The 2021 Core Content of Medical Toxicology.

The Medical Toxicology Subboard approved modifications to the Core Content of Medical Toxicology in March 2021. The document outlines the areas of knowledge considered essential for the practice of medical toxicology. The Core Content provides the organizational framework for the development of the Medical Toxicology Certification and Cognitive Expertise Examinations and serves as a template for the development of curricula for medical toxicology fellowship training programs.

Low rates of thiamine prescribing in adult patients with alcohol-related diagnoses in the emergency department.

Background: Alcohol use disorder (AUD) is associated with thiamine deficiency and Wernicke-Korsakoff Syndrome (WKS). Thiamine supplementation for the prevention of WKS in patients with suspected AUD in the Emergency Department (ED) is generally recommended. As alcohol-related diagnoses are frequent reasons for visits to EDs, ED thiamine prescribing practices are relevant to the overall management and prevention of WKS in patients with AUD.Objective: To determine the prescription rates of thiamine to patients with alcohol-related diagnoses in the ED.Methods: This was a retrospective chart review conducted at two New York City urban teaching hospitals from January 1 to December 31, 2017. All patients 18 years or older who were given an alcohol-related diagnosis (all F10 ICD-10-CM codes) upon disposition were included. Collected data included details of thiamine prescribing practices, patient demographics and patient disposition.Results: A total of 7,529 patient visits with an alcohol-related diagnosis were identified. The overall median age of included patients was 44; 5747 (76.3%) patient visits were by men; 310 (4.1%) patient visits resulted in admission. Out of all patient visits, thiamine was ordered during 167 (2.2%) visits, with thiamine administered parenterally during 129 (77.2%) visits and orally in 38 (22.8%) visits. Out of patient visits specifically associated with an F10.2 (Alcohol Dependence) diagnosis, thiamine was ordered during 105 (17.8%) visits.Conclusion: We found a very low rate of thiamine prescribing during patient visits associated with alcohol-related diagnoses. This may be a missed opportunity to reduce morbidity and mortality among AUD ED patients.

A Rare Case of Mad Honey Disease: A Reversible Cause of Complete Heart Block.

This case describes a patient with hypotension, bradycardia, and third-degree atrioventricular block following ingestion of a grayanotoxin-containing Pieris species, or lily of the valley bush. Although unlikely in metropolitan environments, physicians should be aware of the possibility of grayanotoxin ingestion when confronted with new-onset heart block even in nonendemic areas. (Level of Difficulty: Beginner.).

Mobile Technology to Increase HIV/HCV Testing and Overdose Prevention/Response among People Who Inject Drugs.

The United States faces dramatically increasing rates of opioid overdose deaths, as well as persistent ongoing problems of undiagnosed HIV and HCV infection. These problems commonly occur together in substance using populations that have limited, if any, access to primary care and other routine health services. To collectively address all three issues, we developed the Mobile Intervention Kit (MIK), a tablet computer-based intervention designed to provide overdose prevention and response training and to facilitate HIV/HCV testing in community settings. Intervention content was produced in collaboration with experienced street outreach workers who appear onscreen in a series of educational videos. A preliminary pilot test of the MIK in a Bronx, NY street outreach syringe exchange program found the MIK is feasible and highly acceptable to a population of people who inject drugs. Participants accepted HIV and HCV testing post-intervention, as well as naloxone training to reverse overdose events. Pre-post tests also showed significant increases in knowledge of overdose prevention, HIV testing procedures, and asymptomatic HCV infection. Future iterations of the MIK can be optimized for use in community as well as clinical settings nationwide, and perhaps globally, with a focus on underserved urban populations.

Staff Perspectives on a Tablet-Based Intervention to Increase HIV Testing in a High Volume, Urban Emergency Department.

Emergency departments (EDs) frequently serve people who have limited, if any, additional interactions with health care, yet many ED patients are not offered HIV testing, and those who are frequently decline. ED staff (n = 13) at a high volume urban ED (technicians, nurses, physicians, and administrators) were interviewed to elicit their perspectives on the feasibility and acceptability of a tablet-based intervention designed to increase HIV test rates among patients who initially decline testing. Content-based thematic analysis of semi-structured interviews indicated overall support for interventions to increase HIV testing, but a lack of available staff resources emerged as a potential barrier to widespread implementation. Also, some ED staff questioned whether it was appropriate to shift responsibility for public health services, such as HIV testing, to the ED instead of a primary care setting. Although tablet-based interventions have been shown effective in high volume ED settings and can potentially increase HIV test rates among hard-to-reach populations, additional effort is now required to better integrate this type of intervention into existing workflows.

Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning.

BACKGROUND: Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning. METHODS: Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method. RESULTS: For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid® 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence. CONCLUSION: Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.

Feasibility of a Computer-Based Intervention Addressing Barriers to HIV Testing Among Young Patients Who Decline Tests at Triage.

Young people face greatly increased human immunodeficiency virus (HIV) risk and high rates of undiagnosed HIV, yet are unlikely to test. Many also have limited or inconsistent access to health care, including HIV testing and prevention education, and prior research has documented that youth lack knowledge necessary to understand the HIV test process and to interpret test results. Computer-based interventions have been used to increase HIV test rates and knowledge among emergency department (ED) patients, including those who decline tests offered at triage. However, patients aged 18-24 years have been less likely to test, even after completing an intervention, compared to older patients in the same ED setting. The current pilot study sought to examine the feasibility and acceptability of a new tablet-based video intervention designed to address established barriers to testing among ED patients aged 18-24 years. In particular, we examined whether young ED patients would: agree to receive the intervention; complete it quickly enough to avoid disrupting clinical workflows; accept HIV tests offered by the intervention; demonstrate increased postintervention knowledge; and report they found the intervention acceptable. Over 4 weeks, we recruited 100 patients aged 18-24 in a high-volume urban ED; all of them declined HIV tests offered at triage. Almost all (98%) completed the intervention (mean time <9 mins), 30% accepted HIV tests offered by the tablets. Knowledge was significantly higher after than before the intervention (t = -6.67, p < .001) and patients reported generally high acceptability. Additional research appears warranted to increase postintervention HIV testing.

MOBILE SCREENING TO IDENTIFY AND FOLLOW-UP WITH HIGH RISK, HIV NEGATIVE YOUTH.

BACKGROUND: HIV prevalence remains disproportionately high among youth, especially among young men who have sex with men, young people with substance use disorders, and recently incarcerated youth. However, youth may not report behavioral risks because they fear stigma or legal consequences. While routine HIV screening programs have increased testing, current programs are not designed to identify, or provide prevention services to, high-risk patients who test HIV negative. AIMS: To examine the feasibility and preliminary efficacy of: a tablet-based screening designed to facilitate HIV risk reporting and testing among a sample of young urban emergency department (ED) patients; and a text message-based follow up protocol for patients who test HIV-negative and report increased behavioral risk. METHODS: 100 ED patients aged 18 - 24, who declined HIV tests offered at triage, completed a tablet-based intervention that included a risk screening, an educational video, and offered participants HIV tests. If patients accepted testing and reported increased risk, the tablets offered follow-up text messages. RESULTS: 30 participants accepted HIV tests following the intervention and 21 participants, identified by custom software as high-risk, agreed to receive text messages. Two thirds (66.7%) of text recipients responded to questions at week 6, more than half (57.1%) responded at week 8, one (4.76%) re-tested after week 12. CONCLUSION: Results indicate our intervention provides a feasible way to facilitate risk reporting, increase HIV testing, and maintain ongoing contact with hard-to-reach youth via tablet computers and text messages.

Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity.

BACKGROUND: Following national and regional recommendations, intravenous lipid emulsion (ILE) has become established in clinical practice as a treatment for acute local anesthetic (LA) toxicity, although evidence of efficacy is limited to animal studies and human case reports. A collaborative lipid emulsion workgroup was therefore established by the American Academy of Clinical Toxicology to review the evidence on the effect of ILE for LA toxicity. METHODS: We performed a systematic review of the literature published through 15 December 2014. Relevant articles were determined based on pre-defined inclusion and exclusion criteria. Pre-treatment experiments, pharmacokinetic studies not involving toxicity and studies that did not address antidotal use of ILE were excluded. RESULTS: We included 113 studies and reports. Of these, 76 were human and 38 animal studies. One publication included both a human case report and an animal study. Human studies included one randomized controlled crossover trial involving 16 healthy volunteers. The subclinical LA toxicity design did not show a difference in the effects of ILE versus saline. There was one case series and 73 case reports of ILE use in the context of toxicity (83 patients) including CNS depression or agitation (n = 45, 54%), seizures (n = 49, 59%), hypotension, hypertension, EKG changes, arrhythmias (n = 39, 47%), cardiac arrest (n = 18, 22%), cardiopulmonary resuscitation, and/or requirement for endotracheal intubation and/or mechanical ventilation (n = 35, 42%). There were 81 (98%) survivors including 63 (76%) with no reported sequelae from the LA poisoning or ILE, although the presence or absence of sequelae was not reported in 15 (18%) cases. Animal studies included 29 randomized controlled studies, three observational studies, five case series, and one case report; bupivacaine was used in 29 of these reports (76%). Of 14 controlled experiments in animals, eight showed improved survival or time to return of spontaneous circulation and five no benefit of ILE versus saline or non-ILE treatments. Combining ILE with epinephrine improved survival in five of the six controlled animal experiments that studied this intervention. The studies were heterogeneous in the formulations and doses of ILE used as well as the doses of LA. The body of the literature identified by this systematic review yielded only a very low quality of evidence. CONCLUSION: ILE appears to be effective for reversal of cardiovascular or neurological features in some cases of LA toxicity, but there is currently no convincing evidence showing that ILE is more effective than vasopressors or to indicate which treatment should be instituted as first line therapy in severe LA toxicity.

Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning.

Intravenous lipid emulsion (ILE) therapy is a novel treatment that was discovered in the last decade. Despite unclear understanding of its mechanisms of action, numerous and diverse publications attested to its clinical use. However, current evidence supporting its use is unclear and recommendations are inconsistent. To assist clinicians in decision-making, the American Academy of Clinical Toxicology created a workgroup composed of international experts from various clinical specialties, which includes representatives of major clinical toxicology associations. Rigorous methodology using the Appraisal of Guidelines for Research and Evaluation or AGREE II instrument was developed to provide a framework for the systematic reviews for this project and to formulate evidence-based recommendations on the use of ILE in poisoning. Systematic reviews on the efficacy of ILE in local anesthetic toxicity and non-local anesthetic poisonings as well as adverse effects of ILE are planned. A comprehensive review of lipid analytical interferences and a survey of ILE costs will be developed. The evidence will be appraised using the GRADE system. A thorough and transparent process for consensus statements will be performed to provide recommendations, using a modified Delphi method with two rounds of voting. This process will allow for the production of useful practice recommendations for this therapy.

Efficacy of methylene blue in an experimental model of calcium channel blocker-induced shock.

STUDY OBJECTIVE: Calcium channel blocker poisonings account for a substantial number of reported deaths from cardiovascular drugs. Although supportive care is the mainstay of treatment, experimental therapies such as high-dose insulin-euglycemia and lipid emulsion have been studied in animal models and used in humans. In the most severe cases, even aggressive care is inadequate and deaths occur. In both experimental models and clinical cases of vasodilatory shock, methylene blue improves hemodynamic measures. It acts as a nitric oxide scavenger and inhibits guanylate cyclase that is responsible for the production of cyclic guanosine monophosphate (cGMP). Excessive cGMP production is associated with refractory vasodilatory shock in sepsis and anaphylaxis. The aim of this study is to determine the efficacy of methylene blue in an animal model of amlodipine-induced shock. METHODS: Sprague-Dawley rats were anesthetized, ventilated, and instrumented for continuous blood pressure and pulse rate monitoring. The dose of amlodipine that produced death within 60 minutes was 17 mg/kg per hour (LD50). Rats were divided into 2 groups: amlodipine followed by methylene blue or amlodipine followed by normal saline solution, with 15 rats in each group. Rats received methylene blue at 2 mg/kg during 5 minutes or an equivalent amount of normal saline solution in 3 intervals from the start of the protocol: minutes 5, 30, and 60. The animals were observed for a total of 2 hours after the start of the protocol. Mortality risk and survival time were analyzed with Fisher's exact test and Kaplan-Meier survival analysis with the log rank test. RESULTS: Overall, 1 of 15 rats (7%) in the saline solution-treated group survived to 120 minutes compared with 5 of 15 (33%) in the methylene blue-treated group (difference -26%; 95% confidence interval [CI] -54% to 0.3%). The median survival time for the normal saline solution group was 42 minutes (95% CI 28.1 to 55.9 minutes); for the methylene blue group, 109 minutes (95% CI 93.9 to 124.1 minutes). Pulse rate and mean arterial pressure (MAP) differences between groups were analyzed until 60 minutes. Pulse rate was significantly higher in the methylene blue-treated group beginning 25 minutes after the start of the amlodipine infusion (95% CI 30 to 113 minutes) that was analyzed until 60 minutes. MAP was significantly higher in the methylene blue-treated group starting 25 minutes after the amlodipine infusion (95% CI 2 to 30 minutes) that was analyzed until 60 minutes. CONCLUSION: Methylene blue did not result in a significant difference in mortality risk. There was an increased pulse rate, MAP, and median survival time in the methylene blue group.

Computer-based video to increase HIV testing among emergency department patients who decline.

The Centers for Disease Control and Prevention recommend routine HIV screening in clinical settings, including emergency departments (EDs), because earlier diagnosis enables treatment before symptoms develop and delivery of interventions to reduce continued transmission. However, patients frequently decline testing. This study delivered a 16-min video-based intervention to 160 patients who declined HIV tests in a high volume, urban ED. One third of participants (n = 53) accepted an HIV test post-intervention. Interviews with a subset of participants (n = 40) show that before the video, many were unaware HIV testing could be conducted without drawing blood, or that results could be delivered in 20 min.

Patient perceptions of ultrasound educational scans in the emergency department.

BACKGROUND: Emergency medicine residents may perform bedside ultrasound (BUS) scans that are carried out solely for educational purposes. This may lead to confusion on the part of patients, as the implications in the context of their medical care may be unclear. STUDY OBJECTIVES: We hypothesized that a scripted introduction would improve understanding of the objectives and limitations of educational BUS. METHODS: A perceptual survey was completed by a prospectively enrolled convenience sample of patients in two emergency departments. In phase 1, fifty patients completed the survey after their educational BUS. During phase 2, sonographers were provided with a one-paragraph scripted introduction to use and 50 additional patients were recruited. Group data were analyzed using chi-squared tests, Kruskal-Wallis, and t-test. RESULTS: There were no statistical differences in demographics between the two groups. The scripted introduction changed several survey responses by a statistically significant amount for questions including whether their clinician ordered the study, whether it was part of their medical care, and whether it would be part of their medical record (p < 0.01). The responses as to whether they would tell their doctor that they had an ultrasound done were not significantly changed by the script (p = 0.86). CONCLUSION: This study demonstrates that the use of a scripted introduction regarding the purpose of educational BUS improved patient understanding of the objectives and limitations of such scans. There were still areas where the scripted introduction did not change patient's perception of the educational BUS scan.

How Patient Interactions With a Computer-Based Video Intervention Affect Decisions to Test for HIV.

The current study examines predictors of HIV test acceptance among emergency department patients who received an educational video intervention designed to increase HIV testing. A total of 202 patients in the main treatment areas of a high-volume, urban hospital emergency department used inexpensive netbook computers to watch brief educational videos about HIV testing and respond to pre-postintervention data collection instruments. After the intervention, computers asked participants if they would like an HIV test: Approximately 43% (n = 86) accepted. Participants who accepted HIV tests at the end of the intervention took longer to respond to postintervention questions, which included the offer of an HIV test, F(1, 195) = 37.72, p < .001, compared with participants who did not accept testing. Participants who incorrectly answered pretest questions about HIV symptoms were more likely to accept testing F(14, 201) = 4.48, p < .001. White participants were less likely to accept tests than Black, Latino, or "Other" patients, χ(2)(3, N = 202) = 10.39, p < .05. Time spent responding to postintervention questions emerged as the strongest predictor of HIV testing, suggesting that patients who agreed to test spent more time thinking about their response to the offer of an HIV test. Examining intervention usage data, pretest knowledge deficits, and patient demographics can potentially inform more effective behavioral health interventions for underserved populations in clinical settings.

Optimizing educational video through comparative trials in clinical environments.

Although video is increasingly used in public health education, studies generally do not implement randomized trials of multiple video segments in clinical environments. Therefore, the specific configurations of educational videos that will have the greatest impact on outcome measures ranging from increased knowledge of important public health issues, to acceptance of a voluntary HIV test, remain largely unknown. Interventions can be developed to run on affordable handheld computers, including inexpensive tablets or netbooks that each patient can use individually, and to integrate video delivery with automated data collection. These video interventions can then be used not only to educate patients who otherwise might not be reached, but to examine how content can be optimized for greater effectiveness as measured by cognitive and behavioral outcomes. This approach may prove especially valuable in high volume urban facilities, such as hospital emergency departments, that provide points of contact for lower income, lower literacy, and high-risk populations who may not otherwise interact with healthcare providers or researchers. This article describes the development and evaluation of an intervention that educates emergency department patients about HIV prevention and testing while comparatively examining a set of videos, each based upon competing educational theories. The computer-based video intervention and methodology are both highly replicable and can be applied to subject areas and settings far beyond HIV or the emergency department.

Race and emotion in computer-based HIV prevention videos for emergency department patients.

Computer-based video provides a valuable tool for HIV prevention in hospital emergency departments. However, the type of video content and protocol that will be most effective remain underexplored and the subject of debate. This study employs a new and highly replicable methodology that enables comparisons of multiple video segments, each based on conflicting theories of multimedia learning. Patients in the main treatment areas of a large urban hospital's emergency department used handheld computers running custom-designed software to view video segments and respond to pre-intervention and postintervention data collection items. The videos examine whether participants learn more depending on the race of the person who appears onscreen and whether positive or negative emotional content better facilitates learning. The results indicate important differences by participant race. African American participants responded better to video segments depicting White people. White participants responded better to positive emotional content.

Determining the optimal dose of intravenous fat emulsion for the treatment of severe verapamil toxicity in a rodent model.

OBJECTIVES: Recent animal studies have shown that intravenous fat emulsion (IFE) increases survival and hemodynamics in severe verapamil toxicity. However, the optimal dose of IFE is unknown. The primary objective was to determine the optimal dose of IFE based on survival in severe verapamil toxicity. Secondary objectives were to determine the effects on hemodynamic and metabolic parameters. The hypothesis was that there is a dose-dependent effect of IFE on survival until a maximum dose is reached. METHODS: This was a controlled dose-escalation study. Thirty male rats were anesthetized, ventilated, and instrumented to record mean arterial pressure (MAP) and heart rate (HR). Verapamil toxicity was achieved by a constant infusion of 15 mg/kg/hr. After 5 minutes, a bolus of 20% IFE was given. Animals were divided into six groups based on differing doses of IFE. Arterial base excess (ABE) was measured every 30 minutes. Data were analyzed with analysis of variance. RESULTS: The mean survival time for each dose of IFE was 0 mL/kg = 34 minutes, 6.2 mL/kg = 58 minutes, 12.4 mL/kg = 63 minutes, 18.6 mL/kg = 143.8 minutes, 24.8 mL/kg = 125.6 minutes, and 37.6 mL/kg = 130 minutes. Post hoc testing determined that the 18.6 mL/kg dose resulted in the greatest survival when compared to other doses. It increased survival 107.2 minutes (p = 0.004), 91.2 minutes (p = 0.001), and 80.8 minutes (p = 0.023) when compared to the lower doses of 0, 6.2, and 12.4 mL/kg, respectively. There was no added benefit to survival for doses greater than 18.6 mL/kg. The secondary outcomes of HR, MAP, and ABE showed the most benefit with 24.8 mL/kg of IFE at both 30 and 60 minutes. CONCLUSIONS: The greatest benefit to survival occurs with 18.6 mL/kg IFE, while the greatest benefit to HR, MAP, and BE occurs at 24.8 mL/kg IFE. The optimal dose for the treatment of severe verapamil toxicity in this murine model was 18.6 mL/kg.

Hemodynamic effects of intravenous fat emulsion in an animal model of severe verapamil toxicity resuscitated with atropine, calcium, and saline.

BACKGROUND: Intravenous fat emulsion (IFE) decreases cardiotoxicity from several lipid-soluble drugs, including verapamil. OBJECTIVES: To verify if the addition of IFE to the standard treatment of severe verapamil toxicity would improve hemodynamics and survival. METHODS: Fourteen dogs were instrumented to measure systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), heart rate, cardiac output, central venous pressures, left ventricular pressure changes over time, mixed venous oxygen saturation, pH, and base excess. Verapamil toxicity, defined as a 50% decrease in MAP, was induced with verapamil at 6 mg/kg/hr and maintained for 30 minutes by titrating the verapamil infusion rate. Following verapamil toxicity, the verapamil infusion rate was changed to 2 mg/kg/hr and continued for 90 minutes. All dogs were resuscitated with atropine (0.04 mg/kg intravenously) and calcium chloride (15 mg/kg intravenously every 5 minutes for three doses) and then randomized to receive either IFE (7 mg/kg of 20%) intravenously or equivalent volumes of 0.9% normal saline over 30 minutes. Measurements were recorded for 120 minutes by investigators blinded to the treatment. Data were analyzed using analysis of variance, survival analysis, and log-rank test. RESULTS: Before the 30-minute IFE or normal saline infusion, there were no differences in hemodynamic parameters. After IFE or normal saline infusion, the IFE-treated group had higher MAP at 30 minutes (95% confidence interval [CI] = 5.6 to 44.7 mm Hg), 45 minutes (95% CI = 10.8 to 50.0 mm Hg), and 60 minutes (95% CI = 10.2 to 53.1 mm Hg). Kaplan-Meier 120-minute survival rate was 14% (95% CI = 0.5% to 53%) for the saline group as compared with 100% (95% CI = 59% to 100%) for the IFE group (p = 0.01). CONCLUSIONS: Standard resuscitation and IFE increase MAP and survival in an animal model of severe verapamil toxicity compared with standard resuscitation alone.

Physostigmine does not effect arousal but produces toxicity in an animal model of severe gamma-hydroxybutyrate intoxication.

OBJECTIVES: Physostigmine is an acetylcholinesterase inhibitor and can produce fasciculations, seizures, bradycardia, and asystole. gamma-hydroxybutyrate (GHB) increases acetylcholine levels in the central nervous system and can decrease heart rate. Despite this, physostigmine has been proposed as an arousal agent to treat coma from overdoses of GHB. The authors hypothesized that in the setting of severe GHB intoxication, physostigmine would reverse sedation without producing adverse effects such as a decrease in heart rate, seizures, and fasciculations. METHODS: GHB intoxication was induced in 20 rats by intraperitoneal injection of 700 mg/kg of the GHB precursor gamma-butyrolactone. One hour later, rats were randomly assigned to receive either physostigmine (0.06 mg/kg) intraperitoneally or an equivalent volume of saline. After administration of physostigmine, rats were continuously monitored by a blinded observer for arousal (return of righting reflex), fasciculations, and seizures. Heart rate and respiratory rate were recorded at 0, 5, 15, and 60 minutes after administration of physostigmine. Data were analyzed using repeated-measures analysis of variance and chi-square test. A pretest sample size calculation determined that 10 rats per group would detect a change in arousal from 0% to 50% and a 10% change in heart rate. RESULTS: No rats in either group had arousal within one hour (p = 1.0); however, ten of ten physostigmine-treated rats developed signs of physostigmine toxicity (fasciculations, 7; seizures, 3), while no controls developed signs of physostigmine toxicity (p = 0.00). The authors were unable to detect a decrease in heart rate. CONCLUSIONS: Physostigmine did not produce a 50% change in arousal as measured by a return of righting reflex but did produce physostigmine toxicity (fasciculations and seizures) in this rat model of severe GHB intoxication.

Jimson weed extract as a protective agent in severe organophosphate toxicity.

UNLABELLED: Treatment of patients following an organophosphate (OP) exposure can deplete a hospital's entire supply of atropine. Given the possibility of multiple severe exposures after a terrorist attack using OP nerve agents, there exists a need for either greater atropine stores or the development of alternative antidotes. Jimson weed (Datura stramonium) contains atropine and other anticholinergic compounds and is common and readily available. It is used recreationally for its central anticholinergic effects and is made easily into an extract by boiling the crushed seeds. The extract has rapid onset of effects and may be useful for treatment of OP poisoning. OBJECTIVES: To determine whether pretreatment with an easily stored and prepared Datura seed extract (DSE) will increase survival following a severe OP poisoning. METHODS: Datura stramonium seeds were collected, crushed, and then heated in water to make a 2-mg/mL atropine solution (100 seeds contain approximately 6 mg of atropine or 0.007 mg/seed). Male rats were randomized to pretreatment with either saline (n = 10) or 7.5 mg/kg DSE (n = 10) given as a single intraperitoneal injection 5 minutes prior to a subcutaneous injection of 25 mg/kg of dichlorvos. The endpoint was time to death recorded by a blinded observer. RESULTS: The Kaplan-Meier estimates of the 24-hour survival rate was 90% (95% CI = 56% to 100%) for the DSE-pretreated group and 10% (95% CI = 0% to 45%) for the control group. The log-rank test revealed a statistically significant longer survival for the Datura-treated animals (p = 0.0002). Median survival time was 22 minutes 30 seconds for the control group and greater than 24 hours for the DSE-pretreated group. CONCLUSIONS: Pretreatment with DSE significantly increases survival following severe dichlorvos exposure.