Notes from the Field: Intoxication and Deaths Associated with Ingestion of a Racing Fuel and Carbonated Soft Drink Mixture - Tennessee, January 2016.

In January 2016, the Tennessee Poison Center and Tennessee Department of Health learned of the deaths of two adolescents, and the nonfatal intoxication of two other adolescents, after ingestion of a mixture of racing fuel (approximately 100% methanol) and a carbonated soft drink. The Tennessee Department of Health reviewed medical records and police reports to learn more about the racing fuel source, assess ongoing risk, and guide prevention efforts. These are the first reported deaths in the United States associated with ingestion of this racing fuel mixture.

Antidotal use of lipid emulsion - the pendulum swings.

Intravenous lipid emulsion (ILE) is a widely accepted treatment for local anesthetic systemic toxicity (LAST), particularly resulting from bupivacaine. The past decade has seen interest in antidotal use of ILE for other poisonings wax and wane. Numerous anecdotes have raised enthusiasm while more rigorous reviews have cast skepticism. The truth may lie between these two poles.We illustrate the recent trends in published reports on ILE. We highlight the gaps in our knowledge and suggest sources of data that may clarify how useful ILE may be for poisonings other than LAST. We offer the example of bupropion, which is hazardous in overdose and which has a Log P (octanol-water partition coefficient) similar to that of bupivacaine.Current data sources including the AAPCC National Poison Data System (NPDS), the ACMT Toxic Investigators Consortium (ToxIC), and a voluntary online registry (www.lipidrescue.org) each give an incomplete view of the problem. We propose analysis of newer NPDS data, which will include ILE as a treatment field code beginning with the 2019 data, and a structured, prospective registry of antidotal use of ILE for poisonings other than LAST.

Cutaneous-hemolytic loxoscelism following brown recluse spider envenomation: new understandings.

Background: Brown recluse spider (BRS) (Loxosceles reclusa) envenomation can cause local dermonecrotic lesions, constitutional symptoms, and potentially fatal hemolysis (i.e., cutaneous-hemolytic loxoscelism). As the incidence of hemolysis is low and the spider habitat is limited, little is known regarding the clinical course of cutaneous-hemolytic loxoscelism.Methods: We performed a retrospective observational study of patients following BRS envenomation over an eight-year period. Demographics, clinical course, laboratories, and interventions were assessed. Wilcoxon rank-sum tests and Pearson chi-square tests were used in the univariate analyses. Logistic regression assessed the independent contribution of symptoms in a multivariate analysis.Results: Of the 97 patients, 40.2% (n = 39) developed hemolysis; the majority (66.7%) were 18 years old or younger. Univariate analysis revealed that constitutional symptoms were associated with hemolysis, but multivariate analysis showed only myalgia (aOR: 7.1; 95% CI: 2.2-22.7; p < .001) and malaise (aOR: 12.76; 95% CI: 1.4-119.9; p = .026) were independently associated with hemolysis. The median time to hemolysis onset was 1.0 days (IQR: 1.0-2.5) and all occurred within a week of envenomation. Hemolysis durations were longer in patients DAT positive for IGG antibodies (7.5 vs. 4.0 days; p = .042). Most (76.9%) of hemolyzing patients received blood. In patients with cutaneous-hemolytic loxoscelism, hematuria occurred in 32.4%, rhabdomyolysis occurred in 60.9%, and elevated transaminases with normal hepatic synthetic function occurred in 29.4% but all of these patients developed rhabdomyolysis. Hemolysis was both intravascular and extravascular. Complications (hyperkalemia, INR ≥2.0, metabolic acidosis requiring bicarbonate, hypotension requiring vasopressors, and hypoxia requiring intubation) occurred only in patients with profound hemolytic anemia (hemoglobin <4 g/dL); one patient died.Conclusions: Constitutional symptoms occur in both cutaneous and cutaneous-hemolytic loxoscelism, although they occur more frequently in patients who develop hemolysis. Children may be at a higher risk of hemolysis after envenomation. Renal involvement (as evidenced by hematuria) and rhabdomyolysis may occur more frequently than has been previously reported. Hemolysis was both intravascular and extravascular.

Naloxone reversal of clonidine toxicity: dose, dose, dose.

CONTEXT: Following clonidine ingestion, naloxone is seldom administered as it is considered ineffective in reversing somnolence, bradycardia, or hypotension. However, this conclusion has been based on administration of small doses (2 mg or less) of naloxone. The somnolence is frequently treated with endotracheal intubation (ETI), a procedure with significant morbidity. OBJECTIVE: We aimed to determine if naloxone administration reversed the effects of clonidine or caused any adverse effects. METHODS: We performed a retrospective descriptive cohort (IRB approved) of hospital medical records for pediatric patients (6 months-16 years) with clonidine exposure. Demographics, history, co-ingestants, clinical data, treatments, and outcome were recorded in a de-identified database. RESULTS: The most common clinical findings in the 52 patients were sedation (n = 51), bradycardia (n = 44), and hypotension (n = 11). Of 51 somnolent patients, naloxone administration awoke 40 patients, five of which had co-ingestants. Nine patients experienced recurrent sedation that resolved with a repeat bolus of naloxone. Twenty somnolent bradycardic patients (11 less than 3 years old) received 10 mg naloxone via intravenous bolus. Thirteen awoke; bradycardia persisted in six of the awake patients. Of the remaining 31 patients, 22 awoke following 6 mg or less of naloxone. Naloxone reversed hypotension in 7 of 11 hypotensive patients. Only one hypotensive patient (with a coingestion) received vasopressors for hypotension. Three awake normotensive patients received vasopressors for bradycardia. Seven patients awoke and had normal vital signs following naloxone administration, but were chemically sedated and intubated for transport. There were no adverse events following the administration of any dose of naloxone. CONCLUSIONS: Administration of naloxone to somnolent pediatric patients with clonidine toxicity awoke the majority (40/51) and resolved bradycardia and hypotension in some. Persistent bradycardia was benign. Hypotension was rare and clinically insignificant. No adverse effects occurred in any patient including the 21 patients who received 10 mg naloxone. Morbidity in this overdose may be due to ETI, a procedure that could be prevented if high-dose naloxone (10 mg) were administered. Administration of high-dose naloxone should be considered in all children with clonidine toxicity.

Adverse events are rare after single-dose montelukast exposures in children.

STUDY OBJECTIVE: Montelukast sodium is a leukotriene-receptor antagonist approved as a controller medication for chronic asthma and allergic rhinitis in children and adults. We sought to characterize adverse events associated with single montelukast exposures in children ages 5-17 years and to determine whether adverse events were dose related for all-dose and for ultra-high-dose (≥50 mg) exposures. METHODS: This is a retrospective analysis of data from the National Poison Data System for exposures that included montelukast in individuals aged 5-17 years for calendar years 2000-2016. Filters were applied to identify exposure events in which montelukast was the primary exposure and for which the exact or lowest-possible ingested dose was recorded. Characteristics of adverse events were examined using descriptive statistics and multivariable logistic models were used to examine whether associations of montelukast and adverse events were dose related. RESULTS: During the 17-year study period, there were 17,069 montelukast exposures available for analyses. Patients were median [interquartile range] age 7 (5, 9) years, and 10,907 (64%) male gender. Abdominal pain was the most common adverse event (0.23%). There were 618 ultra-high-dose exposures (≥50 mg). These patients had median age 6 (5, 8) years, and 347 (56%) male gender. Abdominal pain was the most common adverse event (1.46%). Increasing ingested dose was associated with abdominal pain (adjusted odds ratio, 1.01, 95% confidence interval 1.01, 1.02) after adjustment for age and gender. No serious or life-threatening events were reported. CONCLUSIONS: Single-dose exposures of montelukast up to 445 mg are rarely associated with any adverse events and are not associated with serious or life-threatening adverse events in children aged 5-17 years.

Hydrocarbon toxicity: an analysis of AAPCC TESS data.

INTRODUCTION: Human hydrocarbon exposures have the potential to cause significant morbidity and mortality. To determine which hydrocarbons were associated with the most severe adverse outcomes, human exposure data reported to American poison information centers were analyzed. METHODS: Outcome data for single-substance, hydrocarbon exposures reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System from 1994 through 2003 were analyzed. Only cases with definitive medical outcomes were included. Analyses were stratified by five age groups: <6 years, 6-12 years, 13-19 years, 20-59 years, >59 years. Hazard factors were determined by calculating the sum of the major effects and fatalities for each hydrocarbon category and dividing this by the total number of exposures for that category. To normalize the data, the overall rate of major effects and deaths for each age group was assigned hazard factor value of 1. Hydrocarbon categories with a HF of > or = 1.5 were included in the final analyses. Estimated rates of major effect and fatal outcomes (outcomes/1000 people) were also calculated. RESULTS: 318,939 exposures were analyzed. Exposures to benzene, toluene/xylene, halogenated hydrocarbons, kerosene and lamp oil resulted in the highest hazard factor values. CONCLUSIONS: These data demonstrate that hydrocarbons that are absorbed systemically and those with low viscosities are associated with higher hazard factors. The risks associated with hydrocarbons often implicated in abuse by older children and adolescents are also confirmed.

A critical reconsideration of the clinical effects and treatment recommendations for sodium channel blocking drug cardiotoxicity.

The cardiac sodium channel is comprised of proteins that span the cardiac cell membrane and form the channel pore. Depolarisation causes the proteins to move and open the sodium channel. Once the channel is open (active conformation), sodium ions move into the cell. The channel then changes from the active conformation to an inactive conformation - the channel remains open, but influx of sodium ions ceases. Recovery occurs as the channel moves from the inactive conformation back to the closed conformation and is then ready to open following the next depolarisation. Sodium channel blocking drugs (NCBDs) occupy receptors in the channel during the active and inactive conformations. The drug dissociates from most of the channel receptors during recovery, but the time it takes the drug to dissociate slows recovery. The slowed recovery prolongs conduction time, the main toxicity of NCBD overdose. Conduction time is further prolonged if heart rate increases as there are more available active and inactive conformations/unit time, which increases channel receptor binding sites for the NCBD. In addition to prolonging conduction time, NCBDs also decrease inotropy. Treatment of NCBD cardiotoxicity has been based on in vitro and animal experiments, and case reports. Assumptions based on this evidence must now be reassessed. For example, canines consistently develop ventricular tachycardia (VT) when tricyclic antidepressants (TCAs) are administered. Much of the literature discussing NCBD cardiotoxicity assumes that TCA poisoning induces VT in humans with the same regularity that occurs in canines. Seemingly, in support of this assumption was the finding that patients with remote myocardial infarction developed VT when therapeutically ingesting a NCBD. However, conduction is prolonged in myocardium that is or has been ischaemic. NCBD prolong conduction more in previously ischaemic myocardium than in normal myocardium, which causes nonuniform conduction and allows the development of re-entrant arrhythmias such as VT. Although some nonuniform conduction may occur in the healthy heart following a NCBD overdose, there is no evidence that nonuniform conduction occurs to the extent that it will cause re-entrant arrhythmias in this setting. Using various animal models and a variety of NCBDs, sodium ions, bicarbonate ions and alkalosis have been compared for the treatment of ventricular arrhythmias, hypotension and mortality. The results of these experiments have been extrapolated to NCBD overdose in humans. Animal models and single treatment approaches may have narrowed our scope. More recent evidence indicates that properties of each individual NCBD may require unique treatment. There is limited evidence that glucagon, which increases initial sodium ion influx into the cardiac cell, should be considered early in the treatment of cardiotoxicity. Another consideration may be treatment of NCBD with faster kinetics. Conduction time is decreased if a NCBD occupying the receptor is replaced by a NCBD that moves off and on the receptor more quickly. There is less evidence for this treatment, as risk may be greater. With greater understanding of the sodium channel and NCBDs, we must reassess our approach to the treatment of patients with healthy hearts who overdose on NCBD.

Clonidine toxicity revisited.

The incidence of clonidine overdose is increasing, yet there is a paucity of new information regarding treatment options for clonidine toxicity. Reported treatment approaches vary widely, demonstrating the lack of science on which current treatment is based. Available research needs to be reassessed. Neurotransmitters, receptors, endogenous opioids, and baseline sympathetic tone determine the clinical response to clonidine as well as the potential response to drug therapy following clonidine overdose. This article reviews aspects of clonidine toxicity that need to be further investigated. Multicenter research trials will be required to evaluate new treatment options.

Flumazenil--treatment or toxin.

Flumazenil is frequently administered to the poisoned patient. Seizures may be precipitated and resedation may occur in patients who awakened following flumazenil administration. Seizures may increase morbidity and mortality of the overdose. Benefit:Risk ratio of administering flumazenil should be determined in each overdose patient. Indications for flumazenil are limited.