrasound 24.5 vs. 0.0 (p = 0.001). In the handwritten cohort, only the number of cardioversions/defibrillations (26.5 vs 11.5) was statistically increased (p = 0.001). Of the PDA entries, 100% were entered completely, compared to only 91% of the handwritten group, including 4% that were illegible. 10 of 11 questioned residents preferred the PDA procedure log to a handwritten log (mean +/- SD Likert-scale score of 1.6 +/- 0.9). CONCLUSION: Overall use of a PDA did not significantly change EM resident procedure or patient resuscitation documentation when used over a three-year period. Statistically significant differences between the handwritten and PDA groups likely represent alterations in the standard of ED care over time. Residents overwhelmingly preferred the PDA procedure log to a handwritten log and more entries are complete using the PDA. These favorable comparisons and the numerous other uses of PDAs may make them an attractive alternative for resident documentation.
Computers, Handheld↗
Levofloxacin-related seizure activity in a patient with Alzheimer's disease: assessment of potential risk factors.
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Aged↗
Gamma-hydroxybutyrate use in older adults.
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Age Factors↗
Monoamine oxidase inhibitor poisoning resulting from Internet misinformation on illicit substances.
The Internet may represent a new mechanism by which adolescents initiate the use of illicit substances. The existence of multiple partisan websites providing misinformation regarding the safety of these substances may lead to an increase in unsafe behavior among this age group. Adverse outcomes related to Internet-based drug information are rarely identified. We report a case of an adolescent whose use of the Internet to obtain drug information led to severe poisoning from the combination of a monoamine oxidase inhibitor, harmaline, and a hallucinogenic tryptamine, 5-methoxydimethyltryptamine (5-MeO-DMT).
Adolescent↗
Diazepam inhibits organophosphate-induced central respiratory depression.
OBJECTIVES: Current evidence suggests that mortality from acute organophosphate (OP) poisoning is partially mediated through central nervous system (CNS) respiratory center depression (CRD). However, the exact mechanism of OP-induced CRD is unknown. In these studies, the authors investigated the hypothesis that OP-induced CRD is the result of overstimulation of CNS respiratory centers. METHODS: Wistar rats received prophylaxis with either normal saline (controls), atropine, the peripherally acting anticholinergics glycopyrrolate (GLYC), ipratropium bromide (IB), or the CNS respiratory center attenuator diazepam. To determine if a dual CNS/peripheral cholinergic mechanism is responsible for animal death, two additional groups received combination treatment with diazepam plus either IB or GLYC. All treatments were completed 5 minutes before OP with subcutaneous dichlorvos. Differences in 10-minute and 24-hour mortality were assessed by the Fisher exact test. RESULTS: Dichlorvos poisoning resulted in profound fasciculations without obvious seizure in all cohorts. In controls and animals treated with peripherally acting anticholinergics, fasciculations were followed by sedation and respiratory arrest (0% 10-minute survival in all cohorts). In contrast, pretreatment with either atropine or diazepam significantly improved 10-minute survival (100% and 44%, respectively). Although GLYC or IB afforded no protection when given alone, when delivered in conjunction with diazepam, the combination significantly improved survival (both groups 88% at 24 hours), suggesting a dual CNS/pulmonary muscarinic mechanism of lethality. CONCLUSIONS: The central respiratory depressant diazepam paradoxically attenuates organophosphate-induced respiratory depression, and when combined with peripherally acting anticholinergic agents, reduces mortality in a rat model of severe acute OP poisoning.
Animals↗
Early death due to severe organophosphate poisoning is a centrally mediated process.
OBJECTIVE: To distinguish whether early death from severe organophosphate (OP) poisoning with dichlorvos is mediated through peripheral or central nervous system (CNS) actions. METHODS: Wistar rats (n = 72) were randomized to pretreatment with either: normal saline (controls), peripheral anticholinergics (glycopyrrolate [low, medium, or high dose] or nebulized ipratropium bromide), or CNS + peripherally acting anticholinergics (diphenhydramine, nebulized atropine, or injected atropine). All treatments were given prior to a subcutaneous injection of 25 mg/kg dichlorvos (n = 8 per group). Survival was assessed at 10 minutes (early death) and 24 hours (delayed death). Kaplan-Meier (95% confidence intervals [95% CIs]) and chi-squared analysis was then performed to determine differences between treatments. RESULTS: Regardless of treatment, all animals exhibited profound nicotinic effects (fasciculations) without obvious seizures within 2 minutes of poisoning. In rats pretreated with peripherally acting agents, the fasciculations were rapidly followed by reduced motor activity, sedation, and death. Mortality at 10 minutes for saline controls, glycopyrrolate, and ipratropium was 88%, 96%, and 100%, respectively. The single control animal surviving beyond 10 minutes went on to develop peripheral cholinergic manifestations, including hypersalivation, urination, and defecation. Only one of 24 animals treated with injected atropine, nebulized atropine, or diphenhydramine died during the early phase of poisoning; all others survived to 24 hours (p < 0.01). CONCLUSIONS: Death in acute, severe OP poisoning is prevented by pretreatment with anticholinergic agents that cross the blood-brain barrier, but not by agents with only peripheral actions. Early death due to OP poisoning appears to be a centrally mediated process.
Animals↗
Diphenhydramine as a protective agent in a rat model of acute, lethal organophosphate poisoning.
OBJECTIVE: To evaluate the effects of diphenhydramine chloride (DPH) on mortality in a rat model of acute, severe organophosphate poisoning (OP). METHODS: Wistar rats (n = 40) were randomized to pretreatment with either normal saline (controls), 5 mg/kg atropine, 3 mg/kg DPH, 15 mg/kg DPH, or 30 mg/kg DPH given as a single intramuscular injection 5 minutes prior to a subcutaneous injection of 25 mg/kg dichlorvos (n = 8 per group). The primary endpoint was 10-minute survival. Survival at 24 hours was a secondary endpoint. Comparison of survival rates between groups was carried out by ANOVA and the Student-Newman-Keuls test. RESULTS: Dichlorvos exposure resulted in profound fasciculations within 2 minutes of injection in all cohorts. In controls, fasciculations were followed by respiratory arrest within 10 minutes (0% survival). The rats receiving atropine pre-treatment exhibited similar fasciculations (nicotinic effects) without subsequent respiratory arrest, resulting in a significant improvement in survival (88%, p < 0.001). The DPH-treated rats exhibited a significant dose-dependent reduction in mortality, with the 3 mg/kg, 15 mg/kg, and 30 mg/kg groups demonstrating 0%, 25%, and 100% survival, respectively. There was no additional mortality between 10 minutes and 24 hours in any group. There was no significant difference in survival between the high-dose DPH and the atropine groups. CONCLUSIONS: Diphenhydramine chloride significantly reduced mortality in rats with acute, severe dichlorvos exposure.
Animals↗