Acute exposure to hydrazine reported to four United States regional poison centers: reconsidering a paradigm.

INTRODUCTION: Exposures to hydrazines occur during aeronautic and space operations and pose a potential risk to personnel. Historically, extensive preparatory countermeasures have been taken due to concern for severe toxicity. This study seeks to better understand manifestations of acute occupational exposures to hydrazine to guide recommendations for management. MATERIALS AND METHODS: A retrospective database review of records from four United States regional poison centers was conducted of all human exposures to hydrazine, monomethylhydrazine, or 1,1-dimethylhydrazine over two decades. Following case abstraction, descriptive statistics were performed to characterize demographics, manifestations, treatments, and outcomes. RESULTS: One hundred and thirty-five cases were identified, and most were adult males exposed to inhaled hydrazine propellant vapors. Fifty-seven percent of patients were asymptomatic following exposure; otherwise, common symptoms were dyspnea, throat irritation, cough, ocular irritation, and headache. All patients were evacuated or received decontamination, with a few reports of symptomatic treatments, including oxygen supplementation and salbutamol (albuterol). Patients usually recovered quickly and were released after a brief healthcare facility evaluation or observed locally. No patients developed delayed symptoms. Symptoms of severe toxicity were not observed, and there were no deaths. DISCUSSION: Acute exposures to hydrazines during operations within the aerospace industry appear to be limited primarily to mucosal and mild pulmonary irritation without significant neurologic, hepatic, or hematologic toxicity. These findings are contrary to previously established expectations and may be related to low-level exposures or possibly due to current emergency countermeasures. CONCLUSIONS: Care in occupational hydrazine exposure will focus on evacuation, decontamination, and symptomatic management of chemical irritant properties of hydrazines. It is reasonable to manage mild cases outside of a healthcare facility. Continued endeavors in human space exploration and habitation will increase the risk of these exposures, making it imperative that clinicians be comfortable with the care and management of these patients.

2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

Antivenom supply and demand: An analysis of antivenom availability and utilization in South Africa.

Introduction: Snakebites are a neglected tropical disease. In many areas, envenoming incidence and antivenom administration rates are unknown. This study compared antivenom (AV) availability to rates of envenoming and recommendations to treat (RTT) in South Africa. Methods: This retrospective study identified, extracted, and reviewed all cases of envenoming (snake bites and spits) reported to the Poisons Information Helpline of the Western Cape of South Africa (PIHWC) from June 1, 2015 to May 31, 2020 by public hospitals in the Western Cape. A standardized interview was administered to the pharmacies of the 40 hospitals in winter and summer to determine how many vials of monovalent and polyvalent AV they had on hand at the time of the call and their expiration dates. Descriptive analysis was used to compare rates of envenoming and recommendations to treat to antivenom stock in winter and summer and by hospital type and location. Results: Public hospitals reported 300 envenomings, 122 from snakes. The PIHWC recommended antivenom administration in 26% of cases (N = 32). All hospital pharmacies queried answered our questions. Our study demonstrates urban district hospitals have higher ratios of AV vials compared to mean annual rates of envenoming and RTT than rural district hospitals at both the winter and summer timepoints. Conclusion: This study evaluates antivenom supply and demand in a province of South Africa. The findings suggest South African urban hospitals have a relative excess of antivenom, and thus more capacity to meet demand, than their rural counterparts. It supports consideration of a redistribution of antivenom supply chains to match seasonal and local rates of envenoming. It indicates a need for higher quality, prospective data characterizing envenoming incidence and treatment.

2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

Toxic Tetrahydrocannabinol (THC) Dose in Pediatric Cannabis Edible Ingestions.

OBJECTIVE: The study characterizes cannabis toxicity in relation to tetrahydrocannabinol (THC) dose in pediatric edible cannabis ingestions. METHODS: This is a retrospective review of children aged <6 years presenting with edible cannabis ingestions of known THC dose within a pediatric hospital network (January 1, 2015-October 25, 2022). Cannabis toxicity was characterized as severe if patients exhibited severe cardiovascular (bradycardia, tachycardia/hypotension requiring vasopressors or intravenous fluids, other dysrhythmias), respiratory (respiratory failure, apnea, requiring oxygen supplementation), or neurologic (seizure, myoclonus, unresponsiveness, responsiveness to painful stimulation only, requiring intubation or sedation) effects. Cannabis toxicity was characterized as prolonged if patients required >6 hours to reach baseline. The relationship between THC dose and severe and prolonged toxicity was explored using multivariable logistic regression and receiver operator characteristic curve analyses. RESULTS: Eighty patients met inclusion. The median age was 2.9 years. The median THC ingestion was 2.1 mg/kg. Severe and prolonged toxicity was present in 46% and 74%, respectively. THC dose was a significant predictor of severe (adjusted odds ratio 2.9, 95% confidence interval: 1.8-4.7) and prolonged toxicity (adjusted odds ratio 3.2, 95% confidence interval: 1.6-6.5), whereas age and sex were not. Area under the curve was 92.9% for severe and 87.3% for prolonged toxicity. THC ingestions of ≥1.7 mg/kg can predict severe (sensitivity 97.3%) and prolonged toxicity (sensitivity 75.4%). CONCLUSIONS: The THC dose of edible cannabis correlates to the degree of toxicity in children <6 years old. The threshold of 1.7 mg/kg of THC may guide medical management and preventive regulations.

Late hemotoxicity following North American rattlesnake envenomation treated with crotalidae immune F(ab')2 (equine) antivenom and crotalidae immune polyvalent Fab (ovine) antivenom reported to the North American Snakebite Sub-registry.

INTRODUCTION: Late hemotoxicity is common following rattlesnake envenomation treated with crotalidae immune polyvalent Fab (ovine) (FabAV). Initial clinical trials showed crotalidae immune F(ab')2 (equine) (Fab2AV) to be superior to FabAV in preventing late hemotoxicity, but this effect has not been demonstrated in broader populations. This study investigated late hemotoxicity in patients receiving Fab2AV or FabAV after rattlesnake envenomation. METHODS: This is a retrospective analysis of prospectively collected data from patients with snakebite reported to the ToxIC North American Snakebite Registry (NASBR) between January 1, 2019, and December 31, 2020. Inclusion criteria were rattlesnake envenomation and administration of antivenom. Patients were excluded if they received more than one type of antivenom. The primary outcome was occurrence of late hemotoxicity (platelets ≤120 k/mm3 or fibrinogen ≤170 mg/dL) in patients receiving Fab2AV and FabAV. Data collected included demographics, envenomation characteristics, laboratory values, and treatment administered. Statistics including t-test and Fisher's exact test were used. RESULTS: A total of 201 rattlesnake envenomated patients receiving antivenom were reported to the NASBR in the study period; 144 were included. 49 received Fab2AV alone, 45 received FabAV alone and 50 received both antivenoms. Baseline patient and envenomation characteristics were similar between the groups. Late hemotoxicity occurred in 2/49 patients in the Fab2AV group (4% (95% CI 0.7-12.6)) and in 19/45 patients in the FabAV group (42% (95% CI 28.4-59.0); absolute risk reduction 39.1% (95% CI 21.2-46.2) (p = 0.001). On follow up, 0 patients (0%) receiving Fab2AV were retreated with antivenom; 4 patients (9%) receiving FabAV were retreated (p = 0.049). CONCLUSIONS: In the North American Snakebite Registry, late hemotoxicity was less common in rattlesnake envenomated patients treated with Fab2AV compared to FabAV.

Prognostic indicators in critically ill poisoned patients: development of a risk-prediction nomogram.

Objectives The prognosis of acutely poisoned patients is a significant concern for clinical toxicologists. In this study, we sought to determine the clinical and laboratory findings that can contribute to predicting the medical outcomes of poisoned patients admitted to intensive care units (ICUs). Methods This retrospective study was performed from January 2009 to January 2016 in the ICU of Vali-e-Asr Hospital in Birjand, Iran. We included all patients with the diagnosis of acute poisoning admitted to the ICU. Demographic data, laboratory results, the Sequential Organ Failure Assessment (SOFA), and acute physiology score + age points + chronic health points (APACHE) II, and the Simplified Acute Physiology Score (SAPS) II, and outcome were collected. Univariate analysis (Mann-Whitney or t-test), multiple logistic regression, receiver operating characteristics (ROC) curve analysis, and Pearson's correlation test were performed using SPSS, STATA/SE 13.0, and Nomolog software programs. Results The multiple logistic regression analysis revealed that five factors were significant for predicting mortality including age (OR 95% CI: 1.1[1.05-1.12], p<0.001), Glasgow Coma Score (GCS) (OR 95% CI: 0.71[0.6-0.84], p<0.001), white blood cell (WBC) count (OR 95% CI: 1.1[1.01-1.12], p=0.04), serum sodium (Na) (OR 95% CI: 1.08[1.01-1.15], p=0.02), and creatinine levels (Cr) (OR 95% CI: 1.86 [1.23-2.81], p=0.003). We generated a five-variable risk-prediction nomogram which could both predict mortality risk and identify high-risk patients. Conclusions Age, GCS, WBC, serum creatinine, and sodium levels are the best prognostic factors for mortality in poisoned patients admitted to the ICU. The APACHE II score can discriminate between non-survivors and survivors. The nomogram developed in the current study can provide a more precise, quick, and simple analysis of risks, thereby enabling the users to predict mortality and identify high-risk patients.

Prognostic indicators in critically ill poisoned patients: development of a risk-prediction nomogram.

OBJECTIVES: The prognosis of acutely poisoned patients is a significant concern for clinical toxicologists. In this study, we sought to determine the clinical and laboratory findings that can contribute to predicting the medical outcomes of poisoned patients admitted to intensive care units (ICUs). METHODS: This retrospective study was performed from January 2009 to January 2016 in the ICU of Vali-e-Asr Hospital in Birjand, Iran. We included all patients with the diagnosis of acute poisoning admitted to the ICU. Demographic data, laboratory results, the Sequential Organ Failure Assessment (SOFA), and acute physiology score + age points + chronic health points (APACHE) II, and the Simplified Acute Physiology Score (SAPS) II, and outcome were collected. Univariate analysis (Mann-Whitney or t-test), multiple logistic regression, receiver operating characteristics (ROC) curve analysis, and Pearson's correlation test were performed using SPSS, STATA/SE 13.0, and Nomolog software programs. RESULTS: The multiple logistic regression analysis revealed that five factors were significant for predicting mortality including age (OR 95% CI: 1.1[1.05-1.12], p<0.001), Glasgow Coma Score (GCS) (OR 95% CI: 0.71[0.6-0.84], p<0.001), white blood cell (WBC) count (OR 95% CI: 1.1[1.01-1.12], p=0.04), serum sodium (Na) (OR 95% CI: 1.08[1.01-1.15], p=0.02), and creatinine levels (Cr) (OR 95% CI: 1.86 [1.23-2.81], p=0.003). We generated a five-variable risk-prediction nomogram which could both predict mortality risk and identify high-risk patients. CONCLUSIONS: Age, GCS, WBC, serum creatinine, and sodium levels are the best prognostic factors for mortality in poisoned patients admitted to the ICU. The APACHE II score can discriminate between non-survivors and survivors. The nomogram developed in the current study can provide a more precise, quick, and simple analysis of risks, thereby enabling the users to predict mortality and identify high-risk patients.

Digoxin Toxicity in a Patient with Pacemaker: A Case Report.

Digoxin is a cardiac myocyte sodium/potassium ATPase inhibitor with a narrow therapeutic index used to treat patients with conditions such as heart failure with reduced ejection fraction and atrial fibrillation. Currently, digoxin-specific antibody fragments serve as a therapeutic option in patients with digoxin toxicity; however, the indications for digoxin-specific antibody fragments are inconsistent, and some sources report a serum digoxin concentration of >12 ng/mL as a treatment indication. We discuss a case of an asymptomatic elevated digoxin level of 13.5 ng/mL secondary to a dosing error, who was managed without digoxin-specific antibody fragments as well as a brief retrospective chart review for patients with a pacemaker presenting with a high digoxin concentration managed with and without digoxin-specific antibody fragments, with equivocal findings.

Pediatric Death Due to Myocarditis After Exposure to Cannabis.

Since marijuana legalization, pediatric exposures to cannabis have increased.1 To date, pediatric deaths from cannabis exposure have not been reported. The authors report an 11-month-old male who, following cannabis exposure, presented with central nervous system depression after seizure, and progressed to cardiac arrest and died. Myocarditis was diagnosed post-mortem and cannabis exposure was confirmed. Given the temporal relationship of these two rare occurrences - cannabis exposure and sudden death secondary to myocarditis in an 11-month-old - as well as histological consistency with drug-induced myocarditis without confirmed alternate causes, and prior reported cases of cannabis-associated myocarditis, a possible relationship exists between cannabis exposure in this child and myocarditis leading to death. In areas where marijuana is commercially available or decriminalized, the authors urge clinicians to preventively counsel parents and to include cannabis exposure in the differential diagnosis of patients presenting with myocarditis.

Characterization of edible marijuana product exposures reported to United States poison centers.

CONTEXT: Edible marijuana products are sold as brownies, cookies, and candies, which may be indistinguishable from counterparts without marijuana and are palatable to children and adults. The consumption of an entire product containing multiple dose-units may result in overdose. OBJECTIVE: To characterize edible marijuana exposures reported to US poison centers with subgroup analysis by age. METHODS: We analyzed single substance, human exposure calls coded to marijuana brownies, candies, cookies, beverages, or other foods reported to the National Poison Data System from January 2013 to December 2015. Calls were analyzed by state, age, gender, exposure route, clinical effect, therapies, and level of healthcare facility utilization. RESULTS: Four-hundred and thirty calls were reported: Colorado (N = 166, 1.05/100,000 population/year) and Washington (96, 0.46) yielded the highest number of exposures. Three hundred and eighty-one (91%) calls occurred in states with decriminalized medical/recreational marijuana. The number of calls increased every year of the study. The most common age groups were: ≤5 years (N = 109, 0.15/100,000 population/year) and 13-19 (78, 0.09). The most frequent clinical effects were drowsiness/lethargy (N = 118, percentage = 43%), tachycardia (84, 31%), agitated/irritable (37, 14%), and confusion (37, 14%). Children ≤5 years have more drowsiness/lethargy, ataxia, and red eye/conjunctivitis. No deaths were reported. The most common therapies administered were intravenous fluids (85, 20%), dilute/irrigate/wash (48, 11 %), and benzodiazepines (47, 11%). Three patients (ages 4, 10, and 57 years) received intubation. 97 (23%), 217 (50%), and 12 (3%) calls were managed at home, treated/released, admitted to a critical care unit, respectively. DISCUSSION: Although most clinical effects are minor, ventilatory support may be necessary for children and adults. We speculate the increasing exposures may be related to a combination of delayed absorption kinetics of Δ9-tetrahydrocannablnol, lagging packaging regulations, increased accessibility in decriminalized states, and increased familiarity of poison center specialists with edible product codes. CONCLUSIONS: Edible marijuana exposures are increasing and may lead to severe respiratory depression.

NBOMe and 2C substitute phenylethylamine exposures reported to the National Poison Data System.

BACKGROUND: Hallucinogenic designer drugs, especially NBOMe and the 2C substitute phenylethylamine series, have been increasing ubiquitous in past years. The purpose of this study is to characterize and compare clinical features of NBOMe and 2C exposures in humans. METHOD: This is a retrospective cohort study of all single agent exposures to NBOMe and 2C substitute phenylethlamine reported to the National Poison Data System (NPDS) from 1st September 2012 to 30th September 2014. RESULTS: Over the study period, there were a total 341 cases including 148 NBOMe exposures and 193 2C exposures. The majority cases involved men (73.9%); median age was 18 years (Interquartile-range, 16-21). Similar clinical effects were reported in both groups including tachycardia (45.2%), agitation/irritable (44.3%), hallucination/delusion (32.0%), confusion (19.1%) and hypertension (18.5%). There were higher incidences of hallucination/delusion, single episode seizure and benzodiazepine administration in NBOMe exposures (40.5%, 8.8% and 50.0%respectively) than those of 2C exposures (25.4%, 3.1%, and 32.6% respectively). There were 2.3% death; no difference between two groups. DISCUSSION: The higher rate of symptoms in NBOMe is consistent with the higher 5HT2A agonistic effects of NBOMe described in both molecular and animal studies. CONCLUSION: Common clinical effects of NBOMe and 2C exposures were tachycardia, agitation/irritable, hallucination/delusion, confusion, and hypertension. There were higher incidences of hallucination/delusion, single episode seizure and benzodiazepine administration in NBOMe.

Cardiac sodium channel blockade after an intentional ingestion of lacosamide, cyclobenzaprine, and levetiracetam: Case report.

CONTEXT: Lacosamide treats partial seizures by enhancing slow inactivation of voltage-gated sodium channels. The described cardiac toxicity of lacosamide in the literature to date includes atrioventricular blockade (PR prolongation), atrial flutter, atrial fibrillation, sinus pauses, ventricular tachycardia and a single cardiac arrest. We report a second case of cardiac arrest following an intentional lacosamide overdose. CASE DETAILS: A 16 year-old female with a seizure disorder was found unresponsive in pulseless ventricular tachycardia after intentionally ingesting 4.5 g (76 mg/kg) lacosamide, 120 mg (2 mg/kg) cyclobenzaprine and an unknown amount of levetiracetam. Exact time of ingestion was unknown. Her initial electrocardiogram (ECG) demonstrated sinus tachycardia at 139 beats per minute, QRS duration 112 ms, and terminal R-wave in lead aVR > 3 mm. Despite treatment with 150 mEq of sodium bicarbonate, she had persistent EKG findings eight hours after presentation. Her serum lacosamide concentration nine hours after presentation was elevated at 22.8 µg/mL, while serum cyclobenzaprine concentration was 16 ng/mL (therapeutic: 10-30 ng/mL), and serum levetiracetam concentration was 22.7 µg/mL (therapeutic: 12-46 µg/mL). On hospital day three, ECG demonstrated resolution of the terminal R-wave with QRS of 78 ms. The patient recovered without physical or neurologic sequelae. DISCUSSION: The patient's lacosamide, cyclobenzaprine and levetiracetam overdose was associated with QRS prolongation and terminal right axis deviation--suggesting sodium channel blockade as a likely etiology for her cardiac arrest. Cyclobenzaprine has potential for sodium channel blockade and ventricular dysrhythmias although cardiac toxicity due to cyclobenzaprine alone is rare. The combination of cyclobenzaprine with lacosamide may have resulted in cardiovascular collapse. In conclusion, overdose of lacosamide combined with therapeutic concentrations of sodium channel blocking xenobiotics may cause cardiac conduction delays and cardiac arrest.

The use of energy drinks, dietary supplements, and prescription medications by United States college students to enhance athletic performance.

While the use of performance enhancing substances by professional, collegiate, and Olympic athletes is well described, the rate of use in the general population is not well studied. We explored the use of energy drinks, dietary supplements, and prescription medications for the enhancement of athletic performance among college students using an ongoing survey system. We conducted a multi-round online questionnaire collecting data from self-identified students at two-year colleges, four-year colleges, online courses, or technical schools at least part-time during the specified sampling period. The sample is obtained through the use of a survey panel company in which respondents voluntarily register. Survey data were collected from December, 2010 through August, 2011. Subjects who reported participating in athletics were asked if they used any of the following substances to enhance athletic performance (1) energy drinks (2) dietary supplements (3) prescription medications within the last year. Data were analyzed from October, 2011 through January, 2012. There were 462 college students who responded to the survey reporting they participate in sports at various levels. Of these, 397 (85.9 %) responded that within the last year they used energy drinks, dietary supplements, or prescription medications to enhance athletic performance. Energy drinks had the highest prevalence (80.1 %), followed by dietary supplements (64.1 %) and prescription medications (53.3 %). Use was most prevalent amongst intercollegiate athletes (89.4 %) followed by club (88.5 %) and intermural (82.1 %) participants. The vast majority of survey respondents reported using energy drinks, dietary supplements, and prescription medications within the last year for athletic performance enhancement.