Fatal Yellow Oleander Poisoning Masquerading as Benign Candlenut Ingestion Taken for Weight Loss.

BACKGROUND: Candlenuts (Aleurites moluccana) and yellow oleander seeds (Thevetia peruviana) bear a physical resemblance to one another. Candlenuts are benign and marketed as weight loss supplements. Yellow oleander seeds, however, contain toxic cardioactive steroids; as few as 2 seeds may cause fatal poisoning. Because of their physical similarities, the potential for a lethal substitution exists. CASE REPORT: A 63-year-old woman presented to the emergency department with vomiting after ingesting 5 of what she believed to be candlenuts that were ordered online under the colloquial name "Nuez de la India" for the purpose of weight loss. She was bradycardic (nadir pulse of 30 beats/min) and hyperkalemic (serum potassium 7.3 mEq/L). Within hours of presentation she suffered a ventricular fibrillation arrest, followed by a terminal asystolic arrest. Postmortem analyses of liver tissue and the seeds were consistent with fatal T. peruviana poisoning. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: T. peruviana seeds contain toxic cardioactive steroids; their physical resemblance to candlenuts poses a risk of potentially fatal substitution. Therapy with high-dose digoxin specific immune fragments (20-30 vials) may be helpful.

Persistent Hyperinsulinemia Following High-Dose Insulin Therapy: A Case Report.

INTRODUCTION: Overdoses of beta-adrenergic antagonists and calcium channel antagonists represent an uncommonly encountered but highly morbid clinical presentation. Potential therapies include fluids, calcium salts, vasopressors, intravenous lipid emulsion, methylene blue, and high-dose insulin. Although high-dose insulin is commonly used, the kinetics of insulin under these conditions are unknown. CASE REPORT: We present a case of a 51-year-old male who sustained a life-threatening overdose after ingesting approximately 40 tablets of a mixture of amlodipine 5 mg and metoprolol tartrate 25 mg. Due to severe bradycardia and hypotension, he was started on high-dose insulin (HDI) therapy; this was augmented with epinephrine. Despite the degree of his initial shock state, he ultimately recovered, and HDI was discontinued. Insulin was infused for a total of approximately 37 hours, most of which was dosed at 10 U/kg/hour; following discontinuation, serial serum insulin levels were drawn and remained at supraphysiologic levels for at least 24 hours and well above reference range for multiple days thereafter. CONCLUSION: The kinetics of insulin following discontinuation of high-dose insulin therapy are largely unknown, but supraphysiologic insulin levels persist for some time following therapy; this may allow for simple discontinuation rather than titration of insulin at the end of therapy. Dextrose replacement is frequently needed; although the duration is often difficult to predict, prolonged infusions may not be necessary.

Extracorporeal Membrane Oxygenation for Poisonings Reported to U.S. Poison Centers from 2000 to 2018: An Analysis of the National Poison Data System.

OBJECTIVES: To assess trends in the use of extracorporeal membrane oxygenation for poisoning in the United States. DESIGN: Retrospective cohort study. SETTING: The National Poison Data System, the databased owned and managed by the American Association of Poison Control Centers, the organization that supports and accredits all 55 U.S. Poison Centers, 2000-2018. PATIENTS: All patients reported to National Poison Data System treated with extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 407 patients met final inclusion criteria (332 adults, 75 children). Median age was 27 years (interquartile range, 15-39 yr); 52.5% were male. Median number of ingested substances was three (interquartile range, 2-4); 51.5% were single-substance exposures. Extracorporeal membrane oxygenation use in poisoned patients in the United States has significantly increased over time (z = 3.18; p = 0.001) in both adults (age > 12 yr) and children (age ≤ 12 yr), increasing by 9-100% per year since 2008. Increase in use occurred more commonly in adults. We found substantial geographical variation in extracorporeal membrane oxygenation use by geospatially mapping the ZIP code associated with the initial call, with large, primarily rural areas of the United States reporting no cases. Overall survival was 70% and did not vary significantly over the study period for children or adults. Patients with metabolic and hematologic poisonings were less likely to survive following extracorporeal membrane oxygenation than those with other poisonings (49% vs 72%; p = 0.004). CONCLUSIONS: The use of extracorporeal membrane oxygenation to support critically ill, poisoned patients in the United States is increasing, driven primarily by increased use in patients greater than 12 years old. We observed no trends in survival over time. Mortality was higher when extracorporeal membrane oxygenation was used for metabolic or hematologic poisonings. Large, predominantly rural regions of the United States reported no cases of extracorporeal membrane oxygenation for poisoning. Further research should focus on refining criteria for the use of extracorporeal membrane oxygenation in poisoning.

Phenibut exposures and clinical effects reported to a regional poison center.

BACKGROUND: Phenibut is a synthetically produced central nervous system (CNS) depressant that is structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Phenibut has been identified as a drug of abuse with numerous clinical effects in overdose and a withdrawal syndrome with chronic use. The purpose of this study is to report the incidence of exposure calls regarding phenibut to a poison center, describe the reasons for its use and clinical effects. METHODS: Study subjects were identified using Toxicall®, the electronic medical record utilized by the Minnesota Poison Control System. All phenibut exposure calls from January 2000 through December 2018 were included. Analysis was performed on incidence of exposure calls, reported reasons for use, signs and symptoms, coingestants, and outcome. RESULTS: There were 56 exposure calls over 19 years with 48 (85.7%) calls within the past five years. Over 50% of patients had CNS effects and 10.7% had withdrawal concerns. Twenty-seven patients (48%) had abuse as the reason for use and 13 (23%) used phenibut to treat anxiety. There were documented coingestants in 35.7% of patients. No patients died due to reported phenibut use, though 11 patients (19.6%) were intubated. CONCLUSION: Exposure calls to a regional poison center regarding phenibut have increased over the past five years. CNS depression was common, and associated with significant clinical outcomes including respiratory failure requiring intubation. As phenibut is easily attainable and exposures appear to be increasing, physicians should be aware of phenibut-associated CNS and respiratory depression and be prepared to manage airways appropriately.

Physostigmine is superior to non-antidote therapy in the management of antimuscarinic delirium: a prospective study from a regional poison center.

CONTEXT: Poison centers (PCs) frequently manage patients with antimuscarinic delirium. However, controversy surrounds the antidotal use of physostigmine for its treatment. The aim of this study was to prospectively investigate physostigmine versus non-antidote therapy for the management of antimuscarinic delirium in a single regional PC. METHODS: This was a prospective observational analysis of patients diagnosed with antimuscarinic delirium and treated in consultation with a regional PC. Certified Specialists in Poison Information (CSPIs) use a clinical guideline to recommend the use of physostigmine. Using a previously derived altered mental status score, we quantified the rate of delirium improvement with physostigmine compared to non-antidote therapy two hours after initial patient identification. We also recorded adverse events (defined a priori as bradycardia, vomiting, seizures) and resource utilization (intubation and physical restraint). RESULTS: We identified 245 patients and included 154 in the analysis. The most common exposure classes were antihistamines (68%), analgesics (19%), and antipsychotics (19%). CSPIs recommended physostigmine in 81% (125) of cases and the treatment team administered it in 37% (57) of these. We observed delirium control in 79% of patients who received physostigmine versus 36% of those who did not. The odds of delirium control were six times greater for patients receiving physostigmine than for patients treated with non-antidote therapy (OR 6.6). Adverse events were rare and did not differ significantly between the groups. Physostigmine was not associated with changes in the incidence of intubation or restraint. CONCLUSIONS: This study provides further evidence of both the safety and efficacy of physostigmine in the treatment of antimuscarinic delirium.

Anti-factor Xa Monitoring and Activated Charcoal for a Pediatric Patient With Rivaroxaban Overdose.

Rivaroxaban, an oral anticoagulant, directly inhibits factor Xa (FXa). A 35-month-old boy was brought to the emergency department 15 minutes after ingesting 200 mg of rivaroxaban (16 mg/kg). Activated charcoal (AC) was administered; the patient was observed with monitoring of plasma anti-FXa levels and discharged the following day after an uneventful hospital observation. We identified two case series and seven case reports of potentially toxic rivaroxaban ingestion in the literature. No serious adverse effects were reported. The present case is the first reported use of anti-FXa monitoring after rivaroxaban ingestion. The magnitude of the effect of AC administration in this patient is unclear.

High dose insulin for beta-blocker and calcium channel-blocker poisoning.

BACKGROUND/OBJECTIVES: High dose insulin (HDI) is a standard therapy for beta-blocker (BB) and calcium channel-blocker (CCB) poisoning, however human case experience is rare. Our poison center routinely recommends HDI for shock from BBs or CCBs started at 1U/kg/h and titrated to 10U/kg/h. The study objective was to describe clinical characteristics and adverse events associated with HDI. METHODS: This was a structured chart review of patients receiving HDI for BB or CCB poisoning with HDI defined as insulin infusion of ≥0.5U/kg/h. RESULTS: In total 199 patients met final inclusion criteria. Median age was 48years (range 14-89); 50% were male. Eighty-eight patients (44%) were poisoned by BBs, 66 (33%) by CCBs, and 45 (23%) by both. Median nadir pulse was 54 beats/min (range 12-121); median nadir systolic blood pressure was 70mmHg (range, 30-167). Forty-one patients (21%) experienced cardiac arrest; 31 (16%) died. Median insulin bolus was 1U/kg (range, 0.5-10). Median starting insulin infusion was 1U/kg/h (range 0.22-10); median peak infusion was 8U/kg/h (range 0.5-18). Hypokalemia occurred in 29% of patients. Hypoglycemia occurred in 31% of patients; 50% (29/50) experienced hypoglycemia when dextrose infusion concentration ≤10%, and 30% (31/105) experienced hypoglycemia when dextrose infusion concentration ≥20%. CONCLUSIONS: HDI, initiated by emergency physicians in consultation with a poison center, was feasible and safe in this large series. Metabolic abnormalities were common, highlighting the need for close monitoring. Hypoglycemia was more common when less concentrated dextrose maintenance infusions were utilized.

Intentional Recreational Abuse of Quetiapine Compared to Other Second-generation Antipsychotics.

INTRODUCTION: Case reports and poison center data have demonstrated that the second-generation antipsychotic quetiapine is being obtained and used for recreational abuse. The purpose of this study was to describe the relative rates of single-substance abuse for different atypical antipsychotics and compare their demographic and clinical features. METHODS: We conducted a 10-year retrospective analysis of the National Poison Data System (NPDS) database (2003 - 2013). Trained nurses and pharmacists with specialty training in toxicology prospectively collect all NPDS data at poison control centers around the United States. We queried the NPDS for all cases of single-substance second-generation antipsychotic exposures coded as "intentional abuse." The data provided by the NPDS regarding rates and clinical features of quetiapine abuse and the abuse of all other second-generation antipsychotics were compared and described descriptively. RESULTS: During the study period, 2,118 cases of quetiapine abuse and 1,379 cases of other second-generation antipsychotic abuse were identified. Quetiapine abuse was more common than the abuse of other second-generation antipsychotics, compromising 60.6% of all abuse cases during the study period. After quetiapine, the next most frequently abused medications were risperidone (530 cases, 15.2%) and olanzapine (246 cases, 7.0%). For all second-generation antipsychotics including quetiapine, central nervous system clinical effects were most common, including drowsiness, confusion, and agitation. Other serious clinical effects observed with second-generation antipsychotic abuse included hypotension, respiratory depression, and seizures. CONCLUSION: Quetiapine abuse is relatively common, and is abused far more often than any other second-generation antipsychotic. Emergency physicians should be aware of the clinical effects that may occur after second-generation antipsychotic abuse.

An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers.

STUDY OBJECTIVE: Rivaroxaban and apixaban are part of a new group of oral anticoagulants targeting factor Xa and approved by the Food and Drug Administration in 2011 and 2012. These oral anticoagulants are administered at fixed daily doses, without the need for laboratory-guided adjustments. There are limited data available on supratherapeutic doses or overdose of the oral Xa inhibitors. This study characterizes the clinical effect in patients exposed to rivaroxaban and apixaban. METHODS: A retrospective study collected data from 8 regional poison centers covering 9 states. Cases were initially identified by a search of the poison centers' databases for case mentions involving a human exposure to Xarelto, rivaroxaban, Eliquis, or apixaban. Inclusion criteria included single-substance exposure. Exclusion criteria were animal exposure, polysubstance exposure, or information call. Data for the study were collected by individual chart review, including case narratives, and compiled into a single data set. RESULTS: There were 223 patients: 124 (56%) were female patients, mean age was 60 years, and 20 were children younger than 12 years (9%). One hundred ninety-eight patients ingested rivaroxaban (89%) and 25 ingested apixaban (11%). Dose was reported in 182 rivaroxaban patients, with a mean dose of 64.5 mg (range 15 to 1,200 mg), and in 21 apixaban patients, with a mean dose of 9.6 mg (range 2.5 to 20 mg). For rivaroxaban, prothrombin time was measured in 49 patients (25%) and elevated in 7; partial thromboplastin time, measured in 49 (25%) and elevated in 5; and international normalized ratio, measured in 61 (31%) and elevated in 13. For apixaban, prothrombin time was measured in 6 patients (24%) and elevated in none; partial thromboplastin time, measure in 6 (24%) and elevated in none; and international normalized ratio, measured in 5 patients (20%) and elevated in none. Bleeding was reported in 15 patients (7%): 11 rivaroxaban and 4 apixaban. The site of bleeding was gastrointestinal (8), oral (2), nose (1), bruising (1), urine (1), and subdural (1). The subdural bleeding occurred after fall and head injury. All cases with bleeding involved long-term ingestions. Coagulation test results were normal in most patients with bleeding: prothrombin time 5 of 6 (83%), partial thromboplastin time 5 of 6 (83%), and international normalized ratio 5 of 9 (55%). Blood products were used in 7 rivaroxaban patients (1 suicide) and 3 apixaban patients. No bleeding or altered coagulation test results occurred in children, which all involved a one-time ingestion. All 12 suicide attempts involved rivaroxaban: altered coagulation test results occurred for 5 patients (42%), no bleeding occurred in any suicide attempt patient, 1 patient was treated with fresh frozen plasma (international normalized ratio 12.47), and dose by patient history did not predict risk of altered coagulation or bleeding. Two rivaroxaban patients experienced elevation of hepatic transaminase levels greater than 1,000 U/L. CONCLUSION: Bleeding after Xa inhibitor ingestion as a single agent is uncommon. Prothrombin time, partial thromboplastin time, or international normalized ratio may be elevated in a minority of cases but appears unreliable to measure risk of bleeding. Massive acute ingestion in suicide attempt may result in significant anticoagulation. Single exploratory ingestion by children was not associated with toxicity.

Efficacy of activated charcoal administered more than four hours after acetaminophen overdose.

To evaluate whether administration of activated charcoal, in addition to standard N-acetylcysteine (NAC) therapy, after acetaminophen overdose provides additional patient benefit over NAC therapy alone, a 1-year non-randomized prospective, multi-center, observational case series was performed at three poison centers and one poison center system. Entrance criteria were all acute acetaminophen overdoses with: 1) an acetaminophen blood concentration determined to be in the toxic range by the Rumack-Matthew nomogram; and 2) all therapies, including NAC and activated charcoal, initiated between 4 and 16 h post-ingestion. There were 145 patients meeting entrance criteria, of whom 58 patients (40%) received NAC only and 87 patients (60%) received NAC and activated charcoal. Overall, 23 patients had elevations of AST or ALT greater than 1000 IU/L, of which 21 patients received NAC only (38% of total NAC only group) and 2 patients received NAC and activated charcoal (2% of total NAC+AC group). Administration of activated charcoal in this series of patients with toxic acetaminophen concentrations treated with NAC was associated with reduced incidence of liver injury, as measured by elevated serum transaminases and prothrombin times.

Neonatal ergot poisoning: a persistent iatrogenic illness.

Ergot toxicity in the newborn usually manifests itself as respiratory depression, cyanosis, oliguria, and seizures. Death is usually caused by respiratory failure. A limited number of neonatal cases have been reported worldwide, and almost all cases involved confusion of maternal methylergonovine with neonatal vitamin K. Previous case reports provided little information regarding the effectiveness and dosing of antidotal therapy, especially sodium nitroprusside. A full-term male infant was inadvertently given methylergonovine instead of naloxone at birth. Several hours later, he required intubation for respiratory failure. Peripheral perfusion, ventilation, and renal function improved rapidly with nitroprusside infusion, and he was extubated on the third hospital day. Even asymptomatic newborns should be transferred to a neonatal intensive care unit for close observation after methylergonovine administration because toxicity can be life threatening. Rapid recognition of the therapeutic error, ventilatory support, and prompt administration of sodium nitroprusside should lead to a good outcome.