Henry A. Spiller

A one-year evaluation of calcium channel blocker overdoses: Toxicity and treatment

STUDY OBJECTIVEnTo examine the cardiovascular toxicity of calcium channel blockers and the efficacy of various treatments.nnnDESIGNnCase series collected prospectively over one year.nnnSETTINGnThree regional poison control centers.nnnTYPE OF PARTICIPANTSnOne hundred thirty-nine hospitalized patients who had ingested a calcium channel blocker.nnnINTERVENTIONSnCalcium, dopamine, atropine, isoproterenol, glucagon, and pacemakers.nnnMAIN RESULTSnHypotension, sinus node suppression, and dysrhythmias often occur with calcium channel blocker overdoses, but atrioventricular nodal block occurs more often with verapamil (chi 2 test, P < .025). Calcium was administered to 23 patients and was efficacious in reversing depression of cardiac conduction and increasing blood pressure. Dopamine was administered to ten patients and was efficacious in increasing blood pressure. Atropine was administered to eight patients, but only two had a positive response.nnnCONCLUSIONnAtrioventricular nodal depression is more common with verapamil overdoses. Calcium and dopamine are useful in treating toxicity from calcium channel blocker overdose, whereas atropine is sometimes useful.

Calcium channel blocker toxicity

A retrospective review was conducted of all patients who were reported to a regional poison control center after overdose of a calcium channel blocker during a two-year period (1987 and 1988). An analysis of 91 patient cases is presented after excluding allergic reactions, cases involving coingestants, and patients lost to follow-up. Patients who developed any symptoms after ingestion were defined as manifesting toxicity. There were 38 cases of verapamil ingestion with toxicity developing in 18 patients. The mean nontoxic dose was 320 mg, whereas the mean toxic ingestion was 3.2 g. Nine patients became hypotensive, 13 developed conduction system abnormalities (sinus node suppression, atrioventricular nodal block, or bundle branch block), and 11 manifested arrhythmias. Ten developed neurological symptoms. There were 31 cases of nifedipine ingestion with toxicity developing in seven patients. The mean nontoxic dose was 19 mg, while the mean toxic ingestion was 340 mg. Four patients were hypotensive, only one developed cardiac conduction abnormalities, and four developed arrhythmias. Three had neurological symptoms. There were 24 cases of diltiazem ingestion with only minor toxicity developing in four patients. There was no statistically significant difference in the frequency of hypotension, arrhythmias, or neurological symptoms in patients who overdosed with verapamil as compared with nifedipine (by Fishers exact test). However, conduction system abnormalities were more common with verapamil ingestion (P less than .05). Toxic manifestations after diltiazem over-dose were uncommon in our study. Eighteen of the 29 patients who developed toxicity required treatment in excess of gastrointestinal decontamination. Calcium was administered to 14 patients and was helpful in five.

Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management.

The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4–9xa0% in children and 4xa0% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80xa0% occurring in children <19xa0years old and 20xa0% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8xa0g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.

Out-of-Hospital Medication Errors Among Young Children in the United States, 2002–2012

OBJECTIVE: To investigate out-of-hospital medication errors among young children in the United States. METHODS: Using data from the National Poison Database System, a retrospective analysis of out-of-hospital medication errors among children <6 years old from 2002 through 2012 was conducted. RESULTS: During 2002–2012, 696u2009937 children <6 years experienced out-of-hospital medication errors, averaging 63u2009358 episodes per year, or 1 child every 8 minutes. The average annual rate of medication errors was 26.42 per 10u2009000 population. Cough and cold medication errors decreased significantly, whereas the number (42.9% increase) and rate (37.2% increase) of all other medication errors rose significantly during the 11-year study period. The number and rate of medication error events decreased with increasing child age, with children <1 year accounting for 25.2% of episodes. Analgesics (25.2%) were most commonly involved in medication errors, followed by cough and cold preparations (24.6%). Ingestion accounted for 96.2% of events, and 27.0% of medication errors were attributed to inadvertently taking or being given medication twice. Most (93.5%) cases were managed outside of a health care facility; 4.4% were treated and released from a health care facility; 0.4% were admitted to a non–critical care unit; 0.3% were admitted to a critical care unit; and 25 children died. CONCLUSIONS: This is the first comprehensive study to evaluate the epidemiologic characteristics of out-of-hospital medication errors among children <6 years of age on a national level. Increased efforts are needed to prevent medication errors, especially those involving non–cough and cold preparations, among young children.

Pediatric Exposure to Laundry Detergent Pods

OBJECTIVE: Laundry detergent pods are a new product in the US marketplace. This study investigates the epidemiologic characteristics and outcomes of laundry detergent pod exposures among young children in the United States. METHODS: Using data from the National Poison Data System, exposures to laundry detergent pods among children younger than 6 years of age during 2012–2013 were investigated. RESULTS: There were 17u2009230 children younger than 6 years exposed to laundry detergent pods in 2012–2013. From March 2012 to April 2013, the monthly number of exposures increased by 645.3%, followed by a 25.1% decrease from April to December 2013. Children younger than 3 years accounted for 73.5% of cases. The major route of exposure was ingestion, accounting for 79.7% of cases. Among exposed children, 4.4% were hospitalized and 7.5% experienced a moderate or major medical outcome. A spectrum of clinical effects from minor to serious was seen with ingestion and ocular exposures. There were 102 patients (0.6%) exposed to a detergent pod via ingestion, aspiration, or a combination of routes, including ingestion, who required tracheal intubation. There was 1 confirmed death. CONCLUSIONS: Laundry detergent pods pose a serious poisoning risk to young children. This nationwide study underscores the need for increased efforts to prevent exposure of young children to these products, which may include improvements in product packaging and labeling, development of a voluntary product safety standard, and public education. Product constituent reformulation is another potential strategy to mitigate the severity of clinical effects of laundry detergent pod exposure.

Pediatric Exposure to E-Cigarettes, Nicotine, and Tobacco Products in the United States

OBJECTIVES: To investigate the epidemiologic characteristics and outcomes of exposures to electronic cigarettes (e-cigarettes), nicotine, and tobacco products among young children in the United States. METHODS: A retrospective analysis of exposures associated with nicotine and tobacco products among children younger than 6 years old was conducted by using National Poison Data System data. RESULTS: From January 2012 through April 2015, the National Poison Data System received 29u2009141 calls for nicotine and tobacco product exposures among children younger than 6 years, averaging 729 child exposures per month. Cigarettes accounted for 60.1% of exposures, followed by other tobacco products (16.4%) and e-cigarettes (14.2%). The monthly number of exposures associated with e-cigarettes increased by 1492.9% during the study period. Children <2 years old accounted for 44.1% of e-cigarette exposures, 91.6% of cigarette exposures, and 75.4% of other tobacco exposures. Children exposed to e-cigarettes had 5.2 times higher odds of a health care facility admission and 2.6 times higher odds of having a severe outcome than children exposed to cigarettes. One death occurred in association with a nicotine liquid exposure. CONCLUSIONS: The frequency of exposures to e-cigarettes and nicotine liquid among young children is increasing rapidly and severe outcomes are being reported. Swift government action is needed to regulate these products to help prevent child poisoning. Prevention strategies include public education; appropriate product storage and use away from children; warning labels; and modifications of e-cigarette devices, e-liquid, and e-liquid containers and packaging to make them less appealing and less accessible to children.

Could chest wall rigidity be a factor in rapid death from illicit fentanyl abuse

Abstract Background: There has been a significant spike in fentanyl-related deaths from illicit fentanyl supplied via the heroin trade. Past fentanyl access was primarily oral or dermal via prescription fentanyl patch diversion. One factor potentially driving this increase in fatalities is the change in route of administration. Rapid intravenous (IV) fentanyl can produce chest wall rigidity. We evaluated post-mortem fentanyl and norfentanyl concentrations in a recent surge of lethal fentanyl intoxications. Methods: Fentanyl related deaths from the Franklin County coroner’s office from January to September 2015 were identified. Presumptive positive fentanyl results were confirmed by quantitative analysis using liquid chromatography tandem mass spectrometry (LC/MS/MS) and were able to quantify fentanyl, norfentanyl, alfentanyl, and sufentanyl. Results: 48 fentanyl deaths were identified. Mean fentanyl concentrations were 12.5u2009ng/ml, (range 0.5u2009ng/ml tou2009>40u2009ng/ml). Mean norfentanyl concentrations were 1.9u2009ng/ml (range none detected to 8.3u2009ng/ml). No appreciable concentrations of norfentanyl could be detected in 20 of 48 cases (42%) and were less than 1u2009ng/ml in 25 cases (52%). Elevated fentanyl concentrations did not correlate with rises in norfentanyl levels. In several cases fentanyl concentrations were strikingly high (22u2009ng/ml and 20u2009ng/ml) with no norfentanyl detected. Discussion: The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity. An alternate explanation could be a dose-related rapid onset of respiratory arrest. Deaths occurred with low levels of fentanyl in the therapeutic range (1–2u2009ng/ml) in apparent non-naïve opiate abusers. Acute chest wall rigidity is a well-recognized complication in the medical community but unknown within the drug abuse community. The average abuser of illicit opioids may be unaware of the increasing fentanyl content of their illicit opioid purchase. Conclusion: In summary we believe sudden onset chest wall rigidity may be a significant and previously unreported factor leading to an increased mortality, from illicit IV fentanyl use. Fentanyl and norfentanyl ratios and concentrations suggest a more rapid onset of death given the finding of fentanyl without norfentanyl in many of the fatalities. Chest wall rigidity may help explain the cause of death in these instances, in contrast to the typical opioid-related overdose deaths. Intravenous heroin users should be educated regarding this potentially fatal complication given the increasingly common substitution and combination with heroin of fentanyl.

A descriptive study of adverse events from clenbuterol misuse and abuse for weight loss and bodybuilding

ABSTRACT. Background: Clenbuterol is a β2-agonist approved in the United States for veterinary use in nonfood animals. Clenbuterol use is emerging among bodybuilders and fitness enthusiasts attracted to the hypertrophic and lipolytic effects. Cases: This was a retrospective chart review of clenbuterol exposures reported to 2 poison control centers. Misuse of clenbuterol for weight loss and bodybuilding was reported in 11 of 13 clenbuterol users. Reported clinical effects included tachycardia, widened pulse pressure, tachypnea, hypokalemia, hyperglycemia, ST changes on electrocardiogram (ECG), elevated troponin, elevated creatine phosphokinase (CPK), palpitations, chest pain, and tremor. Measured serum clenbuterol concentration was 2983 pg/mL post 4.5 mg ingestion. Coingestants included T3 and anabolic steroids. Treatments included activated charcoal, benzodiazepines, β-blockers, potassium replacement, and intravenous (IV) fluid. Conclusions: There is an increasing use of the Internet for illicit drug use for bodybuilding and weight loss purposes. These patients may not present as the stereotype of illicit drug abusers, but as healthy athletic low-risk patients. Clinical effects persisted greater than 24 hours with evidence of myocardial injury in 2 patients. Clenbuterol is increasingly being abused within the bodybuilding subculture. These cases illustrate the hidden dangers of clenbuterol abuse among bodybuilders and fitness enthusiasts.

The effect of poison control center consultation on accidental poisoning inpatient hospitalizations with preexisting medical conditions.

In 2005, the Kentucky Poison Control Center (PCC) recorded 46,625 poisoning calls; 27% received hospital treatment. Probabilistic data linkage of accidental poisoning inpatient hospital (IPH) discharge data and PCC data (years 2000–2004) was performed. This study compared IPH with/without preexisting medical conditions and IPH with/without PCC consultation, examining total length of stay and total hospitalization charges. When compared to the IPH reference group with no preexisting medical conditions and who did not consult the PCC (mean charges =

Prescription Opioid Exposures Among Children and Adolescents in the United States: 2000–2015

8748, mean length of stay = 3.2 d), PCC consultation without a preexisting medical condition was significantly associated with decreased total hospitalization charges and decreased length of stay (mean charges =